title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The Confidential Enquiry into Maternal Deaths in South Africa: a case study. | The Confidential Enquiry into Maternal Deaths (CEMD) in South Africa has been operational for 15 years. This case study describes the process of notification and independent assessment of maternal deaths, predominantly in facilities. In the earlier years of the Enquiry, institutional maternal mortality ratio increased and was 176.2 per 100 000 live births in the 2008-10 triennium; thereafter it decreased to 146.7 in the 2011/12 period. The slow progress was due to the significant contribution of HIV/AIDs to maternal mortality and challenges in implementing the recommendations that were devised from the findings of the Enquiry. Nevertheless, the CEMD process has been maintained and strengthened so it is currently able to perform routine maternal death surveillance at both national and district levels, identify deficiencies within the health system, generate reports and also provide early warning about alarming trends such as the increasing numbers of deaths due to caesarean-section-associated haemorrhage. | 25,236,634 | [
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Maternal near-miss case reviews: the UK approach. | The UK has a well-established programme of Confidential Enquiries into Maternal Deaths and a national system for research into near-miss maternal morbidities, the UK Obstetric Surveillance System. The addition of a programme of near-miss case reviews, the Confidential Enquiries into Maternal Morbidity, permits a complete examination of the incidence, risk factors, care and outcomes of the severest complications in pregnancy, and enables the lessons learnt to improve future care to be identified more quickly. This in turn allows for more rapid inclusion of recommendations into national guidance and hence the potential of better health for both women and babies. | 25,236,644 | [
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Norms, athletic identity, and concussion symptom under-reporting among male collegiate ice hockey players: a prospective cohort study. | Many athletes fail to report concussion symptoms to coaches or medical personnel, putting them at risk for potentially catastrophic neurologic consequences if additional brain trauma is sustained prior to full recovery. The purpose of this study was to determine whether concussion reporting norms prior to the start of the athletic season predicted reporting symptoms of a possible concussion during the season, and whether this association was moderated by athletic identity. Members of six National Collegiate Athletic Association Division 1 men's ice hockey teams (n = 116) completed written surveys before and after the 2012-2013 collegiate ice hockey season. Participants who at pre-season perceived that "most athletes" were likely to report symptoms of a concussion were themselves more likely to report symptoms during the season. Athletic identity weakly moderated this association. Perceived reporting norms may be an important target of interventions aimed at reducing symptom under-reporting among athletes. | 25,236,670 | [
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ROTAS: a rotamer-dependent, atomic statistical potential for assessment and prediction of protein structures. | Multibody potentials accounting for cooperative effects of molecular interactions have shown better accuracy than typical pairwise potentials. The main challenge in the development of such potentials is to find relevant structural features that characterize the tightly folded proteins. Also, the side-chains of residues adopt several specific, staggered conformations, known as rotamers within protein structures. Different molecular conformations result in different dipole moments and induce charge reorientations. However, until now modeling of the rotameric state of residues had not been incorporated into the development of multibody potentials for modeling non-bonded interactions in protein structures. In this study, we develop a new multibody statistical potential which can account for the influence of rotameric states on the specificity of atomic interactions. In this potential, named "rotamer-dependent atomic statistical potential" (ROTAS), the interaction between two atoms is specified by not only the distance and relative orientation but also by two state parameters concerning the rotameric state of the residues to which the interacting atoms belong. It was clearly found that the rotameric state is correlated to the specificity of atomic interactions. Such rotamer-dependencies are not limited to specific type or certain range of interactions. The performance of ROTAS was tested using 13 sets of decoys and was compared to those of existing atomic-level statistical potentials which incorporate orientation-dependent energy terms. The results show that ROTAS performs better than other competing potentials not only in native structure recognition, but also in best model selection and correlation coefficients between energy and model quality. A new multibody statistical potential, ROTAS accounting for the influence of rotameric states on the specificity of atomic interactions was developed and tested on decoy sets. The results show that ROTAS has improved ability to recognize native structure from decoy models compared to other potentials. The effectiveness of ROTAS may provide insightful information for the development of many applications which require accurate side-chain modeling such as protein design, mutation analysis, and docking simulation. | 25,236,673 | [
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Fine tuning the ionic liquid-vacuum outer atomic surface using ion mixtures. | Ionic liquid-vacuum outer atomic surfaces can be created that are remarkably different from the bulk composition. In this communication we demonstrate, using low-energy ion scattering (LEIS), that for ionic liquid mixtures the outer atomic surface shows significantly more atoms from anions with weaker cation-anion interactions (and vice versa). | 25,236,677 | [
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Effect of tibial tunnel diameter on femoral tunnel placement in transtibial single bundle ACL reconstruction. | The purpose of this study was to identify the impact of tibial reamer size and placement on the position of femoral tunnel placement via a transtibial approach for anterior cruciate ligament (ACL) reconstruction. Eight cadaveric knee specimens were fixed to a stationary table at 90° of flexion and neutral rotation. After removing the anterior capsule and patella, native joint anatomy was recorded with a digitizer (MicroScribe™; CNC Services, Amherst, VA) accurate to 0.05 mm. Tibial and femoral tunnels were drilled via a transtibial ACLR technique using the optimal tibial starting point described by Piasecki et al. On the tibial side, tunnels were drilled progressively with 6-, 7-, 8-, 9-, 10-, and 11-mm reamers. After each reaming, a beath pin was placed in the posterior aspect of the tibial tunnel, positioned relative to the native anatomic ACL femoral footprint, and digitized. Rhino software (McNeel, Seattle, WA) was used to geometrically determine the center of the native femoral footprint and measure in millimeters the relationship of this point with the femoral position achieved using a 7-mm offset femoral guide with each tibial tunnel size. The surface areas of each tibial and femoral insertion were measured using the insertional periphery data recorded with the digitizer. Statistical analysis of continuous variable data was performed with t tests; P values below 0.05 were deemed significant. The center of the femoral ACL footprint was reached with a 9-mm tibial tunnel in six knees, and with an 8-mm tunnel in two knees. A 6- or 7-mm tibial tunnel did not allow for anatomic positioning in any specimen, with femoral positioning significantly more superior than that achieved with a 9-, 10-, or 11-mm tibial tunnel (P < 0.01). The 6- and 7-mm tunnels produced errors of 4.6 ± 1.6 and 2.9 ± 0.5 mm, respectively. After use of the 11-mm tibial reamer, the average tibial tunnel length was 32.1 ± 2.6 mm. Limitations of a transtibial ACLR technique may result in non-anatomic femoral tunnel placement with tibial tunnel sizes smaller than 9 mm. However, tibial tunnels placed in the proximal entry position with at least a 9-mm tunnel size allowed anatomic femoral tunnel placement via a transtibial approach. | 25,236,681 | [
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Direct observation of respiratory treatments in cystic fibrosis: parent-child interactions relate to medical regimen adherence. | Use a standardized system to code parent-child interactions during respiratory treatments for cystic fibrosis (CF) and analyze relations between behaviors during treatments and medical regimen adherence. A total of 15 families (53% girls; M age = 8.9 years; SD = 1.8) had three respiratory treatments recorded in the home environment and coded. Families provided six 24-hr recalls of child medical regimen activities, and electronic airway clearance time was recorded over 3 months to measure medical regimen adherence. Parent positive attention, instructions, and avoidance of negative statements were significantly related to child cooperation during respiratory treatments. Parental presence, positive attention, instructions, and child cooperation during treatments were related to higher respiratory adherence rates. Direct observation methodology has led to effective nutritional adherence intervention for children with CF. These preliminary data demonstrate that an observational method could also be used to develop interventions to promote respiratory medication adherence. | 25,236,709 | [
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Binge alcohol promotes hypoxic liver injury through a CYP2E1-HIF-1α-dependent apoptosis pathway in mice and humans. | Binge drinking, a common pattern of alcohol ingestion, is known to potentiate liver injury caused by chronic alcohol abuse. This study was aimed at investigating the effects of acute binge alcohol on hypoxia-inducible factor-1α (HIF-1α)-mediated liver injury and the roles of alcohol-metabolizing enzymes in alcohol-induced hypoxia and hepatotoxicity. Mice and human specimens assigned to binge or nonbinge groups were analyzed for blood alcohol concentration (BAC), alcohol-metabolizing enzymes, HIF-1α-related protein nitration, and apoptosis. Binge alcohol promoted acute liver injury in mice with elevated levels of ethanol-inducible cytochrome P450 2E1 (CYP2E1) and hypoxia, both of which were colocalized in the centrilobular areas. We observed positive correlations among elevated BAC, CYP2E1, and HIF-1α in mice and humans exposed to binge alcohol. The CYP2E1 protein levels (r = 0.629, p = 0.001) and activity (r = 0.641, p = 0.001) showed a significantly positive correlation with BAC in human livers. HIF-1α levels were also positively correlated with BAC (r = 0.745, p < 0.001) or CYP2E1 activity (r = 0.792, p < 0.001) in humans. Binge alcohol promoted protein nitration and apoptosis with significant correlations observed between inducible nitric oxide synthase and BAC, CYP2E1, or HIF-1α in human specimens. Binge-alcohol-induced HIF-1α activation and subsequent protein nitration or apoptosis seen in wild type were significantly alleviated in the corresponding Cyp2e1-null mice, whereas pretreatment with an HIF-1α inhibitor, PX-478, prevented HIF-1α elevation with a trend of decreased levels of 3-nitrotyrosine and apoptosis, supporting the roles of CYP2E1 and HIF-1α in binge-alcohol-mediated protein nitration and hepatotoxicity. Thus binge alcohol promotes acute liver injury in mice and humans at least partly through a CYP2E1-HIF-1α-dependent apoptosis pathway. | 25,236,742 | [
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Strengthening public health pesticide management in countries endemic with malaria or other major vector-borne diseases: an evaluation of three strategies. | Public health pesticides has been the mainstay control of vectors of malaria and other diseases, and public health pests, but there is increasing concern over how these pesticides are being managed. Poor pesticide management could lead to risks to human health and the environment, or diminish the effectiveness of interventions. Strategies for strengthening the management of public health pesticides, from manufacture to disposal, should be evaluated to propose future directions. The process and outcomes of three strategies were studied in five regions of the WHO (African Region, Eastern Mediterranean Region, South-East Asia Region, Western Pacific Region, and American Region) and 13 selected countries. These strategies are: regional policy development, in-depth country support and thematic support across countries. Consensus, frameworks and action plans on public health pesticide management were developed at regional level. Country support for situation analysis and national action planning highlighted weaknesses over the entire spectrum of pesticide management practices, mainly related to malaria control. The thematic support on pesticide quality control contributed to structural improvements on a priority issue for malaria control across countries. The three strategies showed promising and complementary results, but guidelines and tools for implementation of the strategies should be further improved. Increased national and international priority should be given to support the development of policy, legislation and capacity that are necessary for sound management of public health pesticides. | 25,236,760 | [
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Beef quality traits of heifer in comparison with steer, bull and cow at various feeding environments. | The present review has been focused largely on the sex type differences in beef quality among heifers, cows, steers and bulls in various feeding environments. Genetic groups, feeding systems and gender are the major factors that change carcass characteristics and fatty acid profiles of cattle. Studies identified that heifer beef has super characteristics in eating quality and a better healthy composition in fatty acids than steer, cow and bull. Diet influences the variation of fatty acid profile; particularly the level of polyunsaturated fatty acids (PUFA) interacts with breed and sex. Animals finished in pasture systems were reported to show better ratios of PUFA/ saturated fatty acids and n-6/n-3. Carcasses of roughage-fed beef are lighter and have less marbling and lower quality grades but have higher cutability than carcasses of grain-fed bulls. Heifers and cows are reported to deposit more fat than steers and bulls. Among males, lower production of testosterone by steers favors more fat thickness compared with bulls. Marbling greatly varies among cattle belonging to different sexes, and particularly, females have genetic makeup that efficiently controls deposition. The current review identified that heifers can be a premium beef brand, while steer beef currently take a large part of market share across the world. | 25,236,779 | [
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Enhanced expression of the codon-optimized exo-inulinase gene from the yeast Meyerozyma guilliermondii in Saccharomyces sp. W0 and bioethanol production from inulin. | In the present study, after the exo-inulinase gene INU1 from Meyerozyma guilliermondii was optimized according to the codon usage bias of Saccharomyces cerevisiae, both the optimized gene INU1Y and the native gene INU1 were ligated into the homologous integration expression vector pMIRSC11 and expressed in Saccharomyces sp. W0. It was determined that the inulinase activity of the recombinant yeast Y13 with the optimized gene INU1Y was 43.84 U/mL, which was obviously higher than that (31.39 U/mL) produced by the recombinant yeast EX3 with the native gene INU1. Moreover, it was indicated that the recombinant yeast Y13 could produce 126.30 mg/mL ethanol from 300.0 g/L inulin while the recombinant yeast EX3 and Saccharomyces sp. W0 produced 122.75 mg/mL and 114.15 mg/mL ethanol, respectively, under the same conditions. In addition, the ethanol productivity of the recombinant yeast Y13 was 2.25 mg/mL/h within 48 h of the fermentation, which was obviously higher than that of the recombinant yeast EX3 (1.97 mg/mL/h) and Saccharomyces sp. W0 (1.77 mg/mL/h) within the same period. The results demonstrated that the recombinant yeast Y13 had higher ethanol production and productivity than the recombinant yeast EX3 and Saccharomyces sp. W0. Therefore, it was concluded that the codon optimization of the exo-inulinase gene from M. guilliermondii effectively enhanced inulinase activity and improved ethanol production from inulin by Saccharomyces sp. W0 carrying the optimized inulinase gene. | 25,236,803 | [
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Prevalence of sinus membrane thickening and association with unhealthy teeth: a retrospective review of 831 consecutive patients with 1,662 cone-beam scans. | The purposes of this retrospective review of cone-beam computed tomographic (CBCT) scans were to 1) determine the prevalence of sinus membrane thickening in a consecutive series of patients; 2) identify the prevalence of healthy or unhealthy teeth associated with sinus membrane thickening; and 3) document changes of the sinus membrane after the removal of unhealthy teeth. Consecutive patients had CBCT scans examined and the sinuses were graded. Grade 1 represented membrane thickening of 0 to less than 2 mm; grade 2 represented thickening of 2 to 5 mm; grade 3 represented membrane or material thickening greater than 5 mm to the level of the ostium; and grade 4 represented soft tissue material superior to the ostium. Cross-sectional images were examined using software by the manufacturer of the CBCT scanner. Unhealthy teeth were identified. The examiner used a standardized approach in viewing the CBCT scans. Intraexaminer error was determined. Eight hundred thirty-one patients had 1,662 sinuses evaluated, with thickening of at least 1 sinus membrane in 46.7% (388 patients) and 30.1% (469) of all sinuses evaluated. The prevalence of patients and sinuses with sinus membrane thickening according to the grading criteria was grade 2 for 36.8% of patients and 24.3% of sinuses, grade 3 for 6.0% of patients and 3.7% of sinuses, and grade 4 for 3.6% of patients and 2.2% of sinuses. Unilateral sinus disease was more common than bilateral disease. Of those sinuses with thickening, 80.6% were grade 2, 12.2% were grade 3, and 7.2% were grade 4. Of the 469 sinuses with membrane thickening, 210 were adjacent to unhealthy teeth, 233 were adjacent to healthy teeth, and 26 were in edentulous maxillas. Of the 210 unhealthy teeth, 30 had postextraction CBCT scans available for evaluation. Grade 2 sinus membrane thickening showed a 75% resolution to grade 1 after adjacent tooth removal. Grade 3 sinuses resolved in 25% to grade 1 and grade 2, with 50% remaining at grade 3. There were 2 grade 4 sinuses with follow-up scans, with 1 resolving to grade 2 and the other remaining at grade 4. Sinus membrane thickening is present in 46.7% of patients presenting to an oral and maxillofacial surgical practice. The prevalence of sinus membrane thickening was almost equal in association with unhealthy and healthy teeth. The removal of unhealthy teeth decreased, but did not completely resolve sinus membrane thickening. | 25,236,817 | [
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Public Reporting and Demand Rationing: Evidence from the Nursing Home Industry. | This paper examines an under-explored unintended consequence of public reporting: the potential for demand rationing. Public reporting, although intended to increase consumer access to high-quality products, may have provided the perverse incentive for high-quality providers facing fixed capacity and administrative pricing to avoid less profitable types of residents. Using data from the nursing home industry before and after the implementation of the public reporting system in 2002, we find that high-quality nursing homes facing capacity constraints reduced admissions of less profitable Medicaid residents while increasing the more profitable Medicare and private-pay admissions, relative to low-quality nursing homes facing no capacity constraints. These effects, although small in magnitude, are consistent with provider rationing of demand on the basis of profitability and underscore the important role of institutional details in designing effective public reporting systems for regulated industries. | 25,236,842 | [
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Cytochrome P450 system proteins reside in different regions of the endoplasmic reticulum. | Cytochrome P450 (P450) function is dependent on the ability of these enzymes to successfully interact with their redox partners, NADPH-cytochrome P450 reductase (CPR) and cytochrome b5, in the endoplasmic reticulum (ER). Because the ER is heterogeneous in lipid composition, membrane microdomains with different characteristics are formed. Ordered microdomains are more tightly packed, and enriched in saturated fatty acids, sphingomyelin and cholesterol, whereas disordered regions contain higher levels of unsaturated fatty acids. The goal of the present study was to determine whether the P450 system proteins localize to different regions of the ER. The localization of CYP1A2, CYP2B4 and CYP2E1 within the ER was determined by partial membrane solubilization with Brij 98, centrifugation on a discontinuous sucrose gradient and immune blotting of the gradient fractions to identify ordered and disordered microdomains. CYP1A2 resided almost entirely in the ordered regions of the ER with CPR also localized predominantly to this region. CYP2B4 was equally distributed between the ordered and disordered domains. In contrast, CYP2E1 localized to the disordered membrane regions. Removal of cholesterol (an important constituent of ordered domains) led to the relocation of CYP1A2, CYP2B4 and CPR to the disordered regions. Interestingly, CYP1A1 and CYP1A2 localized to different membrane microdomains, despite their high degree of sequence similarity. These data demonstrate that P450 system enzymes are organized in specific membrane regions, and their localization can be affected by depletion of membrane cholesterol. The differential localization of different P450 in specific membrane regions may provide a novel mechanism for modulating P450 function. | 25,236,845 | [
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Effects of Cd injection on osmoregulation and stress indicators in freshwater Nile tilapia. | Freshwater tilapia (Oreochromis niloticus) were intraperitoneally injected with sublethal doses of cadmium (1.25 or 2.5 mg Cd kg(-1) body mass) and sampled after 1, 4 and 7 days in order to evaluate the mechanisms of Cd toxicity at physiological and biochemical levels. Cd levels were significantly elevated in the gill and kidney following injection however levels in the kidney continued to accumulate while levels in the gill either did not change or decreased with time. Cd caused a generalized stress condition as indicated by an increase in blood glucose, lactate and cortisol levels as well as an oxidative stress indicated by increases in lipid peroxidation and protein carbonyl content. Furthermore, tilapia exhibited impairment in their osmoregulatory status based on the fall in plasma sodium levels. Concerning ion regulatory disruption, the kidney was the most affected organ since there was a generalized increase in renal Na(+)/K(+)-ATPase activity after 1 day of exposure to Cd followed by a significant decrease in day 7. This study provides some insights into the mechanisms of Cd toxicity at physiological and biochemical levels and complements previously reported findings on O. niloticus. The disruption of ion homeostasis, alterations in Na(+)/K(+)-ATPase activity and oxidative damage are the effects of Cd exposure that can be integrated in a comprehensive model for Cd impacts. | 25,236,868 | [
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Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke. | Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate. These alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. Our goal was to evaluate the contribution of TRPM2 to the tissue damage after stroke. In accordance with current quality guidelines, we independently characterized Trpm2 in a murine ischemic stroke model in 2 different laboratories. Gene deficiency of Trpm2 resulted in significantly improved neurological outcome and decreased infarct size. Besides an already known moderate neuroprotective effect of Trpm2 deficiency in vitro, ischemic brain invasion by neutrophils and macrophages was particularly reduced in Trpm2-deficient mice. Bone marrow chimeric mice revealed that Trpm2 deficiency in the peripheral immune system is responsible for the protective phenotype. Furthermore, experiments with mixed bone marrow chimeras demonstrated that Trpm2 is essential for the migration of neutrophils and, to a lesser extent, also of macrophages into ischemic hemispheres. Notably, the pharmacological TRPM2 inhibitor, N-(p-amylcinnamoyl)anthranilic acid, was equally protective in the stroke model. Although a neuroprotective effect of TRPM2 in vitro is well known, we can show for the first time that the detrimental role of TRPM2 in stroke primarily depends on its role in activating peripheral immune cells. Targeting TRPM2 systemically represents a promising therapeutic approach for ischemic stroke. | 25,236,871 | [
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Efficacy and safety of linagliptin in subjects with long-standing type 2 diabetes mellitus (>10 years): evidence from pooled data of randomized, double-blind, placebo-controlled, phase III trials. | Long duration of type 2 diabetes mellitus (T2DM) is associated with progressive β-cell loss and may pose a challenge to maintenance of good glycemic control. This study aimed to assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in an understudied population of patients with long-standing T2DM. Data from 202 individuals with T2DM for >10 years were pooled from 2 randomized, placebo-controlled, Phase III trials. Participants received either linagliptin 5 mg once daily (n = 122) or placebo (n = 80) for 24 weeks as an add-on to their current glucose-lowering therapy. Long-standing T2DM was associated with older age (mean [SD], 69.1 [10.0] years) and a high prevalence of diabetes-related complications (78% with diabetic kidney disease and 83% with macrovascular disease). The mean baseline glycosylated hemoglobin (HbA1c) level was 8.22% (1.08%), and mean baseline fasting plasma glucose level was 161.8 (49.2) mg/dL. Linagliptin significantly improved glycemic control after 24 weeks, with a placebo-adjusted mean change in HbA1c from baseline of -0.66% (95% CI, -0.95 to -0.38; P < 0.0001). This change was accompanied by a significant reduction in fasting plasma glucose, with a placebo-adjusted mean change from baseline of -15.5 mg/dL (95% CI, -29.6 to -1.3; P = 0.0323) at week 24. Overall, linagliptin was well tolerated, with drug-related adverse events in 21.3% and 16.3% of the linagliptin and placebo groups, respectively. Investigator-reported hypoglycemia occurred more often with linagliptin (25.4%) compared with placebo (12.5%). However, no severe hypoglycemic events were reported with linagliptin. Moreover, in patients not receiving concomitant sulfonylureas, the incidence of hypoglycemia with linagliptin (12.5%) was similar to that with placebo (12.2%). Patients' mean weight remained unchanged in both groups. This pooled analysis found that linagliptin was well tolerated and significantly improved hyperglycemia in a clinically challenging population of patients with long-standing T2DM (>10 years). Although T2DM is commonly associated with diminished β-cell function, the extent of glucose lowering was similar to that in linagliptin trials, which largely included patients in earlier stages of the disease. Thus, this observation supports the hypothesis that regulation of glucagon release from pancreatic α cells may be of particular relevance for improving hyperglycemia in patients with long-term T2DM (NCT01194830 and NCT01084005). | 25,236,917 | [
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Molecular assessment of predation by hoverflies (Diptera: Syrphidae) in Mediterranean lettuce crops. | Hoverflies (Diptera: Syrphidae) are generalist predators of a great variety of pests. Nasonovia ribisnigri (Hemiptera: Aphididae) and Frankliniella occidentalis (Thysanoptera: Thripidae) are two common pests in Mediterranean lettuce crops, where they occur alongside alternative prey (e.g., Collembola). A semi-field experiment was conducted in an experimental lettuce plot where hoverfly predation on N. ribisnigri, F. occidentalis and Collembola was studied by conventional PCR and qPCR using specific primers, as well as by next-generation sequencing (NGS) in order to reveal other potential trophic interactions. Trophic linkages between hoverflies and N. ribisnigri were the strongest both in spring and summer. F. occidentalis and Collembolans were also detected in both seasons, but with less frequency. qPCR detected a higher frequency of consumption than conventional PCR when both tests were run at optimal conditions. NGS analyses showed intraguild predation on other hoverfly species, as well as on anthocorids, spiders and even aphid parasitoids. Conventional PCR and qPCR provided important insights into Mediterranean hoverfly species predation on target pest and non-pest prey. NGS gave a complementary approach revealing a broader diet of these predators within the studied ecosystem. | 25,236,922 | [
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Max D. Cooper and the delineation of two lymphoid lineages in the adaptive immune system. | This article outlines the fundamental contribution of Max D. Cooper to the analysis of the role of the thymus and of the bursa of Fabricius in the development of immunologic competence both before and after birth, placing a new scientific paradigm in the definition of the ontogeny of the lymphoid tissues. | 25,236,938 | [
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The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma. | CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT-cell TCR transgenic mouse model, we demonstrated that CD1d-expressing hematopoietic cells, but not thymic epithelial cells, meditate efficient selection of type II NKT cells. Furthermore, we showed that SAP regulates type II NKT-cell development by controlling early growth response 2 protein and promyelocytic leukemia zinc finger expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IFN regulatory factor 4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP. | 25,236,978 | [
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A novel parainfluenza virus type 3 (PIV3) identified from goat herds with respiratory diseases in eastern China. | Parainfluenza virus type 3 (PIV3) is one of the most important viral respiratory pathogens for humans and for many animals, but goat infection has been rarely reported. Starting in Aug 2013, goats in the Jiangsu and Anhui provinces of eastern China suffered severe respiratory diseases. In order to identify the causative agent, numerous related pathogens were tested with RT-PCR or PCR. A unique PIV3 strain was detected in most of the clinical nasal swabs or serum samples. The virus was isolated on MDBK cells and characterized by RT-PCR, nucleotide sequence analysis and hemagglutination test. The entire M and F gene coding regions, HN, 5'-UTR-N and L gene fragments were amplified using pairs of degenerate primers. Nucleotide, amino acid sequence alignments and phylogenetic analyses based on these genes indicated that the goat-derived PIV3 strain was distinct from previously reported BPIV3 genotypes and HPIV3 strains. The novel isolate, named JS2013, might be a potentially new member of the respirovirus genus. Goats were experimentally infected with JS2013 culture. The virus-inoculated goats displayed coughing and nasal discharges that were related to respiratory diseases. Viremia and virus shedding were detected during 4-10 days post-inoculation (dpi). Virus-specific HI antibodies became positive from 14 dpi. This is the first report of the detection of PIV3 from Chinese goat herds and genetic and pathogenetic characterization of the novel goat-derived PIV3. | 25,236,986 | [
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Dynamic medication adherence modeling in primary prevention of cardiovascular disease: a Markov microsimulation methods application. | Real-world patients' medication adherence is lower than that of clinical trial patients. Hence, the effectiveness of medications in routine practice may differ. The study objective was to compare the outcomes of an adherence-naive versus a dynamic adherence modeling framework using the case of statins for the primary prevention of cardiovascular (CV) disease. Statin adherence was categorized into three state-transition groups on the basis of an epidemiological cohort study. Yearly adherence transitions were incorporated into a Markov microsimulation using TreeAge software. Tracker variables were used to store adherence transitions, which were used to adjust probabilities of CV events over the patient's lifetime. Microsimulation loops "random walks" estimated the average accrued quality-adjusted life-years (QALYs) and CV events. For each 1,000-patient microsimulations, 10,000 outer loops were performed to reflect second-order uncertainty. The adherence-naive model estimated 0.14 CV events avoided per person, whereas the dynamic adherence model estimated 0.08 CV events avoided per person. Using the adherence-naive model, we found that statin therapy resulted in 0.40 QALYs gained over the lifetime horizon on average per person while the dynamic adherence model estimated 0.22 incremental QALYs gained. Subgroup analysis revealed that maintaining high adherence in year 2 resulted in 0.23 incremental QALYs gained as compared with 0.16 incremental QALYs gained when adherence dropped to the lowest level. A dynamic adherence Markov microsimulation model reveals risk reduction and effectiveness that are lower than with an adherence-naive model, and reflective of real-world practice. Such a model may highlight the value of improving or maintaining good adherence. | 25,236,996 | [
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Endometrial apical glycoproteomic analysis reveals roles for cadherin 6, desmoglein-2 and plexin b2 in epithelial integrity. | Implantation failure is one of the major causes of infertility and remains a major barrier to assisted reproduction success. Initial receptivity to implantation is regulated by the endometrial luminal epithelium under maternal hormonal control. Identification of epithelial cell surface components involved in embryo attachment will have translational applications in early pregnancy failure, infertility and contraception. In this study, vectorial biotinylation has been used to characterize the apical glycoproteome of Ishikawa cells, a polarized cell line that serves as a model of the implantation-receptive human endometrial luminal epithelium. Of 46 surface-associated glycoproteins detected by mass spectrometry, half are newly reported in this cell type; a subgroup of these were chosen for evaluation in tissue, and all were shown to be expressed apically in vivo in the mid-secretory (implantation) phase of the menstrual cycle, thus validating the model. Eleven adhesion molecules were detected, some already known to be involved in implantation, others novel. Cadherin 6, desmoglein 2 and plexin b2 were surprisingly found in the apical as well as the lateral membrane domain; their knock-down compromised epithelial integrity. This method of targeting glycosylated apical surface moieties in a polarized epithelial culture model shows excellent selectivity and identifies candidate cell adhesion molecules that are also present in vivo in secretory phase endometrial epithelium. | 25,237,006 | [
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Primordial germ cell development in the marmoset monkey as revealed by pluripotency factor expression: suggestion of a novel model of embryonic germ cell translocation. | Primordial germ cells (PGCs) are the embryonic progenitors of sperm and egg cells. Mammalian PGCs are thought to actively migrate from the yolk sac endoderm over long distances across the embryo to reach the somatic genital ridges. The general principles of mammalian PGC development were discovered in mice. In contrast, little is known about PGC development in primates due to extremely limited access to primate embryos. Here, we analyzed 12 well preserved marmoset monkey (Callithrix jacchus) embryos covering the phase from PGC emergence in the endoderm to the formation of the sexually differentiated gonad (embryonic day (E) 50 to E95). We show using immunohistochemistry that the pluripotency factors OCT4A and NANOG specifically mark PGCs throughout the period studied. In contrast, SALL4 and LIN28 were first expressed ubiquitously and only later down-regulated in somatic tissues. We further show, for the first time, that PGCs are located in the endoderm in E50 embryos in close spatial proximity to the prospective genital ridge, making a long-range migration of PGCs dispensable. At E65, PGCs are already present in the primitive gonad, while significantly later embryonic stages still exhibit PGCs at their original endodermal site, revealing a wide spatio-temporal window of PGC distribution. Our findings challenge the 'dogma' of active long-range PGC migration from the endoderm to the gonads. We therefore favor an alternative model based primarily on passive translocation of PGCs from the mesenchyme that surrounds the gut to the prospective gonad through the intercalar expansion of mesenchymal tissue which contains the PGCs. In summary, we (i) show differential pluripotency factor expression during primate embryo development and (ii) provide a schematic model for embryonic PGC translocation. | 25,237,007 | [
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Complete coding sequences of three members of the kokobera group of flaviviruses. | The Kokobera group of flaviviruses circulates in Australia and Papua, New Guinea, and has been associated with occasional human polyarticular disease. To facilitate future studies to identify virulence determinants, the complete coding regions of the Stratford virus, and isolates of the Bainyik virus and Torres virus were obtained. | 25,237,018 | [
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Draft Genome Assembly of Bordetella bronchiseptica ATCC 10580, a Historical Canine Clinical Isolate. | We present the scaffolded genome of Bordetella bronchiseptica ATCC 10580, assembled into 98 contigs. This 5.1-Mb assembly (68.2% G+C content) contains 4,870 coding regions. The strain was originally isolated from canine lung tissue and is used in quality control testing. | 25,237,025 | [
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Inferences from genetically modified mouse models on the skeletal actions of vitamin D. | Vitamin D has pleiotropic extra-skeletal effects which have been noted in mouse models of deletion of either the 25-hydroxy vitamin D 1α-hydroxylase enzyme, cyp27b1 (1OHase(-/-) mice) or of the vitamin D receptor (Vdr(-/-) mice); these may be preventable or reversible by either restoring normal signaling of the 1,25(OH)2D/VDR system, or in some cases by restoring normal mineral homeostasis. However, effects on skeletal and mineral homeostasis are clearly the major phenotype observed in humans with loss-of-function mutations in either CYP27B1 or VDR. In mouse phenocopies of these human disorders, correction of hypocalcemia and hypophosphatemia reduce elevated circulating parathyroid hormone concentrations and normalize impaired bone mineralization, but restoration of normal 1,25(OH)2D/VDR signaling may be required for optimal bone formation. Induction of high endogenous 1,25(OH)2D concentrations in genetically modified mouse models may cause increased bone resorption and decreased mineralization. Transgenic Vdr overexpression and conditional Vdr deletion in cells of the osteoblastic lineage have also provided insights into the stages of osteoblast differentiation which may mediate these actions. These anabolic and catabolic effects of the 1,25(OH)2D system on bone may therefore be a function of both the ambient concentration of circulating 1,25(OH)2D and the stage of differentiation of the osteoblast. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. | 25,237,033 | [
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The early stage of the atrial electroanatomic remodeling as substrates for atrial fibrillation in hypertensive patients. | Hypertension is one of the most important risk factors for atrial fibrillation (AF). Recent studies suggest right atrial remodeling in hypertensive patients may be associated with increased inducibility of AF. This study sought to characterize the electroanatomic features of left and right atria and pulmonary veins (PVs) in hypertensive patients. A prospective observational study was conducted on patients who underwent ablation for paroxysmal supraventricular tachycardia or paroxysmal AF. Electrophysiological features of the PVs and atria, including event-related potentials, conduction time, and inducibility and vulnerability of AF, were characterized during cardiac catheterization. Anatomic and hemodynamic features were assessed by using echocardiographic and computer tomography imaging. When 15 hypertensive patients with paroxysmal supraventricular tachycardia were compared with 17 normotensive patients with paroxysmal supraventricular tachycardia, the hypertensive patients had significantly shortened PV event-related potentials with increased dispersions (P<0.001) but slightly prolonged atrial event-related potentials (P=NS) and had prolonged interatrial and intra-atrial conduction times (P<0.001). Additionally, the hypertensive patients had increased vulnerability and inducibility of AF and prolonged duration of induced AF (P<0.01). All of these changes were more pronounced in hypertensive patients with paroxysmal AF. Anatomically, compared with the normotensive patients, the diameters of 4 PVs in the hypertensive patients with paroxysmal supraventricular tachycardia were significantly enlarged (P<0.01) and became more remarkable in hypertensive patients with paroxysmal AF (P<0.0001), although the diameter and volume index of the left atrium among 3 groups were similar. The hypertensive patients showed electroanatomic changes associated with increased vulnerability to AF, including shortened event-related potentials with increased dispersion, prolonged conduction time, and increased PV diameter, but these changes were not appreciated in the atria. Additionally, these changes became more dramatic in hypertensive patients with paroxysmal AF. | 25,237,045 | [
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Novel role of kallistatin in vascular repair by promoting mobility, viability, and function of endothelial progenitor cells. | Kallistatin exerts pleiotropic activities in inhibiting inflammation, apoptosis, and oxidative stress in endothelial cells. Because endothelial progenitor cells (EPCs) play a significant role in vascular repair, we investigated whether kallistatin contributes to vascular regeneration by enhancing EPC migration and function. We examined the effect of endogenous kallistatin on circulating EPCs in a rat model of vascular injury and the mechanisms of kallistatin on EPC mobility and function in vitro. In deoxycorticosterone acetate-salt hypertensive rats, we found that kallistatin depletion augmented glomerular endothelial cell loss and diminished circulating EPC number, whereas kallistatin gene delivery increased EPC levels. In cultured EPCs, kallistatin significantly reduced tumor necrosis factor-α-induced apoptosis and caspase-3 activity, but kallistatin's effects were blocked by phosphoinositide 3-kinase inhibitor (LY294002) and nitric oxide (NO) synthase inhibitor (l-NAME). Kallistatin stimulated the proliferation, migration, adhesion and tube formation of EPCs; however, kallistatin's actions were abolished by LY294002, l-NAME, endothelial NO synthase-small interfering RNA, constitutively active glycogen synthase kinase-3β, or vascular endothelial growth factor antibody. Kallistatin also increased Akt, glycogen synthase kinase-3β, and endothelial NO synthase phosphorylation; endothelial NO synthase, vascular endothelial growth factor, and matrix metalloproteinase-2 synthesis and activity; and NO and vascular endothelial growth factor levels. Kallistatin's actions on phosphoinositide 3-kinase-Akt signaling were blocked by LY294002, l-NAME, and anti-vascular endothelial growth factor antibody. Endogenous kallistatin plays a novel role in protection against vascular injury in hypertensive rats by promoting the mobility, viability, and vasculogenic capacity of EPCs via enhancing NO and vascular endothelial growth factor levels through activation of phosphoinositide 3-kinase-Akt signaling. Kallistatin therapy may be a promising approach in the treatment of vascular diseases. | 25,237,049 | [
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Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli. | Escherichia coli endoribonuclease E has a major influence on gene expression. It is essential for the maturation of ribosomal and transfer RNA as well as the rapid degradation of messenger RNA. The latter ensures that translation closely follows programming at the level of transcription. Recently, one of the hallmarks of RNase E, i.e. its ability to bind via a 5'-monophosphorylated end, was shown to be unnecessary for the initial cleavage of some polycistronic tRNA precursors. Here we show using RNA-seq analyses of ribonuclease-deficient strains in vivo and a 5'-sensor mutant of RNase E in vitro that, contrary to current models, 5'-monophosphate-independent, 'direct entry' cleavage is a major pathway for degrading and processing RNA. Moreover, we present further evidence that direct entry is facilitated by RNase E binding simultaneously to multiple unpaired regions. These simple requirements may maximize the rate of degradation and processing by permitting multiple sites to be surveyed directly without being constrained by 5'-end tethering. Cleavage was detected at a multitude of sites previously undescribed for RNase E, including ones that regulate the activity and specificity of ribosomes. A potentially broad role for RNase G, an RNase E paralogue, in the trimming of 5'-monophosphorylated ends was also revealed. | 25,237,058 | [
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Endovascular treatment of acute intracranial vertebral artery dissection: long-term follow-up results of internal trapping and reconstructive treatment using coils and stents. | Endovascular internal trapping is an effective procedure for the treatment of acute vertebral artery dissection (VAD). However, the outcomes of reconstructive treatment have not been well established. The aim of our study is to evaluate the long-term clinical and angiographic results of endovascular internal trapping or reconstructive treatment of acute VAD. Between 2005 and 2013, 26 patients with acute VAD were managed with internal coil trapping (n=10), stent-assisted coiling (n=14), stent only (n=1), and proximal occlusion (n=1). Stent-assisted coiling included the modified stent-assisted semi-jailing technique (n=10), balloon-in-stent technique (n=2), and coiling followed by balloon mounted stent (n=2). Digital subtraction angiography (DSA) was performed in all patients except for three who died during the acute stage. Of 26 patients with VAD, 14 and 12 presented with hemorrhagic and non-hemorrhagic types, respectively. The dominancy of the relevant artery was defined as dominant (n=9), even (n=12), and non-dominant (n=5). Reconstructive treatment was performed in six patients with ruptured VADs which failed balloon test occlusion and nine with non-hemorrhagic VADs. Clinical outcomes were favorable in 22 (84.6%), severe disability occurred in one, and there were three deaths (11.5%). All patients except the three who died had angiographic follow-up at 6-32 months (mean 10.4 months). The angiographic results of nine cases of internal trapping and one of proximal occlusion all showed a stable occlusion state. Among the 15 cases of reconstructive treatment, follow-up DSAs were available for the 13 surviving patients, 10 of which demonstrated stable occlusion of aneurysmal dilation and patent parent artery. This study suggests that internal trapping is a stable and effective treatment for acute VAD. Reconstructive treatment using stent and coils could also be a feasible alternative modality for hemorrhagic type VAD. However, serial DSA follow-up is essential. | 25,237,069 | [
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Telomeric g-tail length and hospitalization for cardiovascular events in hemodialysis patients. | Telomeric G-tails play a pivotal role in maintaining the intramolecular loop structure of telomeres. Previous in vitro studies have suggested that the erosion of telomeric G-tails triggers cellular senescence, leading to organ dysfunction and atherosclerosis. The authors recently established a method to measure telomeric G-tail length using a hybridization protection assay. Using this method, this study investigated whether telomeric G-tail length could be used as a novel predictor for future cardiovascular events in hemodialysis patients. A prospective observational study was performed involving a cohort of 203 Japanese hemodialysis patients to examine the lengths of telomeric G-tails and total telomeres and subsequent cardiovascular events during a median follow-up period of 48 months. The lengths of telomeric G-tails and total telomeres were also measured in 203 participants who did not have CKD and who were age- and sex-matched to hemodialysis patients. The lengths of telomeric G-tails and total telomeres were significantly shorter in hemodialysis patients than in control subjects. Telomeric G-tails, but not total telomeres, were independently and negatively associated with clinical history of cardiovascular disease. During follow-up, 80 cardiovascular events occurred. Total telomere length did not predict cardiovascular events. However, the length of telomeric G-tails was associated with new-onset cardiovascular events (hazard ratio per log luminescence signals, 0.12; 95% confidence interval, 0.12 to 0.50) that persisted after adjustment for age, sex, diabetes mellitus, clinical history of cardiovascular disease, inflammation, use of vitamin D, and serum levels of phosphate and intact parathyroid hormone. Longer telomeric G-tail length is associated with a lower risk of future cardiovascular events in hemodialysis patients. | 25,237,070 | [
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Organic electronics. Room-temperature coupling between electrical current and nuclear spins in OLEDs. | The effects of external magnetic fields on the electrical conductivity of organic semiconductors have been attributed to hyperfine coupling of the spins of the charge carriers and hydrogen nuclei. We studied this coupling directly by implementation of pulsed electrically detected nuclear magnetic resonance spectroscopy in organic light-emitting diodes (OLEDs). The data revealed a fingerprint of the isotope (protium or deuterium) involved in the coherent spin precession observed in spin-echo envelope modulation. Furthermore, resonant control of the electric current by nuclear spin orientation was achieved with radiofrequency pulses in a double-resonance scheme, implying current control on energy scales one-millionth the magnitude of the thermal energy. | 25,237,097 | [
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The genetic architecture of maize (Zea mays L.) kernel weight determination. | Individual kernel weight is an important trait for maize yield determination. We have identified genomic regions controlling this trait by using the B73xMo17 population; however, the effect of genetic background on control of this complex trait and its physiological components is not yet known. The objective of this study was to understand how genetic background affected our previous results. Two nested stable recombinant inbred line populations (N209xMo17 and R18xMo17) were designed for this purpose. A total of 408 recombinant inbred lines were genotyped and phenotyped at two environments for kernel weight and five other traits related to kernel growth and development. All traits showed very high and significant (P < 0.001) phenotypic variability and medium-to-high heritability (0.60-0.90). When N209xMo17 and R18xMo17 were analyzed separately, a total of 23 environmentally stable quantitative trait loci (QTL) and five epistatic interactions were detected for N209xMo17. For R18xMo17, 59 environmentally stable QTL and 17 epistatic interactions were detected. A joint analysis detected 14 stable QTL regardless of the genetic background. Between 57 and 83% of detected QTL were population specific, denoting medium-to-high genetic background effects. This percentage was dependent on the trait. A meta-analysis including our previous B73xMo17 results identified five relevant genomic regions deserving further characterization. In summary, our grain filling traits were dominated by small additive QTL with several epistatic and few environmental interactions and medium-to-high genetic background effects. This study demonstrates that the number of detected QTL and additive effects for different physiologically related grain filling traits need to be understood relative to the specific germplasm. | 25,237,113 | [
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Adolescent marijuana users have elevated risk-taking on the balloon analog risk task. | Adolescents who engage in regular marijuana use may have a higher propensity to take unsafe risks despite the possible negative consequences. We compared adolescents with a history of regular marijuana use to non-using teens on a behavioral measure of risk-taking. Given the involvement of the pre-frontal cortex in both risk-taking and executive functioning, we also examined whether risk-taking was associated with measures of executive functioning. Fifty-eight demographically similar community youth (ages 17-20; 29% female), including 24 marijuana users and 34 non-using controls, completed the computerized Balloon Analog Risk Task (BART; Lejuez et al., 2002) and measures of substance use and executive function. Primary BART outcome measures included total number of popped balloons and average adjusted pumps (mean pumps excluding popped balloons). Marijuana users had more popped balloons than controls (p<0.05) but did not differ on average adjusted pumps. Using hierarchical multiple regression controlling for age, riskier BART performance (popped balloons) was predictive of past 18-month hard drug use (β=0.30; p<0.05). Having a higher number of popped balloons was also predictive of past 18-month marijuana use (p<0.05), but age was a stronger predictor than marijuana use. Marijuana users performed worse on one test of executive functioning (psychomotor set-shifting, p<0.05), but this did not correlate with risk-taking. Our finding of elevated risk-taking among marijuana users is consistent with previous research that substance users may have impaired risk processing. Further, our results suggest that risk-taking is not always associated with executive dysfunction, implying the involvement of distinct neural subsystems. | 25,237,125 | [
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Arabidopsis myosin XI: a motor rules the tracks. | Plant cell expansion relies on intracellular trafficking of vesicles and macromolecules, which requires myosin motors and a dynamic actin network. Arabidopsis (Arabidopsis thaliana) myosin XI powers the motility of diverse cellular organelles, including endoplasmic reticulum, Golgi, endomembrane vesicles, peroxisomes, and mitochondria. Several recent studies show that there are changes in actin organization and dynamics in myosin xi mutants, indicating that motors influence the molecular tracks they use for transport. However, the mechanism by which actin organization and dynamics are regulated by myosin XI awaits further detailed investigation. Here, using high spatiotemporal imaging of living cells, we quantitatively assessed the architecture and dynamic behavior of cortical actin arrays in a mutant with three Myosin XI (XI-1, XI-2, and XI-K) genes knocked out (xi3KO). In addition to apparent reduction of organ and cell size, the mutant showed less dense and more bundled actin filament arrays in epidermal cells. Furthermore, the overall actin dynamicity was significantly inhibited in the xi3KO mutant. Because cytoskeletal remodeling is contributed mainly by filament assembly/disassembly and translocation/buckling, we also examined the dynamic behavior of individual actin filaments. We found that the xi3KO mutant had significantly decreased actin turnover, with a 2-fold reduction in filament severing frequency. Moreover, quantitative analysis of filament shape change over time revealed that myosin XI generates the force for buckling and straightening of both single actin filaments and actin bundles. Thus, our data provide genetic evidence that three Arabidopsis class XI myosins contribute to actin remodeling by stimulating turnover and generating the force for filament shape change. | 25,237,128 | [
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Rewards and challenges of providing HIV testing and counselling services: health worker perspectives from Burkina Faso, Kenya and Uganda. | The rapid scale-up of human immunodeficiency virus (HIV) testing, counselling and treatment throughout sub-Saharan Africa has raised questions about how to protect patients' rights to consent, confidentiality, counselling and care in resource-constrained settings. The Multi-country African Testing and Counselling for HIV (MATCH) study investigated client and provider experiences with different modes of testing in sub-Saharan Africa. One component of that study was a survey of 275 HIV service providers in Burkina Faso, Kenya and Uganda that gathered quantifiable indicators and qualitative descriptions using a standardized instrument. This article presents provider perspectives on the challenges of obtaining consent, protecting confidentiality, providing counselling and helping clients manage disclosure. It also explores health workers' fear of infection within the workplace and their reports on discrimination against HIV clients within health facilities. HIV care providers in Burkina Faso, Kenya and Uganda experienced substantial rewards from their work, including satisfaction from saving lives and gaining professional skills. They also faced serious resource constraints, including staff shortages, high workloads, lack of supplies and inadequate infrastructure, and they expressed concerns about accidental exposure. Health workers described heavy emotional demands from observing clients suffer emotional, social and health consequences of being diagnosed with HIV, and also from difficult ethical dilemmas related to clients who do not disclose their HIV status to those around them, including partners. These findings suggest that providers of HIV testing and counselling need more resources and support, including better protections against HIV exposure in the workplace. The findings also suggest that health facilities could improve care by increasing attention to consent, privacy and confidentiality and that health policy makers and ethicists need to address some unresolved ethical dilemmas related to confidentiality and non-disclosure, and translate those discussions into better guidance for health workers. | 25,237,134 | [
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Dynamin-related protein 1 (Drp1) promotes structural intermediates of membrane division. | Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. Despite the link between Drp1 malfunction and human disease, the molecular details of its membrane activity remain poorly understood. Here we reconstituted and directly visualized Drp1 activity in giant unilamellar vesicles. We quantified the effect of lipid composition and GTP on membrane binding and remodeling activity by fluorescence confocal microscopy and flow cytometry. In contrast to other dynamin relatives, Drp1 bound to both curved and flat membranes even in the absence of nucleotides. We also found that Drp1 induced membrane tubulation that was stimulated by cardiolipin. Moreover, Drp1 promoted membrane tethering dependent on the intrinsic curvature of the membrane lipids and on GTP. Interestingly, Drp1 concentrated at membrane contact surfaces and, in the presence of GTP, formed discrete clusters on the vesicles. Our findings support a role of Drp1 not only in the formation of lipid tubes but also on the stabilization of tightly apposed membranes, which are intermediate states in the process of mitochondrial fission. | 25,237,193 | [
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Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. | Most genetic defects that arrest B-cell development in the bone marrow present early in life with agammaglobulinemia, whereas incomplete antibody deficiency is usually associated with circulating B cells. We report 3 related individuals with a novel form of severe B-cell deficiency associated with partial persistence of serum immunoglobulin arising from a missense mutation in NFKB2. Significantly, this point mutation results in a D865G substitution and causes a failure of p100 phosphorylation that blocks processing to p52. Severe B-cell deficiency affects mature and transitional cells, mimicking the action of rituximab. This phenotype appears to be due to disruption of canonical and noncanonical nuclear factor κB pathways by the mutant p100 molecule. These findings could be informative for therapeutics as well as immunodeficiency. | 25,237,204 | [
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Guidelines for the Investigation of Mediating Variables in Business Research. | Business theories often specify the mediating mechanisms by which a predictor variable affects an outcome variable. In the last 30 years, investigations of mediating processes have become more widespread with corresponding developments in statistical methods to conduct these tests. The purpose of this article is to provide guidelines for mediation studies by focusing on decisions made prior to the research study that affect the clarity of conclusions from a mediation study, the statistical models for mediation analysis, and methods to improve interpretation of mediation results after the research study. Throughout this article, the importance of a program of experimental and observational research for investigating mediating mechanisms is emphasized. | 25,237,213 | [
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Comparison of the in vitro Effects of One-day Exposure to Amodiaquine and Praziquantel on Schistosoma mansoni Adult Worm Pairs. | It has been demonstrated that continuous exposure to amodiaquine (AQ) alone elicits in vitro antischistosomal activities at concentrations of 1-10 μg/ml. However, orally administered drugs reach a peak blood concentration within one or two hours and then gradually decrease. The blood concentration does not remain at a constant level over several days as in vitro concentration of continuous drug exposure. In vitro activities by one day exposure to AQ better reflect the actual antischistosomal activities after oral administration than those elicited by continuous exposure. The objective of the present study is to compare the antischistosomal potential of one-day exposure to AQ with that to praziquantel (PZQ), a current antischistosomal drug. Schistosoma mansoni adult worm pairs were incubated with 0 (control), 1, 2, 5 and 10 μg/ml AQ as well as 0.01, 0.02, 0.05 and 0.1 μg/ml PZQ for the first day, and were subsequently incubated in drug-free media for a period of 14 days. The one-day exposure to AQ significantly reduced the daily egg output of the worm pairs at 1-10 μg/ml. The inhibitory effect on egg production continued at 5 and 10 μg/ml but proved temporary at 1 and 2 μg/ml. Furthermore, AQ-induced specific morphological alterations (severe swelling and/or localization of hemozoin) were observed in the worms at 5 and 10 μg/ml. The AQ-specific appearance of the male worms gradually faded during subsequent incubation in drug-free media, although the female worms showed elongation. Meanwhile, PZQ inhibited the egg output of adult worm pairs at concentrations of 0.01-0.1 μg/ml during exposure. The inhibitory effect on egg production continued at 0.05 and 0.1 μg/ml but proved temporary at 0.01 and 0.02 μg/ml. Furthermore, PZQ induced a visible contraction and shortening of the male and female worms at 0.05 and 0.1 μg/ml during exposure, but the PZQ-specific alterations quickly disappeared during subsequent incubation in drug-free media. To our knowledge, this is the first report showing that one-day exposure to AQ inhibits the egg production of adult worm pairs at 1-10 μg/ml and induces specific morphological alterations in the worms at 5 and 10 μg/ml. The present findings have important implications for the evaluation of the therapeutic effects of both AQ monotherapy and combination therapy with artesunate on schistosomiasis in clinical field trials. | 25,237,285 | [
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Knowledge-based identification of sleep stages based on two forehead electroencephalogram channels. | Sleep quality is important, especially given the considerable number of sleep-related pathologies. The distribution of sleep stages is a highly effective and objective way of quantifying sleep quality. As a standard multi-channel recording used in the study of sleep, polysomnography (PSG) is a widely used diagnostic scheme in sleep medicine. However, the standard process of sleep clinical test, including PSG recording and manual scoring, is complex, uncomfortable, and time-consuming. This process is difficult to implement when taking the whole PSG measurements at home for general healthcare purposes. This work presents a novel sleep stage classification system, based on features from the two forehead EEG channels FP1 and FP2. By recording EEG from forehead, where there is no hair, the proposed system can monitor physiological changes during sleep in a more practical way than previous systems. Through a headband or self-adhesive technology, the necessary sensors can be applied easily by users at home. Analysis results demonstrate that classification performance of the proposed system overcomes the individual differences between different participants in terms of automatically classifying sleep stages. Additionally, the proposed sleep stage classification system can identify kernel sleep features extracted from forehead EEG, which are closely related with sleep clinician's expert knowledge. Moreover, forehead EEG features are classified into five sleep stages by using the relevance vector machine. In a leave-one-subject-out cross validation analysis, we found our system to correctly classify five sleep stages at an average accuracy of 76.7 ± 4.0 (SD) % [average kappa 0.68 ± 0.06 (SD)]. Importantly, the proposed sleep stage classification system using forehead EEG features is a viable alternative for measuring EEG signals at home easily and conveniently to evaluate sleep quality reliably, ultimately improving public healthcare. | 25,237,291 | [
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Corrigendum: The effect of stimulus context on the buildup to stream segregation. | [This corrects the article on p. 93 in vol. 8, PMID: 24808822.]. | 25,237,292 | [
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Cocaine inhibition of nicotinic acetylcholine receptors influences dopamine release. | Nicotinic acetylcholine receptors (nAChRs) potently regulate dopamine (DA) release in the striatum and alter cocaine's ability to reinforce behaviors. Since cocaine is a weak nAChR inhibitor, we hypothesized that cocaine may alter DA release by inhibiting the nAChRs in DA terminals in the striatum and thus contribute to cocaine's reinforcing properties primarily associated with the inhibition of DA transporters. We found that biologically relevant concentrations of cocaine can mildly inhibit nAChR-mediated currents in midbrain DA neurons and consequently alter DA release in the dorsal and ventral striatum. At very high concentrations, cocaine also inhibits voltage-gated Na channels in DA neurons. Furthermore, our results show that partial inhibition of nAChRs by cocaine reduces evoked DA release. This diminution of DA release via nAChR inhibition more strongly influences release evoked at low or tonic stimulation frequencies than at higher (phasic) stimulation frequencies, particularly in the dorsolateral striatum. This cocaine-induced shift favoring phasic DA release may contribute to the enhanced saliency and motivational value of cocaine-associated memories and behaviors. | 25,237,305 | [
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Predictors of acute kidney injury in geriatric patients undergoing total knee replacement surgery. | Few studies have focused on patients' characteristics that affects acute kidney injury (AKI) after total knee replacement surgery (TKR). The primary objective of this retrospective study was to identify patients' characteristics associated with AKI after TKR. Between January 2008 and December 2009, 659 patients with a mean age of 67.1 years (range, 39-99) underwent TKA at Regional Hospital Knee and Hip Institute. Retrospective chart review was done to identify patients' characteristics that were associated with AKI after TKR. Logistic regression was used to evaluate AKI. AKI occurred in 21.9% of patients. AKI risk decreased between 2008 and 2009 (odds ratio, 0.55; 95% CI, -0.37 to 0.82) but increased with age (P < 0.001), diabetes mellitus (DM), and angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) use (OR, -1.6; 95% CI, -1.0 to 2.5; and OR, -1.5, 95% CI, -1.0 to 2.3, respectively). However, the effects of DM and ACEI/ARB use were not independent; when both were included in the regression model, neither was statistically significant, and both ORs were smaller than combined OR. When examined separately, both DM and preoperative ACEI/ARB use increased the risk of AKI; however these factors were correlated and were not independent predictors of significantly increased risk. Patients with DM have higher tendency to develop AKI and hence, preoperative renal risk stratification should be done in all patients with DM. | 25,237,322 | [
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A highly sensitive kinetic spectrophotometric method for the determination of ascorbic Acid in pharmaceutical samples. | In this study, a new reaction system for quantitative determination of ascorbic acid was introduced. The developed method is based on inhibitory effect of ascorbic acid on the Orange G-bromate system. The change in absorbance was followed spectrophotometrically at 478 nm. The dependence of sensitivity on the reaction variables including reagents concentration, temperature and time was investigated. Under optimum experimental conditions, calibration curve was linear over the range 0.7 - 33.5 μg mL(-1) of ascorbic acid including two linear segments and the relative standard deviations (n = 6) for 5.0 and 20.0 μg mL(-1) of ascorbic acid were 1.08 and 1.02%, respectively. The limit of detection was 0.21 μg mL(-) (1) of ascorbic acid. The effect of diverse species was also investigated. The developed method was successfully applied for the determination of ascorbic acid in pharmaceutical samples. The results were in a good agreement with those of reference method. | 25,237,333 | [
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Modeling of outpatient prescribing process in iran: a gateway toward electronic prescribing system. | Implementation of electronic prescribing system can overcome many problems of the paper prescribing system, and provide numerous opportunities of more effective and advantageous prescribing. Successful implementation of such a system requires complete and deep understanding of work content, human force, and workflow of paper prescribing. The current study was designed in order to model the current business process of outpatient prescribing in Iran and clarify different actions during this process. In order to describe the prescribing process and the system features in Iran, the methodology of business process modeling and analysis was used in the present study. The results of the process documentation were analyzed using a conceptual model of workflow elements and the technique of modeling "As-Is" business processes. Analysis of the current (as-is) prescribing process demonstrated that Iran stood at the first levels of sophistication in graduated levels of electronic prescribing, namely electronic prescription reference, and that there were problematic areas including bottlenecks, redundant and duplicated work, concentration of decision nodes, and communicative weaknesses among stakeholders of the process. Using information technology in some activities of medication prescription in Iran has not eliminated the dependence of the stakeholders on paper-based documents and prescriptions. Therefore, it is necessary to implement proper system programming in order to support change management and solve the problems in the existing prescribing process. To this end, a suitable basis should be provided for reorganization and improvement of the prescribing process for the future electronic systems. | 25,237,369 | [
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Effect of hepatitis B virus genotypes on the efficacy of adefovir dipivoxil antiviral therapy. | Hepatitis B is a common infectious disease in China. Many studies have shown that the genotype of hepatitis B virus (HBV) is probably associated with the efficacy of some antiviral drugs such as interferon α (IFN-α) and Lamivudine (LAM). However, the association between HBV genotype and adefovir dipivoxil (ADV) is controversial. ADV is the most popular antiviral drug in China due to its low price, good antiviral efficacy, few side effects, and convenient of administration. This study focused on the effect of HBV genotypes on antiviral efficacy of ADV in patients with chronic hepatitis B infection (CHB). A total of 526 HBeAg-positive patients with CHB were randomly allocated into two groups. One group took ADV and another group took placebo. Nested Polymerase Chain Reaction (PCR) with multiple pairs of genotype-specific primers (nPCR-MPP) was used to analyze genotypes of HBV in these patients. Antiviral efficacy after treatment for three, six, 12 months was compared among the patients with different HBV genotypes. Genotype B (73.6%) and genotype C (26.4%) were detected in these patients. After treatment for 12 months, the rate of HBV DNA seroclearance, ALT normalization, and HBeAg seroconversion were significantly higher in ADV group than in placebo group (P < 0.05). However, there were no significant differences in these three rates between patients infected with genotype B and C (P > 0.05). HBV genotypes B and C have no significant difference in virologic, biochemical, and immunologic response to ADV. | 25,237,370 | [
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Empyema necessitatis in a patient on peritoneal dialysis. | Empyema necessitatis is a rare complication of an empyema. Although the incidence is thought to be decreased in the post-antibiotic era, immunocompromised patients such as patients with chronic kidney disease on dialysis are still at a higher risk. A 56-year-old woman on peritoneal dialysis presented with an enlarging mass on the right anterior chest wall. The chest computed tomography scan revealed an empyema necessitatis and the histopathologic findings revealed a granulomatous inflammation with caseation necrosis. The patient was treated with anti-tuberculous medication. | 25,237,382 | [
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Sequence Diversity Diagram for comparative analysis of multiple sequence alignments. | The sequence logo is a graphical representation of a set of aligned sequences, commonly used to depict conservation of amino acid or nucleotide sequences. Although it effectively communicates the amount of information present at every position, this visual representation falls short when the domain task is to compare between two or more sets of aligned sequences. We present a new visual presentation called a Sequence Diversity Diagram and validate our design choices with a case study. Our software was developed using the open-source program called Processing. It loads multiple sequence alignment FASTA files and a configuration file, which can be modified as needed to change the visualization. The redesigned figure improves on the visual comparison of two or more sets, and it additionally encodes information on sequential position conservation. In our case study of the adenylate kinase lid domain, the Sequence Diversity Diagram reveals unexpected patterns and new insights, for example the identification of subgroups within the protein subfamily. Our future work will integrate this visual encoding into interactive visualization tools to support higher level data exploration tasks. | 25,237,396 | [
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Prevalence of diabetes mellitus in patients with newly evaluated papillary thyroid cancer. | This study investigates whether diabetes mellitus is a risk factor for the development of papillary thyroid cancer, using an age-, gender-, and race-matched analysis. We retrospectively reviewed the charts of 1559 patients with newly evaluated thyroid cancer over a 4-year period at our institution and identified 1313 patients (84%) with papillary thyroid carcinoma. Characteristics of patients with diabetes versus those without diabetes were compared with a chi-square test for categorical variables and the Wilcoxon Rank Sum test for numeric variables. The prevalence of diabetes among patients with papillary thyroid carcinoma at our institution was compared (using an age-, gender-, and race-matched analysis) with that expected based on data from the continuous National Health and Nutrition Examination Survey (NHANES) from the same time period. For patients with papillary thyroid carcinoma, the median age was 47 years; 74% were female; 83% were white; and the prevalence of diabetes was 8%. Among those with diabetes, 92% had type 2 diabetes, and 24% were treated with insulin. Risk factors for diabetes included age and race. The prevalence of diabetes among patients with papillary thyroid carcinoma of all ages versus that among patients from NHANES of all ages was not significantly different (RR 1.07, CI 0.88 - 1.28). The prevalence of diabetes among patients with papillary thyroid cancer who were 44 years of age or younger versus that among patients from NHANES who were 44 years of age or younger, however, was significantly increased (RR 2.32, CI 1.37 - 3.66). There was no significant difference when subgroup analysis was performed by gender or race. We found an increased prevalence of diabetes in patients with papillary thyroid carcinoma who were 44 years of age or younger. | 25,237,398 | [
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Defining hospitalist physicians using clinical practice data: a systems-level pilot study of Ontario physicians. | Hospitalists have become dominant providers of inpatient care in many North American hospitals. Despite the global growth of hospital medicine, no objective method has been proposed for defining the hospitalist discipline and delineating among inpatient practices on the basis of physicians' clinical volumes. We propose a functional method of identifying hospital-based physicians using aggregated measures of inpatient volume and apply this method to a retrospective, population-based cohort to describe the growth of the hospitalist movement, as well as the prevalence and practice characteristics of hospital-based generalists in one Canadian province. We used human resource databases and financial insurance claims to identify all active fee-for-service physicians working in Ontario, Canada, between fiscal year 1996/1997 and fiscal year 2010/2011. We constructed 3 measures of inpatient volume from the insurance claims to reflect the time that physicians spent delivering inpatient care in each fiscal year. We then examined how inpatient volumes have changed for Ontario physicians over time and described the prevalence of full-time and part-time hospital-based generalists working in acute care hospitals in fiscal year 2010/2011. Our analyses showed a significant increase since fiscal year 2000/2001 in the number of high-volume hospital-based family physicians practising in Ontario (p < 0.001) and associated decreases in the numbers of high-volume internists and specialists (p = 0.03), where high volume was defined as ≥ 2000 inpatient services/ year. We estimated that 620 full-time and 520 part-time hospital-based physicians were working in Ontario hospitals in 2010/2011, accounting for 4.5% of the active physician workforce (n = 25 434). Hospital-based generalists, consisting of 207 family physicians and 130 general internists, were prevalent in all geographic regions and hospital types and collectively delivered 10% of all inpatient evaluation and care coordination for Ontario residents who had been admitted to hospital. These analyses confirmed a substantial increase in the prevalence of general hospitalists in Ontario from 1996 to 2011. Systems-level analyses of clinical practice data represent a practical and valid method for defining and identifying hospital-based physicians. | 25,237,402 | [
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Antiallodynic effect of intrathecal epigallocatechin-3-gallate due to suppression of reactive oxygen species. | Green tea modulates neuropathic pain. Reactive oxygen species (ROS) are suggested as a key molecule in the underlying mechanism of neuropathic pain in the spinal cord. We examined the effect of epigallocatechin-3-gallate (EGCG), the major catechin in green tea, in neuropathic pain and clarified the involvement of ROS on the activity of EGCG. Neuropathic pain was induced in male Sprague-Dawley rats by spinal nerve ligation (SNL). A polyethylene tube was intrathecally located. Nociceptive degree was estimated by a von Frey filament and expressed as a paw withdrawal threshold (PWT). To determine the role of ROS on the effect of EGCG, a free radical donor (tert-BuOOH) was pretreated before administration of EGCG. ROS activity was assayed by xanthine oxidase (XO) and malondialdehyde (MDA). SNL decreased the PWT compared to sham rats. The decrease remained during the entire observation period. Intrathecal EGCG increased the PWT at the SNL site. Intrathecal tert-BuOOH significantly decreased the effect of EGCG. The levels of both XO and MDA in the spinal cord were increased in SNL rats compared to sham. Intrathecal EGCG decreased the level of XO and MDA. EGCG may reduce neuropathic pain by SNL due to the suppression of ROS in the spinal cord. | 25,237,449 | [
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Risk of continuing planned surgery after endovascular repair of subclavian artery injury: a case report. | Endovascular repair with covered stents has been widely used to treat subclavian and axillary artery injuries and has produced promising early results. The possibility of a thromboembolism occurring in cerebral arteries during an endovascular procedure should be a cause for concern. In the case of endovascular management of arterial traumas, a prompt and sufficient period for check-up of the patient's neurological signs is needed, even if it requires postponing elective intervention for the patient's safety. We report a rare case of liver transplantation immediately after endovascular repair of an iatrogenic subclavian arterial injury to describe the risk of continuing planned surgery without neurologic assessment. | 25,237,452 | [
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Anesthetic management of transoral natural orifice transluminal endoscopic surgery: two cases report. | Natural orifice transluminal endoscopic surgery (NOTES) is an evolving field of minimally invasive surgery. NOTES reaches the target organ by inserting the endoscope through a natural orifice (e.g. mouth, anus, urethra, vagina) and offers advantages of less postoperative pain and lower complication rate. Since its first description in 2004, NOTES has progressed from use on animal models to humans. We experienced anesthetic care of two patients who underwent transoral NOTES under general anesthesia. | 25,237,454 | [
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Hope, optimism and delusion. | Optimism is generally accepted by psychiatrists, psychologists and other caring professionals as a feature of mental health. Interventions typically rely on cognitive-behavioural tools to encourage individuals to 'stop negative thought cycles' and to 'challenge unhelpful thoughts'. However, evidence suggests that most individuals have persistent biases of optimism and that excessive optimism is not conducive to mental health. How helpful is it to facilitate optimism in individuals who are likely to exhibit biases of optimism already? By locating the cause of distress at the individual level and 'unhelpful' cognitions, does this minimise wider systemic social and economic influences on mental health? | 25,237,497 | [
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The College reply to Francis misses the big question: a commentary on OP92. | The College has recently published an occasional paper in response to the Francis inquiry into the care at Mid Staffordshire NHS Foundation Trust. We consider that it overlooks one key question implicit in the inquiry's recommendations: 'Is the business model of care fit for purpose?' We question whether the business model in its present form is appropriate for the delivery of healthcare. We suggest there is a need for greater conceptual clarity with regard to the nature of compassionate care and the meaning of person-centred medicine. We recommend that a broader moral and ethical framework is considered not only for psychiatry, but for all healthcare provision which would transcend specialty and Royal College boundaries. | 25,237,535 | [
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The demonisation of psychiatrists in fiction (and why real psychiatrists might want to do something about it). | To encourage psychiatric practitioners to be aware of and to work to counteract the representations of the profession as evil manipulators in fiction, film and popular culture. A wide-ranging number of representative sources portraying psychiatrists are explored. It is demonstrated that psychiatry is overwhelmingly presented in a damagingly negative light. | 25,237,540 | [
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Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism in Iranian Women With Idiopathic Recurrent Pregnancy Losses. | Recurrent pregnancy loss (RPL) is a serious problem for pregnancy. There is evidence that vascular complications play a principal role in RPL. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Polymorphisms (C677T, A1298C) of MTHFR gene are associated with decreased MTHFR activity. The aim of this study was to determine the association between MTHFR polymorphisms (C677T and A1298C) and recurrent pregnancy loss (RPL) in Iranian women. In this case-control study, blood samples were obtained from patients who had three or more consecutive pregnancy losses before the 22(nd) week of pregnancy (n = 204). The control group consisted of 116 age-matched women with at least one alive child and without any history of pregnancy loss or other gestational complications (n = 116). Following DNA extraction, samples were tested for MTHFR C677T and A1298C polymorphisms using the reverse hybridization method. The prevalence of 677TT mutation was 8.8% (18/204) in the patient group and 8.6% (10/116) in the control group (P = 0.434). The prevalence of 1298CC mutation was 12.3 % (25/204) in the patient group and 8% (9/116) in the control group (P = 0.155). Investigation of the distributions of various genotypes of MTHFR C677T and A1298C did not indicate a significant difference between patients with RPL and healthy control subjects. The results suggest that MTHFR mutations might not be associated with RPL in the examined population. | 25,237,572 | [
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Involvement of synaptic genes in the pathogenesis of autism spectrum disorders: the case of synapsins. | Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders characterized by deficits in social interaction and social communication, restricted interests, and repetitive behaviors. Many synaptic protein genes are linked to the pathogenesis of ASDs, making them prototypical synaptopathies. An array of mutations in the synapsin (Syn) genes in humans has been recently associated with ASD and epilepsy, diseases that display a frequent comorbidity. Syns are pre-synaptic proteins regulating synaptic vesicle traffic, neurotransmitter release, and short-term synaptic plasticity. In doing so, Syn isoforms control the tone of activity of neural circuits and the balance between excitation and inhibition. As ASD pathogenesis is believed to result from dysfunctions in the balance between excitatory and inhibitory transmissions in neocortical areas, Syns are novel ASD candidate genes. Accordingly, deletion of single Syn genes in mice, in addition to epilepsy, causes core symptoms of ASD by affecting social behavior, social communication, and repetitive behaviors. Thus, Syn knockout mice represent a good experimental model to define synaptic alterations involved in the pathogenesis of ASD and epilepsy. | 25,237,665 | [
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Five-year outcome of a retrospective cohort study on the rehabilitation of completely edentulous atrophic maxillae with immediately loaded zygomatic implants placed extra-maxillary. | To report retrospectively on the 5-year follow-up results of the rehabilitation of complete edentulous atrophied maxillae, using extra-maxillary zygomatic implants alone or in combination with conventional implants. This retrospective report includes an initial cohort of 39 patients (30 women and 9 men), with a mean age of 53 years, followed for 5 years. The patients were rehabilitated with 39 fixed prostheses and 169 implants (92 zygomatic implants inserted extra-maxillary and 77 conventional dental implants). A provisional prosthesis was manufactured and attached via multiunit abutments secured to the implants on the same day as implant placement. According to patient desires and each clinical situation, either an acrylic resin, a metal-acrylic or metal-ceramic final prosthesis was inserted approximately 6 months after implant placement. Outcome measures were: prosthesis success; implant success; complications; probing pocket depths; marginal bleeding; and marginal bone levels (only for conventional implants). Data were analysed with descriptive statistics. Two patients died after 8 and 30 months of follow-up due to causes unrelated to their oral rehabilitations, and 5 patients dropped out of the study. No prosthesis was lost; one zygomatic implant was removed after 46 months of follow-up, giving cumulative success rates of 97% and 98.8% (patient and implant related, respectively). Twelve complications occurred in 12 patients: 5 sinus infections in 5 patients, all with a previous history of sinusitis and whose sinus membrane was disrupted during surgery; one oroantral communication (leading to removal of the implant), 2 all acrylic resin prostheses fractures, 1 ceramic crown fracture (on a metal-ceramic prosthesis); and 3 screw loosenings. Bleeding on probing was recorded in 6 patients (13 implants). Probing pocket depths >4 mm were present in 13 patients (23 implants) at 5 years of follow-up. The average (standard deviation) marginal bone loss on conventional implants was 1.16 mm (0.77 mm) in those 9 patients having the intraoral radiographs. The long term outcome (5 years) of rehabilitations performed on patients with completely edentulous, severely atrophic maxillae supported by immediately loaded zygomatic implants alone, or in combination with conventional implants, is satisfactory. | 25,237,671 | [
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Orally inhaled drug performance testing for product development, registration, and quality control. | A DPI can be split into three different modules; device, formulation, process. These are developed in parallel, and together with the user they provide the performance of an inhalation product. During product development, these modules are evolving and changing, whereas the requirements on an inhalation product are always expressed in terms of the performance of the final commercial product. To do performance testing during development when the product is not finished presents many challenges and can be confusing and misleading. During development, the performance of the final product is typically being predicted by testing ever changing prototypes. This article describes methods and approaches to manage such development and to, during development, provide relevant predictions of the in vitro and in vivo performances of the final product. | 25,237,712 | [
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Progressive neurodegenerative syndrome in a patient with X-linked agammaglobulinemia receiving intravenous immunoglobulin therapy. | A progressive encephalopathy of unknown etiology has been described in patients with primary immunodeficiency disorders. In this report, we characterize the clinical features of this progressive neurodegenerative dementing disorder in a young man with Bruton agammaglobulinemia, through neuropsychological tests and a video sequence. The clinical course of the encephalopathy seems rather uniform: Cognition, especially frontal lobe function, is affected in the early stages, and some patients develop movement disorders. The syndrome causes severe cognitive and physical disability, and can eventually be fatal. The autoimmunity results from dysregulated immune responses, but the underlying mechanism has not yet been fully explained. | 25,237,746 | [
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Screening for E3-ubiquitin ligase inhibitors: challenges and opportunities. | The ubiquitin proteasome system (UPS) plays a role in the regulation of most cellular pathways, and its deregulation has been implicated in a wide range of human pathologies that include cancer, neurodegenerative and immunological disorders and viral infections. Targeting the UPS by small molecular regulators thus provides an opportunity for the development of therapeutics for the treatment of several diseases. The proteasome inhibitor Bortezomib was approved for treatment of hematologic malignancies by the FDA in 2003, becoming the first drug targeting the ubiquitin proteasome system in the clinic. Development of drugs targeting specific components of the ubiquitin proteasome system, however, has lagged behind, mainly due to the complexity of the ubiquitination reaction and its outcomes. However, significant advances have been made in recent years in understanding the molecular nature of the ubiquitination system and the vast variety of cellular signals that it produces. Additionally, improvement of screening methods, both in vitro and in silico, have led to the discovery of a number of compounds targeting components of the ubiquitin proteasome system, and some of these have now entered clinical trials. Here, we discuss the current state of drug discovery targeting E3 ligases and the opportunities and challenges that it provides. | 25,237,759 | [
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Proteomic profiling during the pre-competent to competent transition of the biofouling polychaete Hydroides elegans. | The polychaete, Hydroides elegans, is a tube-building worm that is widely distributed in tropical and subtropical seas. It is a dominant fouling species and thus a major target organism in antifouling research. Here, the first high-throughput proteomic profiling of pre-competent and competent larvae of H. elegans is reported with the identification of 1,519 and 1,322 proteins, respectively. These proteins were associated with a variety of biological processes. However, a large proportion was involved in energy metabolism, redox homeostasis, and microtubule-based processes. A comparative analysis revealed 21 proteins that were differentially regulated in larvae approaching competency. | 25,237,770 | [
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Stainless steel in coastal seawater: sunlight counteracts biologically enhanced cathodic kinetics. | The influence of sunlight of varying intensity on the performance of UNS S30400 stainless steel (SS) was explored under conditions of natural biofilm development in coastal seawater. In a series of tests performed outdoors under an opaque roof, a range of shades were fashioned to impart varied amounts of diurnal light. These were an ambient level where the underwater illumination was ~ 5% of full sunlight, two intermediate ranges of lighting with ~ 2.5% and ~ 1% of the daylight, and a condition of full darkness. In comparison with the dark, increments of sunlight rendered the SS progressively less aggressive as cathodes in galvanic couples with UNS C70600 alloy. Likewise, welded SS with pre-initiated localized corrosion sites exhibited substantially lower rates of propagation with light. Thus, biofilms and sunlight affected cathodic kinetics in opposite ways. Surface analytical tests showed that the accumulation of manganese (Mn) within the biofilms was small relative to reports from waters of lower salinity. These results not only reveal that extremely low amounts of sunlight are adequate to offset the microbial effect, but also highlight the lack of convincing evidence for Mn cycling as a potent mechanism for enhanced cathodic kinetics in full-strength seawater. | 25,237,771 | [
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Testicular malakoplakia: a rare sonographic mimic of malignancy. | Testicular malakoplakia is a rare, benign condition that most often occurs in an immunocompromised patient with chronic infection. Its occurrence is acute, with pain and testicular enlargement. Sonography is commonly performed to evaluate the patient for epididymitis or torsion. The appearance of testicular malakoplakia on sonography examination has only rarely been described, making its diagnosis challenging. Because its appearance overlaps with testicular neoplasm and infection, it should be considered when making a differential diagnosis of a diffuse testicular abnormality in the appropriate clinical setting. | 25,237,793 | [
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Active liquid crystal tuning of metallic nanoantenna enhanced light emission from colloidal quantum dots. | A system comprising an aluminum nanoantenna array on top of a luminescent colloidal quantum dot waveguide and covered by a thermotropic liquid crystal (LC) is introduced. By heating the LC above its critical temperature, we demonstrate that the concomitant refractive index change modifies the hybrid plasmonic-photonic resonances in the system. This enables active control of the spectrum and directionality of the narrow-band (∼6 nm) enhancement of quantum dot photoluminescence by the metallic nanoantennas. | 25,237,822 | [
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Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases. | The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9. TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications. | 25,237,847 | [
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Human therapies as a successful liaison between chemistry and biology. | The development of novel therapies is arguably one of the most important roles of modern chemistry and biology. Here, we shed light on a particular class of human therapies in which synthetic chemical entities are attached to expressed biologicals (proteins) with the goal to enhance clinical activity. We focus our discussion on three key categories of these derivatized biologicals: proteins conjugated with biologically inert molecules, proteins conjugated with biologically active small molecules and peptides (e.g., antibody drug conjugates [ADCs]), and proteins conjugated with radio isotopes. Overall, it is apparent by the impact on clinical activity as well as the commercial success that chemical modification of recombinant proteins is becoming of increasing importance. Therefore, we argue that deeper understanding of the chemical reactions between large proteinaceous molecules and small molecule reagents will allow for more precise and elegant solutions to existing limitations in this field. | 25,237,852 | [
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The University of North Carolina's Health Care Pharmacy Assistance Progam. | UNC Health Care has a Pharmacy Assistance Program (PAP) that provides financial assistance to uninsured patients in North Carolina who need prescription medications. Despite significant investment in the program, little is known about the patients accessing it or the specific health care services they use. Our objectives were to describe the PAP population, to examine their use of prescription medications and health services, and to characterize changes in prescription medication use and expenditures from 2009 through 2011. We used a repeated cross-sectional study design, merging prescription claims with health records from Carolina Data Warehouse for Health, to measure use of prescription medications and use of inpatient, outpatient, and emergency department care by PAP participants. Prescription claims were grouped into therapeutic categories. We generated descriptive statistics for key variables to examine health service utilization from 2009 through 2011. From 2009 through 2011, PAP served 7,180 patients from 81 counties in North Carolina. PAP users received a mean of 23 prescriptions, at an average cost of $754 per recipient per year. An average of $2.93 million per year was spent on the program, with an 8% rise in spending from 2009 to 2011. Inpatient care and emergency department care were utilized by 30% and 31% of PAP users, respectively, and there was minimal change in these rates over 3 years. Data were limited to medications dispensed through PAP and to health services provided by UNC Health Care. With the state's decision to not expand Medicaid, PAP will continue to be an important resource for North Carolina's low income citizens. | 25,237,867 | [
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Statistical analysis-based error models for the Microsoft Kinect(TM) depth sensor. | The stochastic error characteristics of the Kinect sensing device are presented for each axis direction. Depth (z) directional error is measured using a flat surface, and horizontal (x) and vertical (y) errors are measured using a novel 3D checkerboard. Results show that the stochastic nature of the Kinect measurement error is affected mostly by the depth at which the object being sensed is located, though radial factors must be considered, as well. Measurement and statistics-based models are presented for the stochastic error in each axis direction, which are based on the location and depth value of empirical data measured for each pixel across the entire field of view. The resulting models are compared against existing Kinect error models, and through these comparisons, the proposed model is shown to be a more sophisticated and precise characterization of the Kinect error distributions. | 25,237,896 | [
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TAp73 promotes cell survival upon genotoxic stress by inhibiting p53 activity. | p53 plays a key role in regulating DNA damage response by suppressing cell cycle progression or inducing apoptosis depending on extent of DNA damage. However, it is not clear why mild genotoxic stress favors growth arrest, whereas excessive lesions signal cells to die. Here we showed that TAp73, a p53 homologue thought to have a similar function as p53, restrains the transcriptional activity of p53 and prevents excessive activation of its downstream targets upon low levels of DNA damage, which results in cell cycle arrest. Extensive DNA damage triggers TAp73 depletion through ubiquitin/proteasome-mediated degradation of E2F1, leading to enhanced transcriptional activation by p53 and subsequent induction of apoptosis. These findings provide novel insights into the regulation of p53 function and suggest that TAp73 keeps p53 activity in check in regulating cell fate decisions upon genotoxic stress. | 25,237,903 | [
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Photoinduced hydrogen evolution by a pentapyridine cobalt complex: elucidating some mechanistic aspects. | A new hydrogen evolving cobalt catalyst 1 based on a pentapyridine ligand has been synthesized and characterized. Its photocatalytic activity in the presence of a Ru(bpy)3(2+) sensitizer and ascorbic acid as a sacrificial electron donor has been screened in purely buffered aqueous solutions showing TONs and TOFs strongly dependent on both catalyst concentration and pH with the best results obtained at 50 μM 1 and at pH 4 (TON = 187, TOF = 8.1 min(-1)). The photochemical mechanism, as revealed by flash photolysis, involves reaction of the excited sensitizer with ascorbic acid to yield Ru(bpy)3(+) as a primary photo-generated reductant, capable of electron transfer to 1 with a remarkable rate (bimolecular rate constant k = 5.7 (±0.7) × 10(9) M(-1) s(-1)). For hydrogen generation, two one-electron photochemical reduction steps of 1 are needed along with hydride formation and protonation. Under the experimental conditions used, hydrogen evolution is mainly limited by partial decomposition of both the sensitizer and the catalyst. Moreover, accumulation of the oxidation product of the ascorbic acid donor, dehydroascorbic acid, is observed to strongly decrease the hydrogen production yield. As shown by flash photolysis, this species is capable of quenching the reduced ruthenium species (k = 4.4 (±0.5) × 10(7) M(-1) s(-1)) thus competing with electron transfer to the catalyst. | 25,237,910 | [
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Newly licensed registered nurse job turnover and turnover intent. | Through survey data, this study examines job leaving behaviors of newly licensed registered nurses and identifies educational and managerial issues that need to be addressed to retain them. Within 1.5-2.5 years of graduating, one third of all respondents had left their first job, most for work-related reasons. Predictors of job leaving or intentions to leave included not having had a good orientation, information issues, having difficulties doing a good job, not being rewarded fairly, and low job satisfaction. | 25,237,913 | [
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Teaching nurses how to teach: strategies to enhance the quality of patient education. | This article describes the development of a training course for nurses that focused on teach-back as a key strategy for patient education. It describes evaluative methods used to collect feedback and determine effectiveness of education based on nurses' perception and self-assessment of their patient educational skills and improvements made for future courses. Professional Development Specialists can use the concepts in this article to create similar programs to improve the quality of patient education. | 25,237,917 | [
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Methods to estimate breeding values in honey bees. | Efficient methodologies based on animal models are widely used to estimate breeding values in farm animals. These methods are not applicable in honey bees because of their mode of reproduction. Observations are recorded on colonies, which consist of a single queen and thousands of workers that descended from the queen mated to 10 to 20 drones. Drones are haploid and sperms are copies of a drone's genotype. As a consequence, Mendelian sampling terms of full-sibs are correlated, such that the covariance matrix of Mendelian sampling terms is not diagonal. In this paper, we show how the numerator relationship matrix and its inverse can be obtained for honey bee populations. We present algorithms to derive the covariance matrix of Mendelian sampling terms that accounts for correlated terms. The resulting matrix is a block-diagonal matrix, with a small block for each full-sib family, and is easy to invert numerically. The method allows incorporating the within-colony distribution of progeny from drone-producing queens and drones, such that estimates of breeding values weigh information from relatives appropriately. Simulation shows that the resulting estimated breeding values are unbiased predictors of true breeding values. Benefits for response to selection, compared to an existing approximate method, appear to be limited (~5%). Benefits may however be greater when estimating genetic parameters. This work shows how the relationship matrix and its inverse can be developed for honey bee populations, and used to estimate breeding values and variance components. | 25,237,934 | [
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Tale of two diseases: amyotrophic lateral sclerosis and frontotemporal dementia. | Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) were independently described in clinical and pathological details more than a century ago. Recent breakthrough discoveries identifying common genes that are causal to either ALS or FTD or an overlapping ALS-FTD syndrome have dramatically transformed our view regarding their pathogenesis. Most recently, a massive hexanucleotide (GGGGCC) repeat expansion mutation in C9orf72 gene has been linked to the majority of familial ALS, FTD and mixed ALS-FTD cases. C9orf72 and other genes causal to ALS and FTD are consistently associated with the formation of cellular RNA inclusions and protein aggregates. This article summarizes the recently reported ALS-FTD-linked genes and the emerging common unifying mechanism in the pathogenesis of ALS-FTD spectrum disorders along with a comment on the potential new therapeutic targets in these hitherto incurable diseases. | 25,237,937 | [
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Evaluation of 1p and 14q status, MIB-1 labeling index and progesterone receptor immunoexpression in meningiomas: Adjuncts to histopathological grading and predictors of aggressive behavior. | Meningiomas are benign central nervous system tumors; however, significant fraction recurs, irrespective of histological grade. We performed fluorescence in-situ hybridization for 1p36 and 14q32, and immunohistochemistry for progesterone receptor (PR), p53 and MIB-1 on 84 meningiomas. Sixty-four were convexity tumors (30 grade I, 21 grade II, 13 grade III) and 20 petroclival (grade I; 10 with gross total resection (GTR), 10 with subtotal resection (STR)). Isolated 1p36 deletion was seen in 20% grade I, 28.6% grade II and 30.8% grade III convexity meningiomas, and isolated 14q deletion in one grade III convexity tumor. 1p/14q co-deletion was seen in none of grade I, 28.5% grade II and 30% grade III convexity meningiomas. PR immunoreactivity was less frequent in grade III tumors. Petroclival tumors did not show isolated deletion. However, 1p/14q co-deletion was seen in 20% of petroclival tumors with STR and in none with GTR. Frequency of chromosomal alterations and MIB-1 labeling index both increase with tumor grade. 1p/14q co-deletion is characteristic of grade II/III meningiomas, while PR immunoreactivity inversely correlates with grade, suggesting their use as surrogate markers for grading. Identification of 1p/14q co-deletion in grade I petroclival tumors with STR suggests that unresectable petroclival meningiomas are biologically more aggressive than their grade I convexity counterparts. | 25,237,942 | [
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Subarachnoid hemorrhage with blister aneurysms: Endovascular management. | Blister aneurysms of are rare lesions representing a real challenge for diagnosis and management. They typically show small size, hemispherical shape, fragile wall, broad neck, and are arising from non-branching sites of intracranial arteries. We retrospectively reviewed all aneurysms treated at our institution. Seventeen patients (6 male, 11 female) with 17 blister aneurysms were identified (mean age 53.3, range 41-63 years). Clinical, procedural, angiographic data as well as follow up data were evaluated. All patients presented with aneurysmal subarachnoid hemorrhage. Majority of the blister aneurysms were located in ICA while 1 was located at posterior cerebral artery, 1 at vertebral and 1 involving basilar artery. All patients were treated using single or overlapping stents and if possible additional coiling. There was no intra-operative rupture. Good outcome (mrs 0-2) was seen in 14 patients. Poor clinical outcome (mrs 3-5) was seen in 2 patients due to vasospasm induced ischemic deficits at discharge, both of them improved on follow up (mrs 1 on follow up). There were 3 mortalities, One patient died of rebleeding while other 2 died due to SAH induced complications. Follow-up angiography was available in 16 patients (one patient died before follow up angiogram) and revealed complete or near complete aneurysm occlusion in 11, incomplete obliteration in 1 and no change in 2 cases. Two cases showed post-treatment angiographic aneurysm recurrence. Both cases were managed with repeat coiling and overlapping stent placement. Endovascular management using single/overlapping stent and if possible coil placement is technically safe and feasible in blister aneurysms. Overlapping stents lead to better aneurysm occlusion than a single stent. Blister aneurysm in dorso-medial ICA showed higher tendency of continued growth/recurrence, higher incidence of clinical vasospasm and in these cases early angiographic follow-up is advisable. Repeat treatment should be considered promptly if necessary. | 25,237,945 | [
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Reduction in Pain and Inflammation Associated With Chronic Low Back Pain With the Use of the Medical Food Theramine. | Management of chronic back pain is a challenge for physicians. Although standard treatments exert a modest effect, they are associated with narcotic addiction and serious side effects from nonsteroidal antiinflammatory agents. Moreover, neurotransmitter depletion from both the pain syndrome and therapy may contribute to a poor treatment outcome. Neurotransmitter deficiency may be related both to increased turnover rate and inadequate neurotransmitter precursors from the diet, particularly for essential and semi-essential amino acids. Theramine, an amino acid blend 68405-1 (AAB), is a physician-prescribed only medical food. It contains neurotransmitter precursors and systems for increasing production and preventing attenuation of neurotransmitters. A double-blind controlled study of AAB, low-dose ibuprofen, and the coadministration of the 2 agents were performed. The primary end points included the Roland Morris index and Oswestry disability scale. The cohort included 122 patients aged between 18 and 75 years. The patients were randomized to 1 of 3 groups: AAB alone, ibuprofen alone, and the coadministration of the 2 agents. In addition, C-reactive protein, interleukin 6, and plasma amino acid concentrations were measured at baseline and 28 days time points. After treatment, the Oswestry Disability Index worsened by 4.52% in the ibuprofen group, improved 41.91% in the AAB group, and improved 62.15% in the combination group. The Roland Morris Index worsened by 0.73% in the ibuprofen group, improved by 50.3% in the AAB group, and improved 63.1% in the combination group. C-reactive protein in the ibuprofen group increased by 60.1%, decreased by 47.1% in the AAB group, and decreased by 36% in the combination group. Similar changes were seen in interleukin 6. Arginine, serine, histidine, and tryptophan levels were substantially reduced before treatment in the chronic pain syndrome and increased toward normal during treatment. There was a direct correlation between improvement in amino acid concentration and treatment response. Treatment with amino acid precursors was associated with substantial improvement in chronic back pain, reduction in inflammation, and improvement in back pain correlated with increased amino acid precursors to neurotransmitters in blood. | 25,237,981 | [
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Inhaled drug delivery in the hands of the patient. | Asthma and chronic obstructive pulmonary disease (COPD) are both diseases with an increasing prevalence worldwide. Inhaled therapy for these conditions has a number of advantages over systemic therapy, but requires the patients to use, and to master the use of, an inhaler device. However, many patients cannot use inhalers correctly, and over 50% of patients struggle to use a metered-dose inhaler properly. Poor inhaler technique is associated with a reduced asthma control, worst COPD outcomes, and wastage of economic resources. Of perhaps more concern is the fact that many health professionals also do not know how to use inhalers correctly and are therefore not in a position to coach patients effectively. Training patients and caregivers in the correct inhaler preparation and use is an essential component in the process toward achieving reliable and repeatable medication delivery. Instructions should be inhaler-specific, and they include instruction on how to load or prime the device. Providing only the leaflet that comes with the medicines does not lead to adequate inhalation technique, not even immediately after the patient has read the instructions and practiced with the inhaler. One-on-one sessions with health-care professionals probably represent the most effective educational method. However, it appears that, by itself, even repeated instruction could be insufficient to achieve improved adherence in the long term, as there is a tendency for patients or caregivers to forget what they have learned as time elapses since the training event. Thus, despite the development of several new and improved types of inhaler device, the evidence currently available points to little or no progress having been made with patients' ability to use their inhalers. As the range of drugs delivered by inhalation increases, inhaler technique checks and training need to be an integral part of the routine management of any patient with either asthma or COPD. | 25,238,005 | [
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[In-hospitaltraumamanagement - trauma suite diagnostics]. | Whole-body CT is considered gold standard for diagnosis of the multiple injured patient in the trauma suite. So far, no guidelines exist concerning its indication. The trauma team (Trauma Surgery/Visceral Surgery, Anaesthesiology, Radiology) should use standardized triage-criteria for the indication of whole-body CT. The radiologist is responsible for its individual planning, taking clinical and morphological imaging results into consideration, embedding its implementation between assessment and treatment stage. Fast image analysis by an experienced radiologist (specialist or at least 3 years professional experience) as well as interdisciplinary discussion of all findings is essential. The increased importance of endovascular minimally invasive therapy strategies in the treatment of active bleeding or laceration of solid organs may require the consultation of an interventional radiologist as part of the extended trauma team. In addition to CT, a modern trauma suite should be equipped with conventional x-rays and ultrasound in order to comply with a conventional algorithm consisting of sonography, plain film radiography and region specific CT for diagnosis of less severely injured patients. In children, specific attention must be paid to radiation protection. In these cases, modalities without radiation exposure (ultrasound, MRI) play a major role. Detecting all relevant injuries and evolving a therapy strategy in compliance with aspects of radiation protection (ALARA-principle) and legal guidelines (justifiying indication) during the 'golden hour of shock' should be the aim. | 25,238,013 | [
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Upconversion-agent induced improvement of g-C3N4 photocatalyst under visible light. | Herein, we report the use of upconversion agents to modify graphite carbon nitride (g-C3N4) by direct thermal condensation of a mixture of ErCl3·6H2O and the supramolecular precursor cyanuric acid-melamine. We show the enhancement of g-C3N4 photoactivity after Er(3+) doping by monitoring the photodegradation of Rhodamine B dye under visible light. The contribution of the upconversion agent is demonstrated by measurements using only a red laser. The Er(3+) doping alters both the electronic and the chemical properties of g-C3N4. The Er(3+) doping reduces emission intensity and lifetime, indicating the formation of new, nonradiative deactivation pathways, probably involving charge-transfer processes. | 25,238,039 | [
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The correlation of α-globin gene mutations and the XmnI polymorphism with clinical severity of Hb E/β-thalassemia. | Clinical severity assessment and molecular analysis of β-, α-globin genes and the -158 (C > T) XmnI polymorphism of the (G)γ-globin gene were performed in 80 pediatric patients with Hb E (HBB: c.79G > A)/β-thalassemia (β-thal) to investigate the effects of coinheritance of α-thalassemia (α-thal) and other molecular determinants on their clinical severity. The mean age was 9.4 ± 5.1 years. By using clinical severity score, 35 (43.8%), 27 (33.8%) and 18 cases (22.5%) had moderate, mild and severe disease, respectively. Nine β-thal mutations were identified. All were β⁰ or severe β⁺ mutations. Five patients (6.3%) had coinherited α⁰-thal. All five patients had mild disease with baseline hemoglobin (Hb) values of 7.9 ± 1.5 g/dL, mild hepatosplenomegaly and close-to-normal growth. Only one required a red blood cell transfusion. The disease severity was significantly different among the groups with and without α-thal (p = 0.025), but was not different among the groups with or without the XmnI polymorphism (p = 0.071). This study demonstrates that coinheritance of α⁰-thal alleviates the degree of disease severity in Hb E/β-thal. All our patients with coinherited α⁰-thal have mild disease. | 25,238,043 | [
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Gankyrin is a predictive and oncogenic factor in well-differentiated and dedifferentiated liposarcoma. | Liposarcoma is one of the most common histologic types of soft tissue sarcoma and is frequently an aggressive cancer with poor outcome. Hence, alternative approaches other than surgical excision are necessary to improve treatment of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). For this reason, we performed a two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry/mass spectrometry (MALDI-TOF/MS) analysis to identify new factors for WDLPS and DDLPS. Among the selected candidate proteins, gankyrin, known to be an oncoprotein, showed a significantly high level of expression pattern and inversely low expression of p53/p21 in WDLPS and DDLPS tissues, suggesting possible utility as a new predictive factor. Moreover, inhibition of gankyrin not only led to reduction of in vitro cell growth ability including cell proliferation, colony-formation, and migration, but also in vivo DDLPS cell tumorigenesis, perhaps via downregulation of the p53 tumor suppressor gene and its p21 target and also reduction of AKT/mTOR signal activation. This study identifies gankyrin, for the first time, as new potential predictive and oncogenic factor of WDLPS and DDLPS, suggesting the potential for service as a future LPS therapeutic approach. | 25,238,053 | [
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(Un)targeted metabolomics in Asteraceae: probing the applicability of essential-oil profiles of senecio L. (Senecioneae) taxa in chemotaxonomy. | The possible applicability of (un)targeted metabolomics (volatile metabolites) for revealing taxonomic/evolutionary relationships among Senecio L. species (Asteraceae; tribe Senecioneae) was explored. Essential-oil compositional data of selected Senecio/Senecioneae/Asteraceae taxa (93 samples in total) were mutually compared by means of multivariate statistical analysis (MVA), i.e., agglomerative hierarchical clustering and principal component analysis. The MVA input data set included the very first compositional data on the essential oil extracted from the aerial parts of S. viscosus L. as well as on four different Serbian populations of S. vernalis Waldst. & Kit. (oils from aerial parts and roots; eight samples in total). This metabolomic screening of Senecio/Senecioneae/Asteraceae species (herein presented results and data from the literature) pointed to short-chain alk-1-enes (e.g., oct-1-ene, non-1-ene, and undec-1-ene), with up to now restricted general occurrence in Plantae, as characteristic chemotaxonomic markers/targets for future metabolomic studies of Senecio/Senecioneae taxa. The MVA additionally showed that the evolution of the terpene metabolism (volatile mono- and sesquiterpenoids) within the Asteraceae tribe Senecioneae was not genera specific. However, the MVA did confirm plant-organ specific production/accumulation of volatiles within S. vernalis and suggested the existence of at least two volatile chemotypes for this species. | 25,238,075 | [
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The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. | Adaptation of malignant cells to the hostile milieu present in tumors is an important determinant of their survival and growth. However, the interaction between tumor-linked stress and antitumor immunity remains poorly characterized. Here, we show the critical role of the cellular stress sensor C/EBP-homologous protein (Chop) in the accumulation and immune inhibitory activity of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). MDSCs lacking Chop had decreased immune-regulatory functions and showed the ability to prime T cell function and induce antitumor responses. Chop expression in MDSCs was induced by tumor-linked reactive oxygen and nitrogen species and regulated by the activating-transcription factor-4. Chop-deficient MDSCs displayed reduced signaling through CCAAT/enhancer-binding protein-β, leading to a decreased production of interleukin-6 (IL-6) and low expression of phospho-STAT3. IL-6 overexpression restored immune-suppressive activity of Chop-deficient MDSCs. These findings suggest the role of Chop in tumor-induced tolerance and the therapeutic potential of targeting Chop in MDSCs for cancer immunotherapy. | 25,238,096 | [
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Ctla-4 modulates the differentiation of inducible Foxp3+ Treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis. | In vitro induced Foxp3+ T regulatory (iTreg) cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP)-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease. | 25,238,105 | [
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DNA barcoding of commercially important Grouper species (Perciformes, Serranidae) in the Philippines. | Fish identification is generally challenging because of their unpronounced and overlapping morphological characters which is true in grouper species. In the Philippines, an updated, reliable and accurate inventory of this high value commercial groupers has not been carried out previously. Using molecular tools in the identification and inventory of fish species in the country is confined to few laboratories and experts in the country. In this study, 27 species of the Serranidae family were identified from the grouper samples collected from major fish landing sites and markets in the Philippines. The grouper species were molecularly identified using the cytochrome c oxidase I (COI) sequences for DNA barcoding. The accuracy of the inferred species-level taxonomy based on COI is supported with high similarity search (98-100%) both in BOLD and BLAST, well-distributed genetic distance values and cohesive clustering in the Neighbor-Joining Tree. Aside from reinforcing the classical methodology of grouper identification in the country, this pioneering study on molecular identification of Philippine groupers constitutes a significant contribution to the DNA barcode library of Philippine marine fishes and to the global barcode entries in general, which can be used when dealing with grouper taxonomy, biodiversity, stock assessment and trade. The results reveal the different localities where the grouper species can be possibly sourced out in the country for trade and aquaculture purposes. Several of the grouper species are included in the IUCN Red List of Threatened Species. As a tool for conservation ecology, this study signals the implementation of sustainable fisheries management regulation to protect in particular those which are listed under the IUCN. | 25,238,110 | [
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Parallel alternating sliding knots are effective for ligation of mesenteric arteries during resection and anastomosis of the equine jejunum. | In literature only one article describes and compares methods of achieving hemostasis in equine mesenteric arteries during jejunal resection and anastomosis, and most textbooks favor ligating-dividing mechanical devices. The latter method cannot always be used, not least because the devices are expensive and in some cases even contra-indicated. Various types of knots, including sliding knots, are widely used to provide hemostasis in laparoscopy. Portions of jejunum with associated mesenteric vessels were collected from 12 horses at a local abattoir. These were divided into 24 specimens containing five mesenteric arteries each. Each artery was closed with a triple ligature. In group A, a surgeon's knot was used to tie the ligatures (two circumferential and one modified transfixing) while in group B all ligatures (three circumferential) were tied with a parallel alternating sliding knot. Both groups were divided ino two subgroups depending on suture material used (multifilament or monofilament suture material). Time to perform ligatures for every specimen were recorded and compared between groups. Ligation of mesenteric arteries was significantly faster to perform with sliding knots than with surgeon's knots, both with monofilament and multifilament suture material. With multifilament suture material, the leaking pressure of sliding knot ligatures was significantly higher than that of surgeon's knot ligatures. With monofilament suture, there were no statistically significant differences in leaking pressure between ligature methods. Both ligating methods were stronger with monofilament suture material than with multifilament suture material. Regardless of the ligature used, monofilament suture material performed better than multifilament suture material to achieve hemostatic knots. Independently of the suture material, the sliding knot is comparable or better than the surgeon's knot in providing hemostasis, and is faster to perform. | 25,238,115 | [
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Abdominal circumference or gastric residual volume as measure of feed intolerance in VLBW infants. | The aim of the study was to compare prefeed abdominal circumference (AC) and gastric residual volume (GRV) as a measure of feed intolerance in very-low-birth-weight infants (VLBW). Eighty VLBW infants were randomized to 2 groups; feed intolerance was monitored by measuring either GRV group or prefeed AC group. The primary outcome was time to full enteral feeds (180 mL · kg · day). Other main outcome measures were feed interruption days, duration of parenteral nutrition, incidence of culture positive sepsis, necrotizing enterocolitis, mortality, and duration of hospital stay. The median (interquartile range) time to achieve full feeds was 10 (9-13) versus 14 (12-17.5) days in AC and GRV groups, respectively (P < 0.001). Infants in AC group had fewer feed interruption days (0 [0-2] vs 2.0 [1, 5], P < 0.001) and shorter duration of parenteral nutrition (P < 0.001). The incidence of culture-positive sepsis in AC and GRV groups was 17.5% and 30 %, respectively (P = 0.18). Duration of hospital stay and mortality were comparable in both the groups. Prefeed AC as a measure of feed intolerance in VLBW infants may shorten the time taken to achieve full feeds. | 25,238,118 | [
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Bioactive hemicelluloses alkali-extracted from Fallopia sachalinensis leaves. | Fallopia sachalinensis, regarded as an invasive plant in Europe and designated for disposal, is traditionally used in Japan and China as herbal medicine. Attempted for valorization of the leaves, this paper reports on two protein-free polysaccharide fractions, a neutral (FS-5A) and an acidic (FS-5B) one, obtained via alkali extraction and consecutive purification. Both fractions were characterized by chemical, molecular, structural and bioactive properties. FTIR and 1D/2D NMR analyses revealed that FS-5A consisted of a fucogalactoxyloglucan, whereas, glucuronoxylan was the major hemicellulose in FS-5B accompanied with low proportions of fucosylated xyloglucan and pectic RG-I. Both hemicellulose fractions exhibited significant immunostimulating activity in the complement-fixation test and the latter had noticeable DPPH radical-scavenging ability. The results completed information about neutral and acidic bioactive polysaccharide components present in the leaves of F. sachalinensis. | 25,238,126 | [
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Bis(acetylacetonato)bis(pyrazolato)ruthenate(iii) as a redox-active scorpionate ligand. | The potential of a new anionic octahedral metal complex [Ru(III)(acac)2(pz)2](-) ((-)) (pzH = pyrazole) as a ligand with a scorpionate coordination behaviour like tris(pyrazolyl)borate (tp) and reversible redox activity is presented. Trinuclear metal complexes, [Ru(III)2Zn(II)(acac)4(pz)4] () and [Ru(II)Ru(III)2(acac)4(pz)4] (), were each synthesized by the reaction of ZnCl2 or Ru3(CO)12 with [Ru(III)(acac)2(pz)(pzH)] (H) that is in situ deprotonated and acts as a precursor of (-). Single-crystal X-ray diffraction studies clarified that (-) acts as a scorpionate ligand; two (-) units in and one unit in function as bidentate ligands with two pyrazolates as pincers, while another (-) unit in functions as a tridentate ligand with one oxygen atom as a tail in addition to the two pyrazolate pincers. Moreover, and showed reversible multi-stage redox behaviours based on the Ru(II)/Ru(III) and Ru(III)/Ru(IV) couples of the (-) units in the cyclic voltammetry (CV) measurements. Based on the X-ray, IR, and CV measurements and the comparison with other Ru(ii) complexes with tp derivatives, the (-) unit was found to act as a redox-active scorpionate with electron withdrawing properties compared to the tp. | 25,238,163 | [
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Pomegranate seed oil: Effect on 3-nitropropionic acid-induced neurotoxicity in PC12 cells and elucidation of unsaturated fatty acids composition. | Seed oils are used as cosmetics or topical treatment for wounds, allergy, dandruff, and other purposes. Natural antioxidants from plants were recently reported to delay the onset or progress of various neurodegenerative conditions. Over one thousand cultivars of Punica granatum (Punicaceae) are known and some are traditionally used to treat various ailments. The effect of pomegranate oil on 3-nitropropionic acid- (3-NP) induced cytotoxicity in rat pheochromocytoma (PC12) neuronal cells was analyzed in this study. Furthermore, the analysis of unsaturated fatty acid composition of the seed oil of pomegranate by gas chromatography-electron impact mass spectrometry (GC-MS) was done. GC-MS study showed the presence of 6,9-octadecadiynoic acid (C18:2(6,9)) as a major component (60%) as 4,4-dimethyloxazoline derivative. The total extractable oil with light petroleum ether by Soxhlet from the dry seed of P. granatum was 4-6%. The oil analyzed for 48.90 ± 1.50 mg gallic acid equivalents/g of oil, and demonstrated radical-scavenging-linked antioxidant activities in various in vitro assays like the DPPH (2,2-diphenyl-l-picrylhydrazyl, % IP = 35.2 ± 0.9%), ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), % IP 2.2 ± 0.1%), and β-carotene bleaching assay (% IP = 26 ± 3%), respectively, which could be due the possible role of one methylene interrupted diynoic acid system for its radical-scavenging/antioxidant properties of oil. The oil also reduced lipid peroxidation, suppressed reactive oxygen species, extracellular nitric oxide, lactate/pyruvate ratio, and lactase dehydrogenase generated by 3-NP- (100 mM) induced neurotoxicity in PC12 cells, and enhanced the levels of enzymatic and non-enzymatic antioxidants at 40 μg of gallic acid equivalents. The protective effect of pomegranate seed oil might be due to the ability of an oil to neutralize ROS or enhance the expression of antioxidant gene and the exact mechanism of action yet to be elucidated. | 25,238,165 | [
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Adenocarcinoma in situ of the uterine cervix--a systematic review. | This study aimed to review literature if therapeutic strategies in adenocarcinoma in situ of the cervix could lead to a more conservative approach. A review of the literature was conducted using a Medline search for articles published between 1966 and 2013. Thirty-five studies showed that after a radical cone, 16.5% residual disease in the re-cone or uterus was found. After cone with positive margins, residual abnormalities were found in 49.3%. Thirty-seven studies showed 5% recurrence rate after conservative therapy (large loop excision transformation zone-cold knife conization. After conization with negative margins, the risk of recurrence was 3%. Adenocarcinoma in situ is a relatively rare premalignant but increasingly frequent lesion of the cervix. Although there is a risk of relapse (3%) with a chance of malignancy (<1%), this risk is so small that conservative treatment with negative margins by large loop excision transformation zone or cold knife conization is justified and justifiable not only for women to have children. | 25,238,167 | [
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High resolution 3D diffusion cardiovascular magnetic resonance of carotid vessel wall to detect lipid core without contrast media. | Without the need of contrast media, diffusion-weighted imaging (DWI) has shown great promise for accurate detection of lipid-rich necrotic core (LRNC), a well-known feature of vulnerable plaques. However, limited resolution and poor image quality in vivo with conventional single-shot diffusion-weighted echo planar imaging (SS-DWEPI) has hindered its clinical application. The aim of this work is to develop a diffusion-prepared turbo-spin-echo (DP-TSE) technique for carotid plaque characterization with 3D high resolution and improved image quality. Unlike SS-DWEPI where the diffusion encoding is integrated in the EPI framework, DP-TSE uses a diffusion encoding module separated from the TSE framework, allowing for segmented acquisition without the sensitivity to phase errors. The interleaved, motion-compensated sequence was designed to enable 3D black-blood DWI of carotid arteries with sub-millimeter resolution. The sequence was tested on 12 healthy subjects and compared with SS-DWEPI for image quality, vessel wall visibility, and vessel wall thickness measurements. A pilot study was performed on 6 patients with carotid plaques using this sequence and compared with conventional contrast-enhanced multi-contrast 2D TSE as the reference. DP-TSE demonstrated advantages over SS-DWEPI for resolution and image quality. In the healthy subjects, vessel wall visibility was significantly higher with diffusion-prepared TSE (p < 0.001). Vessel wall thicknesses measured from diffusion-prepared TSE were on average 35% thinner than those from the EPI images due to less distortion and partial volume effect (p < 0.001). ADC measurements of healthy carotid vessel wall are 1.53 ± 0.23 × 10-3 mm2/s. In patients the mean ADC measurements in the LRNC area were significantly lower (0.60 ± 0.16 × 10-3 mm2/s) than those of the fibrous plaque tissue (1.27 ± 0.29 × 10-3 mm2/s, p < 0.01). Diffusion-prepared CMR allows, for the first time, 3D DWI of the carotid arterial wall in vivo with high spatial resolution and improved image quality over SS-DWEPI. It can potentially detect LRNC without the use of contrast agents, allowing plaque characterization in patients with renal insufficiency. | 25,238,168 | [
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Gastric cancer following bariatric surgery: a review. | Bariatric procedures can induce a massive weight loss that lasts for >15 years after surgery; in addition, they achieve important metabolic effects including diabetes resolution in the majority of morbidly obese patients. However, some bariatric interventions may cause gastroesophageal reflux disease and other serious complications. The aim of our study is to evaluate the risk of cancer after bariatric surgery. We conducted a review of the literature about the cases of gastric cancer arising after any bariatric procedure, including a case of adenocarcinoma incidentally discovered by the authors 6 months after laparoscopic adjustable gastric banding. Globally, 17 case reports describing 18 patients were retrieved, including the case study by the authors. The diagnosis of tumor was at a mean of 8.6 years after bariatric surgery, 9.3 years after RYGB, and 8.1 years after restrictive procedures. The adenocarcinoma represented most cases (15 patients, 83%). In the patients with RYGB, the adenocarcinoma was localized in the excluded stomach in 5 patients (83%) and in the pouch in 1 patient (17%). After a restrictive procedure, the cancer was localized in the pouch in 5 patients (62.5%), in the pylorus in 2 patients (25%), and in lesser curvature only in 1 patient (12.5%). There is a lack of evidence about a connection between the late occurrence of gastric adenocarcinoma and the bariatric surgery. For this reason, although the preoperative upper endoscopy is still mandatory, there is no need for a regular endoscopic evaluation of patients after surgery. | 25,238,176 | [
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High performance sulfur, nitrogen and carbon doped mesoporous anatase-brookite TiO₂ photocatalyst for the removal of microcystin-LR under visible light irradiation. | Carbon, nitrogen and sulfur (C, N and S) doped mesoporous anatase-brookite nano-heterojunction titania photocatalysts have been synthesized through a simple sol-gel method in the presence of triblock copolymer Pluronic P123. XRD and Raman spectra revealed the formation of anatase and brookite mixed phases. XPS spectra indicated the presence of C, N and S dopants. The TEM images demonstrated the formation of almost monodisperse titania nanoparticles with particle sizes of approximately 10nm. N2 isotherm measurements confirmed that both doped and undoped titania anatase-brookite materials have mesoporous structure. The photocatalytic degradation of the cyanotoxin microcystin-LR (MC-LR) has been investigated using these novel nanomaterials under visible light illumination. The photocatalytic efficiency of the mesoporous titania anatase-brookite photocatalyst dramatically increased with the addition of the C, N and S non-metal, achieving complete degradation (∼ 100 %) of MC-LR. The results demonstrate the advantages of the synthetic approach and the great potential of the visible light activated C, N, and S doped titania photocatalysts for the treatment of organic micropollutants in contaminated waters under visible light. | 25,238,189 | [
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Nanoparticle tension probes patterned at the nanoscale: impact of integrin clustering on force transmission. | Herein we aimed to understand how nanoscale clustering of RGD ligands alters the mechano-regulation of their integrin receptors. We combined molecular tension fluorescence microscopy with block copolymer micelle nanolithography to fabricate substrates with arrays of precisely spaced probes that can generate a 10-fold fluorescence response to pN-forces. We found that the mechanism of sensing ligand spacing is force-mediated. This strategy is broadly applicable to investigating receptor clustering and its role in mechanotransduction pathways. | 25,238,229 | [
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