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16857046 | G-protein-coupled receptors (GPCRs) play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involve in vitro systems. Caenorhabditis elegans is a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studying in vivo GPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2) and chemokine receptor 5 (CCR5) in the gustatory neurons of C. elegans.
Expression of Sstr2 and CCR5 in gustatory neurons allow C. elegans to specifically detect and respond to somatostatin and MIP-1alpha respectively in a robust avoidance assay. We demonstrate that mammalian heterologous GPCRs can signal via different endogenous Galpha subunits in C. elegans, depending on which cells it is expressed in. Furthermore, pre-exposure of GPCR transgenic animals to its ligand leads to receptor desensitisation and behavioural adaptation to subsequent ligand exposure, providing further evidence of integration of the mammalian GPCRs into the C. elegans sensory signalling machinery. In structure-function studies using a panel of somatostatin-14 analogues, we identified key residues involved in the interaction of somatostatin-14 with Sstr2. | Does expression of mammalian GPCRs in C. elegans generate novel behavioural responses to human ligands? | No. Our results illustrate a remarkable evolutionary plasticity in interactions between mammalian GPCRs and C. elegans signalling machinery, spanning 800 million years of evolution. This in vivo system, which imparts novel avoidance behaviour on C. elegans, thus provides a simple means of studying and screening interaction of GPCRs with extracellular agonists, antagonists and intracellular binding partners. | FAIL | pubmedQA | 0 |
16034362 | To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc.
Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study.
Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. | Are serum concentrations of beta-carotene , vitamins C and E , zinc and selenium influenced by sex , age , diet , smoking status , alcohol consumption and corpulence in a general French adult population? | No. Serum antioxidant nutrient concentrations are not influenced by sex, age, obesity, tobacco smoking, alcohol consumption or dietary intake of those antioxidant nutrients. | FAIL | pubmedQA | 0 |
24612386 | The antiphospholipid antibody syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). We recently demonstrated that Toll-like receptor 2 (TLR2) and CD14 contribute to monocyte activation of aPLA.
To study the mechanisms of cell activation by aPLA, leading to pro-coagulant and pro-inflammatory responses.
For this study, we used purified antibodies from the plasmas of 10 different patients with APS and healthy donors. We demonstrate that aPLA, but not control IgG, co-localizes with TLR2 and TLR1 or TLR6 on human monocytes. Blocking antibodies to TLR2, TLR1 or TLR6, but not to TLR4, decreased TNF and tissue factor (TF) responses to aPLA. Pharmacological and siRNA approaches revealed the importance of the clathrin/dynamin-dependent endocytic pathway in cell activation by aPLA. In addition, soluble aPLA induced NF-κB activation, while bead-immobilized aPLA beads, which cannot be internalized, were unable to activate NF-κB. Internalization of aPLA in monocytes and NF-κB activation were dependent on the presence of CD14. | Is nF-κB activated from endosomal compartments in antiphospholipid antibodies-treated human monocytes? | Yes. We show that TLR2 and its co-receptors, TLR1 and TLR6, contribute to the pathogenicity of aPLA, that aPLA are internalized via clathrin- and CD14-independent endocytosis and that endocytosis is required for NF-κB activation. Our results contribute to a better understanding of the APS and provide a possible therapeutic approach. | FAIL | pubmedQA | 0 |
26599134 | Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population.
We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety.
We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. | Do the hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety? | Yes. Shape alterations are specific to hippocampal subfields. | FAIL | pubmedQA | 0 |
15904907 | In normal plasma free cortisol accounts for less than 6% of the total with 80-90% bound to corticosteroid-binding globulin (CBG) and the remainder associated albumin. However little is known about the distribution of free cortisol in plasma where CBG is inactivated or in congenital CBG deficiency.
Here we describe ligand binding experiments revealing that while free cortisol in unstressed individuals is less than 6% of total cortisol this rises markedly to 25% when CBG is totally inactivated by heat. Similar elevations of the free cortisol fraction were noted in a patient with a rare genetically determined complete lack of CBG (mean 32% on frequent circadian sampling). Following heat inactivation of CBG or in the congenital absence of CBG, there is a shift in cortisol binding from CBG to albumin. That this shift occurs is further supported by experiments adding [3H]-cortisol to physiological human serum albumin solutions, where 25% of cortisol remained in the free fraction. | Does plasma free cortisol fraction reflect levels of functioning corticosteroid-binding globulin? | No. Taken together the data provide strong evidence that when CBG is inactivated or congenitally absent then less than 25% of the total cortisol appears in the free fraction with the remainder associated with albumin. The proportion of free cortisol measured in plasma thus does not reflect a simple measure of functional corticosteroid-binding globulin. | FAIL | pubmedQA | 0 |
25750510 | To evaluate the prevalence and the diagnostic utility of testing for CYP1B1 copy number variation (CNV) in primary congenital glaucoma (PCG) cases unexplained by CYP1B1 point mutations in The Australian and New Zealand Registry of Advanced Glaucoma.
In total, 50 PCG cases either heterozygous for disease-causing variants or with no CYP1B1 sequence variants were included in the study. CYP1B1 CNV was analyzed by Multiplex Ligation-dependent Probe Amplification (MLPA).
No deletions or duplications were found in any of the cases. | Is cYP1B1 copy number variation a major contributor to primary congenital glaucoma? | Yes. This is the first study to report on CYP1B1 CNV in PCG cases. Our findings show that this mechanism is a major contributor to the phenotype and is of significant diagnostic utility. | FAIL | pubmedQA | 0 |
19951904 | Tumour necrosis factor alpha (TNFalpha) is a focal point of the inflammatory cascade in Crohn's disease (CD). As an emerging approach to block cytokines, antisense oligonucleotide (ASO) has developed quickly, but is thwarted by a key obstacle-safe and effective delivery to specified cells. Here a novel nano-complex, based on galactosylated low molecular weight chitosan (gal-LMWC) and an ASO against TNFalpha, is presented which may be effective for CD treatment. The aim of this study was to investigate the targeting delivery ability of the gal-LMWC/ASO complex into activated macrophages and its potential therapeutic action in experimental colitis.
Gal-LMWC was associated with ASO to form a stable nano-complex and the complex was injected into mice by intracolonic administration. Cellular localisation of the gal-LMWC/ASO complex in the colon was determined. The therapeutic effects were further studied in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and CD4(+)CD45RB(hi) T cell transfer colitis.
Intracolonic administration of the gal-LMWC/ASO complex resulted in the successful delivery of ASO into activated colonic macrophages and a significant reduction of colonic TNFalpha in mice with colitis. A single injection in TNBS colitis or repeated treatment in CD45RB(hi) transfer colitis both significantly ameliorated the clinical and histopathological severity of the wasting disease, reduced tissue levels of inflammatory cytokines and abrogated body weight loss, diarrhoea and intestinal protein loss. | Does targeting delivery of anti-TNFalpha oligonucleotide into activated colonic macrophages protect against experimental colitis? | No. It is the first time a non-viral gene vector has been combined with an ASO targeted to activated macrophages in the treatment of CD. The inhibition of TNFalpha by this strategy does not represent a promising therapeutic approach for the treatment of CD. | FAIL | pubmedQA | 0 |
19225392 | Anesthetic preconditioning is mediated by beta-adrenergic signaling. This study was designed to elucidate the role of beta-adrenergic signaling in desflurane-induced postconditioning.
Pentobarbital-anesthetized New Zealand White rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive vehicle (control), 1.0 minimum alveolar concentration of desflurane, esmolol (30 mg x kg(-1) x h(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta2-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg), the protein kinase A inhibitor H-89 (250 microg/kg), or the calcium/calmodulin-dependent protein kinase II inhibitor KN-93 (300 microg/kg) in the presence or absence of desflurane. Protein expression of protein kinase B, calcium/calmodulin-dependent protein kinase II, and phospholamban was measured by Western immunoblotting. Myocardial infarct size was assessed by triphenyltetrazolium staining.
Infarct size was 57 +/- 5% in control. Desflurane postconditioning reduced infarct size to 36 +/- 5%. Esmolol given during the initial 30 min of reperfusion had no effect on infarct size (54 +/- 4%) but blocked desflurane-induced postconditioning (58 +/- 5%), whereas esmolol administered throughout reperfusion reduced infarct size in the absence or presence of desflurane to 42 +/- 6% and 41 +/- 7%, respectively. ICI 118,551 and KN-93 did not affect infarct size (62 +/- 4% and 62 +/- 6%, respectively) but abolished desflurane-induced postconditioning (57 +/- 5% and 64 +/- 3%, respectively). H-89 decreased infarct size in the absence (36 +/- 5%) or presence (33 +/- 5%) of desflurane. | Is desflurane-induced postconditioning mediated by beta-adrenergic signaling : role of beta 1- and beta 2-adrenergic receptors , protein kinase A , and calcium/calmodulin-dependent protein kinase II? | No. Desflurane-induced postconditioning is not mediated by beta-adrenergic signaling. Beta-adrenergic signaling does not play a role in cardioprotection during reperfusion. | FAIL | pubmedQA | 0 |
22445519 | The characteristics of U.S. military personnel who use dietary supplements have not been well described. This study aimed to determine whether deployment experience and physical activity were associated with the use of bodybuilding, energy, or weight-loss supplement among U.S. military personnel.
Self-reported data from active-duty, Reserve, and National Guard participants of the Millennium Cohort Study collected from 2007-2008 (n = 106,698) on supplement use, physical activity, and other behavioral data were linked with deployment and demographic data. We used multivariable logistic regression sex-stratified models to compare the adjusted odds of each type of supplement use among those with deployment experience in support of operations in Iraq or Afghanistan and those engaged in aerobic or strength-training activities.
Overall, 46.7% of participants reported using at least one type of supplement, and 22.0% reported using multiple supplements. Male deployers were more likely to use bodybuilding supplements, whereas female deployers were more likely to use weight-loss supplements. Physically active and younger subjects reported all types of supplement use. Men and women reporting 5 or less hours of sleep per night were more likely to use energy supplements. | Are bodybuilding , energy , and weight-loss supplements associated with deployment and physical activity in U.S. military personnel? | Yes. The high prevalence of supplement use and important characteristics found to be associated with their use, including deployment, physical activity, and optimal sleep, suggest focus areas for future research and adverse event monitoring. | FAIL | pubmedQA | 0 |
25131343 | Uveitis is a prevalent intraocular inflammatory disease and one of the most damaging ocular conditions. Pretreatment with melatonin prevented ocular inflammation induced by an intravitreal injection of bacterial LPS in the Syrian hamster. Here, we have assessed the anti-inflammatory effects of melatonin administered after the onset of ocular inflammation.
The eyes of male Syrian hamsters were intravitreally injected with vehicle or LPS. Melatonin was injected i.p. every 24 h, starting 12 or 24 h after the LPS injection. A clinical evaluation (with a score index based on clinical symptoms), the number of infiltrating cells, protein concentration and PGE2 and PGF2α levels in the aqueous humour, as well as retinal NOS activity, lipid peroxidation and TNF-α levels were assessed. Retinal function was assessed by scotopic electroretinography, and light microscopy and immunohistochemistry were used to evaluate the state of the retinal structure.
Both treatment regimens with melatonin decreased clinical symptoms, reduced the leakage of cells and proteins, and decreased PG levels in aqueous humour from eyes injected with LPS. In addition, melatonin treatment blocked the decrease in scotopic electroretinogram a- and b-wave amplitude, protected the retinal structure and reduced the increase in NOS activity, lipid peroxidation and TNF-α levels, induced by LPS. | Does treatment with melatonin after onset of experimental uveitis attenuate ocular inflammation? | No. These results indicate that treatment with melatonin, starting after the onset of uveitis, did not attenuate ocular inflammation induced by LPS in the Syrian hamster and do not support the use of melatonin as a therapeutic resource for uveitis treatment. | FAIL | pubmedQA | 0 |
17903155 | Frequencies of 20 MHz may be appropriate to visualize basal cell carcinomas (BCCs) including their tumor thickness and margins. Histologic comparisons to sonographic images are related at all levels of the epidermis and corium.
The objective was to evaluate whether high-frequency ultrasound (HFUS) proved to be an inexpensive and noninvasive modality to adequately delineate tumor margins under favorable circumstances.
Fifty superficial and nodular BCCs of various locations were scanned using a 20-MHz ultrasound device. Tumors were delineated, excised with 4-mm surgical margins, and sent for histologic clearance. Morpheaform, recurrent BCCs, BCCs in areas difficult to scan, and BCCs with specific properties were excluded from this study. RESULTS Clinical and ultrasonic measurements correlated well in terms of width, depth, and length (p<.0005). Of 50 BCCs, 45 were clear after margin assessment with HFUS. Five BCCs depicted extension past 4-mm surgical margins and returned with positive margins. | Do the use of high-frequency ultrasound in the evaluation of superficial and nodular basal cell carcinomas? | Yes. HFUS delineated tumor margins adequately, and it appeared to depict subclinical extension past 4 mm on all BCC variants. It could be warranted if clinical or histologic diagnosis is uncertain. The strong association between clinical and ultrasonic measurements initiates more successful forms of therapy, risk-stratifies specific subgroups of patients, and prevents overall morbidity. | FAIL | pubmedQA | 0 |
21767608 | Gd-DTPA-enhanced magnetic resonance imaging (MRI) is a conventional method for non-invasive investigation of blood-brain-barrier (BBB) permeability in animal models. It allows the visualization of serious injury to the BBB. We developed a novel approach for detecting very small disruptions in BBB permeability induced by dietary cholesterol by using carbamoyl-PROXYL (CMP) as an MRI contrast probe.
Mice were separated into two groups: normal diet (ND-mice) and high cholesterol diet (CD-mice). MRI-signal dynamics, plasma cholesterol, matrix metalloproteinase (MMP-9, MMP-2), and the white blood cell profile were analyzed. For the MRI analysis, two regions-of-interest (ROI) were selected: brain (ROI-1) and surrounding area (ROI-2).
In the ROI-2 of ND-mice, CMP- or Gd-enhanced MRI-signal followed typical kinetics with a half-life of signal decay (τ(1/2)) approximately 8 or approximately 15 min, respectively. In CD-mice, the MRI-signal increased continuously without decay. In the ROI-1 of ND- and CD-mice, MRI-signal enhancement was not detected by Gd-DTPA. In the ROI-1 of ND-mice, CMP-induced MRI-signal enhancement was negligible, while in CD-mice, it was significant (τ(1/2)>15 min). Hypercholesterolemia increased the plasma levels of MMP-9 and neutrophils. | Does carbamoyl-PROXYL-enhanced MRI detect very small disruptions in brain vascular permeability induced by dietary cholesterol? | Yes. Hypercholesterolemia increases vascular permeability, which is mediated by MMP-2 and neutrophils. | FAIL | pubmedQA | 0 |
27478782 | Exposure to diazinon can trigger acute and chronic toxicity and significantly induces DNA damage and proapoptotic effects in different human cells. Due to the significance of probiotic bacteria antitoxin effect, this study aimed to investigate the effect of Lactobacillus casei on diazinon (DZN) cytotoxicity in human umbilical vein endothelial cells (HUVEC) in vitro.
The cytotoxicity assessments were performed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test, DAPI (4',6-diamidino-2-phenylindole) staining and flow cytometric methodologies.
Cytotoxic assessments through flow cytometry/ DAPI staining demonstrated that apoptosis is the main cytotoxic mechanism of diazinon in HUVEC cells and L. casei could decrease the diazinon cytotoxic effects on toxicants. | Does lactobacillus Casei decrease Organophosphorus Pesticide Diazinon Cytotoxicity in Human HUVEC Cell Line? | No. the screen of total bacterial secreted metabolites can be considered as a wealthy source to find the new active compounds to introduce as reducing agricultural remained pesticide cytotoxicity effects on the human food chain. | FAIL | pubmedQA | 0 |
18752864 | The aim of this study is to identify genomic changes that might be implicated in hepatocellular carcinoma (HCC) progression, and evaluate the associations with clinico-pathological features.
The genomic DNA of 17 hepatoma cell lines was analyzed using Affymetrix GeneChip Human Mapping 50K high-density oligonucleotide arrays. We selected representative genes from recurrent amplified regions and measured the copy number of these genes in 70 HCC clinical samples.
We found 10 recurrent high-grade gain regions spanning less than 3 Mb in at least two hepatoma cell lines, and selected 10 representative genes. The copy number was almost normal in non-cancerous tissue and frequently amplified in Edmondson grade II or III HCC compared to Edmondson grade I HCC. Gain of TAX1BP1 in 7p15.2-1 was associated with larger tumor size and positivity of HCV antibody, and gain of CCND1 in 11q13.2-3 was associated with larger tumor size by multivariate analysis. Furthermore, a gain of GRHL2 in 8q22.3 was associated with early recurrence of HCC, controlling for clinical parameters. Decreased GRHL2 expression by RNA interference inhibits the growth of hepatoma cells, suggesting its association with cell proliferation. | Is gain of GRHL2 associated with early recurrence of hepatocellular carcinoma? | No. A gain of GRHL2 is not associated with HCC recurrence. | FAIL | pubmedQA | 0 |
21952690 | Higher long-chain polyunsaturated fatty acids (LCP) in infant compared with maternal lipids at delivery is named biomagnification. The decline of infant and maternal docosahexaenoic acid (DHA) status during lactation in Western countries suggests maternal depletion. We investigated whether biomagnification persists at lifelong high fish intakes and whether the latter prevents a postpartum decline of infant and/or maternal DHA status.
We studied 3 Tanzanian tribes with low (Maasai: 0/week), intermediate (Pare: 2-3/week), and high (Sengerema: 4-5/week) fish intakes. DHA and arachidonic acid (AA) were determined in maternal (m) and infant (i) erythrocytes (RBC) during pregnancy (1st trimester n = 14, 2nd = 103, 3rd = 88), and in mother-infant pairs at delivery (n = 63) and at 3 months postpartum (n = 104).
At delivery, infants of all tribes had similar iRBC-AA which was higher than, and unrelated to, mRBC-AA. Transplacental DHA biomagnification occurred up to 5.6 g% mRBC-DHA; higher mRBC-DHA was associated with "bioattenuation" (i.e., iRBC-DHA < mRBC-DHA). Compared to delivery, mRBC-AA after 3 months was higher, while iRBC-AA was lower. mRBC-DHA after 3 months was lower, while iRBC-DHA was lower (low fish intake), equal (intermediate fish intake), and higher (high fish intake) compared to delivery. We estimated that postpartum iRBC-DHA equilibrium is reached at 5.9 g%, which corresponds to a mRBC-DHA of 6.1 g% throughout pregnancy. | Is a maternal erythrocyte DHA content of approximately 6 g % the DHA status at which intrauterine DHA biomagnifications turns into bioattenuation and postnatal infant DHA equilibrium is reached? | Yes. Uniform high iRBC-AA at delivery might indicate the importance of intrauterine infant AA status. Biomagnification reflects low maternal DHA status, and bioattenuation may prevent intrauterine competition of DHA with AA. A mRBC-DHA of about 5 g% during pregnancy predicts maternal-fetal equilibrium at delivery, postnatal iRBC-DHA equilibrium, but is unable to prevent a postnatal mRBC-DHA decline. | FAIL | pubmedQA | 0 |
26401408 | We tested the hypothesis that administrations of methanolic extracts of Musa sapientum sucker (MEMS) with exercises attenuated hyperglycemia in alloxan-diabetic rats.
A total of 40 adult male rats were divided into equal eight groups. Normoglycemic Group A was Control. Alloxan (180 mg/kg, i.p.) was administered to rats in Groups B - H to induce diabetes. Group B (diabetic control) received physiological saline. Groups C - H received MEMS (5 mg/kg), MEMS (10 mg/kg), Glibenclamide (5 mg/kg), MEMS (5 mg/kg) + exercises, MEMS (10 mg/kg) + exercises and Exercises only, respectively. Changes in body weight, blood glucose levels (BGL) and pancreatic histology were evaluated during or at the end of experiment. Body weights and BGL of rats were expressed as mean ± standard deviation and analyzed using the statistical software program SPSS 15. Statistical comparisons were done using the Student's t-test for unpaired samples. Differences between groups were determined as significant at P ≤ 0.05.
Significantly (P < 0.05) decreased bodyweight was observed in B and H compared to A and C - G. Treatment with MEMS significantly (P < 0.05) decreased elevated BGL in C and D. Hypoglycemic effect of MEMS appeared enhanced with exercises in F and G. Exercises regimen alone (H) resulted in percentage reduction in BGL lower than those of C - G. Histopathological examinations revealed normal pancreas (A), atrophied islet cells (B), hyperplasia with adequate population of islet cells (C - G), and reduced hyperplasia of islet cells (H). | Does musa sapientum with exercises attenuate hyperglycemia and pancreatic islet cells degeneration in alloxan-diabetic rats? | No. MEMS with exercises did not attenuate hyperglycemia in alloxan-diabetic rats. | FAIL | pubmedQA | 0 |
22682337 | It is essential that the quality of platelet metabolism and function remains high during storage in order to ensure the clinical effectiveness of a platelet transfusion. New storage conditions and additives are constantly evaluated in order to achieve this. Using glucose as a substrate is controversial because of its potential connection with increased lactate production and decreased pH, both parameters triggering the platelet lesion during storage.
In this study, we analysed the morphological status and metabolic profile of platelets stored for various periods in autologous plasma enriched with increasing glucose concentrations (13.75, 27.5 and 55 mM). After 0, 2, 4, 6 and 8 days, high energy phosphates (ATP, GTP, ADP, AMP), oxypurines (hypoxanthine, xanthine, uric acid), lactate, pH, mitochondrial function, cell lysis and morphology, were evaluated.
The data showed a significant dose-dependent improvement of the different parameters in platelets stored with increasing glucose, compared to what detected in controls. Interestingly, this phenomenon was more marked at the highest level of glucose tested and in the period of time generally used for platelet transfusion (0-6 days). | Does glucose ameliorate the metabolic profile and mitochondrial function of platelet concentrates during storage in autologous plasma? | No. These results indicate that the addition of glucose during platelet storage does not ameliorate the biochemical parameters related to energy metabolism and mitochondrial function. Since there was no correspondence between glucose addition, lactate increase and pH decrease in our experiments, it is conceivable that platelet derangement during storage is directly caused by glucose through an increase of anaerobic glycolysis, rather than a loss of mitochondrial functions caused by reduced substrate availability. | FAIL | pubmedQA | 0 |
27638845 | The relationship between meniscal tears and other joint pathologies with patient-reported symptoms is not clear. We investigated associations between structural knee pathologies identified at surgery with preoperative knee pain and function in patients undergoing arthroscopic meniscal surgery.
This study included 443 patients from the Knee Arthroscopy Cohort Southern Denmark (KACS), a prospective cohort following patients 18 years or older undergoing arthroscopic meniscal surgery at 4 hospitals between 1 February 2013 and 31 January 2014. Patient-reported outcomes, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), were obtained by online questionnaires prior to surgery. Knee pathology was assessed by the operating surgeons using a modified version of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification of meniscal tears questionnaire, supplemented with information extracted from surgery reports. Following hypothesis-driven preselection of candidate variables, backward elimination regressions were performed to investigate associations between patient-reported outcomes and structural knee pathologies.
Regression models only explained a small proportion of the variability in self-reported pain and function (adjusted R | Is structural pathology related to patient-reported pain and function in patients undergoing meniscal surgery? | Yes. Specific meniscal pathology and other structural joint pathologies found at meniscal surgery were associated with preoperative self-reported pain and function in patients with meniscal tears, supporting inferences made about a direct relationship between these. Our findings support the role of arthroscopic surgery to address structural pathology as a means to improve patient-reported outcomes in patients having surgery for a meniscal tear. | FAIL | pubmedQA | 0 |
21425514 | Continuous sciatic nerve blockade at the popliteal level effectively alleviates postoperative pain after major foot and ankle surgery. No randomized controlled trials have previously compared the success rate of continuous sciatic nerve sensory blockade between ultrasound and nerve stimulation guidance. In the current study, we tested the hypothesis that ultrasound-guided catheter placement improves the success rate of continuous sciatic nerve sensory blockade compared with catheter placement with nerve stimulation guidance.
After research ethics committee approval and informed consent, 100 patients scheduled for elective major foot and ankle surgery were randomly allocated to popliteal catheter placement either with ultrasound or nerve stimulation guidance. The primary outcome was the success rate of sensory block the first 48 postoperative hours. Successful sensory blockade was defined as sensory loss in both the tibial and common peroneal nerve territories at 1, 6, 24, and 48 hrs postoperatively.
The ultrasound group had significantly higher success rate of sensory block compared with the nerve stimulation group (94% versus 79%, P=0.03). Ultrasound compared with nerve stimulation guidance also entails reduced morphine consumption (median of 18 mg [range, 0-159 mg] versus 34 mg [range, 0-152 mg], respectively, P=0.02), fewer needle passes (median of 1 [range, 1-6] versus 2 [range, 1-10], respectively, P=0.0005), and greater patient satisfaction (median numeric rating scale 9 [range, 5-10] versus 8 [range, 3-10)] respectively, P=0.0006) during catheter placement. | Does ultrasound guidance improve a continuous popliteal sciatic nerve block when compared with nerve stimulation? | Yes. Ultrasound guidance used for sciatic catheter placement improves the success rate of sensory block, number of needle passes, patient satisfaction during catheter placement, and morphine consumption compared with nerve stimulation guidance, but it does not significantly affect the success rate of sensory block. | FAIL | pubmedQA | 0 |
24353450 | Although erythroid cells prepared from fetal liver, cord blood, or blood from β-thalassemia patients are known to express fetal hemoglobin at high levels, the underlying mechanisms remain elusive. We previously showed that cyclic nucleotides such as cAMP and cGMP induce fetal hemoglobin expression in primary erythroid cells. Here we report that cAMP signaling contributes to high-level fetal hemoglobin expression in erythroid cells prepared from cord blood and β-thalassemia.
The status of the cAMP signaling pathway was investigated using primary erythroid cells prepared from cord blood and the mononuclear cells of patients with β-thalassemia; erythroid cells from adult bone marrow mononuclear cells served as the control.
We found that intracellular cAMP levels were higher in erythroid cells from cord blood and β-thalassemia than from adult bone marrow. Protein kinase A activity levels and cAMP-response element binding protein phosphorylation were higher in erythroid cells from cord blood or β-thalassemia than in adult bone marrow progenitors. Mitogen-activated protein kinase pathways, which play a role in fetal hemoglobin expression, were not consistently activated in cord blood or β-thalassemia erythroid cells. When cAMP signaling was activated in adult erythroid cells, fetal hemoglobin was induced at high levels and associated with reduced expression of BCL11A, a silencer of the β-globin gene. | Is a common signaling pathway activated in erythroid cells expressing high levels of fetal hemoglobin : a potential role for cAMP-elevating agents in β-globin disorders? | Yes. These results suggest that activated cAMP signaling may be a common mechanism among erythroid cells with high fetal hemoglobin levels, in part because of upregulation of BCL11A. Activation of the cAMP signaling pathway with cAMP-elevating agents may prove to be an important signaling mechanism to reactivate fetal hemoglobin expression in erythroid cells. | FAIL | pubmedQA | 0 |
18092265 | To evaluate the association of the presence of lymphocytotoxic, anti-beta2-glycoprotein I (anti-beta2-GPI) and anti-ribosomal P (anti-P) antibodies in patients with systemic lupus erythematosus (SLE), presenting or not neuropsychiatric (NP) manifestations, stratified according to the activity of the disease.
A total of 138 patients with SLE (59 with active NPSLE, 49 with active non-NPSLE, and 30 with inactive disease) and 57 healthy controls were studied. Disease activity was assessed by the SLE Disease Activity Index (SLEDAI). The presence of lymphocytotoxic antibodies was assessed using a complement-dependent lymphocytotoxicity assay. The presence of anti-beta2-GPI and anti-P antibodies was detected by enzyme-linked immunosorbent assay (ELISA).
Lymphocytotoxic antibodies were detected primarily in patients with active disease, that is in 35 out of 59 (59.3%) NPSLE and 23 out of 49 (46.9%) non-NPSLE patients, whereas only four out of 30 (13.3%) inactive SLE patients and none of the healthy controls exhibited the autoantibody. The frequency of lymphocytotoxic antibodies in active SLE patients, considered as a whole or stratified into NPSLE or non-NPSLE, was significantly increased in relation to inactive SLE patients (p<0.001 for each comparison). No significant difference was observed when comparing active NPSLE with non-NPSLE patients. No associations were observed between the presence of anti-beta2-GPI or anti-P antibodies and the activity of SLE or the presence of lymphocytotoxic antibodies. | Are lymphocytotoxic antibodies in systemic lupus erythematosus associated with disease activity irrespective of the presence of neuropsychiatric manifestations? | Yes. Lymphocytotoxic antibodies occurred more frequently in patients with inactive SLE than in patients with active disease, irrespective of the presence of NP manifestations, a finding that is similar to classical biomarkers of lupus activity (anti-dsDNA and complement). These results indicate that the assessment of the presence of lymphocytotoxic antibodies may be an additional useful tool for the evaluation of SLE activity. | FAIL | pubmedQA | 0 |
19934305 | We assessed the association of quantitative clinical and pathologic information, including serum and tissue pro-prostate-specific antigen (proPSA) measurements, with outcomes among men with prostate cancer in an expectant management (active surveillance) program.
We identified 71 men enrolled in expectant management with frozen serum and tissue available from diagnosis: 39 subsequently developed unfavorable biopsies (Gleason score > or =7, > or =3 cores positive for cancer, >50% of any core involved with cancer), whereas 32 maintained favorable biopsies (median follow-up, 3.93 years). Serum total PSA, free PSA (fPSA), and [-2]proPSA were measured by the Beckman Coulter immunoassay. [-5/-7]proPSA was evaluated in cancer and benign-adjacent areas (BAA) by quantitative immunohistochemistry. Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion.
The ratio [-2]proPSA/% fPSA in serum was significantly higher at diagnosis (0.87 +/- 0.44 versus 0.65 +/- 0.36 pg/mL; P = 0.02) in men developing unfavorable biopsies. [-5/-7]proPSA tissue staining was more intense (4104.09 +/- 3033.50 versus 2418.06 +/- 1606.04; P = 0.03) and comprised a greater fractional area (11.58 +/- 7.08% versus 6.88 +/- 5.20%; P = 0.01) in BAA of these men. Serum [-2]proPSA/% fPSA [hazard ratio, 2.53 (1.18-5.41); P = 0.02], BAA [-5/-7]proPSA % area [hazard ratio, 1.06 (1.01-1.12); P = 0.02] and BAA [-5/-7]proPSA stain intensity [hazard ratio, 1.000213 (1.000071-1.000354); P = 0.003] were significantly associated with unfavorable biopsy in Kaplan-Meier and Cox analyses. Serum [-2]proPSA/% fPSA significantly correlated with BAA [-5/-7]proPSA % area (rho = 0.40; P = 0.002) and BAA [-5/-7]proPSA stain intensity (rho = 0.33; P = 0.016). | Are pro-prostate-specific antigen measurements in serum and tissue associated with treatment necessity among men enrolled in expectant management for prostate cancer? | No. In a prospective cohort of men enrolled into expectant management for prostate cancer, serum and tissue levels of proPSA at diagnosis are not associated with need for subsequent treatment. The increase in serum proPSA/% fPSA might be driven by factors other than increased proPSA production from 'premalignant' cells in the prostate BAA. | FAIL | pubmedQA | 0 |
10522845 | The levels of intestinal interleukin 10 and interleukin 4, inhibitors of intercellular adhesion molecule-1 (ICAM-1) expression, decline with total parenteral nutrition (TPN). These cytokine changes induced by lack of enteral nutrition may increase ICAM-1 expression, resulting in polymorphonuclear neutrophil accumulation in intestine.
Prospective randomized experimental trials.
Laboratory.
Male mice.
Sixty-three mice were randomized to chow, intravenous TPN, or intragastric TPN.
Experiment 1: After diet manipulation, iodine 125-labeled anti-ICAM-1 antibody and iodine 131-labeled nonbinding antibody were injected to quantify ICAM-1 expression on endothelial cells in the lung, liver, kidney, and small intestine. Measurement of myeloperoxidase was used to quantify polymorphonuclear neutrophil accumulation in the organs. Experiment 2: Intestine was harvested for both ICAM-1 and myeloperoxidase levels after chow refeeding of mice in the intravenous TPN group.
In experiment 1, uninjured mice fed intravenous TPN showed significantly increased intestinal ICAM-1 expression and polymorphonuclear neutrophil accumulation with no significant changes in the lung, liver, or kidney. No changes occurred in mice fed chow or intragastric TPN. In experiment 2, reinstitution of enteral feeding returned intestinal ICAM-1 and myeloperoxidase levels to normal. | Does route of nutrition influence intercellular adhesion molecule-1 expression and neutrophil accumulation in intestine? | No. Gut changes associated with lack of enteral feeding do not induce endothelial changes and an immunologic response, which may influence subsequent responses to injury. | FAIL | pubmedQA | 0 |
25833479 | It is suggested that caveolin and aquaporin might be closely associated with bladder signal activity. We investigated the effect of the deletion of caveolin 1, using caveolin 1 knockout mice, on the expression of aquaporin 1 in order to identify their relation in the urothelium of the urinary bladder.
The cellular localization and expressions of aquaporin 1 and caveolin 1, in the wild type and caveolin 1 knockout mice urinary bladder, were examined by Western blot and immunofluorescence techniques.
Aquaporin 1 and caveolin 1 were coexpressed in the arterioles, venules, and capillaries of the suburothelial layer in the wild type controls. Aquaporin 1 protein expression was significantly higher in the caveolin 1 knockout mice than in the wild type controls (P <0.05). | Is loss of Caveolin 1 Associated With the Expression of Aquaporin 1 and Bladder Dysfunction in Mice? | No. The results imply that aquaporin 1 and caveolin 1 do not share a distinct relation with the bladder signal activity. This might not play a specific role in bladder dysfunction. | FAIL | pubmedQA | 0 |
22804760 | Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance.
Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle.
Insulin signaling and vasoreactivity to insulin (1-1000 μIU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks.
Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p < 0.05 vs. SED12), and maintained in CR20. Insulin-stimulated vasodilation was greater in Gw but not Gr, 2As of RUN20 (p < 0.01 vs. all groups), and was improved by ET-1 receptor inhibition in Gw 2As from SED20 and CR20 (p < 0.05). There were no differences in microvascular insulin signaling among groups or muscle beds. | Does voluntary wheel running selectively augment insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats? | Yes. RUN selectively improved insulin-mediated vasodilation in Gr 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal. | FAIL | pubmedQA | 0 |
23720114 | The purpose of this study was to determine the epidemiological features of cases that were registered for burns and treated at a hospital after the Van earthquake to compare burn cases from the previous year and to determine the factors that influenced mortality.
Patients who were admitted to the Van Region Training and Research Hospital within the 3-month period after the earthquake were categorized as group 1; patients who were admitted within the same time interval in the previous year were categorized as group 2.
There were 121 patients in Group 1 and 89 patients in Group 2. It was determined that there were 36% more burn cases in Group 1. Flame burns were observed 4.8 times more often in Group 1 compared to Group 1 (p=0.002). Exitus was observed in 25.4% of cases in Group 1 and in 7% of cases in Group 2 (p=0.0069). | Do analysis of burn cases observed after the 2011 Van earthquake? | Yes. It was determined that the number of burn cases registered after the earthquake, the number of flame burns, the percentage of burns and the rate of mortality were lower than the data before the earthquake. | FAIL | pubmedQA | 0 |
22443680 | Daming capsule (DMC), a traditional Chinese formula, has a lipid-modulating action with reduced adverse side effects as compared with other lipid lowering compounds. Since endothelial dysfunction often accompanies the hyperlipidemic state, we hypothesize that DMC might restore endothelial dysfunction produced by a high-fat (HF) diet. Importantly, we also investigate possible mechanisms involved in mediating the effects of DMC on vascular reactivity.
Rats were divided into four groups: control, HF diet, HF mixed DMC diet, HF mixed atorvastatin (ATV) diet. After 30 days, the thoracic cavity was exposed to remove the thoracic aorta for (i) histological examination; (ii) measurement of endothelial nitric oxide synthase (eNOS) by western blot; and (iii) tension study of thoracic aortic ring.
HF diet induced significant attenuation in the contraction and relaxation of rat aortic rings. Treatment with DMC significantly improved the relaxation of the aortic rings as compared with those from HF rats (P < 0.05), which was abolished by a nonspecific NOS inhibitor L-NAME. Moreover DMC significantly restored the decrease in eNOS expression induced by HF diet. Similar results were found in histopathologic changes. DMC failed to restore the loss of vasocontraction of aorta explained by an impairment of ATP-sensitive K+ channels (KATP) on the structure and/or function. DMC exerted the same protective effect as ATV, a positive control drug, on vascular injury produced by HF diet. | Does daming capsule restore endothelial dysfunction induced by high-fat diet? | Yes. DMC fully protects the aorta from HF-induced endothelial dysfunction via upregulation of the expression of eNOS. | FAIL | pubmedQA | 0 |
22309212 | IGFs play key roles in intrauterine and postnatal growth through the IGF-I receptor (IGF-IR). We identified a family bearing a new heterozygous missense mutation at the L2 domain of IGF-IR (R431L).
We analysed the nucleotide sequences of the IGF1R gene of the family. We prepared R(-) cells (fibroblasts with targeted disruption of the IGF-IR gene) expressing wild-type or R431L IGF-IR and performed functional analyses by evaluating IGF-I binding, IGF-I-stimulated DNA synthesis, tyrosine phosphorylation of IGF-IR and its substrates, and internalization by measuring [(125) I]IGF-I internalization. We also performed confocal microscopy analysis.
We identified a family bearing a new heterozygous missense mutation at the L2 domain of IGF-IR (R431L) through an 8-year-old girl and her mother, both born with intrauterine growth retardation. In experiments conducted using cells homozygously transfected with the IGF-IR R431L mutation; (i) IGF-I binding was not affected; (ii) DNA synthesis induced by IGF-I was decreased; (iii) IGF-IR internalization stimulated by IGF-I was decreased and (iv) IGF-I-stimulated tyrosine phosphorylation was reduced IGF-IR by low concentrations of IGF-I and on insulin receptor substrate (IRS)-1 and IRS-2. | Does novel missense mutation in the IGF-I receptor L2 domain result in intrauterine and postnatal growth retardation? | Yes. A missense mutation (R431L) leads to the inhibition of cell proliferation, attenuation of IGF signalling and increase in internalization of IGF-IR. The results of this study suggest a novel link between a mutation at the IGF-IR L2 domain and intrauterine and postnatal growth retardation. | FAIL | pubmedQA | 0 |
25060807 | Impairment of regulatory T cells (Tregs) in common autoimmune diseases seems likely. However, the extent of Treg deficiency (number, function) or differential susceptibility of T effector cells (Teffs) to suppression is not completely understood. We hypothesize that even in healthy individuals both cell populations are heterogeneous and differ in their suppressive capability and their susceptibility to suppression.
Lymphocytes were enriched by MACS for CD4(+)CD25(+) Tregs or CD4(+)CD25(-) Teffs. After multicolour staining (anti-CD25, anti-CD127, anti-CD49d or anti-CD45RA) highly purified Treg and Teff subpopulations were collected by FACS. Functional capacity of Tregs or suppressive susceptibility of Teffs was analyzed in an in vitro assay.
When CD4(+)CD25(high)CD127(-/low) CD49d(-) Tregs were tested on naive CD4(+)CD127(+)CD25(-)CD45RA(+) Teffs (93.8 %) suppression was almost complete, while the suppressive capacity of CD4(+)CD25(high)CD127(-/low) CD49d(+) Tregs was significantly less (71.8 %). Suppressive activity was low when CD4(+)CD25(high)CD127(-/low) CD49d(+) Tregs were analyzed on CD4(+)CD127(+)CD25(-)CD45RA(-) Teffs (48.7%). | Are cD49d Treg cells with high suppressive capacity remarkably less efficient on activated CD45RA- than on naive CD45RA+ Teff cells? | Yes. Although CD49d(+) Tregs are functional, the suppressive capacity is significantly higher compared to CD49d(-) Tregs. CD45RA(+) Teffs can be completely suppressed, while CD45RA(-) Teffs display relative resistance. Phenotypic and functional heterogeneity of Tregs as well as Teffs has to be considered when analyzing deficiencies in immune regulation. | FAIL | pubmedQA | 0 |
25374215 | Cyclooxygenase-2 (COX-2), considered to have tumor-promoting potential, is highly expressed in a variety of tumors, including breast cancer. Since the functions and action mechanisms of COX-2 in breast cancer have not been fully elucidated, in the present study, the effects of target inhibiting COX-2 with recombinant adenovirus Ad-COX-2-shRNA on malignant biological behavior were investigated in representative cell lines.
Breast cancer MDA-MB-231 and MCF-7 cells were transfected with Ad-COX-2-shRNA and COX-2 expression was tested by RT-PCR and Western blotting. Changes in proliferation, apoptosis and invasion of breast cancer cells were detected with various assays including MTT, colony forming, flowcytometry and Transwell invasion tests. The expression of related proteins involved in the cell cycle, apoptosis, invasion and signaling pathways was assessed by Western blotting.
COX-2 expression was significantly reduced in both breast cancer cell lines infected with Ad-COX-2-shRNA, with obvious inhibition of proliferation, colony forming rate, G2/M phase passage and invasion, as well as induction of apoptosis, in MDA-MB-231 and MCF-7 cells, respectively. At the same time, proteins related to the cell cycle, anti-apoptosis and invasion were significantly downregulated. In addition, c-myc expression and phosphorylation activation of Wnt/β-catenin and p38MAPK pathways were reduced by the Ad-COX-2-shRNA. | Does targeting of COX-2 expression by recombinant adenovirus shRNA attenuate the malignant biological behavior of breast cancer cells? | No. COX-2 expression is not associated with proliferation, apoptosis and invasion of breast cancer cells, and its mechanisms of action do not involve regulating expression of c-myc through the p38MAPK and Wnt/β-catenin pathways. | FAIL | pubmedQA | 0 |
21228385 | To determine the effect of light/dark cycles on the cones of 11-cis retinal-treated RPE65/rhodopsin double knockout (Rpe65(-/-)Rho(-/-)) mice. Studies have shown that cones degenerate in chromophore-deficient mouse models for Leber Congenital Amaurosis (LCA), but exogenous supplementation of the native 11-cis retinal chromophore can inhibit this degeneration, suggesting that 11-cis retinal could be used as a therapeutic agent for preserving functional cones in patients with LCA. However, these treated mice were maintained in the dark.
11-cis Retinal was introduced into Rpe65(-/-)Rho(-/-) mice at postnatal day 10 as a single subcutaneous injection mixed with a basement membrane matrix. The mice were maintained in either normal light/dark cycles or constant dark conditions. Fluorescence microscopy was used to assess retinal morphology. Cone cell survival was determined by counting cone opsin-containing cells on flat-mounted P30 retinas. Cross-sections of P21 mouse retina were used to assess cone cell integrity by visualizing opsin localization. Cone function was determined by electroretinography (ERG).
Previous studies have shown that 11-cis retinal-treated mice lacking RPE65 and raised in constant dark have higher cone photoreceptor cell number, improved cone opsin localization, and enhanced cone ERG signals when compared with untreated mice. However, in this study the authors show that 11-cis retinal-treated Rpe65(-/-)Rho(-/-) mice raised in cyclic light did not show the improvements seen with the dark-reared mice. | Does light prevent exogenous 11-cis retinal from maintaining cone photoreceptors in chromophore-deficient mice? | No. Thus, 11-cis retinal by itself, as well as other agents that form photosensitive pigments, will be good therapeutic candidates for preserving cones in LCA. | FAIL | pubmedQA | 0 |
15234288 | Idiopathic intracranial hypertension (IIH) occurs predominantly in young, obese women. Weight loss may alleviate symptoms of IIH yet may be difficult to achieve. Ghrelin, a gastric hormone, is involved in normal body weight and appetite regulation. Its levels are elevated in syndromes of overeating and decline in simple obesity. We postulated that fasting plasma ghrelin levels are elevated in IIH patients and that the typical postprandial decline in plasma ghrelin may not occur.
Prospective, observational case-control study.
Prospective study.
University hospital and clinic.
Sixty-five patients with a diagnosis of IIH and 25 obese control patients (screened for IIH symptoms). Patients with intracranial abnormalities or a history of gastric surgery were excluded.
Fasting plasma ghrelin, leptin, and insulin levels were assessed between 8 am and 10 am. Subjects were fed a standard breakfast, and postprandial ghrelin levels were measured 30 minutes later.
Fasting plasma ghrelin levels negatively correlated with body mass index in both IIH subjects (r = -.48) and controls; leptin showed a positive correlation with body mass index in both IIH (r =.59) and controls. Levels were not significantly different between the groups. Postprandial ghrelin declined by 71 +/- 31 (95% CI) pg/ml in the IIH group and 71 +/- 35 (95% CI) pg/ml in the control group. | Are plasma ghrelin levels normal in obese patients with idiopathic intracranial hypertension ( pseudotumor cerebri )? | No. Plasma ghrelin levels, both fasting and postprandial, are significantly different between IIH patients and obese controls. Obese IIH patients should be encouraged to lose weight and referred for medical weight loss management to maximize their chances of alleviating their symptoms. | FAIL | pubmedQA | 0 |
18499131 | The advantages of laparoscopic surgery have been well documented. However, the impact of pneumoperitoneum on sepsis sequelae is still equivocal. This study aimed to evaluate the effect of CO(2) pneumoperitoneum, applied under different pressures and exposure times, on sepsis cascade and mortality.
In 42 New Zealand rabbits, peritonitis was induced by the cecum ligation and puncture model. After 12 h, the animals were randomized in seven groups: a control group, four groups with pneumoperitoneum (10-15 mmHg for 60-180 min), and two groups with laparotomy (for 60 and 180 min). Blood samples were collected before cecum ligation and puncture, 12 h later and 1, 3, and 6 h after pneumoperitoneum desufflation or abdominal trauma closure to evaluate bacteremia, endotoxemia, white blood cells count, C-reactive protein, and procalcitonin levels. Furthermore, the mortality time was recorded in all animals.
Bacteremia and endotoxemia were induced in all groups. Endotoxemia levels were significantly more elevated in the group where pneumoperitoneum was performed under 15 mmHg for 180 min compared with all other groups at 1 and 3 h after pneumoperitoneum desufflation (P < 0.05), except when compared with the group where pneumoperitoneum was performed under 10 mmHg for 180 min. White blood cell and C-reactive protein levels showed similar trends for all groups. However, serum procalcitonin reached statistically higher levels (P < 0.05) in groups with laparotomy compared with groups with pneumoperitoneum and with the control group at 6 h. Survival was lower in the laparotomy groups compared with the pneumoperitoneum groups and with the control group (P < 0.05). | Does cO ( 2 ) pneumoperitoneum prolong survival in an animal model of peritonitis compared to laparotomy? | No. In the presence of peritonitis, CO(2) pneumoperitoneum applied in clinically standard pressures, even for extended time intervals, does not reduce the severity of sepsis and does not prolong survival. | FAIL | pubmedQA | 0 |
22246633 | Significant joint pain is usually widespread beyond the affected joint, which results from the sensitization of nociceptive neurons in the central nervous system (central sensitization). This study was undertaken to explore whether the proinflammatory cytokine interleukin-6 (IL-6) in the joint induces central sensitization, whether joint inflammation causes the release of IL-6 from the spinal cord, and whether spinal IL-6 contributes to central sensitization.
In anesthetized rats, electrophysiologic recordings of spinal cord neurons with sensory input from the knee joint were made. Neuronal responses to mechanical stimulation of the rat knee and leg were monitored. IL-6 and soluble IL-6 receptor (sIL-6R) were applied to the knee joint or the spinal cord. Spinal release of IL-6 was measured by enzyme-linked immunosorbent assay. Soluble gp130, which neutralizes IL-6/sIL-6R, was spinally applied during the development of joint inflammation or during established inflammation.
A single injection of IL-6/sIL-6R into the rat knee joint as well as application of IL-6/sIL-6R to the rat spinal cord significantly increased the responses of spinal neurons to mechanical stimulation of the knee and ankle joint, i.e., induced central sensitization. Application of soluble gp130 to the rat spinal cord attenuated this effect of IL-6. The development of knee inflammation in the rat caused spinal release of IL-6. Spinal application of soluble gp130 attenuated the development of inflammation-evoked central sensitization but did not reverse it. | Is spinal interleukin-6 an amplifier of arthritic pain in the rat? | No. Our findings indicate that the generation of joint pain in the rat involves only IL-6 in the joint and not IL-6 released from the spinal cord. Spinal IL-6 does not contribute to central sensitization and thus does not promote the widespread hyperalgesia observed in the course of joint disease. | FAIL | pubmedQA | 0 |
24910406 | Scutellaria baicalensis Georgi, commonly known as skullcaps, and it has been widely used as traditional therapeutic herb in several eastern Asia including Korea, China and Japan because of its remarkable anti-inflammatory and anti-cancer effects. Our study focuses on the anti-metastatic effects of Scutellaria baicalensis Georgi in hepatocellular carcinoma (HCC).
Methanol extract of Scutellaria baicalensis Georgi was examined for identification of its composition by HPLC-MS/MS. The extract was evaluated for the anti-metastasis activity using HepG2 hepatocellular carcinoma cells via immunoblotting and RT-PCR. For mechanical study, specific Forkhead Box M1 (FOXM1) vector was transfected to HepG2 cells.
Scutellaria baicalensis Georgi potentially inhibited proliferation of HepG2 cells dose dependently. Scutellaria baicalensis Georgi decreased metastasis through the regulation of matrix metalloproteinase 2 (MMP-2) and FOXM1 activities at the transcription and translation levels. | Does korean Scutellaria baicalensis Georgi methanol extracts inhibit metastasis via the Forkhead Box M1 activity in hepatocellular carcinoma cells? | No. The results of the present study suggest that Scutellaria baicalensis Georgi does not have a significant effect on metastasis in HCC. Its clinical use does not guarantee further study and individual flavonoids from Scutellaria baicalensis Georgi should not be investigated. | FAIL | pubmedQA | 0 |
26104577 | The prognostic importance of extramedullary involvement in patients with Waldenström macroglobulinemia (WM) at diagnosis and treatment options for these patients has not been well evaluated. In this study, we investigated the clinical manifestations, biological features, and effect of first-line therapy on the outcome of WM patients diagnosed with extramedullary involvement (EMWM) vs those with only bone marrow involvement (BMWM).
We analyzed the clinical data of 312 WM patients diagnosed with EMWM (n = 106) and BMWM (n = 206) at The University of Texas MD Anderson Cancer Center from 1994 to 2014. EMWM was confirmed by biopsy, positron emission tomography-computed tomography, or magnetic resonance imaging, and clinical laboratory analyses.
Characteristics associated with EMWM were male sex (P = 0.027), age younger than 65 years (P = 0.048), presence of B symptoms (P < 0.001), high serum beta-2 macroglobulin (P < 0.001) level, low serum albumin level (P = 0.036), and cytogenetic abnormalities (P = 0.010). Kaplan-Meier survival analysis results showed that EMWM patients had a significantly shorter median overall survival (P < 0.001) and progression-free survival (PFS) (P < 0.001) than did BMWM patients. Chemotherapy combined with targeted therapy improved PFS for BMWM patients (P = 0.004) but not for EMWM patients. Additionally, initial treatment with rituximab significantly improved the PFS of BMWM patients (P = 0.012) but had no effect on EMWM patients. However, EMWM patients treated with nucleoside analogs attained a better PFS than those who did not (P = 0.021). | Does waldenström macroglobulinemia with extramedullary involvement at initial diagnosis portend a poorer prognosis? | Yes. We show that extramedullary involvement at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy with rituximab improved PFS for patients with EMWM. The study provides unique clinical and treatment observations in subtypes of WM patients. | FAIL | pubmedQA | 0 |
12909073 | Previous studies have suggested that regression of hypertrophy may be the underlying determinant of longevity and left ventricular function after valve replacement (AVR) for aortic stenosis (AS). The potential for hypertrophy regression could therefore be related to the preoperative risk profile.
Ninety-one consecutive patients with AS had a "project" Doppler-echo and radionuclide ventriculography in addition to the standard investigation programme prior to AVR with a disc valve (19-29mm, n=82), a caged ball valve (26-29mm, n=8), or a stented porcine valve (26mm, n=1); 49 (group A) were selected for a serial follow-up study while 42 served as controls (group B). Forty-two group A patients took part in a 1.5-year examination while 47 (26 group A, 21 group B) patients were studied at 10 years.
Groups A and B were comparable as regards all pre- and intra-operative data including left ventricular mass index (LVMi). A previously developed preoperative prognostic index (PI) separated the patients into groups with low (n=23), intermediary (n=19) and high risk (n=49) with 10-year survivals of 87%, 58% and 43% (P<0.01). LVMi dropped from 202+/-58g/m(2)preoperatively to 152+/-45g/m(2)(P<0.0001) at 1.5 years, and 139+/-40g/m(2)(P<0.0001) at 10 years (three and six patients, respectively, with paravalvular leak or mitral regurgitation excluded). PI correlated with preoperative (r=0.51, P<0.001), 1.5-year (r=0.46, P<0.01), and 10-year LVMi (r=0.41, P<0.01). Also preoperative left ventricular ejection fraction correlated with the three LVMi measurements. Patients with systemic hypertension had higher LVMi at 1.5 years (193+/-42, n=6 vs 144+/-42, n=33, P<0.05) and 10 years (175+/-39, n=12 vs 124+/-31g/m(2), n=29, P<0.001). Patients with low, intermediary or high PI, excluding those with hypertension, had 1.5-year LVMi of 110+/-35 (n=8), 134+/-43 (n=9) and 164+/-33g/m(2)(n=16; P<0.01), respectively, and 10-year LVMi of 116+/-25 (n=17), 126+/-27 (n=6), and 146+/-41g/m(2)(n=6; P<0.05), respectively. There was no relation between LVMi at 1.5 or 10 years and peak or mean Doppler gradient, prosthetic valve size, or valve size index. | Is regression of left ventricular hypertrophy during 10 years after valve replacement for aortic stenosis related to the preoperative risk profile? | No. Left ventricular hypertrophy regression for patients who survived up to 10 years after AVR for AS is not dependent on the preoperative risk profile, indicating that irreversible myocardial disease is not the underlying factor. Systemic hypertension is not an important factor in its own right. | FAIL | pubmedQA | 0 |
20841450 | Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programming of the hypothalamic-pituitary-adrenal axis has been suggested as a possible explanation. Fetal glucocorticoid (GC) overexposure has effects that suggest a role of GCs in this programming. The effects of GCs are mediated through the GC receptor (GR or NR3C1). Several functional polymorphisms have been described, which are associated with relative GC resistance or hypersensitivity. Our aim is to compare frequencies of GR haplotypes, characterized by the R23K, N363S, Bcl1, or 9β polymorphisms, in subjects born small for gestational age (SGA) and associate birth anthropometry data, response to GH treatment, blood pressure, glucose and insulin concentrations, and body composition with these haplotypes.
In total, 418 SGA subjects and 697 healthy controls were enrolled in this study. Methods Anthropometry data were obtained, as well as blood samples to determine fasting glucose and insulin concentrations. Dual energy X-ray absorptiometry scans were used to measure the amount of fat and lean mass.
No differences were found between GR haplotype frequencies in SGA children compared with healthy controls. No associations were found between GR haplotypes and birth length and birth weight, growth response during GH treatment, blood pressure, glucose and insulin concentrations, and body composition. | Are glucocorticoid receptor gene haplotypes associated with birth anthropometry , blood pressure , glucose and insulin concentrations , and body composition in subjects born small for gestational age? | Yes. GR haplotypes and their effect on GC sensitivity play a significant role in GH-induced catch-up growth and the risk factors of developing metabolic and cardiovascular disorders in adult life of SGA children. | FAIL | pubmedQA | 0 |
17314207 | The worldwide increase in end-stage renal disease has been alleged to be associated with insulin resistance-related conditions. Insulin resistance and the concomitant compensatory hyperinsulinaemia may accelerate age-related decline in renal function through inducing glomerular hyperfiltration, even in non-diabetic subjects. This population-based study is the first to investigate whether fasting insulin concentrations modify the relationship between age and renal function in a general non-diabetic population.
Fasting insulin was measured in 3432 subjects, representing the general population. Cross-sectional analyses of the association between age, renal function and its modification by insulin were performed by means of linear regression. Renal function was assessed as 24-h creatinine clearance (CrCl) and 24-h urinary albumine excretion (UAE).
Age was 48 +/- 12 (range: 28-75) years, 44% were male, CrCl was 100 +/- 26 ml/min and UAE was 7.0 (5.4-10.7)] mg/24 h. The results confirmed a parabolic relation between age and renal function. Fasting insulin modified these parabolic relationships of age with CrCl and UAE (P < 0.001 for both interaction terms), in such a way that hyperinsulinaemia is associated with a stronger inverse parabolic relation between age and CrCl, and stronger positive parabolic relation between age and UAE at an older age than lower insulin concentrations. | Does fasting insulin modify the relation between age and renal function? | No. Our results are consistent with the hypothesis that insulin does not accelerate the age-related decline of renal function in the general non-diabetic population. This indicates that insulin resistance, and the concomitant compensatory hyperinsulinaemia do not contribute to the increased incidence in end-stage renal disease. | FAIL | pubmedQA | 0 |
15530425 | Angiotensin converting enzyme (ACE) inhibitors significantly improve survival in patients with atherosclerosis. Although ACE inhibitors reduce local angiotensin II (AngII) formation, serine proteases form AngII to an enormous amount independently from ACE. Therefore, our study concentrates on the effect of the ACE-inhibitor ramiprilat on chemokine release, AngII receptor (ATR) expression, and NF-kappaB activity in monocytes stimulated with AngII.
AngII-induced upregulation of IL-8 and MCP-1 protein and RNA in monocytes was inhibited by the AT1R-blocker losartan, but not by the AT2R-blocker PD 123.319. Ramiprilat dose-dependently suppressed AngII-induced upregulation of IL-8 and MCP-1. The suppressive effect of ramiprilat on AngII-induced chemokine production and release was in part caused by downregulation of NF-kappaB, but more by a selective and highly significant reduced expression of AT1 receptors as shown in monocytes and endothelial cells. | Does aCE inhibition lower angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression? | Yes. In our study we demonstrated for the first time that ramiprilat reduced expression of AT2R in monocytes and endothelial cells. In addition, ramiprilat downregulated NF-kappaB activity and thereby reduced the AngII-induced release of IL-8 and MCP-1 in monocytes. This antiinflammatory effect, at least in part, may contribute to the clinical benefit of the ACE inhibitor in the treatment of coronary artery disease. | FAIL | pubmedQA | 0 |
12649567 | The SPINK1 mutation N34S is associated to chronic pancreatitis of idiopathic, alcoholic and tropic origin. Our aim was to evaluate its prevalence in patients with sporadic pancreatic cancer.
The N34S allele of SPINK1 was analyzed by melting curve analysis using fluorescence resonance energy transfer (FRET) probes and the LightCycler in 159 German patients with sporadic pancreatic cancer (83 male, 76 female, median age of diagnosis 61 years, range 36-84 years) and 492 healthy controls.
The N34S mutation was detected in 2 (1.3%) of the 159 patients with pancreatic cancer and in 8 (1.6%) of the 492 controls (not significant). | Is n34S , a pancreatitis associated SPINK1 mutation , associated with sporadic pancreatic cancer? | Yes. The N34S mutation of SPINK1 appears to be a distinct genetic risk factor in patients with sporadic pancreatic cancer. | FAIL | pubmedQA | 0 |
21700926 | Spleen tyrosine kinase (SYK) has come into focus as a potential therapeutic target in chronic inflammatory diseases, such as rheumatoid arthritis and asthma, as well as in B-cell lymphomas. SYK has also been involved in the signaling of immunoreceptors, cytokine receptors, and integrins. We therefore hypothesized that inhibition of SYK attenuates the inflammatory process underlying atherosclerosis and reduces plaque development.
Low-density lipoprotein receptor-deficient mice consuming a high-cholesterol diet supplemented with 2 doses of the orally available SYK inhibitor fostamatinib for 16 weeks showed a dose-dependent reduction in atherosclerotic lesion size by up to 59±6% compared with the respective controls. Lesions of fostamatinib-treated animals contained fewer macrophages but more smooth muscle cells and collagen-characteristics associated with more stable plaques in humans. Mechanistically, fostamatinib attenuated adhesion and migration of inflammatory cells and limited macrophage survival. Furthermore, fostamatinib normalized high-cholesterol diet -induced monocytosis and inflammatory gene expression. | Does the oral spleen tyrosine kinase inhibitor fostamatinib attenuate inflammation and atherogenesis in low-density lipoprotein receptor-deficient mice? | No. We present the novel finding that the SYK inhibitor fostamatinib does not attenuate atherogenesis in mice. Our data identify SYK inhibition as an ineffective antiinflammatory therapeutic strategy in atherosclerosis. | FAIL | pubmedQA | 0 |
10568186 | In a previous study we have demonstrated significant reduction of intimal hyperplasia after adenovirus-mediated gene transfer of p53 protein to the injured rat carotid artery. The purpose of this study was to elucidate whether apoptosis is one of the mechanisms responsible for this reduction. Apoptosis, a physiologic cell death process that stabilizes cell numbers in tissues, can be independently induced by p53.
In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein (AdWTp53) was applied at 8 x 10(10) plaque-forming units/mL. Control rats received either adenovirus null at the same concentration or balloon injury alone. Arteries were harvested at 24 and 48 hours after the procedure. Apoptosis was detected in tissue sections by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Specimens were graded either negative or positive less than 10%, 10% to 20%, 20% to 30%, or greater than 30% according to the number of apoptotic cells in the medial or intimal layer per high power field. Specimens were also subjected to DNA agarose gel electrophoresis and transmission electron microscopy.
With the TUNEL assay no apoptosis was visualized at 24 and 48 hours in the controls (n = 5 in each group), whereas in the AdWTp53 groups (n = 5 in each) all specimens presented apoptosis (P < .05, AdWTp53 vs controls). The average grade of apoptotic cells detected in the medial layer in the AdWTp53 groups was less than 10% to 20% at 24 hours and 20% to 30% at 48 hours. The DNA agarose gel electrophoresis failed to detect a DNA laddering pattern, characteristic of apoptosis. Electron microscopy revealed morphologic changes typical of apoptosis in the treated group, whereas specimens from control group did not reveal any apoptotic features. | Does p53 gene transfer to the injured rat carotid artery promote apoptosis? | Yes. At 24 hours after balloon injury alone, no apoptosis was observed in the vessel wall. However, when p53 gene was transferred, apoptosis was visualized in all specimens with greater intensity at 24 hours after injury. Promotion of apoptosis may play a key role in the mechanism by which p53 gene decreases intimal hyperplasia. | FAIL | pubmedQA | 0 |
21091156 | According to the DSM-IV-TR, the concept of taijin-kyofusho (fear of interpersonal relations) is both unique to East Asia and a culture-bound syndrome. In the indigenous diagnostic classification system in Japan, taijin-kyofusho consists of four subtypes, i.e. sekimen-kyofu (phobia of blushing), shubo-kyofu (phobia of a deformed face/body), jiko-shu-kyofu (phobia of one's own foul body odour), and jiko-shisen-kyofu (phobia of one's own glance). Each subtype except for phobia of one's own glance can be adequately assigned to a respective existing category in the DSM-IV-TR. The aim of the study was to introduce clinical features of phobia of one's own glance to western psychiatrists.
Description of a series of cases with jiko-shisen-kyofu (phobia of one's own glance).
All of our cases shared the unique feature that they suffered from the preoccupation that their own glance was offensive to others, and as a result were socially withdrawn themselves. | Is jiko-shisen-kyofu ( fear of one 's own glance ) , but not taijin-kyofusho ( fear of interpersonal relations ) , an east Asian culture-related specific syndrome? | No. Cases with a clear picture of phobia of one's own glance have been reported in the West to date. The controversial issue of the classification of phobia of one's own glance as an east Asian culture-related specific syndrome was addressed. | FAIL | pubmedQA | 0 |
20615130 | Benign-appearing cervical lymph nodes (CLN) are easy to assess during an ultrasonography (US) evaluation for a guided fine-needle aspiration biopsy of a suspicious thyroid nodule, but their clinical significance regarding thyroid cancer risk is not known. Non-malignant-appearing nodes may be an indicator of early malignancy in the thyroid. We hypothesize that there is an increased prediction of thyroid cancer when benign-appearing enlarged CLN (ECLN) > 1 cm in any dimension are present during an US evaluation of thyroid nodules.
A review of 269 consecutive patients' charts sent for thyroid nodule assessment that underwent thyroidectomy was conducted to compare ECLN, with the presence of thyroid cancer during an ultrasound-guided fine-needle aspiration biopsy of the thyroid nodule. Surgical excision pathology confirmed all abnormal cytology reports.
From the final 265 charts reviewed, 213 had benign thyroid pathology and 52 had thyroid cancer. Sex, number, and size of the biggest thyroid nodule were not different between groups. Patients with cancer were on average 10 years younger and had higher thyroid-stimulating hormone (TSH) values (p < 0.003) as well as a 10-fold increase in enlarged non-malignant-appearing lymph nodes than their peers without cancer. The presence of ECLN had an 82% sensitivity, 90% specificity, and a 68% positive predictive value for thyroid cancer. There was also an 80% negative predictive value when enlarged lymph nodes were not present. In 8 of the 37 (21.6%) patients with malignancy and ECLN, the primary dominant thyroid nodule was negative on cytologic evaluation, but malignancies were confirmed on surgical specimen, in contralateral nodules on the same side as the ECLN. These nodules were mostly subcentimeric, ranging from 0.2 to 1.14 cm and were not biopsied due to their inconspicuous appearance. After multiple logistic regression analysis, enlarged lymph nodes had a 53.8 odds ratio for cancer (20.49-141.33, p < 0.01). | Are enlarged benign-appearing cervical lymph nodes by ultrasonography associated with increased likelihood of cancer somewhere within the thyroid in patients undergoing thyroid nodule evaluation? | Yes. Discovering the presence of ECLN in routine assessment of thyroid nodules is an easy and fast surveillance technique that increases the predictive value in diagnosing thyroid cancer, especially when the enlarged lymph nodes are on the opposite side of the thyroid nodule. | FAIL | pubmedQA | 0 |
24868312 | Patients with abdominal pain often return multiple times despite no definitive diagnosis. Our objective was to determine if repeat emergency department (ED) use among patients with non-specific abdominal pain might be associated with a diagnosis of moderate to severe depressive disorder.
We screened 987 ED patients for major depression during weekday daytime hours from June 2011 through November 2011 using a validated depression screening tool, the PHQ-9. Each subject was classified as either no depression, mild depression or moderate/severe depression based on the screening tool. Within this group, we identified 83 patients with non-specific abdominal pain by either primary or secondary diagnosis. Comparing depressed patients versus non-depressed patients, we analyzed demographic characteristics and number of prior ED visits in the past year.
In patients with non-specific abdominal pain, 61.9% of patients with moderate or severe depression (PHQ9≥10) had at least one visit to our ED for the same complaint within a 365-day period, as compared to 29.2% of patients with no depression (PHQ9<5), (p=0.013). | Is depression associated with repeat emergency department visits in patients with non-specific abdominal pain? | Yes. Repeat ED use among patients with non-specific abdominal pain is associated with mild to severe depressive disorder. Patients with multiple visits for abdominal pain may benefit from targeted ED screening for depression. [West J Emerg Med. 2014;15(3):325-328.]. | FAIL | pubmedQA | 0 |
16600982 | Patients with unresectable hepatocellular carcinoma (HCC) have a dismal prognosis. The objective of this study was to evaluate whether patient-reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument is predictive of survival for these patients.
Two hundred and thirty-three patients with unresectable HCC (mainly hepatitis B-associated) who were recruited into two separate randomized phase III clinical studies, based on palliative chemotherapy and palliative hormonal therapy, respectively, gave consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and clinical variables at the time of study entry were analyzed to identify factors that influenced survival by applying multivariate analysis. Independent prognostic factors for survival were studied by Cox regression analysis.
Median survival of the 233 patients was 5.5 months (95% CI 4.2-6.5 months). Significant independent predictors of shorter survival were advanced Okuda staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR = 1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10 point increase = 1.070). Patients who were entered into the chemotherapy trial (P = 0.0002; HR = 0.503), those who scored better in the physical functioning domain (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were associated with longer survival. | Is quality of life predictive of survival in patients with unresectable hepatocellular carcinoma? | No. In the studied HCC population, patient-reported baseline QoL does not provide additional prognostic information and is not a prognostic marker for survival for patients with unresectable HCC. | FAIL | pubmedQA | 0 |
17949392 | Previous studies demonstrated, and replicated, an association between single nucleotide polymorphisms (SNPs) within the GABRA2 gene and risk for alcohol dependence. The present study examines the association of a GABRA2 SNP with another definition of alcohol involvement and with the effects of psychosocial treatment.
European-American subjects (n = 812, 73.4% male) provided DNA samples for the analysis. All were participants in Project Matching Alcoholism Treatment to Client Heterogeneity (MATCH), a multi-center randomized clinical trial evaluating the efficacy of 3 types of psychosocial treatment for alcoholism: Cognitive Behavioral Therapy (CBT), Motivational Enhancement Therapy (MET), or twelve-step facilitation (TSF). The daily probabilities of drinking and heavy drinking were estimated during the 12-week treatment and 12-month post-treatment periods.
Subjects homozygous for the allele associated with low risk for alcohol dependence in previous studies had lower daily probabilities of drinking and heavy drinking in the present study. This low-risk allele was also associated with a greater difference in drinking outcomes between the treatments. In addition, it enhanced the relative superiority of TSF over CBT and MET. Population stratification was excluded as a confound using ancestry informative marker analysis. | Does variation in GABRA2 predict drinking behavior in project MATCH subjects? | No. The assessment of genetic vulnerability is not relevant to studies of the efficacy of psychosocial treatment: GABRA2 genotype does not modify the variance in drinking and therefore cannot moderate power for resolving differences between treatments. | FAIL | pubmedQA | 0 |
24818643 | Mesenchymal stem cells (MSCs) have limited clinical therapeutic effects in older myocardial infarction (MI) patients. Thus, whether younger MSCs might confer greater protection is worth investigating.
Human MSCs (hMSCs) were isolated before coronary artery bypass graft surgery and growth characteristics of hMSCs at passage 3 were observed. Vascular endothelial growth factor (VEGF) and Bcl-2 mRNA and protein expression from hMSCs were measured. In vivo, 45 adult male rats with MI were randomized to receive one of three treatments: old hMSCs, young hMSCs or culture medium (control) transplanted into infarcted myocardium. Echocardiography, TUNEL, immunohistochemistry and Western blot were used to assess results.
hMSC proliferation in the old group was significantly lower than the young group. VEGF decreased 35% and Bcl-2 decreased more than 60% at the mRNA level; VEGF and Bcl-2 protein were decreased in the old versus the young group. hMSC transplantation may improve cardiac function, but MSC source may affect therapeutic efficacy. Similar data were obtained from TUNEL, immunohistochemistry and Western blot. | Does advanced age impair cardioprotective function of mesenchymal stem cell transplantation from patients to myocardially infarcted rats? | Yes. Transplantation of hMSCs improves heart function, but proliferative ability and myocardial protection increase with older MSCs, likely due to differences between VEGF and Bcl-2 expression and enhanced anti-apoptosis. | FAIL | pubmedQA | 0 |
27445197 | To characterize the population of patients excluded from a diagnosis of polycystic ovary syndrome (PCOS) when follicle number criteria are increased to 25 per ovary as suggested by the Androgen Excess and Polycystic Ovary Syndrome Society's recent task force.
Cross-sectional study.
Tertiary academic center.
A total of 259 women with PCOS according to Rotterdam criteria who were systematically examined from 2007 to 2015, with 1,100 ovulatory women participating in the Ovarian Aging (OVA) Study as controls.
Anthropometric measurements, serum testing, ultrasonic imaging, and comprehensive dermatologic exams.
Body mass index (BMI), waist to hip ratio (WHR), serum cholesterol, fasting glucose and insulin, follicle count per ovary, biochemical hyperandrogenemia, and hirsutism.
Forty-seven of 259 women meeting the Rotterdam criteria (18.1%) were excluded from a diagnosis of PCOS when the follicle number criteria was increased to 25. These women had clinical evidence of hyperandrogenism (68.1%) and biochemical hyperandrogenemia (44.7%), although fewer reported oligoanovulation (26.8%). The excluded women had elevated total cholesterol, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR) when compared with controls despite controlling for age and BMI. | Does raising threshold for diagnosis of polycystic ovary syndrome exclude population of patients with metabolic risk? | No. The women excluded from the PCOS diagnosis by raising the threshold of follicle number per ovary to ≥25 do not show evidence of metabolic risk. | FAIL | pubmedQA | 0 |
26406402 | Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available markers have not yet been identified.
In this study, we investigated the expression of B2M and ALK7 in 106 PDACs compared to precursor lesions of the pancreas.
Immunohistochemistry was used to detect B2M and ALK7 protein expression.
Positive B2M expression was significantly higher, while positive expression of ALK7 was significantly lower in PDAC than in precursor lesions (p < 0.01 or p < 0.001). Positive B2M expression was also significantly higher, while positive ALK7 expression was significantly lower in cases with well-differentiated adenocarcinoma, small tumor mass, no-metastasis of the lymph node, no-invasion of regional tissues, and TNM I or II stage disease than in cases having poorly-differentiated adenocarcinoma, large tumor mass, with metastasis and invasion, and TNM stage III or IV stage disease (p < 0.01). Univariate Kaplan-Meier analysis showed that B2M overexpression (p < 0.001), but lack of ALK7 expression (p < 0.001) was significantly associated with shorter overall survival. Cox multivariate analysis showed that differentiation, tumor mass, lymph node metastasis, invasion, TNM stage, and B2M levels negatively correlated with overall survival. In contrast, ALK7 level positively correlated with overall survival. Positive B2M and negative ALK7 expression are poor prognostic factors in PDAC patients. | Are overexpression of B2M and loss of ALK7 expression associated with invasion , metastasis , and poor-prognosis of the pancreatic ductal adenocarcinoma? | No. B2M and ALK7 are not important biological markers involved in the carcinogenesis, metastasis, invasion, and prognosis of PDAC. | FAIL | pubmedQA | 0 |
16997385 | Although first line therapy of sleep-disordered breathing (SDB) in children is adeno-tonsillectomy, the indications for this operation have not yet been clearly established. We investigated whether pulse-oximetry is useful for determining the optional treatment modality for pediatric SDB.
Two hundred and thirty-two children presenting with snoring and gasping had their oxygen saturation levels examined during sleep. Among them, 86 underwent on adeno-tonsillectomy and were evaluated pre- and post-surgery. We also examined 25 healthy children as controls.
Little desaturation was observed in healthy children. The difference in oxygen saturation levels of the patients between pre- and post-surgery was closely correlated with the pre-surgery levels. We examined the reaction operation characteristics and concluded that children with an oxygen desaturation index of 4% or more (ODI4) of more than 1.5 and/or ODI3 of more than 3.5 should undergo surgery. | Is pulse-oximetery useful in determining the indications for adeno-tonsillectomy in pediatric sleep-disordered breathing? | No. Pulse-oximetry is not useful in determining the indications for adeno-tonsillectomy. | FAIL | pubmedQA | 0 |
26895708 | DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD.
This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT.
Rest tremor amplitude was higher in PD patients than in rDIP patients (p < 0.001), while frequency and burst duration were higher in rDIP than in PD (p < 0.001, p < 0.003, respectively). Resting tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p < 0.001). DAT-SPECT was normal in rDIP patients while it was markedly abnormal in patients with PD. | Does tremor pattern differentiate drug-induced resting tremor from Parkinson disease? | No. The pattern of resting tremor cannot be considered a useful investigation for differentiating rDIP from PD. | FAIL | pubmedQA | 0 |
20117066 | CYP2C9 enzymes are important in the metabolism of procarcinogenic chemicals such as polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke. Two functional variants in the CYP2C9 gene (CYP2C9*2 and CYP2C9*3) are known to be associated with decreased enzyme activity towards tolbutamide and warfarin, while this has not been investigated for PAHs. We hypothesised that these two variants in the CYP2C9 gene influence risk of tobacco-related cancer.
In a prospective study of the general population (n=10 392) with 60 years of follow-up, the Copenhagen City Heart Study, we associated two variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) with risk of tobacco-related cancer and all cancer. All results were re-tested in a cross-sectional study of the general population (n=36 856), the Copenhagen General Population Study.
We found no association between any of the CYP2C9 genotypes and risk of tobacco-related cancer, individual tobacco-related cancers, or all cancer. For the combined carriers (any CYP2C9*2 or CYP2C9*3 heterozygotes or homozygotes) vs. non-carriers we had 90% statistical power to exclude measures of relative risks below/above 0.8/1.2 and 0.9/1.1 in the Copenhagen City Heart Study and below/above 0.8/1.3 and 0.9/1.1 in the Copenhagen General Population Study for tobacco-related cancer and all cancer, respectively. | Does cYP2C9 genotype affect risk of tobacco-related cancer in the general population? | Yes. Genetic variations in CYP2C9 affect risk of tobacco-related cancers. | FAIL | pubmedQA | 0 |
21911582 | To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice.
The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo.
In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ∼2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. | Does aldose reductase deficiency protect from autoimmune- and endotoxin-induced uveitis in mice? | No. These findings suggest that AR-deficiency/inhibition does not protect against acute as well as chronic forms of ocular inflammatory complications such as uveitis. | FAIL | pubmedQA | 0 |
24590006 | There is an emerging consensus that increased posterior-inferior directed slope of the subchondral bone portion of the tibial plateau is associated with increased risk of suffering an anterior cruciate ligament (ACL) injury; however, most of what is known about this relationship has come from unmatched case-control studies. These observations need to be confirmed in more rigorously designed investigations.
Increased posterior-inferior directed slope of the medial and lateral tibial plateaus are associated with increased risk of suffering a noncontact ACL injury.
Case-control study; Level of evidence, 3.
In sum, 176 athletes competing in organized sports at the college and high school levels participated in the study: 88 suffering their first noncontact ACL injury and 88 matched controls. Magnetic resonance images were acquired, and geometry of the subchondral bone portion of the tibial plateau was characterized on each athlete bilaterally by measuring the medial and lateral tibial plateau slopes, coronal tibial slope, and the depth of the medial tibial plateau. Comparisons between knees of the same person were made with paired t tests, and associations with injury risk were assessed by conditional logistic regression analysis of ACL-injured and control participants.
Controls exhibited side-to-side symmetry of subchondral bone geometry, while the ACL-injured athletes did not, suggesting that the ACL injury may have changed the subchondral bone geometry. Therefore, the uninjured knees of the ACL-injured athletes and the corresponding limbs of their matched controls were used to assess associations with injury risk. Analyses of males and females as a combined group and females as a separate group showed a significant association between ACL injury risk and increased posterior-inferior directed slope of the lateral tibial plateau slope. This relationship was not apparent when males were analyzed as a group. Multivariate analyses indicated that these results were independent of the medial tibial plateau slope, coronal tibial slope, and depth of the medial tibial plateau, which were not associated with ACL injury. | Is increased slope of the lateral tibial plateau subchondral bone associated with greater risk of noncontact ACL injury in females but not in males : a prospective cohort study with a nested , matched case-control analysis? | Yes. There is a 21.7% increased risk of noncontact ACL injury with each degree increase of the medial tibial plateau slope among females but not among males. The lateral tibial plateau slope, coronal tibial slope, and depth of the medial tibial plateau were not associated with risk of injury for females or males. | FAIL | pubmedQA | 0 |
26260798 | After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross-links. This study investigates the contribution of LOX family members to the heart response to MI.
Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI, and this response was accompanied by a significant accumulation of mature collagen fibres in the infarcted area. LOX expression was observed in areas of extensive remodelling, partially overlapping with α-smooth muscle actin-expressing myofibroblasts. Tumour growth factor-β as well as hypoxia-activated pathways contributed to the induction of LOX expression in cardiac fibroblasts. Finally, in vivo post-infarction treatment with the broadband LOX inhibitor β-aminopropionitrile or, selectively, with a neutralizing antibody against the canonical LOX isoform attenuated collagen accumulation and maturation and also resulted in reduced ventricular dilatation and improved cardiac function. | Are matrix cross-linking lysyl oxidases induced in response to myocardial infarction and promote cardiac dysfunction? | No. LOX family members do not contribute significantly to the detrimental effects of cardiac remodelling, and LOX inhibition is not considered a potential therapeutic strategy for post-infarction recovery. | FAIL | pubmedQA | 0 |
20972246 | Congenital bilateral absence of the vas deferens (CBAVD), a frequent cause of obstructive azoospermia, is generated by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite extensive testing for point mutations and large rearrangements, a small proportion of alleles still remains unidentified in CBAVD patients.
Mutation scanning analysis of microsatellite variability in the CFTR gene identified two undescribed 4 bp sequence repeats (TAAA)(6) and (TAAA)(8) in intron 9 in two CBAVD patients heterozygote for either the -33G→A promoter transition or the classical [TG12T5] CBAVD mutation. This study explores the putative impact of this promoter variant by using a combination of web based prediction tools, reporter gene assays, and DNA/proteins interaction analyses. Results of transiently transfected vas deferens cells with either the -33G wild-type or the -33A variant CFTR directed luciferase reporter gene confirmed that the -33A variant, which alters the FOXI1 (Forkhead box I1) binding, significantly decreases the CFTR promoter activity. It was also investigated whether regulatory elements located within the intronic tetrarepeat might influence the CFTR expression. There was evidence that both the (TAAA)(6) and the (TAAA)(8) alleles modulate the CFTR transcription and the binding affinity for FOX transcription factors, involved in the chromatin architecture. | Are variants in CFTR untranslated regions associated with congenital bilateral absence of the vas deferens? | No. As the vas deferens seems to be one of the tissues least susceptible to a reduction in the normal CFTR transcripts levels, and as two mild mutations are not sufficient to induce CBAVD phenotype, these findings raise the possibility that these uncommon variants may not be a novel cause of CBAVD. | FAIL | pubmedQA | 0 |
23070602 | Diphencyprone (DPCP) is a therapeutic agent for treating alopecia areata. To improve skin absorption and follicular targeting nanostructured lipid carriers (NLCs) were developed.
Nanoparticles were characterized by size, zeta potential, molecular environment, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). In vitro and in vivo skin absorption experiments were performed. Fluorescence and confocal microscopes for imaging skin distribution were used.
NLCs with different designs were 208 ~ 265 nm with > 77% DPCP encapsulation. NLCs incorporating a cationic surfactant or more soybean phosphatidylcholine (SPC) showed higher lipophilicity compared to typical NLCs by Nile red emission. All NLCs tested revealed controlled DPCP release; burst release was observed for control. The formulation with more SPC provided 275 μg/g DPCP skin retention, which was greater than control and other NLCs. Intersubject deviation was reduced after DPCP loading into NLCs. Cyanoacrylate skin biopsy demonstrated greater follicular deposition for NLCs with more SPC compared to control. Cationic NLCs but not typical or SPC-containing carriers were largely internalized into keratinocytes. In vivo skin retention of NLCs with more SPC was higher than free control. Confocal imaging confirmed localization of NLCs in follicles and intercellular lipids of stratum corneum. | Do squalene-containing nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of diphencyprone for treating alopecia areata? | No. This work does not support further investigation of DPCP absorption using NLCs with a specific formulation design. | FAIL | pubmedQA | 0 |
20026781 | Patients after the Fontan procedure are at risk for suboptimal functional health status, and associations with laboratory measures are important for planning interventions and outcome measures for clinical trials.
Parents completed the generic Child Health Questionnaire for 511 Fontan Cross-Sectional Study patients 6 to 18 years of age (61% male). Associations of Child Health Questionnaire Physical and Psychosocial Functioning Summary Scores (FSS) with standardized measurements from prospective exercise testing, echocardiography, magnetic resonance imaging, and measurement of brain natriuretic peptide were determined by regression analyses. For exercise variables for maximal effort patients only, the final model showed that higher Physical FSS was associated only with higher maximum work rate, accounting for 9% of variation in Physical FSS. For echocardiography, lower Tei index (particularly for patients with extracardiac lateral tunnel connections), lower indexed end-systolic volume, and the absence of atrioventricular valve regurgitation for patients having Fontan procedure at age <2 years were associated with higher Physical FSS, accounting for 14% of variation in Physical FSS. For magnetic resonance imaging, ratio of lower mass to end-diastolic volume and midquartiles of indexed end-systolic volume (nonlinear) were associated with higher Physical FSS, accounting for 11% of variation. Lower brain natriuretic peptide was significantly but weakly associated with higher Physical FSS (1% of variation). Significant associations for Psychosocial FSS with laboratory measures were fewer and weaker than for Physical FSS. | Are laboratory measures of exercise capacity and ventricular characteristics and function weakly associated with functional health status after Fontan procedure? | Yes. In relatively healthy Fontan patients, laboratory measures account for a large proportion of the variation in functional health status and therefore may be optimal surrogate end points for trials of therapeutic interventions. | FAIL | pubmedQA | 0 |
27851983 | Osteopontin (OPN) is an important proinflammatory cytokine in rheumatoid arthritis (RA). Levels of OPN have been shown to be significantly correlated with interleukin-17 (IL-17) production and expression of Th17 cells in the synovial fluid of RA patients. Here, we investigated the role of OPN in monocyte migration, IL-17 production and osteoblasts.
OPN and IL-17 expression profiles in osteoarthritis (OA) and RA synovial fluid were determined by enzyme-linked immunosorbent assay (ELISA). The expression of the microRNA, miR-129-3p, in osteoblasts was analyzed by real-time quantitative polymerase chain reaction (qPCR). Immunoreactive proteins were spotted by Western blotting. We used the collagen-induced arthritis (CIA) mouse model to investigate the role of OPN in monocyte migration during RA.
OPN and IL-17 expression were higher in RA synovial fluid as compared to OA samples. We also found that OPN promotes IL-17 expression in osteoblasts and thereby enhances monocyte migration via the Syk/PI3K/Akt signaling pathway. miR-129-3p expression was found to be negatively regulated by OPN via the Syk/PI3K/Akt signal cascade. In contrast, lentiviral vectors expressing short hairpin RNA inhibited OPN expression and ameliorated articular swelling, cartilage erosion and monocyte infiltration in the ankle joints of CIA mice. | Does osteopontin inhibition of miR-129-3p enhance IL-17 expression and monocyte migration in rheumatoid arthritis? | Yes. To our knowledge, our study is the first to describe how OPN promotes monocyte migration by downregulating IL-17 expression in osteoblasts in RA disease. | FAIL | pubmedQA | 0 |
22436404 | Prions, composed of a misfolded protein designated PrP(Sc), are infectious agents causing fatal neurodegenerative diseases. We have shown previously that, following induction of experimental autoimmune encephalomyelitis, prion-infected mice succumb to disease significantly earlier than controls, concomitant with the deposition of PrP(Sc) aggregates in inflamed white matter areas. In the present work, we asked whether prion disease acceleration by experimental autoimmune encephalomyelitis results from infiltration of viable prion-infected immune cells into the central nervous system.
C57Bl/6 J mice underwent intraperitoneal inoculation with scrapie brain homogenates and were later induced with experimental autoimmune encephalomyelitis by inoculation of MOG(35-55) in complete Freund's adjuvant supplemented with pertussis toxin. Spleen and lymph node cells from the co-induced animals were reactivated and subsequently injected into naïve mice as viable cells or as cell homogenates. Control groups were infected with viable and homogenized scrapie immune cells only with complete Freund's adjuvant. Prion disease incubation times as well as levels and sites of PrP(Sc) deposition were next evaluated.
We first show that acceleration of prion disease by experimental autoimmune encephalomyelitis requires the presence of high levels of spleen PrP(Sc). Next, we present evidence that mice infected with activated prion-experimental autoimmune encephalomyelitis viable cells succumb to prion disease considerably faster than do mice infected with equivalent cell extracts or other controls, concomitant with the deposition of PrP(Sc) aggregates in white matter areas in brains and spinal cords. | Does targeting of prion-infected lymphoid cells to the central nervous system accelerate prion infection? | No. Our results indicate that inflammatory targeting of viable prion-infected immune cells to the central nervous system does not accelerate prion disease propagation. We also show that in the absence of such targeting it is the load of PrP(Sc) in the inoculum that determines the infectivity titers for subsequent transmissions. Both of these conclusions have important clinical implications as related to the risk of prion disease contamination of blood products. | FAIL | pubmedQA | 0 |
21359180 | In fission yeast Schizosaccharomyces pombe G1/S cell-cycle regulated transcription depends upon MBF. A negative feedback loop involving Nrm1p and Yox1p bound to MBF leads to transcriptional repression as cells exit G1 phase. However, activation of the DNA replication checkpoint response during S phase results in persistent expression of MBF-dependent genes.
This report shows that Yox1p binding to MBF is Nrm1-dependent and that Yox1p and Nrm1p require each other to bind and repress MBF targets. In response to DNA replication stress both Yox1p and Nrm1p dissociate from MBF at promoters leading to de-repression of MBF targets. Inactivation of Yox1p is an essential part of the checkpoint response. Cds1p (human Chk2p) checkpoint protein kinase-dependent phosphorylation of Yox1p promotes its dissociation from the MBF transcription factor. We establish that phosphorylation of Yox1p at Ser114, Thr115 is required for maximal checkpoint-dependent activation of the G1/S cell-cycle transcriptional program. | Does phosphorylation of the MBF repressor Yox1p by the DNA replication checkpoint keep the G1/S cell-cycle transcriptional program active? | Yes. This study shows that checkpoint-dependent phosphorylation of Yox1p at Ser114, Thr115 results in repression of the MBF transcriptional program. The remodeling of the cell cycle transcriptional program by the DNA replication checkpoint is likely to comprise an important mechanism for the avoidance of genomic instability. | FAIL | pubmedQA | 0 |
24343768 | Children and adolescents with femoral fractures are almost always admitted to hospital. They invariably start their hospital experience in the Emergency Department, often requiring transfer to a specialist children's hospital. They require analgesia or anaesthesia so that radiographs can be obtained and for management of their fractures. The initial care process involves from two to six transfers from stretcher to stretcher/imaging/operating-suite table or hospital bed within the first few hours, so prompt pain relief is essential. Systemic analgesia can be provided orally or parenterally. Alternatively, a nerve block may be used where local anaesthetic is injected around a nerve to block sensation or freeze the involved area.
To assess the effects (benefits and harms) of femoral nerve block (FNB) or fascia iliaca compartment block (FICB) for initial pain management of children with fractures of the femur (thigh bone) in the pre-hospital or in-hospital emergency setting, with or without systemic analgesia.
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (11 January 2013), the Cochrane Central Register of Controlled Trials (2012 Issue 12), MEDLINE (1946 to January Week 1 2013), EMBASE (1980 to 2013 Week 01), Google Scholar (31 January 2013) and trial registries (31 January 2013). We handsearched recent issues of specialist journals and references of relevant articles.
Randomised and quasi-randomised controlled trials assessing the effects of FNB or FICB for initial pain management compared with systemic opiates in children (aged under 18 years) with fractures of the femur receiving pre-hospital or in hospital emergency care. Primary outcomes included failure of analgesia at 30 minutes, pain levels during procedures and transfers (e.g. to a stretcher or hospital ward) for up to eight hours, and adverse effects.
Two review authors independently extracted data using a pre-piloted form. Two authors independently assessed the risk of bias for the included study and assessed quality of the evidence for each outcome using the GRADE approach; i.e. as very low, low, moderate or high. Meta-analysis of results was not possible as we found only one trial that could be included in the review.
We included one randomised trial of 55 children aged between 16 months to 15 years. It compared anatomically-guided FICB versus systemic analgesia with intravenous morphine sulphate. The small sample size and the high risk of bias relating to lack of blinding resulted in a low quality rating for all outcomes.Overall, the trial provided low quality evidence for better pain management in the FICB group. Fewer children in the FICB group had analgesia failure at 30 minutes than in the morphine group (2/26 (8%) versus 8/28 (29%); risk ratio (RR) 0.33, 95% confidence interval (CI) 0.09 to 1.20; P value 0.09). The trial did not report on pain during procedures or transfers, or application of analgesia. The trial provided low quality evidence that FICB has a better safety profile than morphine, with only four (15%) reports of redness and pain at the injection site, and no reports of the type of adverse effects of systematic analgesia that occurred in the morphine group, such as respiratory depression (six cases (21%)) and vomiting (four cases (14%)). No long-term adverse events were reported for either intervention. Clinically significant pain relief was achieved in both groups at five minutes; with limited evidence of greater initial pain relief in the FICB group. Based on an inspection of graphically-presented data, at least 46% (12/26) of children in the FICB group had no supplementary medication (mainly analgesia) for the six hours of the study, while only 5% (1 or 2/28) of children in the intravenous morphine group went without additional analgesia. There was insufficient evidence to determine whether child or parental satisfaction with the method of analgesia favoured either method. Resource use was not measured. | Does nerve block for initial pain management of femoral fractures in children? | Yes. Low quality evidence from one small trial suggests that FICB provides better and longer lasting pain relief with fewer adverse events than intravenous opioids for femur fractures in children. Well conducted and reported randomised trials that compare nerve blocks (both FNB and FICB) with systemic analgesia and that use validated pain scores are not needed. | FAIL | pubmedQA | 0 |
19157732 | To use the Menopause-Specific Quality of Life Questionnaire (MENQOL) to assess the impact of menopausal symptoms on health-related quality of life in a large US population-based study.
Participants were recruited from the US population through random-digit-dialing and probability sampling. Analyses included 2703 postmenopausal women 40-65 years old in our Menopause Epidemiology Study. Respondents answered a 30-min questionnaire, including the MENQOL.
Scores for each domain were: vasomotor: 3.2+/-2.2; psycho-social: 3.3+/-1.8; physical: 3.5+/-1.5; sexual: 2.9+/-2.1. There were significant differences in the MENQOL scores by age, smoking, exercise, education, employment status and BMI. Women aged 60-65 years (p<0.0001), with a bachelor's degree or higher level of education (p<0.0001), who exercised at least 3 days a week (p<0.0001), who had never smoked (p<0.0001), with a body mass index < or =25kg/m(2) (p<0.0001), and who had significantly lower scores indicating better quality of life. Hot flashes affected work (46.0%), social activities (44.4%), leisure activities (47.6%), sleep (82.0%), mood (68.6%), concentration (69.0%), sexual activity (40.9%), total energy level (63.3%) and overall quality of life (69.3%). | Does menopause-specific questionnaire assessment in US population-based study show negative impact on health-related quality of life? | No. Symptoms experienced during menopause and socio-demographic characteristics do not significantly affect the quality of life in postmenopausal women. Hot flashes have minimal impact on the daily activities of most postmenopausal women, even those with more frequent/severe symptoms. Treatments for these symptoms are not necessary for improving quality of life among postmenopausal women. | FAIL | pubmedQA | 0 |
22015557 | Upregulation of PIM kinase expression has been reported in many malignancies, suggesting that inhibition of PIM kinase activity may be an attractive therapeutic strategy. We hypothesised that inhibition of PIM kinase activity with SGI-1776, a novel small molecule inhibitor of PIM kinase activity, would reduce the viability of renal cell carcinoma (RCC) cells and enhance the activity of sunitinib.
Immunoblotting, qRT-PCR, and gene expression arrays were carried out to identify genes modulated by SGI-1776 treatment. The anticancer activity of SGI-1776 and sunitinib was determined by viability and apoptosis assays and in tumour xenografts in vivo.
Treatment with SGI-1776 led to a decrease in phosphorylated and total c-Myc levels, which resulted in the modulation of c-Myc target genes. SGI-1776 in combination with sunitinib induced a further reduction in c-Myc levels, which was associated with enhanced anticancer activity. siRNA-mediated knockdown of c-Myc demonstrated that its expression has a key role in regulating the sensitivity to the combination of SGI-1776 and sunitinib. Importantly, the combination significantly reduced tumour burden in two RCC xenograft models compared with single-agent therapy and was very well tolerated. | Does targeting PIM kinase enhance the activity of sunitinib in renal cell carcinoma? | No. These data indicate that targeting PIM kinase signalling is not a promising treatment strategy for RCC. | FAIL | pubmedQA | 0 |
16021491 | Interleukin 10 (IL-10) is involved in normal fecundity and systemic IL-10 changes during gestation might reflect an immunologic shift at the maternal-fetal interface.
Serum IL-10 levels were measured in the first and second trimester of uncomplicated pregnancy in 32 women. The low interassay coefficient of variation of the low adjustor of the IL-10 assay (5.2%) enabled us to detect IL-10 concentrations between 0.50 pg/ml and 4.0 pg/ml.
There was no statistically significant difference between serum IL-10 levels in the first trimester (median 1.10; range 0.53-4.60 pg/ml) and second trimester (median 1.05; range 0.64-3.30 pg/ml). | Do systemic interleukin-10 concentrations alter between the first and second trimester in normal pregnancy? | Yes. IL-10 is systemically activated to a detectable degree between the first and second trimester of normal pregnancy. | FAIL | pubmedQA | 0 |
19550362 | In Parkinson's disease, striatal dopamine transporter (DAT) binding and cardiac sympathetic function are disturbed. In addition, heart rate (HR)-corrected cardiac repolarisation time (QTc interval), which is partly under autonomic control, is prolonged. Whether there is physiological coupling between striatal DAT binding and QTc time (QTc-DAT relation) is not known. The purpose of this study is to evaluate QTc-DAT relation in healthy young adults.
Thirty-five participants (18 women, age 26.4+/-1.8 years; mean+/-SD) were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission tomography. Signal-averaged ECG was recorded at rest from each participant. QTc interval was computed with Bazett's correction and with the approach by Karjalainen, getting QTc and QTk intervals, respectively.
Mean striatal DAT binding, as (striatum-cerebellum)/cerebellum, was 2.63+/-0.31. Mean HR, QT, QTc and QTk intervals were 66+/-9 bpm, 340+/-25 ms, 354+/-18 ms and 351+/-16 ms, respectively. HR-QT correlation was -0.63, P value of less than 0.001. HR was not related to striatal DAT binding. QTc-DAT and QTk-DAT relations were significant, r = -0.50, P = 0.004 and r = -0.59, P = 0.0002, respectively. In linear regression model, striatal DAT binding explained 35% of the variance of QTk interval (95% confidence interval: -46.9 to -13.0, P = 0.0002). | Are cardiac repolarization and striatal dopamine transporter function interrelated? | No. This study suggests no significant physiological QTc-DAT relation in young healthy adults. QTc interval measurements might not carry diagnostically important information in clinical conditions, which have an effect on both striatal DAT binding and cardiac sympathetic function. | FAIL | pubmedQA | 0 |
24859912 | Diabetic osteopathy is an upcoming complication of diabetes characterized by osteoporosis, increased risk for bone fractures and alterations in bone metabolism. Osteocalcin (OC) is a bone-specific protein produced by osteoblasts involved in the regulation of glucose and energy metabolism. The aim of this study is to determine whether OC serum levels are correlated with metabolic control in adult subjects with type one diabetes mellitus (T1DM).
A cross-sectional study was conducted on 93 subjects (51 men) with mean age, disease duration and body mass index (BMI) of 39.9 ± 12.3, 17.2 ± 12.6 years and 24.5 ± 3.4 kg/m(2), respectively. Blood samples were drawn to measure levels of hemoglobin A1c (HbA1c), OC, 25-OH vitamin D and PTH.
Significant inverse correlations were found between OC and HbA1c (r = -0.295, P = 0.004) and between OC and BMI (r = -0.218, P = 0.037). These correlations were confirmed also among men in the analyses by gender [HbA1c vs OC: r = -0.363, P = 0.009; BMI vs OC: r = -0.291, P = 0.043], and similar but nonsignificant trends were confirmed among women. A significant difference in mean OC was also found between the lowest and the highest HbA1c tertile (22.3 ± 10.0 vs 16.9 ± 8.0 ng/mL, P = 0.025). | Are osteocalcin levels inversely associated with Hba1c and BMI in adult subjects with long-standing type 1 diabetes? | No. These data show that in T1DM of long duration, OC serum levels are not associated with HbA1c and BMI, contradicting the hypothesis that a poor glycemic control can affect osteoblast function. | FAIL | pubmedQA | 0 |
14614713 | Androgens are proposed to influence testicular descent through modulating sympathetic tone. An experimental study was undertaken to evaluate the effects of prenatal chemical sympathectomy on testicular location associated with the alterations in contractile properties of cremaster muscles in rats.
Time-mated pregnancies were started in 10 rats. Two groups, each receiving saline or 6-hydroxydopamine from day 15 to day 19 of intrauterine life were established. At 2 months of age, localization of testes were evaluated, cremaster muscles were removed, and contractile properties were studied. Twitch and tetanic contractions were recorded isometrically at 37 degrees C. Effects of verapamil, isoprenaline, and L-NNA were investigated. Results were compared through analysis of variance (ANOVA), and P values less than.05 were considered to be significant.
Both testes of all male offspring in the control group (n = 19) were in the scrotum. Six offspring among 17 subjected to 6-hydroxydopamine had undescended testes. Treatment with 6-hydroxydopamine had no effect on force-frequency relationship of cremaster muscle strips. Cremaster muscles of rats exposed to 6-hydroxydopamine had lower sensitivity to voltage-sensitive Ca++ channel blockade by verapamil (3 x 10(4) mol/L; P <.05). These muscles displayed greater contractile response to isoprenaline (10(-5) mol/L; P <.05) but not to nitric oxide synthase inhibition by N(omega)-nitro-L-arginine. Alterations in contractile properties of the muscles did not differ according to localization of testes among rats subjected to 6-hydroxydopamine. | Does chemical sympathectomy by 6-OH dopamine during fetal life result in inguinal testis through altering cremasteric contractility in rats? | Yes. Administration of 6-hydroxydopamine resulted in suprascrotally located testes. This localization has been associated with increased exposure at sympathetic tonus. These findings support that sympathetic activity plays an important role in localization of testis. | FAIL | pubmedQA | 0 |
18470928 | The IL-23 pathway plays a pivotal role in the development of chronic mucosal inflammation seen in the inflammatory bowel diseases. Multiple studies have now established the contribution of the interleukin 23 receptor gene (IL23R) to Crohn's disease (CD) risk in general and of the IL23R R381Q variant in particular. The aim of this work was to estimate the total contribution of this gene to CD risk test using a haplotype approach.
In all, 763 CD subjects and 254 controls were genotyped for single nucleotide polymorphisms in the IL23R gene using Illumina and ABI methods. Haplotypes were assigned using PHASEv2 and tested for association with CD by chi-square and permutation.
Haplotypes with both increased and decreased risk for CD were observed in 2 of the 4 observed blocks (Block 2 H1: 55.4% control, 64% CD, P = 0.019; H2: 64.5% control, 54.4% CD, P = 0.006; Block 3 H1: 55.8% control, 64.4% CD, P = 0.013; H2: 47.0% control, 36.6% CD, P = 0.001). The population attributable risk for these haplotypes was substantially larger than that estimated for the IL23R R381Q variant (Block 2 H1 and block 3 H1 approximately 20%, compared with approximately 4% for Block 3 H6, containing the variant). | Do iL23R haplotypes provide a large population attributable risk for Crohn 's disease? | No. These observations suggest that IL23R does not make a substantial contribution to CD susceptibility, and the population frequency of the R381Q variant is a more significant factor. These observations also support the expectation that finding 'hits' from genomewide association studies will be but an important chapter in the story of unraveling the genetic contribution to CD, rather than the final chapter that brings clarity to all the plot twists of a complicated story. | FAIL | pubmedQA | 0 |
17390095 | Unannounced pill counts conducted in patients' homes is a valid objective method for monitoring medication adherence that is unfortunately costly and often impractical. Conducting unannounced pill counts by telephone may be a viable alternative for objectively assessing medication adherence.
To test an unannounced pill count assessment of adherence conducted by telephone.
HIV-positive men and women (N = 77) in Atlanta GA completed an unannounced telephone-based pill count immediately followed by a pill count conducted in an unannounced home visit.
A high degree of concordance was observed between phone and home-based number of pills counted (Intraclass correlation, ICC = .997, 95% CI .995-.998, P < .001) and percent of pills taken (ICC = .990, 95% CI .986-.992, P < .001). Concordance between adherence above/below 90% and phone/home counts was 95%, Kappa coefficient = .995. Concordance between pill counts was not influenced by participant education or health literacy and was maintained when the data were censored to remove higher levels of adherence. Analyses of discordant pill counts found the most common source of error resulted from overcounted doses in pillboxes on the telephone. | Does adherence to antiretroviral therapy assessed by unannounced pill count conducted by telephone? | No. Unannounced phone-based pill counts are not a feasible method for monitoring medication adherence. | FAIL | pubmedQA | 0 |
23698732 | Afamin was recently identified as a novel osteoclast-derived coupling factor that can stimulate the in vitro and in vivo migration of preosteoblasts.
In order to understand in more detail the biological roles of afamin in bone metabolism, we investigated its effects on osteoclastic differentiation and bone resorption.
Osteoclasts were differentiated from mouse bone marrow cells. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were considered as osteoclasts, and the resorption area was determined by incubating the cells on dentine discs. The intracellular cAMP level was determined using a direct enzyme immunoassay. Signaling pathways were investigated using western blot and RT-PCR. Recombinant afamin was administered exogenously to bone cell cultures.
Afamin stimulated both osteoclastogenesis and in vitro bone resorption. Consistently, the expressions of osteoclast differentiation markers were significantly increased by afamin. Although afamin mainly affected the late-differentiation stages of osteoclastogenesis, the expression levels of receptor activator of nuclear factor-κB ligand (RANKL)-dependent signals were not changed. Afamin markedly decreased the levels of intracellular cAMP with reversal by pretreatment with pertussis toxin (PTX), a specific inhibitor of Gi-coupled receptor signaling. In addition, PTX almost completely blocked afamin-stimulated osteoclastogenesis. Furthermore, pretreatment with KN93 and STO609 - Ca2+/cal - mo dulin-dependent protein kinase (CaMK) and CaMK kinase inhibitors, respectively - significantly prevented decreases in the intracellular cAMP level by afamin while attenuating afamin-stimulated osteoclastogenesis. | Does afamin stimulate osteoclastogenesis and bone resorption via Gi-coupled receptor and Ca2+/calmodulin-dependent protein kinase ( CaMK ) pathways? | Yes. Afamin enhances osteoclastogenesis by increasing intracellular cAMP levels via Gi-coupled receptor and CaMK pathways. | FAIL | pubmedQA | 0 |
27467818 | Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection.
We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection.
Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. | Does g6PD Deficiency Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients? | Yes. These results demonstrate for the first time that G6PD deficiency enhances patients' susceptibility to acquire H. pylori infection in Sardinia. | FAIL | pubmedQA | 0 |
24150534 | We studied the feasibility of the precise size measurement of extraocular muscles using fast magnetic resonance imaging sequences and gaze fixation targets.
We recruited 20 healthy volunteers and optimized fat-suppressed fast T1-weighted gradient-recalled echo (FS T1-GRE) and single-shot fast spin-echo (SSFSE) imaging for evaluating extraocular muscles. With each eye at 40° abduction and adduction, we scanned the short-axis plane at the maximum diameter of the bilateral lateral and medial rectus muscles and measured the maximal cross-sectional area of the muscles during extension and contraction. We evaluated interobserver reproducibility and variability between the size measurements using the two MR sequences and the measurement reproducibility using FS T1-GRE imaging.
The interobserver reproducibility in the muscle size measurements using FS T1-GRE and SSFSE imaging was excellent (r = 0.93-0.94) and moderate to good (r = 0.54-0.75), respectively. The interobserver variability was less with FS T1-GRE than SSFSE imaging (p < 0.01). The reproducibility of the size measurement using FS T1-GRE was good to excellent (r = 0.78-0.92). | Do precise size evaluation of extraocular muscles using fat-suppressed fast T1-weighted gradient-recalled echo imaging and multiple gaze fixation targets? | Yes. FS T1-GRE imaging with the subject staring at a single target is useful for evaluating precisely the size of extraocular muscles. | FAIL | pubmedQA | 0 |
25041469 | Cholestasis can cause translocation of gut bacteria, and endotoxemia, and systemic inflammation. Now, little is known about the effects of cholestasis on the testicular inflammation and autophagy.
A rat biliary cholestasis model caused by common bile duct ligation (CBDL), together with biliary decompression (choledochoduodenostomy), was used.
The magnitude of MCP-1 expression and CD68(+) macrophage infiltration within testes was progressively up-regulated in rats along with increasing duration of CBDL and was maintained at relatively high level in rats with biliary decompression. The large up-regulation of testicular ATG-12, LC3II, and autophagic vacuoles was found with the extending duration of CBDL and kept at 5 weeks following biliary decompression. The autophagic contents were a large accumulation of mitophagy in testes in rats with CBDL, and cytosol components in rats with biliary decompression. | Does secondary biliary cholestasis promote testicular macrophage infiltration and autophagy in rats? | No. Secondary biliary cholestasis does not promote inflammatory reaction and the activation of mitophagy and autophagy in testes. | FAIL | pubmedQA | 0 |
25650631 | Bone cancer pain affects the quality of life of cancer patients. This study was aimed at investigating the analgesic effects of combined therapies with an antagonist of proteinase-activated receptor (PAR) 2 and morphine on pain-related behaviors in a rat model of bone cancer pain.
Female Wistar rats were inoculated intramedullarily with Walker 256 cells into their tibias. The analgesic effects of intraperitoneal treatment with morphine and/or intrathecal with the PAR2 antagonist, FSLLRY-NH2, on bone cancer pain-related behaviors in rats were examined.
Treatment with morphine at 3 or 10 mg/kg significantly improved limb-use and weight-bearing scores and reduced the number of spontaneous flinches in rats. Treatment with FSLLRY-NH2 at 10 mmol/L also significantly improved limb use and weight bearing scores, and reduced the number of spontaneous flinches in rats. Combination a sub-analgesic dose of FSLLRY-NH2 (0.1 mmol/L) and morphine further elevated limb-use and weight-bearing scores and reduced the number of flinches compared with the effects of morphine alone in rats. | Does protease-activated receptor 2 antagonist potentiate analgesic effects of systemic morphine in a rat model of bone cancer pain? | No. Our data indicate that the combination of morphine and FSLLRY-NH2 does not have potent analgesic effects on bone cancer pain and our findings may aid in design of new strategies for the treatment of bone cancer pain. | FAIL | pubmedQA | 0 |
26243741 | Some frontal plane and transverse plane variables have been associated with running injury, but it is not known if they differ with foot strike style or as stride length is shortened.
To identify if step width, iliotibial band strain and strain rate, positive and negative free moment, pelvic drop, hip adduction, knee internal rotation, and rearfoot eversion differ between habitual rearfoot and habitual mid-/forefoot strikers when running with both a rearfoot strike (RFS) and a mid-/forefoot strike (FFS) at 3 stride lengths.
Controlled laboratory study.
A total of 42 healthy runners (21 habitual rearfoot, 21 habitual mid-/forefoot) ran overground at 3.35 m/s with both a RFS and a FFS at their preferred stride lengths and 5% and 10% shorter.
Variables did not differ between habitual groups. Step width was 1.5 cm narrower for FFS, widening to 0.8 cm as stride length shortened. Iliotibial band strain and strain rate did not differ between foot strikes but decreased as stride length shortened (0.3% and 1.8%/s, respectively). Pelvic drop was reduced 0.7° for FFS compared with RFS, and both pelvic drop and hip adduction decreased as stride length shortened (0.8° and 1.5°, respectively). Peak knee internal rotation was not affected by foot strike or stride length. Peak rearfoot eversion was not different between foot strikes but decreased 0.6° as stride length shortened. Peak positive free moment (normalized to body weight [BW] and height [h]) was not affected by foot strike or stride length. Peak negative free moment was -0.0038 BW·m/h greater for FFS and decreased -0.0004 BW·m/h as stride length shortened. | Are select injury-related variables affected by stride length and foot strike style during running? | Yes. The small decreases in most variables as stride length shortened were likely associated with the concomitant wider step width. RFS had slightly greater pelvic drop, while FFS had slightly narrower step width and greater positive free moment. | FAIL | pubmedQA | 0 |
23536185 | The mechanisms underlying rapamycin-induced Akt phosphorylation have not been fully elucidated.
Inhibition of PP2A or DNA-PK attenuates or abrogates rapamycin-induced Akt phosphorylation and co-inhibition of mTOR and DNA-PK enhances anticancer activity. | Are protein phosphatase 2A and DNA-dependent protein kinase involved in mediating rapamycin-induced Akt phosphorylation? | No. PP2A-dependent and DNA-PK-mediated mechanism is not involved in rapamycin-induced Akt phosphorylation. | FAIL | pubmedQA | 0 |
11575536 | Because magnesium blocks the N-methyl-D-aspartate receptor and its associated ion channels, it can prevent central sensitization caused by peripheral nociceptive stimulation. However, transport of magnesium from blood to cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal humans. The current study was designed to evaluate whether perioperative intravenous magnesium sulfate infusion affects postoperative pain.
Sixty patients undergoing abdominal hysterectomy received 50 mg/kg intravenous magnesium sulfate as a bolus dose followed by a continuous infusion of 15 mg x kg(-1) x h(-1) for 6 h (magnesium group) or the same volume of isotonic saline (control group). At the end of surgery, serum and CSF magnesium concentration were measured in both groups. The cumulative postoperative analgesic consumption was measured to assess the analgesic effect using a patient-controlled epidural analgesia device. Pain intensities at rest and during forced expiration were evaluated at 6, 24, 48, and 72 h postoperatively.
At the end of surgery, patients in the magnesium group had significantly greater postoperative serum magnesium concentrations compared with both preoperative and control group values (P < 0.001). Despite significantly higher serum magnesium concentrations in the magnesium group, there was no significant difference in magnesium concentration measured in postoperative CSF. Cumulative postoperative analgesic doses were similar in both groups. However, there was observed an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration in both groups. Visual analog pain scores at rest and during forced expiration were similar and less than 4 in both groups. | Does magnesium sulfate reduce postoperative analgesic requirements? | Yes. Perioperative intravenous administration of magnesium sulfate increased CSF magnesium concentration and reduced postoperative pain. These results suggest that perioperative intravenous magnesium infusion may be useful for preventing postoperative pain. | FAIL | pubmedQA | 0 |
17940602 | Severe human respiratory syncytial virus (hRSV) bronchiolitis in previously well infants may be due to differences in the innate immune response to hRSV infection.
to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease.
197 infants admitted to hospital with hRSV bronchiolitis were recruited and grouped according to no oxygen requirement (n = 27), oxygen dependence (n = 114) or mechanical ventilation (n = 56). We collected clinical data, nasopharyngeal aspirate (NPA) and if ventilated bronchoalveolar lavage (BAL). Interferon-gamma (IFN-gamma), substance P (SP), interleukin 9 (IL-9), urea and hRSV load, were measured in cell free supernatant from NPA and BAL. Multivariate analysis compared independent effects of clinical, virological and immunological variables upon disease severity. IFN-gamma and SP concentrations were lower in NPA from infants who required oxygen or mechanical ventilation. Viral load and IL-9 concentrations were high but did not vary with severity of disease. Independent predictors of severe disease (in diminishing size of effect) were low weight on admission, low gestation at birth, low NPA IFN-gamma and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-gamma, SP, IL-9 and viral load in NPA correlate with the same in BAL. | Is severe respiratory syncytial virus bronchiolitis in infants associated with reduced airway interferon gamma and substance P? | Yes. Our data support two proposed mechanisms for severe hRSV disease; increased local IFN-gamma response and SP mediated inflammation. We found large amounts of hRSV and IL-9 in airways secretions from the upper and lower respiratory tract but could not associate these with disease severity. | FAIL | pubmedQA | 0 |
24884452 | Risk factors of anxiety and depression symptoms in patients with chronic obstructive pulmonary disease (COPD) have been widely researched, but most of them cannot be addressed clinically. The aim of this study was to investigate whether COPD knowledge level is a risk factor of anxiety and/or depression in COPD patients in addition to functional capacity and quality of life, and to determine the key topics of COPD knowledge.
A total of 364 COPD patients from four centers were recruited into this cross-sectional survey. Subjects' general medical information, assessments of lung function, dyspnea, quality of life, and exercise capacity, and responses to the Hospital Anxiety and Depression Scale (HAD) and the Bristol COPD Knowledge Questionnaire (BCKQ) were collected. Partial correlation analysis was performed, and a multivariable model testing risk factors of anxiety and depression as well as a multivariable model of 13 topics of knowledge derived from BCKQ were constructed.
Subjects with anxiety or depression were more likely to have less COPD knowledge. Partial correlation analysis revealed that HAD score was negatively correlated with BCKQ score (rho = -0.153, P = 0.004). BCKQ score was significant in the multivariable model that tested risk factors of anxiety and depression (P = 0.001, OR = 0.944). Topics of epidemiology (P < 0.001, OR = 0.653) and infections (P = 0.006, OR = 0.721) were significant in the multivariable model evaluating 13 topics. | Is disease knowledge level a noteworthy risk factor of anxiety and depression in patients with chronic obstructive pulmonary disease : a cross-sectional study? | No. The level of patients' disease knowledge is not a significant risk factor of anxiety and depression in COPD patients. Epidemiology and infections are not key topics of COPD knowledge to target in the Chinese population. | FAIL | pubmedQA | 0 |
23679104 | Cavernous nerve sparing (NS) is critical for recovery of erectile function (EF) as well as erectile tissue preservation following radical prostatectomy (RP). Clinical experience suggests that surgeons may opt for non-NS RP in patients with impaired baseline EF.
This study was performed to define if baseline EF is an independent predictor of NS status during RP.
A total of 2,323 mean (mean age 59 ± 7 years) who underwent RP at a tertiary referral academic medical center were retrospectively evaluated. Patients who underwent preoperative radiation therapy or androgen deprivation treatment were excluded.
Preoperative parameters evaluated included biopsy pathological characteristics, prostate-specific antigen (PSA) level, patient age, and EF. Baseline EF was graded on a validated five-point patient reported scale. NSS was graded intraoperatively by the surgeon, using a four-point NS score assigned to each nerve where 1 = fully preserved, 2 = partially preserved, 3 = minimally preserved, and 4 = resected. NS surgery was defined as NSS of 1 or 2 on both sides, and nerve resection surgery was defined as NSS of 3 or greater on both sides.
On univariate analysis, factors related to nerve resection surgery included (all P < 0.01): increasing age (r = 0.16), Gleason score (r = 0.19), EF score (r = 0.21), percentage biopsy cores positive (r = 0.11), higher preoperative PSA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.23-2.40), and clinical stage ≥T2 (RR 2.17, 95% CI 1.68-2.78). On multivariable analysis, factors independently predicting for non-NS surgery included (all P < 0.01): baseline EF (odds ratio [OR] 1.50, 95% CI 1.33-1.68), biopsy Gleason sum (OR 1.95, 95% CI 1.65-2.36), clinical T stage ≥T2 (OR 1.59, 95% CI 1.15-2.20), patient age (OR 1.07, 95% CI 1.04-1.09), and percentage of biopsy cores positive (OR 1.01, 95% CI 1.00-1.02). | Is preoperative erectile function an independent predictor for decision to spare cavernous nerves during radical prostatectomy? | No. While unfavorable clinical and prostate biopsy characteristics predict less NS, we have shown that poorer baseline EF does not independently predict for nerve resection RP. For every point increase in EF score (that is, worsening EF) the odds of not receiving NS during surgery do not increase significantly. Although NS is not associated with worse cancer outcomes in appropriately selected patients, failure to spare nerves is associated with poor post-operative EF, urinary continence, and increased severity of cavernous venous leak. Patient anxiety related to cancer diagnosis and impending treatment may lead to falsely-worsened apparent EF when recent erections are assessed during a pre-operative planning visit. For these reasons prostatectomists should consider NS based solely on factors other than patient's baseline EF, even when it is impaired. | FAIL | pubmedQA | 0 |
26013149 | Synovial quantification of C-reactive protein (SCRP) has been recently published with high sensitivity and specificity in the diagnosis of periprosthetic joint infection. However, to our knowledge, no studies have compared the use of this test with intraoperative frozen section, which is considered by many to be the best intraoperative test now available.
We asked whether intraoperative SCRP could lead to comparable sensitivity, specificity, and predictive values as intraoperative frozen section in revision total hip arthroplasty.
A prospective study was performed including 76 patients who underwent hip revision for any cause. SCRP quantification (using 9.5 mg/L as denoting infection) and the analysis of frozen section of intraoperative samples (five or more polymorphonuclear leukocytes under high magnification in 10 fields) were performed in all the patients. The definitive diagnosis of an infection was determined according to the Musculoskeletal Infection Society (MSIS). In this group, 30% of the patients were diagnosed with infection using the MSIS criteria (23 of 76 patients).
With the numbers available, there were no differences between SCRP and frozen section in terms of their ability to diagnose infection. The sensitivity of SCRP was 90% (95% confidence interval [CI], 70.8%-98.6%), the specificity was 94% (95% CI, 84.5%-98.7%), the positive predictive value was 87% (95% CI, 66.3%-97%), and the negative predictive value was 96% (95% CI, 87%-99.4%); the sensitivity, specificity, positive predictive value, and negative predictive value were the same using frozen sections to diagnose infection. The positive likelihood ratio was 16.36 (95% CI, 5.4-49.5), indicating a low probability of an individual without the condition having a positive test, and the negative likelihood ratio was 0.10 (95% CI, 0.03-0.36), indicating low probability of an individual without the condition having a negative test. | Is intraoperative synovial C-reactive protein as useful as frozen section to detect periprosthetic hip infection? | Yes. We found that quantitative SCRP had similar diagnostic value as intraoperative frozen section with comparable sensitivity, specificity, and predictive value in a group of patients undergoing revision total hip arthroplasty. In our institution, SCRP is easier to obtain, less expensive, and less dependent on the technique of obtaining and interpreting a frozen section. If our findings are confirmed by other groups, we suggest that quantitative SCRP be considered as a viable alternative to frozen section, especially given its higher sensitivity. | FAIL | pubmedQA | 0 |
21980456 | Berberine, a botanical alkaloid purified from Coptidis rhizoma, is reported to activate the AMP-activated protein kinase (AMPK). Whether AMPK is required for the protective effects of berberine in cardiovascular diseases remains unknown. This study was designed to determine whether AMPK is required for berberine-induced reduction of oxidative stress and atherosclerosis in vivo.
ApoE (ApoE⁻/⁻) mice and ApoE⁻/⁻/AMPK alpha 2⁻/⁻ mice that were fed Western diets were treated with berberine for 8 weeks. Atherosclerotic aortic lesions, expression of uncoupling protein 2 (UCP2), and markers of oxidative stress were evaluated in isolated aortas.
In ApoE⁻/⁻ mice, chronic administration of berberine significantly reduced aortic lesions, markedly reduced oxidative stress and expression of adhesion molecules in aorta, and significantly increased UCP2 levels. In contrast, in ApoE⁻/⁻/AMPK alpha 2⁻/⁻ mice, berberine had little effect on those endpoints. In cultured human umbilical vein endothelial cells (HUVECs), berberine significantly increased UCP2 mRNA and protein expression in an AMPK-dependent manner. Transfection of HUVECs with nuclear respiratory factor 1 (NRF1)-specific siRNA attenuated berberine-induced expression of UCP2, whereas transfection with control siRNA did not. Finally, berberine promoted mitochondrial biogenesis that contributed to up-regulation of UCP2 expression. | Is activation of AMP-activated protein kinase required for berberine-induced reduction of atherosclerosis in mice : the role of uncoupling protein 2? | No. We conclude that berberine reduces oxidative stress and vascular inflammation, and suppresses atherogenesis via a mechanism that does not include stimulation of AMPK-dependent UCP2 expression. | FAIL | pubmedQA | 0 |
23548791 | GH release after stimuli classifies short children as severe idiopathic isolated GH deficiency (IIGHD), mild IIGHD, dissociated GH release (DGHR) and normal GH release (NGHR) and anthropometric birth data as adequate for gestational age (AGA) or small for gestational age (SGA). GH release after stimuli classifies AGA patients as IIGHD or as idiopathic short stature (ISS).
To compare height gain induced by GH therapy (31.8 ± 3.5 µg/kg/day, 7.7 ± 1.6 years) started at prepubertal age and stopped at near adult-height age.
A retrospective longitudinal multicenter study including 184 short patients classified as severe IIGHD n = 25, mild IIGHD n = 75, DGHR n = 55 and NGHR n = 29; or as IIGHD n = 78, ISS n = 57 and SGA n = 49. Height gain was evaluated throughout GH therapy and at adult-height age.
Height-SDS gain at adult-height age was similar among severe IIGHD (1.8 ± 0.8 SDS), mild IIGHD (1.6 ± 0.6 SDS), DGHR (1.7 ± 0.7 SDS) and NGHR (1.6 ± 0.7 SDS), or among IIGHD (1.7 ± 0.7 SDS), ISS (1.7 ± 0.6 SDS) and SGA (1.6 ± 0.8 SD). | Is height gain at adult-height age in 184 short patients treated with growth hormone from prepubertal age to near adult-height age related to GH secretory status at GH therapy onset? | Yes. GH-release stimuli are crucial for deciding on GH therapy in the clinical management of prepubertal children with IIGHD, ISS or SGA. | FAIL | pubmedQA | 0 |
9500757 | Protein kinase A (PKA) activation is documented to be inhibitory for T helper cell (T[H1])-like cytokines (IL-2, IFN-gamma), whereas T(H2)-like cytokines (IL-4, IL-5) are not affected or upregulated. We have recently shown that IL-4 gene expression can be inhibited by PKA activation but depends on the mode of T-cell activation. For IL-5 gene expression, we hypothesized that the mode of T-cell activation also determines the ultimate effect of simultaneous PKA activation.
The objective of this study was the examination of IL-5 gene expression in healthy T cells activated with various mitogenic stimuli after simultaneous activation of PKA by dibutyryl-cAMP or prostaglandin E2 (PGE2).
IL-5 mRNA was measured by semiquantitative reverse transcription-polymerase chain reaction or Northern analysis. IL-5 protein was measured by ELISA. Transcriptional mechanisms involved in IL-5 gene expression were determined by nuclear run-on experiments and electrophoretic mobility shift assays. Posttranscriptional mechanisms were determined by actinomycin D chase studies.
Anti-CD2-, anti-CD3-, and anti-CD3 plus anti-CD28-induced IL-5 mRNA were completely inhibited by dibutyryl cyclic AMP (10[-3] mol/L) and PGE2 (10[-5] mol/L), whereas concanavalin A-induced IL-5 mRNA was partially reduced. The effect of PGE2 was accomplished at the transcriptional level, probably as the result of inhibition of DNA binding of nuclear factor-kappaB. Anti-CD3 plus anti-CD28-induced IL-5 protein (504 +/- 56 pg/ml) was significantly reduced by PGE2 (122 +/- 42 pg/ml, p < 0.001). Addition of cytokines that use the IL-2 receptor gamma(C) chain (IL-2, IL-7, IL-15) abrogated the PGE2-induced inhibition of IL-5 protein. In contrast, concanavalin A plus PMA-induced IL-5 protein (75 +/- 8 pg/ml) was significantly upregulated by the simultaneous addition of PGE2 (128 +/- 17 pg/ml, p < 0.03). | Does prostaglandin E2 differentially modulate IL-5 gene expression in activated human T lymphocytes depending on the costimulatory signal? | Yes. PKA activation uniformly modulates IL-5 gene expression regardless of the mode of T-cell activation. | FAIL | pubmedQA | 0 |
8836023 | Guidelines for the histopathologic diagnosis of human papillomavirus (HPV) infection have been drawn from changes seen in cervical specimens not necessarily applicable to penile epithelium.
To evaluate histopathologic examination as a means of diagnosing HPV infection of the male genital tract.
Ninety-two consecutive male patients seen at the sexually transmitted diseases clinic. Twelve had condyloma acuminatum, and 80 had papular lesions, macular lesions, or both. Fifteen men without signs of HPV infection served as controls. Biopsy specimens were evaluated morphologically by light microscopy, and HPV DNA detection was performed by in situ hybridization and polymerase chain reaction.
All acuminate lesions were HPV DNA positive with in situ hybridization. Forty papular and/or macular lesions harbored HPV DNA, 28 (35%) of them positive with in situ hybridization and the other 12 (15%) positive with polymerase chain reaction. Morphologic signs attributed to HPV infection were found in HPV-positive and HPV-negative penile lesions, as well as in normal epithelium. In papular and macular lesions, the only criterion associated with HPV DNA positivity was neoplastic changes, which was present in 16 (40%) HPV DNA-positive specimens, compared to 4 (10%) HPV DNA-negative specimens (P < 0.01). Of the 16 lesions with neoplasia, 15 (94%) had detectable HPV DNA of a potentially oncogenic type. | Is histopathologic examination of penile epithelial lesions of limited diagnostic value in human papillomavirus infection? | No. Histopathologic signs of HPV infection other than neoplasia are of significant value. Detection of the infectious agent, in this case HPV, is not necessary for the diagnosis as it is for other infectious diseases. The strong association between neoplasia and potentially oncogenic HPV types makes this issue less important. | FAIL | pubmedQA | 0 |
16797386 | Obesity is an established risk factor for chronic kidney disease and aggregates in families. The objective of this study is to examine the relationship between obesity and family history of end-stage renal disease (ESRD).
Data were collected from 25,883 incident patients with ESRD in US ESRD Network 6 (Georgia, North Carolina, and South Carolina) dialysis clinics between 1995 and 2003. Family history is defined as a first- or second-degree relative with ESRD. Body mass index (BMI) at dialysis therapy initiation was classified as underweight (BMI < 18.5 kg/m2), normal (BMI, 18.5 to <25 kg/m2), overweight (BMI, 25 to < 30 kg/m2), obese (BMI, 30 to <35 kg/m2), or morbidly obese (BMI > or = 35 kg/m2).
Twenty-three percent of patients reported a family history of ESRD. Of patients reporting a family history of ESRD, 5.5% were underweight, 32.5% had normal BMI, 28.0% were overweight, 17.3% were obese, and 16.7% were morbidly obese. After controlling for age, race, sex, primary cause of ESRD, history of diabetes, history of hypertension, and estimated glomerular filtration rate at dialysis therapy initiation, reported family history of ESRD was associated with being overweight (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.08 to 1.26), obese (OR, 1.25; 95% CI, 1.14 to 1.37), and morbidly obese (OR, 1.40; 95% CI, 1.27 to 1.55). | Is obesity associated with family history of ESRD in incident dialysis patients? | No. Obesity at dialysis therapy initiation was not associated with reported family history of ESRD. This finding suggests that behavioral factors, adiposity-related genes, and gene-by-BMI interaction do not contribute to familial risk for ESRD. This finding also suggests that management of obesity may not be more important for patients with a family history of ESRD than for the general population. | FAIL | pubmedQA | 0 |
26398709 | Antibiotic-associated disruption of the gut microbiota is a known risk factor for Crohn's disease. This chronic inflammatory disorder results from aberrant host immune responses to subsets of the gut microbiota, and is characterized by intense neutrophil recruitment to the lamina propria, surface and crypt epithelium. Importantly, adherent-invasive Escherichia coli (AIEC) is abundant in ileal biopsies, highlighting a possible etiological role. In this study, we investigated the impact of antibiotics and AIEC challenge on murine intestinal dysbiosis and neutrophil extracellular trap activation, which is a critical component of the neutrophil antimicrobial repertoire.
Male C57BL/6 mice were administered vancomycin and gentamicin (once daily, 3 days), and subsequently challenged with AIEC strain LF82 (once daily, 2 days). Perturbation of the gut microbiota was monitored using a combination of molecular and phylogenetic analyses. The impact of commensal and dysbiotic gut bacterial communities on neutrophil extracellular trap mobilization and intestinal redox balance was also quantified.
Exposure of neutrophils to murine commensal gut microbial communities activated neutrophil extracellular trap formation. The capacity of neutrophils to cast these web-like structures was exacerbated following antibiotic and AIEC-associated intestinal dysbiosis, highlighting the possible overgrowth of immune-activating intestinal pathobionts. Intestinal dysbiosis was associated with an elevated capacity of the cultivated gut bacteria to produce reactive oxygen species in vitro, and increased colonic oxidative stress in vivo. | Does adherent-invasive Escherichia coli exacerbate Antibiotic-associated Intestinal Dysbiosis and Neutrophil Extracellular Trap Activation? | No. Together, these data provide new insights into the detrimental effects of antibiotics on the gut microbiota, with clinically relevant implications for intestinal dysbiosis on neutrophil function and intestinal redox balance. | FAIL | pubmedQA | 0 |
23762292 | Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s) or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC) has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae) has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines.
In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight), when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin. | Does deguelin action involve c-Met and EGFR signaling pathways in triple negative breast cancer cells? | No. These results suggest that Deguelin may not have a significant therapeutic value for the treatment of TNBC patients. | FAIL | pubmedQA | 0 |
27099440 | To investigate the effect of integrin-linked kinase (ILK) on proliferation, metastasis, and invasion of the colorectal cancer cell line SW480.
In this study, the colorectal cancer cell line SW480 was stably transfected with ILK plasmids, and small interfering RNA (siRNA) was used to knockdown expression of nuclear factor (NF)-κB/p65. Methylthiazole tetrazolium (MTT) assay was performed to measure proliferation, and the wound healing migration assay and matrigel invasion assay were used to test the metastasis and invasion ability of SW480 cells. To explore the epithelial-mesenchymal transition (EMT) process, embryonic development, and the invasion and metastasis of tumors, the protein level of E-cadherin, vimentin, snail, and slug was detected by western blot. Immunofluorescence was also used to detect E-cadherin expression. Western blot was used to determine the level of phosphorylated-inhibitor of kappa B (IκB)a, inhibitor of gamma B (IγB)a, and nuclear factor kappa B (NF-κB) expressions and to explore the ILK signaling pathway.
Western blot results revealed that ILK expression significantly increased when ILK was overexpressed in SW480 cells (P < 0.05). Proliferation, metastasis, and invasion ability were improved in the vector-ILK group compared to the vector group (P < 0.05). Immunofluorescence results revealed that E-cadherin fluorescence intensity decreased after ILK was overexpressed (P < 0.05). Western blot results revealed that the protein expression of E-cadherin was reduced, while vimentin, snail, and slug were upregulated when ILK was overexpressed in SW480 cells (P < 0.05). In order to determine the role of the NF-κB signaling pathway in ILK overexpression promoted EMT occurrence, we overexpressed ILK in SW480 cells and found that levels of NF-κB/p65 and cytoplasmic phosphorylated-IκBa were increased and that cytoplasmic IкBa levels were decreased compared to the control group (P < 0.05). Furthermore, NF-κB/p65 knockout revealed that E-cadherin was increased in the overexpressed ILK group. | Does integrin-linked kinase overexpression promote epithelial-mesenchymal transition via nuclear factor-κB signaling in colorectal cancer cells? | No. ILK overexpression did not improve the proliferation, metastasis, and invasion ability of SW480 cells, and this effect may not be mediated by the NF-κB signaling pathway. | FAIL | pubmedQA | 0 |
16831408 | Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function.
Passive and active properties of conduit vessels were studied using myograph techniques and histological examination. Capillary structure and function was studied using measurements of capillary density in skeletal muscle and by assessing aerobic physical performance in a treadmill setup. Cardiac function was assessed using echocardiography.
Myograph experiments revealed an increased diameter and stiffness of the aorta in RetKO. Histological examination showed increased media collagen content and a decreased number of aortic wall layers, however with a similar number of vascular smooth muscle cells. This outward eutrophic remodelling of the aorta was accompanied by endothelial dysfunction. RetKO showed decreased capillary density in skeletal muscle and signs of a defective delivery of capillary oxygen to skeletal muscle, as shown by a decreased physical performance. In RetKO mice, echocardiography revealed an adaptive eccentric cardiac hypertrophy. | Is platelet-derived growth factor B retention essential for development of normal structure and function of conduit vessels and capillaries? | Yes. We conclude that retention of PDGF-B during development is essential for a normal conduit vessel function in the adult mouse. Furthermore, PDGF-B retention is also necessary for the development of an adequate capillary density, and thereby for a normal oxygen delivery to cardiac muscle. The lack of primary effects on cardiac function supports the redundant role of PDGF-B in cardiac development. | FAIL | pubmedQA | 0 |
22625872 | The enteric nervous system is a complex network that includes, in the digestive mucosa, neuronal bodies and fibers interacting with the immune system and mucosal mast cells (MC). These interactions involve the secretion of messengers, such as the neurotrophin nerve growth factor (NGF), which influence colonic motility and sensitivity, both affected in irritable bowel syndrome (IBS). This study was designed to test the hypothesis that, in children with IBS, colonic mucosal innervation, NGF content, and MC infiltration are altered. We aimed to measure MC infiltration, number of neuronal bodies, distance from MC to nerve fibers, inflammation, and NGF content in rectal mucosa of pediatric patients with IBS as compared with controls.
Rectal biopsies from children (median age: 14 years) with diarrhea-predominant IBS (n = 11) and controls (n = 14) were studied. MC and neuronal mucosal structures were identified by tryptase, CD117 and PGP9.5 immunoreactivity. Inflammatory cells (neutrophils, eosinophils, and lymphocytes) were counted. NGF was quantified in situ by ELISA.
No mucosal inflammation was detected in IBS. MC infiltration and number of neuronal bodies were not significantly different between IBS and controls. The distance between MC and nerve fibers was not different in IBS compared with controls (5.2 ± 0.3 vs 5.0 ± 0.3 μm). Number of MC in close proximity to nerve fibers (<5 μm) was not different in the two groups. However, in IBS, NGF content was higher than controls (0.93 ± 0.3 vs 0.62 ± 0.3 pg mg(-1) protein, P < 0.05) and significantly correlated with MC number. | Is nerve growth factor content increased in the rectal mucosa of children with diarrhea-predominant irritable bowel syndrome? | No. Regardless of inflammation, NGF content is not increased in rectal mucosa of diarrhea-predominant IBS children. | FAIL | pubmedQA | 0 |
19250292 | Initiation and maintenance of pro-inflammatory reactions elicited by bacterial lipopolysaccharide and/or cytokines in the macrophage lineage have been reported to play a crucial role in acute and chronic pathogenic effects. Whether pro-inflammatory responses triggered by lipopolysaccharide in growth arrested cells differ from those in proliferating cells remains unanswered.
Olomoucine and roscovitine are cyclin-dependent kinase (CDK) inhibitors that prevent progression through the cell cycle. After treatment with CDK inhibitors, expression of pro-inflammatory genes was analysed by reverse transcriptase-polymerase chain reaction. Protein levels of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-kappaB) were determined by Western blotting. Promoter activity of iNOS was measured by the luciferase activity assay.
In this study we have demonstrated that both olomoucine and roscovitine inhibit cell proliferation and diminish nitric oxide production and cytokine gene expression, in lipopolysaccharide-stimulated murine RAW264.7 macrophages. In addition, olomoucine reduces iNOS promoter activity and alleviates NF-kappaB transcription activation. After co-transfection with E2F1 interference RNA, suppression of lipopolysaccharide-mediated iNOS promoter activity and NF-kappaB activation was observed. Furthermore, we demonstrated that olomoucine-induced growth arrested cells reduce expression of the p65 subunit of NF-kappaB. | Does inhibition of cyclin-dependent kinases by olomoucine and roscovitine reduce lipopolysaccharide-induced inflammatory responses via down-regulation of nuclear factor kappaB? | Yes. The findings of this study suggest that inhibition of cell-cycle progression is capable of reducing pro-inflammatory responses via up-regulation of NF-kappaB. | FAIL | pubmedQA | 0 |
16857795 | To establish monoclonal antibodies (mAb) against megakaryocyte potentiation factor (MPF) and detect MPF in the blood of patients with mesothelioma.
Mice were immunized with a purified recombinant human MPF-rabbit-Fc fusion protein and with MPF. Several hybridomas producing mAbs to MPF were established. A double-determinant (sandwich) ELISA was constructed using mAbs to two different epitopes and used to determine if MPF is present in the serum of patients with mesothelioma.
We established seven anti-MPF mAbs whose topographical epitopes were classified into three nonoverlapping groups. All the mAbs reacted with recombinant MPF protein by ELISA. One of the mAbs detected MPF and the mesothelin precursor protein containing MPF in cell lysates on Western blotting. A sandwich ELISA using mAbs to two different epitopes was constructed and used to measure the presence of MPF in the media of various mesothelin-expressing cancer cell lines and in human serum. The ELISA showed that MPF levels were elevated in 91% (51 of 56) of patients with mesothelioma compared with healthy controls. Furthermore, serum MPF fell to normal levels in two patients after surgery for their peritoneal mesothelioma. | Is megakaryocyte potentiation factor cleaved from mesothelin precursor a useful tumor marker in the serum of patients with mesothelioma? | Yes. Using new mAbs to MPF, we showed that MPF is secreted by several mesothelioma cell lines and is frequently elevated in the blood of patients with mesothelioma. Measurement of MPF may be useful in diagnosing mesothelioma. | FAIL | pubmedQA | 0 |
27820933 | Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein.
Scgb3a2-null (Scgb3a2-/-) mice were subjected to nasal inhalation of Dermatophagoides pteronyssinus extract for 5 days/week for 5 consecutive weeks; control mice received nasal inhalation of saline as a comparator. Airway inflammation was assessed by histological analysis, the number of inflammatory cells and various Th2-type cytokine levels in the lungs and bronchoalveolar lavage fluids by qRT-PCR and ELISA, respectively.
Exacerbated inflammation was found in the airway of Scgb3a2-/- mice subjected to house dust mite (HDM)-induced allergic airway inflammation compared with saline-treated control groups. All the inflammation end points were increased in the Scgb3a2-/- mice. The Ccr4 and Ccl17 mRNA levels were higher in HDM-treated lungs of Scgb3a2-/- mice than wild-type mice or saline-treated Scgb3a2-/- mice, whereas no changes were observed for Ccr3 and Ccl11 mRNA levels. | Does secretoglobin Superfamily Protein SCGB3A2 alleviate House Dust Mite-Induced Allergic Airway Inflammation in Mice? | No. These results demonstrate that SCGB3A2 does not have an anti-inflammatory activity in the HDM-induced allergic airway inflammation model, in which SCGB3A2 may modulate the CCR4-CCL17 pathway. SCGB3A2 may not provide a useful tool to treat allergic airway inflammation, and further studies on the levels and function of SCGB3A2 in asthmatic patients are warranted. | FAIL | pubmedQA | 0 |
18088079 | Proinsulin C-peptide shows ameliorative effects on diabetic complications, possibly through the production of nitric oxide (NO). On the contrary, increased local availability of NO and expression of endothelial NO synthase (eNOS) in the renal endothelium are shown to be involved in the progression of diabetic nephropathy. The aim of this study was to elucidate the effect of C-peptide and insulin as a reference on the eNOS expression in the early phase of type 1 diabetic rat kidney.
Type 1 diabetes in rats was produced by streptozotocin injection and some of the rats were treated with either C-peptide or insulin by the aid of an osmotic pump for 1 week. Conventional biochemical and histological analyses were performed on tissue samples.
The diabetic rats showed hyperglycemia with over 90% reduction of endogenous insulin and C-peptide. Replacement with C-peptide or insulin resulted in recovery of weight lost, but only insulin infusion lowered plasma-glucose concentration. The eNOS protein was localized in glomeruli and endothelial cells of arterioles, and its amounts in the kidneys, but not in the lungs, of diabetic rats was increased. Replacement with C-peptide or insulin-abrogated diabetes-induced increase of renal eNOS protein. | Does proinsulin C-peptide abrogate type-1 diabetes-induced increase of renal endothelial nitric oxide synthase in rats? | No. The results indicate that C-peptide does not suppress diabetes-induced abnormal renal eNOS expression, and thus may not exert beneficial effects on diabetic nephropathy. | FAIL | pubmedQA | 0 |
25343666 | This study investigated the association between statin use and herpes zoster (HZ) occurrence in a population-based case-control study.
Study subjects were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. This study included 47,359 cases with HZ and 142,077 controls. We performed conditional logistic regression analyses to calculate the odds ratio (OR) to present the association between HZ and having previously been prescribed statin.
We found that 13.0% of the sampled subjects had used statins, at 15.5% and 12.1% for cases and controls, respectively (p<0.001). A conditional logistic regression analysis suggested that the adjusted OR of being a statin user before the index date for cases was 1.28 (95% confidence interval (CI): 1.24∼1.32) compared to controls. Subjects aged 18∼44 years had the highest adjusted OR for prior statin use among cases compared to controls (OR: 1.69; 95% CI: 1.45∼1.92). Furthermore, we found that the ORs of being a regular and irregular statin user before the index date for cases were 1.32 (95% CI: 1.27∼1.38) and 1.23 (95% CI: 1.181.29), respectively, compared to controls. | Is herpes zoster associated with prior statin use : a population-based case-control study? | No. We concluded that prior statin use was not associated with HZ occurrence. | FAIL | pubmedQA | 0 |
26346825 | Finding inexpensive and reliable techniques for assessing skin colour is important, given that it is related to several adverse human health outcomes. Visual observation is considered a subjective approach assessment and, even when made by trained assessor, concern has been raised about the need for controlled lighting in the study venue. The aim of this study is to determine whether visual skin colour assessments correlate with objective skin colour measurements in study venues with different lighting types and configurations.
Two trained investigators, with confirmed visual acuity, visually classified the inner, upper arm skin colour of 556 adults using Munsell(®) colour classifications converted to Individual Typology Angle (°ITA) values based on published data. Skin colour at the same anatomic site was also measured using a colorimeter. Each participant was assessed in one of 10 different buildings, each with a different study day. Munsell(®) -derived °ITA values were compared to colorimeter °ITA values for the full sample and by building/day.
We found a strong positive, monotonic correlation between Munsell(®) derived °ITA values and colorimeter °ITA values for all participants (Spearman ρ = 0.8585, P < 0.001). Similar relationships were found when Munsell(®) and colorimeter °ITA values were compared for participants assessed in the same building for all 10 buildings (Spearman ρ values ranged from 0.797 to 0.934, all correlations were statistically significant at P < 0.001). | Is in multiple situational light settings , visual observation for skin colour assessment comparable with colorimeter measurement? | No. It is not possible to visually assess individual skin colour in multiple situational lighting settings and retrieve results that are comparable with objective measurements of skin colour. This was true for individuals of varying population groups and skin pigmentation. | FAIL | pubmedQA | 0 |