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The formation of cognitive maps of adjacent environments: evidence from the head direction cell system. In 2 experiments the authors tested whether the head direction (HD) cell system underlies a sense of direction maintained across environments. In Experiment 1, HD neurons failed to maintain their firing directions across T mazes in adjacent environments but rather reoriented to the T maze within each environment. Such reorientation suggests that familiar landmarks override an internal directional sense, so in Experiment 2 the authors recorded HD neurons as rats walked between novel and familiar "rooms" of a 4-chamber apparatus. In novel rooms, HD neurons maintained the firing direction of the preceding environment. However, in familiar rooms, HD neuron firing directions shifted to agree with the landmarks therein. With repeated experience, a homogeneous representation of all rooms developed in a subset of the rats.

77Se solid-state NMR of As2Se3, As4Se4 and As4Se3 crystals: a combined experimental and computational study. (77)Se NMR parameters for three prototypical crystalline compounds (As2Se3, As4Se4 and As4Se3) have been determined from solid-state NMR spectra in the framework of an investigation concerning AsxSe(1-x) glass structure understanding. Density functional NMR calculations using the gauge including projector augmented wave methodology have been performed on X-ray and optimized crystal structures for a set of selenium-based crystals. These theoretical results have been combined with the experimental data in order to achieve a precise assignment of the spectral lines. This work and the high sensitivity of solid-state NMR to local order show that the structure of As4Se3 should be reinvestigated using state-of-the-art diffraction techniques. Calculations performed on several molecules derived from the crystal structures have demonstrated the limited effect of interlayer or intermolecular interactions on the isotropic chemical shifts. These interactions are therefore not responsible for the unexpected large chemical shift difference observed between these three systems that could mostly be attributed to the presence of short rings.

Advances in drug metabolism screening. Developments in automation, analytical technologies and molecular biology are being exploited by drug metabolism scientists in order to provide enhanced in vitro systems for the study of the metabolic disposition of potential drug candidates. Routine investigation of factors such as metabolic stability and induction and inhibition of drug metabolizing enzymes is now preferred in the early stages of drug discovery. This, in turn, should provide a greater understanding of the underlying principles governing these processes and allow a greater role for drug metabolism in the design of new drug molecules.

Analysis of the mechanism of the vasodepressor effect of urocortin in anesthetized rats. The aim was to examine if the depressor effect of urocortin involves activation of the nitric oxide (NO)/L-arginine pathway, production of prostanoids or opening of K(+)-channels. I. v. bolus urocortin (0.1-3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The depressor effect of urocortin was unaffected by pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, inhibitor of NO synthase, i.v. bolus) or noradrenaline (i.v. infusion), which increased arterial pressure to a similar level as that produced by L-NAME. In addition, methylene blue (inhibitor of soluble guanylyl cyclase, i.v. infusion), indomethacin (cyclooxygenase inhibitor, i.v. bolus), glibenclamide (blocker of ATP-sensitive K(+)-channels, i.v. bolus) or tetraethylammonium (a non specific K(+)-channel blocker, i.v. bolus) did not affect the depressor effect of urocortin. In conclusion, the depressor effect of urocortin in anesthetized rats is not mediated via the NO/L-arginine pathway, activation of soluble guanylyl cyclase, production of prostanoids, opening of TEA sensitive K(+)-channels nor opening of ATP sensitive K(+)-channels.

[The Etest--an alternative to the NCLLS standard for susceptibility testing of yeasts?]. The Etest and the NCCLS method are not much differing in respect to their reproducibility. Only single observations exist on the clinical correlation of both tests. The correlation between both tests are known as being dependent on the yeast species and antifungals used. Due to the easy and simple handling the Etest is attractive for routine laboratories. The Etest has to be more evaluated before it can be generally recommended. The NCCLS method also is not validated until now. Different test methods should be compared thoroughly with the above mentioned standard.

Putative risk factors for postoperative pneumonia which affects poor prognosis in patients with gastric cancer. Several recent studies identified that postoperative infectious complications contribute to recurrence and poor outcome in patients with gastric cancer. This study was designed to investigate the prognostic impact of postoperative pneumonia, and to identify the putative risk factors for its occurrence. We retrospectively analyzed 1,415 consecutive patients who underwent curative gastrectomy for gastric cancer between 1997 and 2013. A total of 31 (2.2 %) patients developed postoperative pneumonia (Clavien-Dindo classification ≥II). Patients with postoperative pneumonia showed a significantly poorer prognosis than patients without (P < 0.001). Concerning the occurrence of postoperative pneumonia, univariate and multivariate analyses identified older age (≥65 years; P = 0.010; odds ratio [OR] 3.59), lower nutritious status (albumin <3 0; P = 0.029; OR 4.51), advanced stage (pStage ≥II; P = 0.045; OR 2.35), concurrent hypertension (P = 0.042; OR 2.21) and total gastrectomy (P = 0.026; OR 2.42) as independent risk factors. Postoperative pneumonia was shown to be associated with long-term poor outcome in patients with gastric cancer. Care should be taken for patients with clinical factors such as older age, lower nutritional status, advanced stage, concurrent hypertension, and total gastrectomy.

Interview with a quality leader: Dr. John Combes on boards and governance. Dr. Combes is senior vice president at the American Hospital Association (AHA) and president and COO of the Center for Healthcare Governance. The Interview with Dr. John Combes on Boards and Governance provides a perspective on key changes, issues, competencies, and metrics that hospital boards must address. The role of quality professionals to be effective with boards is also described.

[Assessment of the new TNM classification for resected lung cancer]. To evaluate the revised TNM classification, we investigated the prognoses of 552 consecutive patients who had resection of non-small-cell lung cancer between April 1982 and March 1996. According to the new classification, the 5-year survival rate was 76.9% for stage I A, 57.2% for stage I B (I A versus I B, p < 0.0005), 47.7% for stage IIA, 49.8% for stage IIB, 18.6% for stage IIIA (IIB versus IIIA, p = 0.005), 16.7% for stage IIIB, and 7.9% for stage IV (IIIB versus IV, p = 0.02). Especially for patients in stage I A, there was significant difference in survival between patients with the tumor size within 1.5 cm and those with larger than 1.5 cm. The survival rate for T3N0M0 patients was significantly better than that for T3N1-2M0, but there was no significant difference between patients with T3N0M0 disease and those with T2N1M0 disease. Concerning the pm1 patients, the survival rate was significantly better than other stage IIIB patients. Our results supported the revision for dividing stage I and putting T3N0M0 into stage IIB. However, the classification is controversial about dividing stage II and putting pm1 as T4 disease. Furthermore, subgrouping of T1N0M0 disease by tumor size, T3 by tumor invaded organ will be necessary in the next revisions.

Nine things to know about elicitins. 888 I. 888 II. 889 III. 889 IV. 889 V. 891 VI. 891 VII. 891 VIII. 892 IX. 892 X. 893 XI. 893 893 References 893 SUMMARY: Elicitins are structurally conserved extracellular proteins in Phytophthora and Pythium oomycete pathogen species. They were first described in the late 1980s as abundant proteins in Phytophthora culture filtrates that have the capacity to elicit hypersensitive (HR) cell death and disease resistance in tobacco. Later, they became well-established as having features of microbe-associated molecular patterns (MAMPs) and to elicit defences in a variety of plant species. Research on elicitins culminated in the recent cloning of the elicitin response (ELR) cell surface receptor-like protein, from the wild potato Solanum microdontum, which mediates response to a broad range of elicitins. In this review, we provide an overview on elicitins and the plant responses they elicit. We summarize the state of the art by describing what we consider to be the nine most important features of elicitin biology.

[Nutritional status of native and non-native population of Russia's Extreme North and Far East]. Daily diets studied in various groups of native and non-native population living in the Far North and East of Russia (Kamchatka, Chukotka, Sakhalin) are shown to be inadequate for the adult capable population. Chemical composition of food provides insufficient supply of vegetable oil, calcium, vitamins, magnesium.

Integration host factor (IHF) modulates the expression of the pyrimidine-specific promoter of the carAB operons of Escherichia coli K12 and Salmonella typhimurium LT2. We report the identification of Integration Host Factor (IHF) as a new element involved in modulation of P1, the upstream pyrimidine-specific promoter of the Escherichia coli K12 and Salmonella typhimurium carAB operons. Band-shift assays, performed with S-30 extracts of the wild type and a himA, hip double mutant or with purified IHF demonstrate that, in vitro, this factor binds to a region 300 bp upstream of the transcription initiation site of P1 in both organisms. This was confirmed by deletion analysis of the target site. DNase I, hydroxyl radical and dimethylsulphate footprinting experiments allowed us to allocate the IHF binding site to a 38 bp, highly A+T-rich stretch, centred around nucleotide -305 upstream of the transcription initiation site. Protein-DNA contacts are apparently spread over a large number of bases and are mainly located in the minor groove of the helix. Measurements of carbamoyl-phosphate synthetase (CPSase) and beta-galactosidase specific activities from car-lacZ fusion constructs of wild type or IHF target site mutants introduced into several genetic backgrounds affected in the himA gene or in the pyrimidine-mediated control of P1 (carP6 or pyrH+/-), or in both, indicate that, in vivo, IHF influences P1 activity as well as its control by pyrimidines. IHF stimulates P1 promoter activity in minimal medium, but increases the repressibility of this promoter by pyrimidines. These antagonistic effects result in a two- to threefold reduction in the repressibility of promoter P1 by pyrimidines in the absence of IHF binding. IHF thus appears to be required for maximal expression as well as for establishment of full repression. IHF could exert this function by modulating the binding of a pyrimidine-specific regulatory molecule.

Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice. Nude mice bearing xenografts of MIA PaCa-2 human pancreatic cancer cell line were treated for 4 weeks with AN-51, a somatostatin octapeptide analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) containing methotrexate attached to the alpha-amino group of D-Phe in position 1. Control groups of mice received saline, RC-121 or methotrexate. Drugs were given in equimolar doses by daily s.c. injections. After 7 days of treatment with 25 micrograms/day of AN-51, tumor growth was completely inhibited although the treatment had to be suspended because of toxic side effects, especially on the gastrointestinal tract, accompanied by major weight loss of the animals. Mice were allowed to recover for 1 week and treatment was continued with 12.5 micrograms/day AN-51. After 2 weeks of additional therapy, tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased, compared with controls, only in the group treated with AN-51. Methotrexate and RC-121 also inhibited tumor growth, but their effects were not statistically significant. AN-51 retained its hormonal activity and decreased serum growth hormone levels in mice. Binding affinity of AN-51 for somatostatin receptors on MIA PaCa-2 cells was found to be 2.5-times lower than that of parent compound RC-121. This is the first report on inhibition of human pancreatic cancer growth in vivo by somatostatin analogs carrying cytotoxic radicals.

Surveyor Nuclease: a new strategy for a rapid identification of heteroplasmic mitochondrial DNA mutations in patients with respiratory chain defects. Molecular analysis of mitochondrial DNA (mtDNA) is a critical step in diagnosis and genetic counseling of respiratory chain defects. No fast method is currently available for the identification of unknown mtDNA point mutations. We have developed a new strategy based on complete mtDNA PCR amplification followed by digestion with a mismatch-specific DNA endonuclease, Surveyor Nuclease. This enzyme, a member of the CEL nuclease family of plant DNA endonucleases, cleaves double-strand DNA at any mismatch site including base substitutions and small insertions/deletions. After digestion, cleavage products are separated and analyzed by agarose gel electrophoresis. The size of the digestion products indicates the location of the mutation, which is then confirmed and characterized by sequencing. Although this method allows the analysis of 2 kb mtDNA amplicons and the detection of multiple mutations within the same fragment, it does not lead to the identification of homoplasmic base substitutions. Homoplasmic pathogenic mutations have been described. Nevertheless, most homoplasmic base substitutions are neutral polymorphisms while deleterious mutations are typically heteroplasmic. Here, we report that this method can be used to detect mtDNA mutations such as m.3243A>G tRNA(Leu) and m.14709T>C tRNA(Glu) even when they are present at levels as low as 3% in DNA samples derived from patients with respiratory chain defects. Then, we tested five patients suffering from a mitochondrial respiratory chain defect and we identified a variant (m.16189T>C) in two of them, which was previously associated with susceptibility to diabetes and cardiomyopathy. In conclusion, this method can be effectively used to rapidly and completely screen the entire human mitochondrial genome for heteroplasmic mutations and in this context represents an important advance for the diagnosis of mitochondrial diseases.

Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer. Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n = 3), FA-G (n = 1) and FA-I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland.

The physiological effects of vasopressin when used to control intra-abdominal bleeding. Vasopressin was used in ten critically ill patients with massive intra-abdominal bleeding unresponsive to conventional therapy. Vasopressin controlled bleeding in four patients, three of whom had continued to bleed following laparotomy for haemostasis; in two other patients, bleeding was reduced. All the patients were intensively monitored throughout the period of the vasopressin treatment; this enabled other physiological effects of vasopressin to be documented and reported. Mean arterial pressure and central venous pressure increased following the administration of vasopressin and there was a decrease in heart rate. Core body temperature rose significantly. Although all the patients had impaired renal function before receiving vasopressin, five had a prompt diuresis following its administration. Eight patients died but only three of intra-abdominal bleeding; two patients survived to leave hospital. Four patients had post-mortem evidence of ischaemia in the heart, liver and gastrointestinal tract; vasopressin may have contributed to the development of this. Vasopressin may have a place in the management of patients with life-threatening intra-abdominal haemorrhage but its use should be confined to those patients in whom conventional therapy has failed.

Molecular Engineering of Phenylbenzimidazole-Based Orange Ir(III) Phosphors toward High-Performance White OLEDs. To develop B-O complementary-color white organic light-emitting diodes (WOLEDs) exhibiting high efficiency and low roll-off as well as color stability simultaneously, we have designed two orange iridium(III) complexes by simply controlling the position of the methoxyl group on the cyclometalated ligand. The obtained emitters mOMe-Ir-BQ and pOMe-Ir-BQ show good photophysical and electrochemical stabilities with a broadened full width at half-maximum close to 100 nm. The corresponding devices realize highly efficient electrophosphorescence with a maximum current efficiency (CE) and power efficiency (PE) of 24.4 cd A-1 and 15.3 lm W-1 at a high doping concentration of 15 wt %. Furthermore, the complementary-color all-phosphor WOLEDs based on these phosphors exhibit good performance with a maximum CE of 31.8 cd A-1, PE of 25.0 lm W-1, and external quantum efficiency of 15.5%. Particularly, the efficiency of this device is still as high as 29.3 cd A-1 and 14.2% at the practical brightness level of 1000 cd m-2, giving a small roll-off. Meanwhile, extremely high color stability is achieved by these devices with insignificant chromaticity variation.

Amino acid substitutions in mitochondrial ATPase subunit 9 of Saccharomyces cerevisiae leading to oligomycin or venturicidin resistance. A series of isonuclear oligomycin-resistant mutants of Saccharomyces cerevisiae carrying mutations in the mitochondrial oli1 gene has been studied. DNA sequence analysis of this gene has been used to define the amino acid substitutions in subunit 9 of the mitochondrial ATPase complex. A domain of amino acids involved in oligomycin resistance can be recognized which encompasses residues in each of the two hydrophobic portions of the subunit 9 polypeptide that are thought to span the inner mitochondrial membrane. Certain amino acid substitutions also confer cross-resistance to venturicidin: these residues define an inner domain for venturicidin resistance. The expression of venturicidin resistance resulting from one particular substitution is modulated by nuclear genetic factors.

[Posibility of term pregnancy in patients with chronic kidney disease]. Pregnancy is a physiological process that brings many changes to the mother's body, undergoing a process of adaptation to complications avoid, however, in the context of chronic kidney disease, these become manifest most frequently maternal and fetal impact on morbidity and mortality. A review of the subject is presented, emphasizing aspects that must be present at the time of a patient with this condition, accompanied by one of our cases treated with the sole purpose of gaining a better understanding of the issue and how to address it based on problems at the time of evaluation initial. The case of patient pregnant with chronic kidney disease in stage advanced that required start of replacement therapy in renal function due to uremia and retention fluid in malaise their 20 weeks of gestation, referred late for your attention. However, it was possible to improve you overall condition in all respects, allowing take up to 38 weeks with abdominal delivery via scheduled electively, with favorable results for the newborn exceed the statistics described in these patients.

Annual immunisation coverage report, 2010. This, the fourth annual immunisation coverage report, documents trends during 2010 for a range of standard measures derived from Australian Childhood Immunisation Register (ACIR) data. These include coverage at standard age milestones and for individual vaccines included on the National Immunisation Program (NIP). For the first time, coverage from other sources for adolescents and the elderly are included. The proportion of children 'fully vaccinated' at 12, 24 and 60 months of age was 91.6%, 92.1% and 89.1% respectively. For vaccines available on the NIP but not currently assessed for 'fully immunised' status or for eligibility for incentive payments (rotavirus and pneumococcal at 12 months and meningococcal C and varicella at 24 months) coverage varied. Although pneumococcal vaccine had similar coverage at 12 months to other vaccines, coverage was lower for rotavirus at 12 months (84.7%) and varicella at 24 months (83.0%). Overall coverage at 24 months of age exceeded that at 12 months of age nationally and for most jurisdictions, but as receipt of varicella vaccine at 18 months is excluded from calculations, this represents delayed immunisation, with some contribution from immunisation incentives. The 'fully immunised' coverage estimates for immunisations due by 60 months increased substantially in 2009, reaching almost 90% in 2010, probably related to completed immunisation by 60 months of age being introduced in 2009 as a requirement for GP incentive payments. As previously documented, vaccines recommended for Indigenous children only (hepatitis A and pneumococcal polysaccharide vaccine) had suboptimal coverage at around 57%. Delayed receipt of vaccines by Indigenous children at the 60-month milestone age improved from 56% to 62% but the disparity in on-time vaccination between Indigenous and non-Indigenous children at earlier age milestones did not improve. Coverage data for human papillomavirus (HPV)from the national HPV register are consistent with high coverage in the school-based program (73%) but were lower for the catch-up program for women outside school (30-38%). Coverage estimates for vaccines on the NIP from 65 years of age were comparable with other developed countries.

Proctosigmoidoscopy and rectal biopsy in infants and children. The medical records of all patients ages 0 to 21 years who underwent proctosigmoidoscopy and/or rectal biopsy over a 27 month period of time were reviewed to determine the efficacy and safety of these procedures in pediatric patients. One hundred twenty-one patients underwent proctosigmoidoscopy; 91 of these also had rectal biopsies. Median age was two years; 21% were less than six months and 8% less than one month of age. Depth of examination was 10 to 15 cm in most patients greater than 10 years of age. Induced friability was the most frequently observed mucosal abnormality. Abnormal findings were almost always present in patients with bloody diarrhea and were quite common in those with rectal bleeding, but less common in those with chronic diarrhea and abdominal pain. Colitis of various causes was the most common cause of blood in the stool; anal fissures were found in only four of 23 patients with rectal bleeding. Both proctosigmoidoscopy and rectal biopsy were needed to exclude the presence of colitis. Mobidity was 0% with proctosigmoidoscopy and 0.34% with rectal suction biopsy.

Electrostatic interactions between hyaluronan and proteins at pH 4: how do they modulate hyaluronidase activity. Hyaluronan (HA) hydrolysis catalyzed by hyaluronidase (HAase) is inhibited at low HAase over HA ratio and low ionic strength, because HA forms electrostatic complexes with HAase, which is unable to catalyze hydrolysis. Bovine serum albumin (BSA) was used as a model to study the HA-protein electrostatic complexes at pH 4. At low ionic strength, there is formation of (i) neutral insoluble complexes at the phase separation and (ii) small positively-charged or large negatively-charged soluble complexes whether BSA or HA is in excess. According to the ionic strength, different types of complex are formed. Assays for HA and BSA led to the determination of the stoichiometry of these complexes. HAase was also shown to form the various types of complex with HA at low ionic strength. Finally, we showed that at 0 and 150 mmol L(-1) NaCl, BSA competes with HAase in forming complexes with HA and thus induces HAase release resulting in a large increase in the hydrolysis rate. These results, in addition to data in the literature, show that HA-protein complexes, which can exist under numerous and varied conditions of pH, ionic strength and protein over HA ratio, might control the in vivo HAase activity.

A nuclear overhauser study of heme orientational isomerism in monomeric Chironomus hemoglobins. The nuclear Overhauser effect (NOE) was used to investigate heme orientation and to obtain assignments for all resolved resonances in the 1H-NMR spectrum of met-cyano Chironomus thummi thummi monomeric hemoglobins III and IV (Hb III and Hb IV). The only non-heme resolved resonance was found to be from Phe-38 (CD1), and NOE dipolar connectivity between this resonance and the heme 5- and 8-methyls was used to establish the absolute orientation of the heme for each heme-insertion isomer present. The assignments of resonances and heme disorder permitted structural comparisons between the various components, including those due to a point mutation in Hb III. Finally, the characteristic differences of NOE patterns to amino-acid protons from substituents on heme pyrroles I and II formed the basis for assigning resonances and heme orientation relative to native Hb IV for deuterohemin-reconstituted Hb IV, for which there are no X-ray data available.

Human immunodeficiency virus replication induces monocyte chemotactic protein-1 in human macrophages and U937 promonocytic cells. We have recently described a significant correlation between human immunodeficiency virus-1 (HIV-1) RNA replication and monocyte chemotactic protein-1 (MCP-1) levels in the cerebrospinal fluid (CSF) of individuals with the acquired immunodeficiency syndrome (AIDS) with HIV encephalitis (E). Because local macrophages (microglia) are the cells predominantly infected in the brain, we investigated whether in vitro HIV infection affects MCP-1 production in mononuclear phagocytes (MP). MCP-1 secretion and expression were consinstently upregulated over constitutive levels in human monocyte-derived macrophages (MDM) infected with the M-tropic R5 BaL strain of HIV-1. HIV replication was required for this effect, as demonstrated by the absence of chemokine upregulation after infection in the presence of 3'-azido-3'-deoxythimidine (AZT) or cell-exposure to heat-inactivated (triangle up degrees ) virus. MCP-1 induction was not restricted to HIV-1 BaL, but was also observed during productive infection of MDM with two primary isolates differing for entry coreceptor usage and of U937 cells with the X4 HIV-1 MN strain. Based on the observation that exogenous HIV-1 Tat induced MCP-1 expression in astrocytes, we also investigated its role in MDM and U937 cells. Exogenous Tat induced MCP-1 production from MDM in a concentration-dependent manner, however, it was not effective on uninfected U937 cells or on the chronically infected U937-derived cell line U1. Transfection of Tat-expressing plasmids moderately activated HIV expression in U1 cells, but failed to induce MCP-1 expression in this cell line or in uninfected U937 cells. HIV replication-dependent expression of MCP-1 in MP may be of particular relevance for the pathogenesis of HIV infection in nonlymphoid organs such as the brain.

Known risk factors do not explain disparities in gallstone prevalence between Denmark and northeast Germany. Gallstones are a common disease worldwide, with disparities in the prevalence of the disease in different settings. The aim of the present study was to assess if different distributions of risk factors could explain the disparities in the prevalence of gallstone disease between Denmark and northeast Germany. Data of 5,559 subjects from the Danish MONICA survey and of 3,647 subjects of the German Study of Health in Pomerania were investigated. Gallstone disease was defined as a prior history of cholecystectomy or the presence of sonographically diagnosed gallstones. Logistic regression models were performed to assess the confounding effect of selected risk factors on regional disparities in gallstone disease. After adjustment for age and vocational training, German subjects (women: Odds ratio, OR, 2.46 (95% confidence interval, CI: 2.07-2.91); men: OR, 1.89 (95% CI: 1.52-2.36)) had approximatively twice the odds of gallstones than Danes. Inclusion of lifestyle factors (smoking, alcohol intake, coffee use) did not affect this result, whereas adjustment for body mass index (BMI), lipids, diabetes, and use of oral contraceptives, menopausal hormone therapy (MHT) and parity (women only) changed the estimates considerable, but still Germans (women: OR, 1.65 (95% CI: 1.36-2.00); men: OR, 1.61 (95% CI: 1.27-2.04)) had higher odds than Danes. German individuals had a higher prevalence of gallstones than Danes. This difference was partly explained by a higher BMI, unfavorable lipid levels, higher prevalence of diabetes, and a more frequent use of OR and MHT in German subjects. Further research is needed to evaluate the impact of unmeasured predictors, including genetic components, on the population-related risk of gallstones.

The prevalence of frontotemporal dementia. To estimate the prevalence of frontotemporal dementia (FTD) and other degenerative early-onset dementias in a geographically defined population. Early-onset dementia (at age <65 years) results in high psychiatric morbidity and caregiver burden. Prevalence figures are available for early-onset AD but not for FTD, a dementia that is almost invariably of early onset. Case ascertainment was by review of case records of three specialist clinic databases and inpatient admissions at a university hospital in Cambridge, United Kingdom, for patients with dementia who were <65 years of age, living in Cambridge City or East or South Cambridgeshire (population 326,019) on May 30, 2000. All the relevant health services in the area were also contacted for potential cases. Diagnosis of various dementias was based on published criteria. All patients with potential FTD were examined by the study investigators and underwent structural neuroimaging. The 1998 population estimates for the area were used to calculate age and sex prevalence with confidence intervals for AD, FTD, and other causes of dementia. A total of 108 patients (66 men and 42 women) with dementia with onset before they were 65 years of age were identified, of whom 60 were <65 years on the census date, giving an overall prevalence of 81 (95% CI, 62.8 to 104.5) per 100,000 in the 45- to 64-year age group. The prevalences of early-onset FTD and AD were the same: 15 per 100,000 (8.4 to 27.0) in the 45- to 64-year-old population. The mean age at onset of FTD was 52.8 years and there was a striking male preponderance (14:3). It is possible case ascertainment methods resulted in a relative underrepresentation of some forms of dementia. Frontotemporal dementia is a more common cause of early-onset dementia than previously recognized and appears to be more common in men.

Outcomes of Patients Implanted Using a Left Thoracotomy Technique for a Miniaturized Centrifugal Continuous-Flow Pump. As ventricular-assist devices (VADs) are increasingly employed in heart failure management, a leading cause of mortality, new literature is consistently published on less-invasive implantation techniques. Although early perioperative outcomes have been shown to be favorable with minimally invasive left thoracotomy (LT) approaches compared with conventional sternotomy (CS), studies comparing long-term outcomes are lacking. We set out to evaluate long-term follow up between LT and CS approach. In a single center, retrospective review, data on patients with similar demographic profiles were collected. HeartWare (HVAD) implantation was performed by either CS or LT. Analysis was performed on perioperative adverse outcomes, and 6 month postoperative adverse events. Primary objectives of the study included comparative outcomes of morbidity and mortality between both groups at 180 days postimplantation. Eighty-one (n = 81) bridge to transplant (BTT) patients underwent CS or LT HVAD implantation. Perioperative transfusion (p = 0.04) favored the LT cohort compared with CS, with a median of 6 units and 8 units transfused for each group, respectively. No survival difference was observed between both groups at 6 months postimplantation (p = 0.52). Clinical outcomes at an average of 6 month follow up showed no difference in adverse events, including common postoperative VAD complications such as infection and right heart failure. Miniaturization of LVAD size and improvement in technology has allowed expansion of interest in alternative surgical approaches for HVAD implantation. For BTT patients, no difference in early outcome was observed 6 months after implantation using a left LT versus CS technique.

Reconstruction of the maxilla and midface--surgical management, outcome, and prognostic factors. Loss of the maxilla due to tumor ablation has both functional and aesthetic consequences. Even small defects become obvious because of missing bone and soft tissue. Reconstruction of the maxilla and midface in these patients presents a challenge to the surgeon although several possibilities are available for this purpose. The long term benefit to patients of the different modalities remains unclear due to wide individual variation. One hundred and twenty-one patients with maxillary oral squamous cell carcinoma were treated with curative intent. One hundred and five patients were surgically reconstructed using local or free microsurgical flaps. All parameters were collected from case records. Kaplan-Meier plots and univariate log-rank test and multivariate Cox proportional hazards regression models were used to determine the association between possible predictor variables and survival time of patients suffering from oral squamous cell carcinomas. After controlling for age, resection margins, nodal stage, and surgical management, which were independent and dependent predictors of survival, the type of reconstruction and involvement of surgical margins were associated with survival (HR=0.50, p=0.044, 95% CI, 0.25-0.98 and HR=3.16, p=0.007, 95% CI, 1.38-7.25). Various types of maxillary defects can be reconstructed successfully using different reconstructive techniques. The size and complexity of defects does not correlate with prognosis in oral squamous cell carcinoma patients. The criteria for reconstruction with a free flap were based on extensive defects in which local flaps were insufficient, on medical co-morbidities, and previous treatment.

Clinician compliance with laboratory regulations requiring submission of relevant clinical data: A one year retrospective analysis. The College of American Pathologists (CAP) recognizes the need for clinical data in the interpretation of specimens submitted for histopathologic evaluation. Anecdotal evidence indicates that clinician compliance with requests for clinical history is variable. Quality assurance data from August 1, 2010 to September 31, 2011 were searched for all cases listing no clinical history. Four consecutive weeks of surgical pathology request forms were also reviewed for the presence or absence of clinical history and its accuracy. 21,700 cases were accessioned in the study period and 1293 (5.9%) requisitions contained no clinical history. The four-week review documented that 143 of 1698 (8.4%) requisitions had no clinical history and 12 cases contained incorrect history (0.7%). Between 5.9% and 8.4% of requisitions contain no clinical history. In 0.2% of cases, clinical history was incorrect. Compliance with the CAP policy for clinical history appears poor.

Poly(alkylcyanoacrylate) nanocapsules: physicochemical characterization and mechanism of formation. Nanocapsules of poly(isobutylcyanoacrylate) and poly(isohexylcyanoacrylate) were prepared by addition of the monomer to an organic phase and subsequent mixing of the organic phase to an aqueous phase containing poloxamer 188, 238 or 407. Gel permeation chromatography indicated that in contrast to literature reports, polymerization occurred in the organic phase and nanocapsules were obtained by interfacial precipitation of the polymer without any significant change of the molecular weight. Addition of SO2 to the organic phase before the introduction of the monomer allowed preparation of nanocapsules with a lower molecular weight. Nanospheres were prepared in a similar way albeit using an organic phase that was completely miscible within the aqueous phase so that solid spheres were obtained. Density gradient centrifugation revealed that nanocapsules had a density intermediate between nanospheres and an emulsion prepared in the same way without addition of monomer to the organic phase. Further, the process used to prepare nanocapsules had a high yield since no oil droplets or nanospheres were obtained by this process. Zeta potential of the nanocapsules and spheres was found to be related to the molecular weight of the polymer: values as high as approximately -42 mV were obtained for low molecular weight nanocapsules (MW approximately 1000) compared to approximately -10mV for the emulsion and the high molecular weight nanocapsules (MW approximately 100,000). Surface charge of the nanocapsules and molecular weight of their polymeric wall conditioned the adsorption capacity of poloxamers. Moreover, the highest adsorption was measured with the most hydrophobic poloxamer. These observations agree with previous work conducted on hydrophobic surfaces.

Evaluation of cellular and humoral systemic immune response against Giardia duodenalis infection in cattle. Giardia duodenalis causes diarrhoea in humans and a wide range of mammals, including cattle. In cattle, the infection often has a chronic character. Infected calves may excrete cysts for several months, suggesting that Giardia is able to suppress and evade the immune response. In this study six calves were infected with G. duodenalis assemblage A and E and housed in an environment that allowed reinfection. Cyst excretion was monitored twice a week and blood was collected every 2 weeks, until decreasing cyst counts indicated the development of protective immunity. The kinetics of the circulating memory cells and serum antibodies were followed up throughout this period. Cyst excretion started 1 week post-infection and remained high until week 14. Low cyst counts from week 15 p.i. onwards indicated that the calves had developed immunity. From week 5 p.i. significant proliferation of CD4(+) αβ T-cells was observed after in vitro stimulation with G. duodenalis antigen. Characterisation of the proliferating CD4(+) T-cells using real time qPCR showed that at the peak of antigen driven PBMC proliferation the majority of cells were CD4(+) T-cells expressing IL-17 and to a lesser extent FoxP3. The cell proliferation was strongly reduced after plastic adhesion of the PBMC, suggesting a role for antigen-presenting cells. Failure to restore proliferation of depleted PBMC with Giardia-stimulated monocyte-derived dendritic cells (MoDC) and unchanged proliferation after depletion of CD21(+) B-cells showed that other antigen-presenting cells than MoDC and B-cells were important for T-cell proliferation. Analysis of the antibody response indicated that serum IgG1 and IgA levels against G. duodenalis assemblage A and E increased from week 11 post-infection. From the start of the antibody response, all trophozoites stained positive in an immunofluorescence assay with serum antibodies, indicating that a broad repertoire of antibodies was produced against all variant-specific surface proteins. Further research is necessary to determine which effector T-cell subset produces IL-17 and which cells play a role in antigen presentation.

Gas chromatographic evaluation of trapidil and its desethyl metabolite in biological fluids for pharmacokinetic and bioavailability investigations. This paper describes a suitable and cost-saving method for quantitative analysis of trapidil (5-methyl-7-diethylamino-s-triazolo [1,5-a]pyrimidine) and its desethyl metabolite in plasma and urine for pharmacokinetic and bioavailability investigations. Trapidil and desethyl-trapidil were extracted from plasma, concentrated and injected into the gas chromatography without any derivatization process. The authors suggest a series of internal standards. A thermoionic specific detector enables high sensitivity to be achieved, i.e. 20 ng/ml, and good specificity. The method is cost-saving in that it allows about 30 analyses a day to be performed without automatic integrators, and about 50 analyses a day with these integrators.

TNF Block Gene Variants Associate With Pain Intensity in Black Southern Africans With HIV-associated Sensory Neuropathy. HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN. Single-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. One SNP allele, rs28445017*A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017*G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons. We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.

Inhibition of glycoprotein catabolism in vivo and in the perfused rat liver. Leupeptin is a peptide which inhibits several of the lysosomal proteases. When this compound was added in low concentrations to a perfused liver, the degradation of 125I-asialo-fetuin by the liver was dramatically slowed. When 5 mg leupeptin were added to the perfusate 1 h prior to the radioactive glycoprotein, the liver retained from 70 to 90% or the radioisotope 60 min after infusing 125I-asialo-fetuin. However, untreated livers contained less than 20% of the radioactivity at that time. Subcellular fractionation experiments showed that the radioactivity accumulated in the heavy and light mitochondrial fractions (ML) of the homogenate. At 80 min after the glycoprotein was added, almost 40% of the radioactivity was still located with these fractions. Very similar inhibitory effects were seen upon treating rats intravenously with 5 mg of leupeptin 60 min prior to injection of 125I-labelled asialo-fetuin. A 7 fold increase in liver radioactivity was observed 6 hrs after the glycoprotein had been given to the treated animals. Purified human liver cathepsin B digested fetuin to about 3% of total hydrolysis and the major peptide fragment produced had an SDS-electrophoretic mobility equivalent to that of ovalbumin.

Volatile and non-volatile/semi-volatile compounds and in vitro bioactive properties of Chilean Ulmo (Eucryphia cordifolia Cav.) honey. Ulmo honey originating from Eucryphia cordifolia tree, known locally in the Araucania region as the Ulmo tree is a natural product with valuable nutritional and medicinal qualities. It has been used in the Mapuche culture to treat infections. This study aimed to identify the volatile and non-volatile/semi-volatile compounds of Ulmo honey and elucidate its in vitro biological properties by evaluating its antioxidant, antibacterial, antiproliferative and hemolytic properties and cytotoxicity in Caco-2 cells. Headspace volatiles of Ulmo honey were isolated by solid-phase microextraction (SPME); non-volatiles/semi-volatiles were obtained by removing all saccharides with acidified water and the compounds were identified by GC/MS analysis. Ulmo honey volatiles consisted of 50 compounds predominated by 20 flavor components. Two of the volatile compounds, lyrame and anethol have never been reported before as honey compounds. The non-volatile/semi-volatile components of Ulmo honey comprised 27 compounds including 13 benzene derivatives accounting 75% of the total peak area. Ulmo honey exhibited weak antioxidant activity but strong antibacterial activity particularly against gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA), the main strain involved in wounds and skin infections. At concentrations >0.5%, Ulmo honey reduced Caco-2 cell viability, released lactate dehydrogenase (LDH) and increased reactive oxygen species (ROS) production in a dose dependent manner in the presence of foetal bovine serum (FBS). The wide array of volatile and non-volatile/semi-volatile constituents of Ulmo honey rich in benzene derivatives may partly account for its strong antibacterial and antiproliferative properties important for its therapeutic use. Our results indicate that Ulmo honey can potentially inhibit cancer growth at least partly by modulating oxidative stress.

[Early parenteral nutrition in complex post-operative periods]. The protein hypercatabolic state in critically ill pediatric patients can be minimized by an effective nutrition therapy. We conducted a study to evaluate the benefits of early parenteral nutrition (EPN) assessing its effect on nutritional parameters and clinical relevance after complex surgical procedures. Prospective randomized study in patients undergoing abdominal surgery in which nothing by mouth is anticipated for a period ≥ 3 days, between 2012 and 2014. Blood tests were performed assessing nutritional parameters in the first 24 hours and the 5th postoperative day. Two groups were created, starting EPN in group A and standard fluid therapy in group B, after the extraction of the first sample. Forty-four patients were included, 18 in group A and 26 in group B. In the first analysis all had decreased levels of prealbumin and retinol-binding protein. On the 5th day, 55,6% of group A normalized prealbumin levels compared to 11,5% of B (p: 0.003, EF = 80%) whereas retinol-binding protein was normalized in 66,7% and 34.6%, respectively (p: 0,07, EF = 48,4%). Three patients in group A (16,7%) had postoperative infectious complications compared to 8 in B (30,8%), difference no statistically significant but clinically relevant (NNT=7,1), since the latter showed low prealbumin levels and longer hospital stay. No complications related to EPN were detected. Administration of EPN in the complex postoperative patients appears to be safe and beneficial for their recovery, being the prealbumin an early indicator of good nutritional response.

Structured white light scanning of rabbit Achilles tendon. The cross-sectional area (CSA) of a material is used to calculate stress under load. The mechanical behaviour of soft tissue is of clinical interest in the management of injury; however, measuring CSA of soft tissue is challenging as samples are geometrically irregular and may deform during measurement. This study presents a simple method, using structured light scanning (SLS), to acquire a 3D model of rabbit Achilles tendon in vitro for measuring CSA of a tendon. The Artec Spider™ 3D scanner uses structured light and stereophotogrammetry technologies to acquire shape data and reconstruct a 3D model of an object. In this study, the 3D scanner was integrated with a custom mechanical rig, permitting 360-degree acquisition of the morphology of six New Zealand White rabbit Achilles tendons. The reconstructed 3D model was then used to measure CSA of the tendon. SLS, together with callipers and micro-CT, was used to measure CSA of objects with a regular or complex shape, such as a drill flute and human cervical vertebra, for validating the accuracy and repeatability of the technique. CSA of six tendons was measured with a coefficient of variation of less than 2%. The mean CSA was 9.9±1.0mm2, comparable with those reported by other researchers. Scanning of phantoms demonstrated similar results to μCT. The technique developed in this study offers a simple and accurate method for effectively measuring CSA of soft tissue such as tendons. This allows for localised calculation of stress along the length, assisting in the understanding of the function, injury mechanisms and rehabilitation of tissue.

Multivariate modelling of infectious disease surveillance data. This paper describes a model-based approach to analyse multivariate time series data on counts of infectious diseases. It extends a method previously described in the literature to deal with possible dependence between disease counts from different pathogens. In a spatio-temporal context it is proposed to include additional information on global dispersal of the pathogen in the model. Two examples are given: the first describes an analysis of weekly influenza and meningococcal disease counts from Germany. The second gives an analysis of the spatio-temporal spread of influenza in the U.S.A., 1996-2006, using air traffic information. Maximum likelihood estimates in this non-standard model class are obtained using general optimization routines, which are integrated in the R package surveillance.

Immunogenicity of hepatitis A vaccine in children with celiac disease. The response to hepatitis A vaccine has not been studied in children with celiac disease (CD). The aim of the present study was to evaluate the immunogenicity of an inactivated hepatitis A virus (HAV) vaccine and the effect of the human leukocyte antigen (HLA) type on immunogenicity in children with CD. Thirty-three patients with CD and 62 healthy controls were enrolled in the study. Inactivated HAV vaccine (Havrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) containing 720 enzyme-linked immunosorbent assay units of alum-adsorbed hepatitis A antigen was administered intramuscularly in a 2-dose schedule at 0 and 6 months. Seroconversion rates and antibody titers of HAV were measured at 1 and 7 months. At 1 month, seroconversion rates were 78.8% and 77.4% and geometric mean titers were 50.7 and 49.9 mIU/mL in the CD and control groups, respectively (P > 0.05). At 7 months, seroconversion rates were 97% and 98.4% and geometric mean titers were 138.5 and 133 mIU/mL in the CD and control groups, respectively (P > 0.05). The most frequent HLA types were HLA-DQ2, -DR3, and -DR7 alleles in patients with CD and HLA-DQ3, -DQ6, -DR11, and -DR14 in the controls. There was no association between HLA alleles and antibody titers of hepatitis A vaccine. Children with CD have a good immune response to hepatitis A vaccine, similar to healthy controls.

Disparity of innate immunity-related gene effects on asthma and allergy on Karelia. We investigated the interactive effects of 11 innate immunity-related genes (IL10, IL12b, IL8, TLR2, TLR4, CD14, IFNGR, CC16, IFNg, CMA1, and TGFB) and four IgE response genes (IL4, IL13, IL4RA, and STAT6) with 'Western' or 'Eastern' environments/lifestyles on asthma and allergy in Karelian children. Karelian children (412 Finnish and 446 Russian) were recruited and assessed for a range of allergic conditions, with 24 single-nucleotide polymorphisms genotyped in 15 genes. The genotype-phenotype relationships differed in Finnish and Russian Karelian children. The interaction between polymorphisms and the variable representing 'Western' and 'Eastern' environments/ lifestyles was significant for IL10-1082 (p = 0.0083) on current rhinitis, IL12b 6408 on current conjunctivitis (p = 0.016) and atopy (p = 0.034), IL8 781 on atopic eczema (p = 0.0096), CD14 -550 on current rhinitis (p = 0.022), IFNgR1 -56 on atopic eczema(p = 0.038), and STAT6 2964 on current itchy rash (p = 0.037) and total serum IgE (p = 0.042). In addition, the G allele of IL13 130 was associated with a lower level of total serum IgE in Finnish (p = 0.003) and Russian (p = 0.01) children and overall (pooling the two populations together, p = 0.00006). After adjusting for multiple tests, the association between IL13 130 and IgE and the interactive effects of IL10-1082 on current rhinitis and IL8 781 on atopic eczema were significant by controlling a false-positive rate of 0.05 and 0.10, respectively. Living in an Eastern vs. Western environment was associated with a different genetic profile associated with asthma and allergy in the Karelian populations.

Diagnostic value of emergency medical services provider judgement in the identification of head injuries among trauma patients. Previous studies have reported that many patients with a severe head injury are not transported to a higher-level trauma centre where the necessary round-the-clock neurosurgical care is available. The aim of this study was to analyse the diagnostic value of emergency medical services (EMS) provider judgement in the identification of a head injury. In this multicentre cohort study, all trauma patients aged 16 years and over who were transported with highest priority to a trauma centre were evaluated. The diagnostic value of EMS provider judgement was determined using an Abbreviated Injury Scale score of ≥1 in the head region as reference standard. A total of 980 (35.4%) of the 2766 patients who were included had a head injury. EMS provider judgement (Abbreviated Injury Scale score ≥1) had a sensitivity of 67.9% and a specificity of 87.7%. In the cohort, 208 (7.5%) patients had a severe head injury. Of these, 68% were transported to a level I trauma centre. Identification of a head injury on-scene is challenging. EMS providers could not identify 32% of the patients with a head injury and 21% of the patients with a severe head injury. Additional education, training and a supplementary protocol with predictors of a severe head injury could help EMS providers in the identification of these patients.

A formal enantioselective acetate Mannich reaction: the nitro functional group as a traceless agent for activation and enantiocontrol in the synthesis of beta-amino acids. A two-step procedure involving the enantioselective addition of alpha-nitro esters to imines, followed by reductive denitration, provides a convenient new enantioselective synthesis of beta-amino acids. Specifically, beta-phenyl alanine derivatives with up to 98% ee are formed in good yield (64-88%) over two steps. The utility of the approach is demonstrated through the first enantioselective synthesis of the key beta-amino acid of (+)-chaenorhine.

Tumour micrometastases: the influence of angiogenesis. Many cancer patients have undetected micrometastatic disease at first presentation which ultimately progresses. Angiogenesis-the development of an independent blood supply-is a key event in the growth of metastases. Improved understanding of the influence of angiogenesis on micrometastatic growth may lead to new therapeutic intervention. This study examines current concepts of the significance of micrometastases and the role of angiogenesis in their development and destruction. A comprehensive review of the literature on micrometastasis and angiogenesis was performed using the Medline database between 1966 and 1999. Advances in technology have improved our ability to diagnose metastatic disease, but micrometastases in loco-regional lymph nodes and at distant sites can only be detected by sophisticated histological techniques. While the significance of micrometastases remains controversial, there is increasing evidence that micrometastatic status provides useful prognostic information and should be part of standard staging techniques. Anti-angiogenic therapy has the potential to favourably influence management of certain cancers by manipulating a number of key events in the metastatic process.

Maternal satisfaction with active management of labor: a randomized controlled trial. Active management of labor reduces the length of labor and rate of prolonged labor, but its effect on satisfaction with care, within a randomized controlled trial, has not previously been reported. The study objectives were to establish if a policy of active management of labor affected any aspect of maternal satisfaction, and to determine the independent explanatory variables for satisfaction with labor care in a low-risk nulliparous obstetric population. Nulliparous women at National Women's Hospital in Auckland, New Zealand, in spontaneous labor at term with singleton pregnancy, cephalic presentation, and without fetal distress were randomized after the onset of labor to active management (n = 320) or routine care (n = 331). Active management included early amniotomy, two-hourly vaginal assessments, and early use of high dose oxytocin for slow progress in labor. Routine care was not prespecified. Maternal satisfaction with labor care was assessed by postal questionnaire at 6 weeks postpartum. Sensitivity analyses were performed, and logistic regression models were developed to determine independent explanatory variables for satisfaction. Of the 651 women randomized in the trial, 482 (74%) returned the questionnaires. Satisfaction with labor care was high (77%) and did not significantly differ by treatment group. This finding was stable when sensitivity analysis was performed. The first logistic regression model found independent associations between satisfaction and adequate pain relief, one-to-one midwifery care, adequate information and explanations by staff, accurate expectation of length of labor, not having a postpartum hemorrhage, and fewer than three vaginal examinations during labor. The second model found fewer than three vaginal examinations and one-to-one midwifery care as significant explanatory variables for satisfaction with labor care. Active management did not adversely affect women's satisfaction with labor and delivery care in this trial. Future studies should concentrate on measurement of potential predictors before and during labor.

Astrocyte lipid metabolism is critical for synapse development and function in vivo. The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682.

Physicochemical properties of cross-linked and acetylated starches and products of their hydrolysis in continuous recycle membrane reactor. The aim of the present work was to study the physicochemical properties of doubly modified, by cross-linking and acetylating, starches as well as the products of their enzymatic hydrolysis. A two step procedure of hydrolysis, including the batch and membrane reactors, were investigated. The second step of enzymatic processes were carried out in a continuous recycle membrane reactor (CRMR). Three kinds of commercial starches--two preparations of acetylated distarch adipate E1422 of different degrees of cross-linking, as well as one preparation of acetylated distarch phosphate E1414 were examined. It was found that the degree of substitution of acetyl groups in the macromolecules of starch did not influence the effectiveness of hydrolysis. However, the degree of cross-linking with adipate groups slightly decreased the efficiency of processing in the CRMR. Additionally, the relationship between the type of hydrocolloid and its adsorption activity in the air/water and oil/water systems was considered. All obtained derivatives revealed adsorption properties and reduced the surface/interface tension in the air/water and oil/water systems. The efficiency and effectiveness of adsorption of the investigated hydrocolloids were affected by the type of modification as well as the degree of substitution of acetyl groups in the macromolecules of starch. Particle size distributions formed in aqueous solutions for all investigated hydrolyses were determined and compared with results obtained for commercial products.

Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis. Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.

Constitutive expression of p21H-Ras(Val12) in neurons induces increased axonal size and dendritic microtubule density in vivo. The small G protein p21Ras is a key signal transducer mediating cellular growth and proliferation responses to extracellular stimuli. We investigated by electron microscopy the effects of augmented p21Ras activity on neuronal processes and microtubule arrangement in vivo. We used transgenic mice with a neuron-specific overexpression of p21H-RasVal12, which starts postnatally around Day 15. Axonal and dendritic diameters and the numerical density of dendritic microtubules were analyzed at postnatal Day 12 before the onset of transgene expression and in adult mice. In adult transgenic mice, calibers of both axons (corpus callosum) and dendrites (layers II/III of somatosensory cortex) were enlarged by about 57% and 79%, respectively. The increase in dendritic calibers was associated with an increment in the amount of microtubules. Even in dendrites of equivalent diameters, the number of microtubules was higher in transgenic mice compared to that in wild-type mice suggesting an elevated microtubule density. Changes in process diameters or microtubule density were not observed at postnatal Day 12 before relevant transcription of transgenic p21H-RasVal12. The present results extend previous findings on neuronal hypertrophy as a consequence of p21H-RasVal12 expression and suggest a profound influence on the dendritic microtubule network.

High-Efficiency Polymer Solar Cells with Sm/Ca Bilayer Cathode Buffer. The Sm/Ca bilayer buffers together with Al as the cathode, instead of Al or Ca/Al cathodes are applied into bulk heterojunction polymer solar cells. Accompanied with the optimization of Sm/Ca buffer thicknesses, a high power conversion efficiency of 3.98%, an enhanced short-circuit current density (J(SC)) of 10.87 mA/cm², and a fill factor (FF) of 0.61 are achieved in the poly(3-hexylthiophene): [6,6]-phenyl-C₆₁-butyric acid methyl ester (P3HT:PCBM)-based cell. Analysis on the film’s scanning electron microscopy images, light absorption characteristics, the electromagnetic fields distribution, and scattering illustrates that absorption enhancement induced by Sm clusters via the localized surface plasmon resonance and scattering plays a major role in the enhancement of J SC, while a highly efficient electron extraction and a further resulting large FF is dominated by the Cabuffer.

Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action. Oxidative stress, involved in many diseases, is defined as an impaired balance between reactive oxygen species (ROS) production and antioxidant defences. Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in diminishing oxidative stress. Thus, the removal of ROS by exogenous SODs could be an effective preventive strategy against various diseases. The poor bioavailability of exogenous SODs has been criticized. However, improvements in SOD formulation may overcome this limitation and boost interest in its therapeutic properties. Here, we provide a review of animal and human studies about SODs supplementation in order to evaluate their therapeutic value. Protective effects have been observed against irradiation, carcinogenesis, apoptosis and neurodegeneration. SODs administration has also been reported to alleviate inflammatory, infectious, respiratory, metabolic and cardiovascular diseases and genitourinary and fertility disorders, raising the question of its mechanism of action in these diverse situations. Some authors have shown an increase in endogenous antioxidant enzymes after exogenous SODs administration. The induction of endogenous antioxidant defence and, consequently, a decrease in oxidative stress, could explain all the effects observed. Further investigations need to be carried out to test the hypothesis that SODs supplementation acts by inducing an endogenous antioxidant defence.

Chromosome-breakage syndromes: different genes, different treatments, different cancers. Comparison of the strikingly different distributions of types of cancer that occur in the genetic disorders that feature chromosome instability raises several interesting points. (a) Bloom's syndrome: the distribution suggests that many of the cancers that occur with regularity in the general population just occur more commonly and at an earlier age. (b) Ataxia telangiectasia: cancers of many types are increased in frequency, but lymphoreticular cancers are exceptionally common, the case also in several other genetically determined immunodeficiency disorders. Both Bloom's syndrome and ataxia telangiectasia share defective immunity as a major clinical feature, but the respective roles, if any, of it and of chromosome instability in producing the cancer predispositions are unknown. (c) Fanconi's anemia: cancer apparently has become common only recently. The types and distribution which occur are unusual. Fanconi's anemia cells have been shown to be hypertransformable by oncogenic virus and to be defective in handling certain types of DNA damage (as well as to manifest chromosome instability) so that the recent increase in cancer incidence is both surprising and unexplained. The degree of cancer proneness of Fanconi's anemia per se, untreated by modern methods, must at present be considered unknown. (d) Xeroderma pigmentosum: the cancer predisposition apparently extends only to cells which receive solar damage, i.e., to skin and eye. This would not have been predicted in view of the fact that the cellular mechanism is defective for repairing DNA damage produced not just by sunlight but also by certain classes of chemical carcinogens.

Oral factor Xa inhibitors for venous thromboembolism prevention in major orthopedic surgery: a review. Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopedic surgery, and routine thromboprophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of VTE in major orthopedic surgery include low-molecular-weight heparins, vitamin K antagonists and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, these drugs have several limitations, and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors of factor Xa, rivaroxaban, apixaban, LY517717, YM150 and betrixaban. Specifically, the results of phase II and III studies and the designs of ongoing clinical trials in patients undergoing elective hip and knee replacement are reviewed.

Surface-governed molecular regulation of blood coagulation. Among extracellular biological processes the spatial control of blood clotting is a unique phenomenon. Localization in space has very important consequences in both normal and pathological conditions. Under physiological circumstances a clot is formed only in the vicinity of injury, albeit the prerequisites of coagulation are almost completely given in the whole circulation. The local character of blood clotting is secured by the following major conditions: The regulatory signal initiating coagulation-the damaged vascular wall-is itself a surface on which the majority of clotting reactions take place. The first enzyme, factor XII, of the intrinsic coagulation pathway is activated on the collagen fibers exposed in the damaged vascular wall, although the significance of this reaction in respect of the clotting process is ambiguous. On the membrane of platelets adhered to the damaged blood vessel is activated factor XI, too, which is a well-established participant of the intrinsic clotting process. The further consecutive reactions of coagulation are confined to the surface produced by injury, because the enzymes involved contain gamma-carboxyl-glutamyl side chains which are anchored through calcium bridges to the phospholipids of the platelet membrane. The last enzyme of the sequence is thrombin, which is released from the surface. The reactions taking place on the surface form an enzyme cascade, which amplifies the relatively weak triggering signal by several orders of magnitudes. Amplification is ensured not only by the enzyme-substrate relationship of the consecutive reaction partners, but also by spatial confinement, which endows the process with higher efficacy than could be expected on a statistical basis from reactions in solution. It contributes to the efficiency of enzyme cascade that the non-enzymatic regulatory proteins increase the activity of factors IXa and Xa, and thereby the overall process. While the partner of factor IXa, factor VIII, is captured from plasma, factor V, the partner of factor Xa, is derived from the platelets adhered to the damaged surface and orients the binding of factor Xa. The surface localization ensures the protection of the members of clotting system: In the activator complexes found on the surface, the spatial arrangement of clotting factors prevents the inactivation of factors by physiological inhibitors or by proteolytic enzymes and specific antibodies that appear in the circulation in pathological conditions. Platelet factor 4, derived from platelets, binds heparin and thereby markedly decreases the reactivity of antithrombin III, the physiological inhibitor of clotting factors. The above two circumstances are

Reforming nursing home quality regulation. Impact on cited deficiencies and nursing home outcomes. The federally-mandated nursing home survey and certification process has been criticized for focusing more on the potential of each facility to provide good care than on the demonstrated quality of care delivered or on resultant resident outcomes. This paper presents the results of an evaluation of the pilot of a new federal survey process (Patient Care and Services, PaCS) that concentrates surveyor time on the review of resident care, reduces surveyor time spent reviewing policy and procedures, and, for the first time, mandates personal interviews with a sample of facility residents. In Rhode Island, a randomized control design was used to evaluate the impact of the survey on both the number and type of deficiencies cited, as well as on resident outcomes at six month follow-up. The PaCS team cited significantly more deficiencies, in total, than the traditional survey team, and significantly more patient-oriented deficiencies. However, no significant differences in resident outcomes were found when comparing nursing homes in which PaCS was administered and nursing homes in which only the traditional survey was administered.

Health Promotion Schools of Excellence: a model program for Kentucky and the nation. This article reviews the development and progress of an innovative, comprehensive school health project in the Jefferson County school district known as the Health Promotion Schools of Excellence (HPSE). This project features unique working relationships between public and private entities seeking a common goal: "A Healthier Community." The goals and development of HPSE have been formulated to coincide with the emerging directives of the Kentucky Education Reform Act (KERA) as well as the growing pressures to control health care costs through effective preventive measures. The results of testing following the first and second years of the project show an encouraging trend of improved physical fitness levels for all students (grades K-12) and improving levels of health knowledge and attitudes in elementary level children (grades 4-8) as well as school faculty and staff. These initial results, although encouraging, will only be meaningful if they translate over time into a healthier, more responsible cohort of adolescents and young adults when compared to their peers not involved in the project. The project, while only in its third year of development, has already been recognized at regional and national levels as a successful model of a comprehensive school health program. As the project continues and grows, the authors anticipate developing one of the nation's largest and most comprehensive longitudinal data bases of childhood and adolescent health information.

Ripple-like intraocular lens damage from a neodymium:YAG laser. We report a case of accidental intraocular lens (IOL) damage during a neodymium:YAG laser capsulotomy. After a single pulse of 0.9 mJ of laser energy, a large area of ripple-like opacity with more than 10 concentric circles surrounding a small hole in a 2.0 diopter IOL was noted. The opacity extended more than one fourth of the IOL diameter and caused a significant visual effect.

Are caregivers adherent to their own medications? To explore caregiver adherence to chronic medications and predictors of appropriate medication use. Descriptive, nonexperimental, cross-sectional study. United States in May 2009. 2,000 adults randomly selected from a large national consumer panel. Web-based survey of community pharmacy patients. Self-reported medication adherence. 21% of those invited (3,775) responded to the survey invitation. Of the 2,000 individuals who were eligible to participate, 38% described themselves as caregivers. Among caregivers, 45% agreed that they were more likely to forget their own medications than medications for their caregivees. Caregivers were 10% more likely to forget to take their medications, 11% more likely to stop taking medications if they felt well, and 13% more likely to forget to refill their medications than noncare-givers (P < 0.001 for all). In fully adjusted models, caregivers had 36% greater odds (95% CI 0.52-0.79) of reporting that they were nonadherent compared with noncare-givers and increased medication use among caregivees was associated with worse adherence among caregivers (P < 0.05). Medication nonadherence was common in this population, and caregivers were more likely to report poor medication adherence than noncaregivers. Considering that caregivers often engage health professionals, physicians and pharmacists may choose to screen for caregiving status. Pharmacists are uniquely positioned to intervene to enhance appropriate medication adherence.

Crystallization of a polymorphic hydrate system. Nitrofurantoin can form two monohydrates, which have the same chemical composition and molar ratio of water, but differ in the crystal arrangements. The two monohydrates (hydrates I and II) could be produced independently via evaporative crystallization, where supersaturation and solvent composition were both found to have an effect. Hydrate I showed much slower crystallization than hydrate II. During cooling crystallization, the nucleation and growth of hydrate II was again dominant, consuming all supersaturation and leading to no hydrate I formation. Seeding of hydrate I during cooling crystallization was also applied, but the hydrate I seeds were not able to initiate its nucleation rather than dissolving into crystallizing solution. Although solubility tests revealed that hydrate II is more stable than hydrate I due to its lower solubility (110 +/- 4 and 131 +/- 12 microg/mL for hydrates II and I, respectively), this difference is rather small. Therefore, the small free energy difference between the two hydrates, together with the slow crystallization of hydrate I, both lead to a hindrance of hydrate I formation. Furthermore, the crystal structure of hydrate II demonstrated a higher H-bonding extent than hydrate I, suggesting its more favorable crystallization. This is in good agreement with experimental results.

MPTP-Induced pallidal lesions in rhesus monkeys. Dopamine neurons in the substantia nigra of the midbrain are the primary neuronal population affected by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) toxicity, which produces the pathological and behavioral features of Parkinson's disease in nonhuman primates and man. We have identified another injury site in magnetic resonance imaging (MRI) brain scans in 13 of 37 rhesus monkeys taken 10-12 months after administration of this neurotoxin via the right carotid artery. Focal lesions, ranging in volume from 6.75 to 60 mm3 in the rostral globus pallidus region, were seen on the right side of the brain in these 13 animals in addition to the midbrain effects. While no significant differences were seen between globus pallidus lesioned and nonlesioned animals in the severity of MPTP-induced parkinsonian symptoms, the response to levodopa was muted in pallidal-lesioned animals. To confirm the role of neurotoxicity in producing the lesions, brain scans from an additional 12 monkeys were evaluated during the acute period following exposure to either MPTP (n = 6) or saline (n = 6). Focal lesions in the rostral globus pallidus were seen as early as 2-4 h following a carotid artery infusion in two of six MPTP recipients, but no evidence of injury was seen in saline recipients. The globus pallidus includes important components of the neural circuitry regulating motor functions. The present results indicate that in addition to midbrain dopamine neurons, a focal region of the rostral globus pallidus is selectively vulnerable to MPTP toxicity.

Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. Excitotoxicity might play an important role in neurodegenerative disorders such as Alzheimer's disease. In the mouse brain, kainic acid (KA) lesioning results in neurodegeneration patterns similar to those found in human disease. For this study, two sets of experiments were performed in order to determine if Cerebrolysin ameliorates the alterations associated with KA administration. In the first set of experiments, mice received intraperitoneal KA injections followed by Cerebrolysin administration, while in the second, mice were pretreated with Cerebrolysin for 4 weeks and then challenged with KA. Behavioral testing in the water maze and assessment of neuronal structure by laser scanning confocal microscopy showed a significant protection against KA lesions in mice pretreated with Cerebrolysin. In contrast, mice that received Cerebrolysin after KA injections did not show significant improvement. This study supports the contention that Cerebrolysin might have a neuroprotective effect in vivo against excitotoxicity.

Neoadjuvant chemotherapy with cisplatin, ifosfamide and 5-fluorouracil in the treatment of locally advanced cervical cancer. The objective of this study was to evaluate clinical and histological response, resectability, and survival in patients with cervical epidermoid carcinoma stage IB2 to IIIB with the use of neoadjuvant chemotherapy followed by radical surgery and/or radiation therapy. Between September 1989 and February 1996, 53 patients were admitted to this study. They were given three cycles of cisplatin 30 mg/m2/day, 5-fluorouracil 500 mg/m2/day, ifosfamide 2000 mg/m2/day i.v., and mesna 400 mg/m2/day i.v. at hour 0 and 400 mg/m2 at hours 4 and 8 during three days every 21-28 days. We evaluated 47 patients. Global clinical response obtained was 85% {95% (CI), 75-97%, CR in 14 patients (30%) and PR in 26 patients (55%)}. Twenty-three patients underwent surgery. Six patients (13%) had a complete histological response. Median follow-up was 42 months (5-96). In resected patients, with a median follow-up of 57 months (5-96), the estimated five-year disease-free survival was 78%. Global survival estimated to 60 months was 83% for stage IB2, 70% for IIB, and 20% for IIIB. This mode of therapy offers a new option to improve survival in locally advanced cervical cancer. Randomized trials are required in order to establish a definitive role for this therapeutic strategy.

Associative network based on cyclodextrin polymer: a model system for drug delivery. Associative networks have been elaborated by mixing in aqueous media a cyclodextrin polymer to a dextran bearing adamantyl groups. The two polymers interact mainly via inclusion complexes between adamantyl groups and cyclodextrin cavities, as evidenced by the high complexation constants determined by isothermal titration microcalorimetry (approximately 10(4) L mol(-1)). Additional interaction mechanisms participating in the strength of the network, mainly hydrogen bonding and electrostatic interactions, are sensitive to the pH and ionic strength of the medium, as shown by pH-dependent rheological properties. The loading and release of an apolar model drug, benzophenone, has been studied at two pH values and different cyclodextrin polymer content. Slow releases have been obtained (10-12 days) with slower kinetics at pH 2 than at pH 7. Analysis of the experiments at pH 7 shows that drug release is controlled both by diffusion in the network and by inclusion complex interactions with cyclodextrin cavities.

Evaluation of two minimally invasive techniques for electroencephalogram recording in wild or freely behaving animals. Insight into the function of sleep may be gained by studying animals in the ecological context in which sleep evolved. Until recently, technological constraints prevented electroencephalogram (EEG) studies of animals sleeping in the wild. However, the recent development of a small recorder (Neurologger 2) that animals can carry on their head permitted the first recordings of sleep in nature. To facilitate sleep studies in the field and to improve the welfare of experimental animals, herein, we test the feasibility of using minimally invasive surface and subcutaneous electrodes to record the EEG in barn owls. The EEG and behaviour of four adult owls in captivity and of four chicks in a nest box in the field were recorded. We scored a 24-h period for each adult bird for wakefulness, slow-wave sleep (SWS), and rapid-eye movement (REM) sleep using 4 s epochs. Although the quality and stability of the EEG signals recorded via subcutaneous electrodes were higher when compared to surface electrodes, the owls' state was readily identifiable using either electrode type. On average, the four adult owls spent 13.28 h awake, 9.64 h in SWS, and 1.05 h in REM sleep. We demonstrate that minimally invasive methods can be used to measure EEG-defined wakefulness, SWS, and REM sleep in owls and probably other animals.

Isolation of two distinct activator proteins for lipoprotein lipase from ovine plasma. Two distinct activator proteins for lipoprotein lipase (LPL) have been isolated in approximately equal amounts from ovine plasma. These low molecular weight proteins were readily separated from each other on the basis of size and charge. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated proteins of Mr about 8000 and 5000, with pI in urea-containing gels of about 5.1 and 4.8 respectively. Each of the ovine activator proteins was as effective as human apolipoprotein C-II (apo C-II) in activating LPL, with 1 microgram/ml giving near to maximum activation, and in lowering the apparent Km of LPL for triolein substrate. As the ratio of activator to triolein increased from 0.16 to 5.2 (micrograms/mg) the apparent Km fell from about 0.5 to 0.18 mM. Whereas human apo C-II and the two ovine activators were equally effective in stimulating the hydrolysis of triolein, differences were observed between the human and ovine activators when p-nitrophenylbutyrate was used as substrate. Unlike human apo C-II, which produced significant inhibition of p-nitrophenylbutyrate hydrolysis, the ovine activators were without effect. This suggests that the interaction between the ovine activators and LPL is different from that of human apo C-II.

Perimeter growth of a branched structure: application to crackle sounds in the lung. We study an invasion percolation process on Cayley trees and find that the dynamics of perimeter growth is strongly dependent on the nature of the invasion process, as well as on the underlying tree structure. We apply this process to model the inflation of the lung in the airway tree, where crackling sounds are generated when airways open. We define the perimeter as the interface between the closed and opened regions of the lung. In this context we find that the distribution of time intervals between consecutive openings is a power law with an exponent beta approximately 2. We generalize the binary structure of the lung to a Cayley tree with a coordination number Z between 2 and 4. For Z=4, beta remains close to 2, while for a chain, Z=2 and beta=1, exactly. We also find a mean field solution of the model.

[Surgical treatments of nonconfluent pulmonary arteries with congenital cardiac defects]. Pulmonary artery angioplasty or reconstruction was performed in seven patients with nonconfluent pulmonary arteries and congenital cardiac defects. Age of these patients were ranged from 6 months to 41 years old. Five of them had pulmonary truncal atresia and complex cardiac anomalies. Two of these five patients demonstrated nonconfluent pulmonary arteries due to deformities at ductal insertion of pulmonary arteries. Three patients had had previous systemic to pulmonary artery shunt operations which caused pulmonary artery distortions. Other two patients had intrapulmonary arterial obstructions due to pulmonary artery thrombosis. Patch pulmonary artery plasty was carried out in three patients, dilatation of severe stenotic pulmonary artery was done in one patient simultaneously with pulmonary valvotomy. Central shunt operation was added in one patient with the pulmonary artery which was unable to be reconstructed. Last two patients underwent intrapulmonary artery reconstruction with the rolled pericardial graft. Hospital death occurred in one patient with unproperly increased pulmonary blood flow by central shunt. Average follow-up period of these six survivors after operation was 1.4 +/- 0.8 years. As definite repairs, two patients had Fontan operation, two patients had right ventricle to pulmonary artery reconstruction. And remaining two patients are still to be followed until sufficient growth of pulmonary artery suitable for Fontan operation.

[Sentinel node biopsy using dye methods]. At first, sentinel node identification was performed using dyes such as isosulfan blue dye and patent blue dye. Although dye localization is a simple and cheap method, this procedure requires training and the success rate and accuracy are not very good. It is considered that the addition of a radiocolloid injection is needed for sentinel node biopsy in melanoma and breast cancer. For gastrointestinal tract malignancies, good results were reported in several feasibility studies. However, the validity of sentinel node biopsy for those malignancies depends on the results of a large ongoing clinical trial.

Esthetic rehabilitation of anterior discolored teeth with lithium disilicate all-ceramic restorations. The esthetic treatment of darkened anterior teeth represents a great challenge to dentists, because dental materials ideally should match the natural teeth. The optical behavior of the final restoration is determined by the color of the underlying tooth structure, the color of the luting agent, and the thickness and opacity of the ceramic material used. This article reports a case in which veneers and full crowns made of heat-pressed, lithium disilicate glass-ceramic were used for the esthetic rehabilitation of anterior discolored teeth. The patient was referred for treatment with defective anterior composite resin restorations, provisional acrylic resin crowns, darkening of the gingival margins, and uneven gingival contours. The multidisciplinary treatment plan included dental bleaching, periodontal plastic surgery to create gingival symmetry, and indirect all-ceramic restorations using high-opacity lithium disilicate glass-ceramic ingots. The treatment was successful and an excellent esthetic result was achieved.

Residue analysis of 500 high priority pesticides: better by GC-MS or LC-MS/MS? This overview evaluates the capabilities of mass spectrometry (MS) in combination with gas chromatography (GC) and liquid chromatography (LC) for the determination of a multitude of pesticides. The selection of pesticides for this assessment is based on the status of production, the existence of regulations on maximum residue levels in food, and the frequency of residue detection. GC-MS with electron impact (EI) ionization and the combination of LC with tandem mass spectrometers (LC-MS/MS) using electrospray ionization (ESI) are identified as techniques most often applied in multi-residue methods for pesticides at present. Therefore, applicability and sensitivity obtained with GC-EI-MS and LC-ESI-MS/MS is individually compared for each of the selected pesticides. Only for one substance class only, the organochlorine pesticides, GC-MS achieves better performance. For all other classes of pesticides, the assessment shows a wider scope and better sensitivity if detection is based on LC-MS.

Diagnosis of Benign and Malignant Breast Lesions on DCE-MRI by Using Radiomics and Deep Learning With Consideration of Peritumor Tissue. Computer-aided methods have been widely applied to diagnose lesions detected on breast MRI, but fully-automatic diagnosis using deep learning is rarely reported. To evaluate the diagnostic accuracy of mass lesions using region of interest (ROI)-based, radiomics and deep-learning methods, by taking peritumor tissues into consideration. Retrospective. In all, 133 patients with histologically confirmed 91 malignant and 62 benign mass lesions for training (74 patients with 48 malignant and 26 benign lesions for testing). 3T, using the volume imaging for breast assessment (VIBRANT) dynamic contrast-enhanced (DCE) sequence. 3D tumor segmentation was done automatically by using fuzzy-C-means algorithm with connected-component labeling. A total of 99 texture and histogram parameters were calculated for each case, and 15 were selected using random forest to build a radiomics model. Deep learning was implemented using ResNet50, evaluated with 10-fold crossvalidation. The tumor alone, smallest bounding box, and 1.2, 1.5, 2.0 times enlarged boxes were used as inputs. The malignancy probability was calculated using each model, and the threshold of 0.5 was used to make a diagnosis. In the training dataset, the diagnostic accuracy was 76% using three ROI-based parameters, 84% using the radiomics model, and 86% using ROI + radiomics model. In deep learning using the per-slice basis, the area under the receiver operating characteristic (ROC) was comparable for tumor alone, smallest and 1.2 times box (AUC = 0.97-0.99), which were significantly higher than 1.5 and 2.0 times box (AUC = 0.86 and 0.71, respectively). For per-lesion diagnosis, the highest accuracy of 91% was achieved when using the smallest bounding box, and that decreased to 84% for tumor alone and 1.2 times box, and further to 73% for 1.5 times box and 69% for 2.0 times box. In the independent testing dataset, the per-lesion diagnostic accuracy was also the highest when using the smallest bounding box, 89%. Deep learning using ResNet50 achieved a high diagnostic accuracy. Using the smallest bounding box containing proximal peritumor tissue as input had higher accuracy compared to using tumor alone or larger boxes. 3 Technical Efficacy: Stage 2.

The role of stigma in the quality of life of older adults with severe mental illness. Stigma and discrimination against older people with mental illness is a seriously neglected problem. (1) To investigate whether stigmatisation of older adults with mental disorder is associated with the type of residential institution they live in or the type of disorder they suffer and (2) to assess the role of stigma experiences in their quality of life. A cross-sectional study was carried out of 131 older adults with severe mental illness, recruited in 18 elder care homes operating supported living programmes and in eight psychiatric hospitals throughout the Netherlands. Stigmatisation was assessed with an 11-item questionnaire on stigma experiences associated with mental illness. Quality of life was assessed with the Manchester Short Assessment of Quality of Life (MANSA). To better ascertain the role of stigma, we also assessed in comparison the relationship of social participation to quality of life. Some 57% of the respondents had experienced stigmatisation. No association emerged between residential type or disorder type and the extent of stigma experiences. Stigmatisation did show a negative association with quality of life, a connection stronger than that between social participation and quality of life. A feeling of belonging, as contrasted with being excluded, is at least as important for the quality of life of older people with severe mental illness as their actual participation in the community.

Morphometry of terminal hepatic veins. 2. Follow up in chronically alcohol-fed baboons. Alcohol induced perivenular fibrosis of terminal hepatic veins (THV) is claimed to be a precursor lesion leading to fibrosis development in man and baboon. The nature and significance of the THV lesions found in four baboons chronically fed with alcohol were studied in liver biopsies obtained during a three year period. The surface of THV wall and the number of mesenchymal cells were assessed with a semi-automatic image analyser. Histologically, THV were characterized as (a) phlebitic, in the presence of an inflammatory cell infiltrate involving the venous wall; (b) oedematous, when the connective tissue of the THV wall was disrupted or dissociated and (c) fibrotic, when perivenular scarring appeared as an increased rim. These lesions were present simultaneously and their intensity and distribution were independent of the duration of alcohol intoxication. Morphometric data obtained from these THV confirmed the thickening of the THV wall (WS/IS in: oedematous 1.05 +/- 0.36; phlebitic 1.65 +/- 1.04; fibrotic 1.47 +/- 0.36); and revealed an increased number of mesenchymal cells in fibrotic (439 microns 2/cell; p less than 0.01) and in phlebitic THV (510 microns 2/cell; p less than 0.05). A constant relationship was found between phlebitis and the presence of inflammatory infiltrate within the hepatic acini. Fibrotic THV was a less frequent finding and the lesion disappeared in the sequential biopsies of one of the baboons. In conclusion, THV lesions were heterogeneous and the collagen deposition in the THV wall was potentially reversible during the three year alcohol intoxication period, regardless the inflammatory reaction and, thus, did not indicate early irreversible hapatic fibrosis.

Wound care into the new millennium. "There has never been a time in the history of management of wounds when so many have been so well prepared to effect improvement in the quality of care being delivered at reduced costs and with improved outcomes," says Dick Meer, founder and executive director of the Center for Tissue Trauma Research and Education (CTTRE) in Jensen Beach, Fla.

Identification of differently timed motor components of conditioned blink responses. Electromyographic recordings were made from the orbicularis oculi muscles of cats in order to identify differently timed motor components of conditioned eye blink responses (CRs). Conditioning was established rapidly by pairing electrical stimulation of the hypothalamus (HS) with a click conditioned stimulus (CS) and a glabella tap unconditioned stimulus (US). Analysis of the EMG responses disclosed five different motor components of the CR that could be distinguished and characterized according to their latencies of occurrence. Four were associated with an increase in EMG activity elicited by the CS (16-48 ms, alpha(1); 48-80 ms, alpha(2); 80 to 120 ms, beta; >/=120 ms, gamma), and one was associated with a decrease in activity (16 to 60 ms, alpha(i)). Analysis of the amplitudes of the different components of the CR during the course of conditioning and extinction disclosed that short latency, alpha(1) components of the CRs were acquired and extinguished in a manner equivalent to longer latency components of the CRs. The observations supported the hypothesis that short and long latency components of blink responses represented comparable rather than substantially different forms of Pavlovian conditioning. The alpha(2) response was present before conditioning began, and increased with other components after conditioning. The alpha(i) response component was also observed prior to conditioning, and represents a previously undetected, inhibitory consequence of presenting weak (70 dB) acoustic stimuli. It could play a role in conditioned inhibition, latent inhibition and blocking as well as suppression of the conditioned motor response during extinction.

Self-Care Behaviors of Nepalese Adults With Type 2 Diabetes: A Mixed Methods Analysis. Most previously reported literature on diabetes self-care is either solely quantitative or qualitative research conducted in developed countries; findings may not be generalizable to developing countries with different sociodemographic and cultural factors. The study aims to develop an explanatory mediation model for self-care and enhance model interpretation through qualitative input. A quantitatively driven, sequential, mixed method design was used. Structured questionnaires were used to collect data for the quantitative component from 230 participants. Participants for the qualitative interview were selected using maximum variation sampling (n = 13), and interviewing was guided by semistructured questions. Diabetes management self-efficacy had the strongest influence on diabetes self-care (standardized path coefficient = .42, p < .001), followed by perceived social support (standardized path coefficient = .26, p < .001), and educational status (standardized path coefficient = -.22, p < .001). Diabetes management self-efficacy significantly and partially mediated the relationship between diabetes duration and diabetes self-care (Sobel's z = 2.65, p < .001) and between expectation regarding aging and diabetes self-care (Sobel's z = 3.03, p < .001). Perceived social support significantly and partially mediated the relation between educational status and diabetes self-care (Sobel's z = -2.81, p < .001). The qualitative component elucidated nine themes interwoven in Nepalese culture, social structure, and religious belief. Responsibilities toward family and belief in God acted as boosters for self-care in the case of Nepalese adults, which differed by age, gender, and literacy status. The results from this study suggest that tailored psychosocial interventions to promote diabetes management self-efficacy may be beneficial in promoting self-care among Nepalese adults with diabetes mellitus.

Agronomic importance of first development of chickpea (Cicer arietinum L.) under semi-arid conditions: II. Seed imbibition. Due to the slowness growth and weakness of the first developments of chickpea (Cicer arietinum L.), it could not combated with weeds and easily caught up by Ascochyta blight (Ascochyta rabiei (Pass) Labr.) disease. Additionally, due to biotic and abiotic stress factors, esp. at the late sowing, important seed yield losses could be happened. To be able to avoid from them is only possible to accelerate of its first development as possible as. So, one of the best solutions to is to use chemical compounds such as Humic Acid (HA) known soil regulator under the semi-arid conditions. With this aim this research was performed in a Randomized Complete Block Design (RCBD) with four replications under semi-arid field conditions during (2008/2009) and (2009/2010) in Turkiye. Two cultivars (V1 = Gokce and V2 = Ispanyol) and four seed imbibition methods (A0 = 0, A1 = Tap Water, A2 = 1/2 Tap Water + 1/2 Humic acid (HA), A3 = Full HA, as w/w) and seven yield components Plant Height (PH), Number of Branches per Plant (NBP), Number of Pods per Plant (NPP), First Pod Height (NFP), Number of Seeds per Pod (NSP), Seed Weight per Plant (SWP) and 100-Seed weight (HSW) were investigated. The PH and FPH were affected the A0, the NBP, NPP and NSP were affected the A2 and the SWP and HSW were given the varied but not clear responses according to varieties for all the parameters in A1. The A0 and A1 were encouraged the germination and top soil of the plant but, the A2 to A3 were encouraged root system's development. It was concluded that the A2 is a promising method which makes the maximum and positive effect to the first development of the chickpea agronomy under the semi-arid conditions.

Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. The disposition of the long-acting opioid methadone, used to prevent opiate withdrawal and treat short- and long-lasting pain, is highly variable. Methadone undergoes N -demethylation to the primary metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP), catalyzed in vitro by intestinal, hepatic, and expressed cytochrome P450 (CYP) 3A4. However, the role of CYP3A4 in human methadone disposition in vivo is unclear. This investigation tested the hypothesis that CYP3A induction (or inhibition) would increase (or decrease) methadone metabolism and clearance in humans. Healthy volunteers were studied in a randomized, balanced, 4-way crossover study. They received intravenous (IV) midazolam (to assess CYP3A4 activity) and then simultaneous oral deuterium-labeled and IV unlabeled methadone after pretreatment with rifampin (INN, rifampicin) (hepatic/intestinal CYP3A induction), troleandomycin (hepatic/intestinal CYP3A inhibition), grapefruit juice (selective intestinal CYP3A inhibition), or nothing. Methadone effects were measured by dark-adapted pupil diameter. CYP isoforms catalyzing methadone metabolism by human liver microsomes and expressed CYPs in vitro were also evaluated. Methadone had high oral bioavailability (70%) and low intestinal (22%) and hepatic (9%) extraction, and there was a significant correlation ( r = 0.94, P <.001) between oral bioavailability and intestinal (but not hepatic) availability. Rifampin decreased bioavailability and oral and IV methadone plasma concentrations and increased IV clearance (4.42 +/- 1.00 mL. kg -1. min -1 versus 1.61 +/- 0.67 mL. kg -1. min -1, P <.05) and oral clearance (8.50 +/- 3.68 mL. kg -1. min -1 versus 2.05 +/- 0.92 mL. kg -1. min -1, P <.05), EDDP/methadone area under the curve (AUC) ratios, EDDP formation clearances, and hepatic extraction (0.27 +/- 0.06 versus 0.09 +/- 0.04, P <.05). Troleandomycin and grapefruit juice decreased the EDDP/methadone AUC ratio after oral methadone (0.17 +/- 0.10 and 0.14 +/- 0.06 versus 0.27 +/- 0.20, P <.05) but not IV methadone and had no effect on methadone plasma concentrations, IV clearance (1.29 +/- 0.41 mL. kg -1. min -1 and 1.48 +/- 0.55 mL. kg -1. min -1 ) or oral clearance (2.05 +/- 1.52 mL. kg -1. min -1 and 1.89 +/- 1.07 mL. kg -1. min -1 ), or other kinetic parameters. There was no correlation between methadone clearance and hepatic CYP3A4 activity. Pupil diameter changes reflected plasma methadone concentrations. In vitro experiments showed a predominant role for both CYP3A4 and CYP2B6 in liver microsomal methadone N -demethylation. First-pass intestinal metabolism is a determinant of methadone bioavailability. Intestinal and hepatic CYP3A activity only slightly affects human methadone N -demethylation but has no significant effect on methadone concentrations, clearance, or clinical effects. Greater rifampin effects, compared with troleandomycin and grapefruit juice, on methadone disposition suggest a major role for intestinal transporters and for other CYPs, such as CYP2B6. Interindividual variability and drug interactions affecting intestinal transporter and hepatic CYP3A and CYP2B6 activity may alter methadone disposition.

Shindigs, brunches, and rodeos: the neural basis of event words. Events (e.g., "running" or "eating") constitute a basic type within human cognition and human language. We asked whether thinking about events, as compared to other conceptual categories, depends on partially independent neural circuits. Indirect evidence for this hypothesis comes from previous studies showing elevated posterior temporal responses to verbs, which typically label events. Neural responses to verbs could, however, be driven either by their grammatical or by their semantic properties. In the present experiment, we separated the effects of grammatical class (verb vs. noun) and semantic category (event vs. object) by measuring neural responses to event nouns (e.g., "the hurricane"). Participants rated the semantic relatedness of event nouns, as well as of two categories of object nouns-animals (e.g., "the alligator") and plants (e.g., "the acorn")-and three categories of verbs-manner of motion (e.g., "to roll"), emission (e.g., "to sparkle"), and perception (e.g., "to gaze"). As has previously been observed, we found larger responses to verbs than to object nouns in the left posterior middle (LMTG) and superior (LSTG) temporal gyri. Crucially, we also found that the LMTG responds more to event than to object nouns. These data suggest that part of the posterior lateral temporal response to verbs is driven by their semantic properties. By contrast, a more superior region, at the junction of the temporal and parietal cortices, responded more to verbs than to all nouns, irrespective of their semantic category. We concluded that the neural mechanisms engaged when thinking about event and object categories are partially dissociable.

Attitudes towards carrier testing in minors: a systematic review. The objective of this article is to review the attitudes of the different stakeholders (minors, healthcare professionals, parents and relatives of affected individuals) towards carrier testing in minors. The databases Pubmed, Google Scholar, Psychinfo, Biological Abstracts, Francis, Anthropological Index online, Web of Science, and Sociological Abstracts were searched using key words for the period 1990-2004. Studies were included if they were published in a peer reviewed journal in English and described the attitudes of minors, parents or healthcare professionals towards carrier testing in minors in a family context. The results were presented in a summary form. In total 20 relevant studies were retrieved (2 studies reported the attitudes of two stakeholders). Only one study reported the attitudes of adolescents, two studies reported the attitudes of adults who had undergone carrier testing in childhood. In total six studies have been retrieved discussing the parental attitudes towards carrier testing in their children. Over all studies, most parents showed interest in detecting their children's carrier status and responded they wanted their child tested before the age of majority: some parents even before 12 years. Eight studies were retrieved that reported the attitudes of relatives of affected individuals. Most were in favor of carrier testing before 18 years. The studies retrieved suggest that most parents are interested in the carrier status of their children and want their children to be tested before they reach legal majority (and some even in childhood). This can lead to tensions between parents and healthcare professionals regarding carrier testing in minors. Guidelines of healthcare professionals advise to defer carrier testing on the grounds that children should be able to decide for themselves later in life to request a carrier test or not.

Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. To develop a feasible magnetic resonance imaging (MRI)-based scoring system for spinal inflammation in patients with spondylarthropathy that requires minimal scan time, does not require contrast enhancement, evaluates the extent of lesions in 3 dimensional planes, and limits the number of vertebral levels that are scored because MRI demonstrates characteristic inflammatory lesions in the spine of patients with ankylosing spondylitis (AS) prior to the development of typical features on plain radiographic. Our scoring method was based entirely on the assessment of increased signal denoting bone marrow edema on T2-weighted STIR sequences. Blinded MRI films were assessed in random order at 2 sites by 3 blinded readers at each of the 2 sites (the Universities of Alberta and Toronto). Intra- and interreader reliability was assessed by intraclass correlation coefficient. The 24-week response of patients with AS randomized to infliximab:placebo (8:3) was assessed by effect size and standardized response mean. An initial analysis of all discovertebral units (DVUs) in the spine of 11 patients demonstrated a mean of 3.2 (95% confidence interval 3.2, 5.2) affected units, while limiting the scoring to a maximum of 6 units captured most of the affected units. We scanned 11 patients with AS with clinically active disease and 20 additional patients randomized to a 24-week trial of either infliximab or placebo. Intraobserver reproducibility for the 6-DVU STIR score ranged from 0.93 to 0.98 (P < 0.0001). Interobserver reproducibility of scores by readers from both sites was 0.79 (P < 0.0001) for status score and 0.82 (P < 0.0001) for change score. Analysis of pretreatment and posttreatment scores for all 20 patients randomized to infliximab/placebo showed a large degree of responsiveness (standardized response mean = 0.87). Reproducibility and responsiveness were only slightly improved by using contrast enhancement with gadolinium diethylenetriaminepentaacetic acid. The Spondyloarthritis Research Consortium of Canada MRI index is a feasible, reproducible, and responsive index for measuring spinal inflammation in AS.

Prognostic significance of serum lactate dehydrogenase level in osteosarcoma: a meta-analysis. A number of studies have investigated the role of serum lactate dehydrogenase (LDH) level in patients with osteosarcoma but have yielded inconsistent and inconclusive results. Thus, we conducted a meta-analysis to assess its prognostic value more precisely. Systematic computerized searches of PubMed, Embase and Web of Science databases were performed. The pooled hazard ratio (HR) with 95 % confidence intervals (95 % CI) of overall survival was used to assess the prognostic role of serum LDH level. Ten studies published between 1997 and 2013 with a total of 943 osteosarcoma patients were included. Overall, the pooled HR for all ten eligible studies evaluating high LDH level on overall survival was 1.92(95 % CI 1.53-2.40). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was some possibility of publication bias risk in the meta-analysis. This meta-analysis shows that high serum LDH level is obviously associated with lower overall survival rate in patients with osteosarcoma, and it is an effective biomarker of prognosis.

Managed care organizations publicly reporting three years of HEDIS measures. The author compares the results of MCOs that have publicly reported their Health Plan Employer Data and Information Set (HEDIS) rates for 1997 through 1999 with health plans that did not report publicly. Managed care plans that publicly reported for three consecutive years performed better on preventive health measures than those that did not. Newer measures, such as beta-blocker treatment after a heart attack, showed the greatest improvement over time. Health care plans rated high in consumer experience also had higher clinical performance rates. Finally, plans that sought accreditation by the National Committee for Quality Assurance had better performance on their HEDIS measures, although the differences narrowed for those reporting HEDIS rates for three consecutive years.

Race Factors Affecting Performance Times in Elite Long-Track Speed Skating. Analysis of sport performance can provide effects of environmental and other venue-specific factors in addition to estimates of within-athlete variability between competitions, which determines smallest worthwhile effects. To analyze elite long-track speed-skating events. Log-transformed performance times were analyzed with a mixed linear model that estimated percentage mean effects for altitude, barometric pressure, type of rink, and competition importance. In addition, coefficients of variation representing residual venue-related differences and within-athlete variability between races within clusters spanning ~8 d were determined. Effects and variability were assessed with magnitude-based inference. A 1000-m increase in altitude resulted in very large mean performance improvements of 2.8% in juniors and 2.1% in seniors. An increase in barometric pressure of 100 hPa resulted in a moderate reduction in performance of 1.1% for juniors but an unclear effect for seniors. Only juniors competed at open rinks, resulting in a very large reduction in performance of 3.4%. Juniors and seniors showed small performance improvements (0.4% and 0.3%) at the more important competitions. After accounting for these effects, residual venue-related variability was still moderate to large. The within-athlete within-cluster race-to-race variability was 0.3-1.3%, with a small difference in variability between male (0.8%) and female juniors (1.0%) and no difference between male and female seniors (both 0.6%). The variability in performance times of skaters is similar to that of athletes in other sports in which air or water resistance limits speed. A performance enhancement of 0.1-0.4% by top-10 athletes is necessary to increase medal-winning chances by 10%.

Scorpion ARMS primers for SNP real-time PCR detection and quantification of Pyrenophora teres. summary We have developed a quantitative PCR detection method that can be used to determine the seed infection levels of Pyrenophora teres, a seed-borne fungal pathogen of barley. This method uses Scorpion Amplified Refractory Mutation System (ARMS) technology with real-time PCR detection. Scorpion ARMS primers were designed and optimized such that a single nucleotide base mismatch in the primer sequence could distinguish P. teres from P. graminea, a closely related seed-borne pathogen of barley. It is necessary to distinguish between these two agriculturally important pathogens since different disease management decisions are made, based on the presence and level of infection measured for each. The advance in development of sensitive and specific fluorescent probes has enabled the current PCR test to detect Pyrenophora spp. pathogenic on barley to be enhanced with the advantage that it can now specifically detect P. teres in a single reaction, whilst previously, two reactions were required to discriminate P. teres from P. graminea.

Estimating six-cycle efficacy of the Dot app for pregnancy prevention. To assess six-cycle perfect and typical use efficacy of Dynamic Optimal Timing (Dot), an algorithm-based fertility app that identifies the fertile window of the menstrual cycle using a woman's period start date and provides guidance on when to avoid unprotected sex to prevent pregnancy. We are conducting a prospective efficacy study following a cohort of women using Dot for up to 13 cycles. Study enrollment and data collection are being conducted digitally within the app and include a daily coital diary, prospective pregnancy intentions and sociodemographic information. We used data from the first six cycles to calculate life-table failure rates. We enrolled 718 women age 18-39 years. Of the 629 women 18-35 years old, 15 women became pregnant during the first six cycles for a typical use failure rate of 3.5% [95% CI 1.7-5.2]. All pregnancies occurred with incorrect use, so we did not calculate a perfect use failure rate. These findings are promising and suggest that the 13-cycle results will demonstrate high efficacy of Dot. While final 13-cycle efficacy results are forthcoming, 6-cycle results suggest that Dot's guidance provides women with useful information for preventing pregnancy.

Results of balloon valvuloplasty in 40 dogs with pulmonic stenosis. The records of 43 dogs presenting with severe pulmonic stenosis in which balloon valvuloplasty was attempted were reviewed. Thirty-four dogs (79 per cent) were symptomatic at initial presentation. All patients were selected for balloon valvuloplasty on the basis of a Doppler-derived trans-stenotic pressure gradient of over 80 mmHg and concurrent evidence of mild to severe right ventricular hypertrophy. Forty dogs underwent balloon valvuloplasty; the procedure was not performed in three dogs because of an aberrant coronary artery in two cases and because catheterisation of the pulmonary artery was not possible in the third. Overall, 37 out of the 40 dogs (93 per cent) were successfully ballooned, resulting in a mean reduction in the pressure gradient of 46 per cent, with a mean pressure gradient of 124 mmHg on presentation and 67 mmHg six months after the procedure. Three dogs died during balloon valvuloplasty (all of which had a concurrent defect) and three dogs showed a poor clinical response to the procedure. Thus balloon valvuloplasty was successful and resulted in a sustained clinical improvement in 80 per cent of previously symptomatic cases. This study was undertaken to document the results of balloon valvuloplasty in a larger population of dogs than has previously been published.

Effect of zinc supplementation on ethanol-mediated bone alterations. Ethanol consumption leads to bone alterations, mainly osteoporosis. Ethanol itself may directly alter bone synthesis, but other factors, such as accompanying protein malnutrition--frequently observed in alcoholics, chronic alcoholic myopathy with muscle atrophy, alcohol induced hypogonadism or hypercortisolism, or liver damage, may all contribute to altered bone metabolism. Some data suggest that zinc may exert beneficial effects on bone growth. Based on these facts, we analyzed the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in the form of zinc sulphate, on bone histology, biochemical markers of bone formation (osteocalcin) and resorption (urinary hydroxyproline excretion), and hormones involved in bone homeostasis (insulin growth factor 1 (IGF-1), vitamin D, parathormone (PTH), free testosterone and corticosterone), as well as the association between these parameters and muscle fiber area and liver fibrosis, in eight groups of adult Sprague Dawley rats fed following the Lieber de Carli model during 5 weeks. Ethanol showed an independent effect on TBV (F=14.5, p<0.001), causing it to decrease, whereas a low protein diet caused a reduction in osteoid area (F=8.9, p<0.001). Treatment with zinc increased osteoid area (F=11.2, p<0.001) and serum vitamin D levels (F=3.74, p=0.057). Both ethanol (F=45, p<0.001) and low protein diet (F=46.8, p<0.01) decreased serum osteocalcin levels. Ethanol was the only factor independently related with serum IGF-1 (F=130.24, p<0.001), and also showed a synergistic interaction with protein deficiency (p=0.027). In contrast, no change was observed in hydroxyproline excretion and serum PTH levels. No correlation was found between TBM and muscle atrophy, liver fibrosis, corticosterone, or free testosterone levels, but a significant relationship was observed between type II-b muscle fiber area and osteoid area (rho=0.34, p<0.01). Osteoporosis is, therefore, present in alcohol treated rats. Both alcohol and protein deficiency lead to reduced bone formation. Muscle atrophy is related to osteoid area, suggesting a role for chronic alcoholic myopathy in decreased bone mass. Treatment with zinc increases osteoid area, but has no effect on TBV.

Confined hydrogen atom by the Lagrange-mesh method: energies, mean radii, and dynamic polarizabilities. The Lagrange-mesh method is an approximate variational calculation which resembles a mesh calculation because of the use of a Gauss quadrature. The hydrogen atom confined in a sphere is studied with Lagrange-Legendre basis functions vanishing at the center and surface of the sphere. For various confinement radii, accurate energies and mean radii are obtained with small numbers of mesh points, as well as dynamic dipole polarizabilities. The wave functions satisfy the cusp condition with 11-digit accuracy.

Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II. Type II cGMP-dependent protein kinase (cGKII) isolated from pig intestinal brush borders and type I alpha cGK (cGKI) purified from bovine lung were compared for their ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR)-Cl- channel in excised, inside-out membrane patches from NIH-3T3 fibroblasts and from a rat intestinal cell line (IEC-CF7) stably expressing recombinant CFTR. In both cell models, in the presence of cGMP and ATP, cGKII was found to mimic the effect of the catalytic subunit of cAMP-dependent protein kinase (cAK) on opening CFTR-Cl-channels, albeit with different kinetics (2-3-min lag time, reduced rate of activation). By contrast, cGKI or a monomeric cGKI catalytic fragment was incapable of opening CFTR-Cl- channels and also failed to potentiate cGKII activation of the channels. The cAK activation but not the cGKII activation was blocked by a cAK inhibitor peptide. The slow activation by cGKII could not be ascribed to counteracting protein phosphatases, since neither calyculin A, a potent inhibitor of phosphatase 1 and 2A, nor ATP gamma S (adenosine 5'-O-(thiotriphosphate)), producing stable thiophosphorylation, was able to enhance the activation kinetics. Channels preactivated by cGKII closed instantaneously upon removal of ATP and kinase but reopened in the presence of ATP alone. Paradoxically, immunoprecipitated CFTR or CF-2, a cloned R domain fragment of CFTR (amino acids 645-835) could be phosphorylated to a similar extent with only minor kinetic differences by both isotypes of cGK. Phosphopeptide maps of CF-2 and CFTR, however, revealed very subtle differences in site-specificity between the cGK isoforms. These results indicate that cGKII, in contrast to cGKI alpha, is a potential activator of chloride transport in CFTR-expressing cell types.

Aging alters visual processing of objects and shapes in inferotemporal cortex in monkeys. Visual perception declines with age. Perceptual deficits may originate not only in the optical system serving vision but also in the neural machinery processing visual information. Since homologies between monkey and human vision permit extrapolation from monkeys to humans, data from young, middle aged and old monkeys were analyzed to show age-related changes in the neuronal activity in the inferotemporal cortex, which is critical for object and shape vision. We found an increased neuronal response latency, and a decrease in the stimulus selectivity in the older animals and suggest that these changes may underlie the perceptual uncertainties found frequently in the elderly.

[Adacolumn apheresis for hepatitis C virus in patients waiting for kidney transplant. Preliminary study]. Hepatitis C virus (HCV) infection occurs much more frequently in the hemodialysis population than in the general population. Patients with chronic kidney disease with persistent HCV infection may develop serious and progressive chronic liver disease, with associated long-term morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Monocytes and macrophages are known to produce extrahepatic breeding sites and spread the disease. Our aim was to lower the levels of macrophages, granulocytes, monocytes, proinflammatory cells and viremia using an extracorporeal device: the Adacolumn ® leukocyte apheresis system (Otsuka). The Adacolumn is a direct hemoperfusion-type leukapheresis device. The column is a single-use (disposable) polycarbonate column with a capacity of about 335 mL, filled with 220-g cellulose acetate beads of 2 mm in diameter bathed in physiological saline. The carriers adsorb ''activated'' granulocytes and monocytes/macrophages that bear Fc and complement receptors. The patients underwent five 1-hour sessions for five consecutive days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. A reduction of viremia was observed in all patients in association with a decrease in cytokine levels and a proportional decrease in immune cells. Although this study investigated responses in a small number of patients, it was shown that the Adacolumn changed the cellular immunity and promoted early viral response.

Uridine kinase, adenylate kinase, and guanase in human lung tumors. In pulmonary neoplasms, the uridine kinase concentration was higher (2- to 20-fold) than in the noninvolved lung portions of each of the 12 subjects studied. The extent of elevation of uridine kinase in the different tumors showed a significant positive correlation with the rises (1.5- to 30-fold) in thymidine kinase, suggesting that neoplastic transformation in human lung involved coordinated increases in the capacity for the reutilization of different nucleoside phosphates. Adenylate kinase was always at lower levels in neoplasms compared to noninvolved areas of the same lung, and the extent of this loss in the different tumors correlated inversely with the gain in uridine kinase and thymidine kinase. Normal fetal human lung was also deficient in adenylate kinase, while its uridine kinase and thymidine kinase (and also guanase) activities were above the adult levels. The guanase activities of the different neoplasms, unrelated to their uridine kinase or thymidine kinase content, correlated with the activities in the subjects' noninvolved lung. These individual differences were much more striking than those between the neoplastic and control samples. Variations in guanase activity thus appear to be "random," whereas observations on the three other enzymes attest to the orderly nature of biochemical differences among individual tumors and between normal and neoplastic lung.

1H, 13C, and 15N NMR spectra of some pyridazine derivatives. (1)H, (13)C, and (15)N NMR chemical shifts for pyridazines 4-22 were measured using 1D and 2D NMR spectroscopic methods including (1)H-(1)H gDQCOSY, (1)H-(13)C gHMQC, (1)H-(13)C gHMBC, and (1)H-(15)N CIGAR-HMBC experiments.

IRTA1+ monocytoid B cells in reactive lymphadenitis show a unique topographic distribution and immunophenotype and a peculiar usage and mutational pattern of IgVH genes. The origin and function of monocytoid B cells (MBCs) are poorly understood. Taking advantage of their strong expression of IRTA1 (a receptor that is also associated with MALT marginal zone B cells), we have comprehensively analysed MBCs in 25 cases of lymphadenitis of different aetiologies, shedding new light on the topographical distribution, immunophenotype and IgV(H) gene usage and mutational profile of this B cell subset. IRTA1(+) MBCs, although predominantly located in the subcapsular and intermediary sinuses, were also observed scattered within germinal centres (GCs) in all lymphadenitis cases examined. The molecular characterization of IgV(H) genes revealed that IRTA1(+) MBCs residing in different areas of the lymph node (subcapsular sinus, intermediary sinuses and GCs) can be clonally related (with intraclonal variation), and that those located in GCs are consistently more mutated and selected for expression of a functional antigen receptor than those located in the sinuses. Moreover, by contrast, IRTA1(+) MBCs in GCs express the memory B cell marker CD27. Finally, in toxoplasmic lymphadenitis, the IRTA1(+) MBC population shows a highly preferential usage of the V(H) genes 3-7 and 3-30 (without any obvious peculiarity in their CDR3s), possibly suggesting that a superantigen expressed by Toxoplasma gondii may be involved in the early activation of this B cell subset.

Computer networking in an ambulatory health care setting. Computers are a ubiquitous part of the ambulatory health care environment. Although stand-alone computers may be adequate for a small practice, networked computers can create much more powerful and cost-effective computerized systems. Local area networks allow groups of computers to share peripheral devices and computerized information within an office or cluster of offices. Wide area networks allow computers to securely share devices and information across a large geographical area. Either singly or in combination, these networks can be used to create robust systems to help physicians automate their practices and improve their access to important clinical information. In this article, we will examine common network configurations, explain how they function, and provide examples of real-world implementations of networking technology in health care.

Vaccination of cattle against Mycobacterium bovis. Protection of cattle against bovine tuberculosis by vaccination could be an important control strategy in countries where there is persistence of Mycobacterium bovis infection in wildlife and in developing countries where it is not economical to implement a 'test and slaughter' control programme. Early field trials with Bacille Calmette Guerin (BCG) M. bovis vaccine in cattle produced disappointing results, with induction of tuberculin skin-test reactivity following vaccination and low levels of protection. However, recent studies using a low dose of BCG vaccine in cattle have produced more encouraging results and field trials should now be carried out in developing countries to determine whether this low dose BCG vaccination strategy will reduce the spread of infection. The options for new candidate tuberculosis vaccines have increased markedly in the last decade with the advent of new attenuated strains of M. bovis, and sub-unit protein and recombinant DNA vaccines. Some of these new types of vaccines have recently been tested in cattle. New attenuated M. bovis vaccines induced greater protection than BCG vaccine in cattle which had been sensitized to environmental mycobacteria prior to vaccination. In contrast, it has proved difficult to stimulate appropriate immune responses in cattle necessary for protection with sub-unit protein and recombinant DNA vaccines and better immunological adjuvants are required for these types of vaccines. Progress in the development of new tuberculosis vaccines has been very rapid in the past decade and the prospects for vaccination to control and eradicate bovine tuberculosis are encouraging.

Development of antibody to human GM3 synthase and immunodetection of the enzyme in human tissues. Polyclonal antibody was raised to a cloned fragment of human GM3 synthase. Affinity purified R27C1 antibody to the tagged recombinant protein inhibited GM3 synthase activity in human liver and HL-60 cells in a dose-dependent manner. However, the R27C1 antibody did not affect liver sialyltransferase activity towards asialofetuin. We are the first to measure GM3 synthase activity in human liver (194 +/- 60 pmol NeuAc/h per mg protein), which was about 10-fold lower than in phorbol myristate acetate-stimulated HL-60 cells (1353 +/- 573 pmol NeuAc/h per mg protein). On immunoblotting the R27C1 antibody recognized a common protein band in a number of human tissues (liver, brain, atherosclerotic aortic intima, HL-60 cells) with molecular mass of about 60 kD, which is similar to that of the purified GM3 synthase from rat liver. In human liver and aortic intima, the 60-kD band was almost a single band, which makes possible the use of the R27C1 antibody for immunohistochemical studies in these tissues.

Brain metastases from epithelial ovarian cancer: a review of the literature. Brain metastases from epithelial ovarian cancer (EOC) are rare. This report is based on a review of the literature. This review summarizes the incidence, clinical features, pathophysiology, and diagnostic evaluation of EOC. The section on current treatment includes a thorough evaluation of the literature, highlights controversies over treatment options, and provides insight into novel approaches. Current treatment options include surgical resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery, and chemotherapy. Corticosteroids and anticonvulsant medications are commonly used for the palliation of mass effects and seizures, respectively. In the reviewed series, a better outcome was seen following surgical resection and WBRT with or without chemotherapy for solitary and resectable brain metastases. The prognosis for patients with brain metastases from EOC is poor. A better outcome might be obtained using multimodality therapy. Because of the small number of patients included in the reported studies, multicenter clinical trials are needed for further investigation in order to critically evaluate the clear benefit of these treatment options in selected patients.

Evolution of HLA-class I compared to HLA-class II polymorphism in Terena, a South-American Indian tribe. We have studied the HLA alleles of 60 unrelated healthy Terena and 10 Terena families. They are members of an isolated Brazilian tribe located in Mato Grosso do Sul (South Central Brazil). Six novel alleles were found in this population: HLA-A*0219 (gf = 0.02), A*0222 (gf = 0.15), HLA-B* 3520 (gf = 0.01), B*3521 (gf = 0.03), B*3912 (gf = 0.03) and B*4803 (gf = 0.16). Five of the six novel alleles differ from their putative progenitors by amino acid replacements in residues that contribute to the pockets of the peptide-binding site. Many of the variants defined by molecular methods were not identified correctly by serological typing. We calculated heterozygosity values (H) for HLA-A, -B, -C, DRB1, DQB1 and DPB . The highest values were observed at the HLA-B locus, followed by HLA-A, -DRB1 and DQB1. Residue positions 9, 24, 45, 62, 67, 95, 114, 116, 156, and 163 of HLA class I showed heterozygosity values greater than 0.50. Nine of them contribute to the peptide-binding specificity pockets and one to the T cell receptor binding site. If HLA antigens are useful for defense against pathogenic agents, heterozygosity would offer an advantage by allowing binding of a larger repertoire of peptides to the class I molecules. Individuals that are heterozygous at these positions would probably have a wider repertoire of peptide presentation to T cells. The observed results including the presence of novel alleles in the class I HLA loci suggest a functionally significant, more rapid evolution of class I compared to class II loci in this South American isolated population.

Genetic and clinical features of p450 oxidoreductase deficiency. P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder of steroidogenesis with multiple clinical manifestations. POR is the electron donor for all microsomal P450 enzymes, including the three steroidogenic enzymes P450c17 (17alpha-hydroxylase/17,20-lyase), P450c21 (21-hydroxylase), and P450aro (aromatase). Since the first description of POR mutations in 2004, about 50 patients have been reported. Serum steroid profiles indicate partial deficiencies in 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase. The 17-OH progesterone levels are elevated, as in 21-hydroxylase deficiency, while androgen levels are low; cortisol may be normal but is poorly responsive to adrenocorticotropic hormone. Most patients also have associated skeletal malfor- mations (craniosynostosis, radio-ulnar synostosis, midface hypoplasia, bowed femora) termed Antley-Bixler syndrome. Antley-Bixler syndrome with normal steroidogenesis is caused by autosomal dominant gain-of-function mutations in fibroblast growth factor receptor 2. Males with POR deficiency are often undervirilized, while females can be virilized. The prognosis for patients with POR deficiency appears to depend on the severity of the bony malformations and their timely treatment. The potential impact of POR mutations on drug metabolism by other hepatic P450 enzymes requires further investigation. Given the varied physical and biochemical phenotype of POR deficiency and the risk of adrenal insufficiency, clinicians should be alert to this potential diagnosis.

Quantum interferometric optical lithography: exploiting entanglement to beat the diffraction limit Classical optical lithography is diffraction limited to writing features of a size lambda/2 or greater, where lambda is the optical wavelength. Using nonclassical photon-number states, entangled N at a time, we show that it is possible to write features of minimum size lambda/(2N) in an N-photon absorbing substrate. This result allows one to write a factor of N2 more elements on a semiconductor chip. A factor of N = 2 can be achieved easily with entangled photon pairs generated from optical parametric down-conversion. It is shown how to write arbitrary 2D patterns by using this method.