title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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A semi-dominant mutation in the general splicing factor SF3a66 causes anterior-posterior axis reversal in one-cell stage C. elegans embryos. | Establishment of anterior-posterior polarity in one-cell stage Caenorhabditis elegans embryos depends in part on astral microtubules. As the zygote enters mitosis, these microtubules promote the establishment of a posterior pole by binding to and protecting a cytoplasmic pool of the posterior polarity protein PAR-2 from phosphorylation by the cortically localized anterior polarity protein PKC-3. Prior to activation of the sperm aster, the oocyte Meiosis I and II spindles assemble and function, usually at the future anterior pole, but these meiotic spindle microtubules fail to establish posterior polarity through PAR-2. Here we show that a semi-dominant mutation in the general splicing factor SF3a66 can lead to a reversed axis of AP polarity that depends on PAR-2 and possibly on close proximity of oocyte meiotic spindles with the cell cortex. One possible explanation is that reduced levels of PKC-3, due to a general splicing defect, can result in axis reversal due to a failure to prevent oocyte meiotic spindle microtubules from interfering with AP axis formation. | 25,188,372 | [
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Emergence of assortative mixing between clusters of cultured neurons. | The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, as well as a rich-club core, which shapes a 'connectivity backbone' in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture. | 25,188,377 | [
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When is spillover from marine reserves likely to benefit fisheries? | The net movement of individuals from marine reserves (also known as no-take marine protected areas) to the remaining fishing grounds is known as spillover and is frequently used to promote reserves to fishers on the grounds that it will benefit fisheries. Here we consider how mismanaged a fishery must be before spillover from a reserve is able to provide a net benefit for a fishery. For our model fishery, density of the species being harvested becomes higher in the reserve than in the fished area but the reduction in the density and yield of the fished area was such that the net effect of the closure was negative, except when the fishery was mismanaged. The extent to which effort had to exceed traditional management targets before reserves led to a spillover benefit varied with rates of growth and movement of the model species. In general, for well-managed fisheries, the loss of yield from the use of reserves was less for species with greater movement and slower growth. The spillover benefit became more pronounced with increasing mis-management of the stocks remaining available to the fishery. This model-based result is consistent with the literature of field-based research where a spillover benefit from reserves has only been detected when the fishery is highly depleted, often where traditional fisheries management controls are absent. We conclude that reserves in jurisdictions with well-managed fisheries are unlikely to provide a net spillover benefit. | 25,188,380 | [
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Characterization of a spontaneous retinal neovascular mouse model. | Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease. | 25,188,381 | [
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Combined use of systemic agents for psoriasis: a systematic review. | Combined use of systemic agents may be necessary to achieve disease control in therapy-resistant patients. However, to our knowledge, an overview of evidence, including quality assessments, is not yet available, and no guidance on monitoring, contraindications, and interactions exists. To summarize and critically appraise the evidence on efficacy and safety of combination therapy with systemic agents in plaque-type psoriasis. Through March 2013, an electronic search limited to randomized clinical trials was performed in MEDLINE, EMBASE, The Cochrane Library, and ongoing trial registers. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. The initial search retrieved 2583 records, of which 17 met the inclusion criteria. Most studies favored combination therapy, albeit with low significance and low quality of evidence. Etanercept plus methotrexate was the only combination therapy investigated with an adequate sample size (n = 478). In the short term, this combination had superior efficacy with a moderate quality of evidence compared with etanercept monotherapy (Psoriasis Area and Severity Index, 75; relative risk, 1.28; 95% CI, 1.14-1.45). Although this finding coincided with an increase in adverse events (relative risk, 1.25; 95% CI, 1.10-1.42), the overall safety profile remained acceptable. This systematic review provides a comprehensive overview on the validity of different systemic combination therapies. For most combinations, insufficient evidence is available. Initial results indicate that combined therapy with etanercept plus methotrexate may be beneficial in patients that are therapy resistant under intensive follow-up. Dose reductions should be taken into account to minimize adverse effects. | 25,188,393 | [
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Tissue-specific RNA expression marks distant-acting developmental enhancers. | Short non-coding transcripts can be transcribed from distant-acting transcriptional enhancer loci, but the prevalence of such enhancer RNAs (eRNAs) within the transcriptome, and the association of eRNA expression with tissue-specific enhancer activity in vivo remain poorly understood. Here, we investigated the expression dynamics of tissue-specific non-coding RNAs in embryonic mouse tissues via deep RNA sequencing. Overall, approximately 80% of validated in vivo enhancers show tissue-specific RNA expression that correlates with tissue-specific enhancer activity. Globally, we identified thousands of tissue-specifically transcribed non-coding regions (TSTRs) displaying various genomic hallmarks of bona fide enhancers. In transgenic mouse reporter assays, over half of tested TSTRs functioned as enhancers with reproducible activity in the predicted tissue. Together, our results demonstrate that tissue-specific eRNA expression is a common feature of in vivo enhancers, as well as a major source of extragenic transcription, and that eRNA expression signatures can be used to predict tissue-specific enhancers independent of known epigenomic enhancer marks. | 25,188,404 | [
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The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review and meta-analysis. | Several studies have suggested that neuron-specific enolase (NSE) in serum may be a biomarker of traumatic brain injury. However, whether serum NSE levels correlate with outcomes remains unclear. The purpose of this review was to evaluate the prognostic value of serum NSE protein after traumatic brain injury. PubMed and Embase were searched for relevant studies published up to October 2013. Full-text publications on the relationship of NSE to TBI were included if the studies concerned patients with closed head injury, NSE levels in serum after injury, and Glasgow Outcome Scale (GOS) or Extended GOS (GOSE) scores or mortality. Study design, inclusion criteria, assay, blood sample collection time, NSE cutoff, sensitivity and specificity of NSE for mortality prediction (if sufficient information was provided to calculate these values), and main outcomes were recorded. Sixteen studies were eligible for the current meta-analysis. In the six studies comparing NSE concentrations between TBI patients who died and those who survived, NSE concentrations correlated with mortality (M.D. 0.28, 95% confidence interval (CI), 0.21 to 0.34; I2 55%). In the eight studies evaluating GOS or GOSE, patients with unfavorable outcomes had significantly higher NSE concentrations than those with favorable outcomes (M.D. 0.24, 95% CI, 0.17 to 0.31; I2 64%). From the studies providing sufficient data, the pooled sensitivity and specificity for mortality were 0.79 and 0.50, and 0.72 and 0.66 for unfavorable neurological prognosis, respectively. The areas under the SROC curve (AUC) of NSE concentrations were 0.73 (95% CI, 0.66-0.80) for unfavorable outcome and 0.76 (95% CI, 0.62-0.90) for mortality. Mortality and unfavorable outcome were significantly associated with greater NSE concentrations. In addition, NSE has moderate discriminatory ability to predict mortality and neurological outcome in TBI patients. The optimal discrimination cutoff values and optimal sampling time remain uncertain because of significant variations between studies. | 25,188,406 | [
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Role of the DNA base excision repair protein, APE1 in cisplatin, oxaliplatin, or carboplatin induced sensory neuropathy. | Although chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of platinum drugs, the mechanisms of this toxicity remain unknown. Previous work in our laboratory suggests that cisplatin-induced CIPN is secondary to DNA damage which is susceptible to base excision repair (BER). To further examine this hypothesis, we studied the effects of cisplatin, oxaliplatin, and carboplatin on cell survival, DNA damage, ROS production, and functional endpoints in rat sensory neurons in culture in the absence or presence of reduced expression of the BER protein AP endonuclease/redox factor-1 (APE1). Using an in situ model of peptidergic sensory neuron function, we examined the effects of the platinum drugs on hind limb capsaicin-evoked vasodilatation. Exposing sensory neurons in culture to the three platinum drugs caused a concentration-dependent increase in apoptosis and cell death, although the concentrations of carboplatin were 10 fold higher than cisplatin. As previously observed with cisplatin, oxaliplatin and carboplatin also increased DNA damage as indicated by an increase in phospho-H2AX and reduced the capsaicin-evoked release of CGRP from neuronal cultures. Both cisplatin and oxaliplatin increased the production of ROS as well as 8-oxoguanine DNA adduct levels, whereas carboplatin did not. Reducing levels of APE1 in neuronal cultures augmented the cisplatin and oxaliplatin induced toxicity, but did not alter the effects of carboplatin. Using an in vivo model, systemic injection of cisplatin (3 mg/kg), oxaliplatin (3 mg/kg), or carboplatin (30 mg/kg) once a week for three weeks caused a decrease in capsaicin-evoked vasodilatation, which was delayed in onset. The effects of cisplatin on capsaicin-evoked vasodilatation were attenuated by chronic administration of E3330, a redox inhibitor of APE1 that serendipitously enhances APE1 DNA repair activity in sensory neurons. These outcomes support the importance of the BER pathway, and particularly APE1, in sensory neuropathy caused by cisplatin and oxaliplatin, but not carboplatin and suggest that augmenting DNA repair could be a therapeutic target for CIPN. | 25,188,410 | [
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Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data. | Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT). The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets) and network information (IMPACT-modules). Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1) handles multiple profiles per gene, (2) rescues genes with weak phenotypes and (3) accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens. | 25,188,415 | [
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The relation between resting state connectivity and creativity in adolescents before and after training. | An important component of creativity is divergent thinking, which involves the ability to generate novel and useful problem solutions. In this study, we tested the relation between resting-state functional connectivity of brain areas activated during a divergent thinking task (i.e., supramarginal gyrus, middle temporal gyrus, medial frontal gyrus) and the effect of practice in 32 adolescents aged 15-16. Over a period of two weeks, an experimental group (n = 16) conducted an 8-session Alternative Uses Task (AUT) training and an active control group (n = 16) conducted an 8-session rule switching training. Resting-state functional connectivity was measured before (pre-test) and after (post-test) training. Across groups at pre-test, stronger connectivity between the middle temporal gyrus and bilateral postcentral gyrus was associated with better divergent thinking performance. The AUT-training, however, did not significantly change functional connectivity. Post hoc analyses showed that change in divergent thinking performance over time was predicted by connectivity between left supramarginal gyrus and right occipital cortex. These results provide evidence for a relation between divergent thinking and resting-state functional connectivity in a task-positive network, taking an important step towards understanding creative cognition and functional brain connectivity. | 25,188,416 | [
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Noise-induced hearing loss: an occupational medicine perspective. | Up to 30 million workers in the United States are exposed to potentially detrimental levels of noise. Although reliable medications for minimizing or reversing noise-induced hearing loss (NIHL) are not currently available, NIHL is entirely preventable. The purpose of this article is to review the epidemiology and pathophysiology of occupational NIHL. We will focus on at-risk populations and discuss prevention programs. Current prevention programs focus on reducing inner ear damage by minimizing environmental noise production and through the use of personal hearing protective devices. NIHL is the result of a complex interaction between environmental factors and patient factors, both genetic and acquired. The effects of noise exposure are specific to an individual. Trials are currently underway evaluating the role of antioxidants in protection from, and even reversal of, NIHL. Occupational NIHL is the most prevalent occupational disease in the United States. Occupational noise exposures may contribute to temporary or permanent threshold shifts, although even temporary threshold shifts may predispose an individual to eventual permanent hearing loss. Noise prevention programs are paramount in reducing hearing loss as a result of occupational exposures. | 25,188,429 | [
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Natural history, presentation, and diagnosis of hidradenitis suppurativa. | The diagnosis of hidradenitis suppurativa (HS) is based on a characteristic history and physical exam. The anatomic sites of involvement include the axillae (most common), groin, and buttocks, and the perianal, perineal, and mammary regions. Initially, HS manifests with open comedones (usually with two or more "heads") and tender subcutaneous acneiform papules. Without intervention, the natural history of HS is chronic and progressive. More painful subcutaneous nodules form, which rupture and drain a thick, mucopurulent, foul-smelling fluid. Later, sinus tracts form, and, over time, ropelike fibrotic subcutaneous scarring occurs, which can lead to disabling contractures of the affected limbs. Clinically, the severity of disease is classified using the Hurley staging system, which provides guidance for choosing among treatment options. | 25,188,458 | [
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Improved adverse postoperative outcomes with revised American College of Cardiology/American Heart Association guidelines for patients with cardiac stents. | In 2007, the American College of Cardiology/American Heart Association guidelines were revised for patients with cardiac stents in need of subsequent surgery to recommend delaying elective noncardiac surgery by 365 days in patients with drug-eluting stents (DESs). To examine the effect of the guidelines on postoperative major adverse cardiac events (MACEs) in subsequent noncardiac surgery. Patients receiving a cardiac stent between fiscal years 2005 and 2010 were identified by International Classification of Diseases, Ninth Revision diagnosis codes in the Veterans Affairs Medical SAS data sets. The Veterans Affairs Surgical Quality Improvement Program data were used to identify subsequent operations in the 2 years following stenting. The preguideline period was defined as fiscal years 2005 through 2007 and the postguideline period was defined as fiscal years 2008 through 2010. Surgery patients admitted through the emergency department or transferred from another hospital were excluded from analyses. Overall, 16,634 elective noncardiac operations were identified (8034 [48.3%] in the preguideline period; 8600 [51.7%] in the postguideline period). Composite 30-day postoperative MACEs. We used χ² tests to examine differences in bivariate frequencies and used logistic models to examine adjusted associations with 2-year postoperative MACEs. The median time to surgery was 364 days (interquartile range, 184-528 days). A total of 11,026 operations (66.3%) followed DES placement, and 5608 (33.7%) followed bare metal stent placement. After the guidelines' publication, surgery timing increased following DES placement from 323 to 404 days (P < .001) and decreased following bare metal stent placement from 402 to 309 days (P < .001). In addition, postoperative MACE rates decreased from 4.2% to 3.3% (P = .002). After adjusting for cardiac risk factors and procedure characteristics, there was an overall absolute risk reduction of 0.9% for MACEs (odds ratio = 0.74; 95% CI, 0.62-0.89). On further examination of trends across time, MACE rates with DES placement began to decrease prior to the guidelines' publication from 5.5% in 2005 to 4.3% in 2006 and remained stable through 2010. In contrast, MACE rates with bare metal stent placement increased from 4.3% in 2005 to 8.0% in 2007 but decreased to 4.8% following the guidelines' publication. After the guidelines' publication, noncardiac surgery was delayed in patients with DESs but not bare metal stents. With a 26% reduction in MACEs following the guidelines, it would appear that the guidelines did improve postoperative outcomes; however, when examined over time, it becomes evident that there are many more factors influencing management of patients with cardiac stents in need of subsequent surgery. | 25,188,466 | [
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Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. | In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. These are commonly used in the treatment of relapsed/refractory (R/R) multiple myeloma (MM), but there is no universally accepted standard treatment. Salvage therapy must be tailored according to an individual patient's clinical profile, with the risks and potential effects of treatment-related adverse events being major determinants of the choice of therapy. Two novel agents in phase II studies to investigate their potential for the treatment of R/R MM are carfilzomib, a selective, irreversible next-generation PI, and pomalidomide, a next-generation thalidomide analog. This review will discuss the side-effect profiles of the currently approved immunomodulatory agents and bortezomib, as well as those of the newer agents, carfilzomib and pomalidomide. | 25,188,481 | [
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Validity and reliability assessment of detailed scoring checklists for use during perioperative emergency simulation training. | Few valid and reliable grading checklists have been published for the evaluation of performance during simulated high-stakes perioperative event management. As such, the purposes of this study were to construct valid scoring checklists for a variety of perioperative emergencies and to determine the reliability of scores produced by these checklists during continuous video review. A group of anesthesiologists, intensivists, and educators created a set of simulation grading checklists for the assessment of the following scenarios: severe anaphylaxis, cerebrovascular accident, hyperkalemic arrest, malignant hyperthermia, and acute coronary syndrome. Checklist items were coded as critical or noncritical. Nonexpert raters evaluated 10 simulation videos in a random order, with each video being graded 4 times. A group of faculty experts also graded the videos to create a reference standard to which nonexpert ratings were compared. P < 0.05 was considered significant. Team leaders in the simulation videos were scored by the expert panel as having performed 56.5% of all items on the checklist (range, 43.8%-84.0%), and 67.2% of the critical items (range, 30.0%-100%). Nonexpert raters agreed with the expert assessment 89.6% of the time (95% confidence interval, 87.2%-91.6%). No learning curve development was found with repetitive video assessment or checklist use. The κ values comparing nonexpert rater assessments to the reference standard averaged 0.76 (95% confidence interval, 0.71-0.81). The findings indicate that the grading checklists described are valid, are reliable, and could be used in perioperative crisis management assessment. | 25,188,486 | [
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MYCN repression of Lifeguard/FAIM2 enhances neuroblastoma aggressiveness. | Neuroblastoma (NBL) is the most common solid tumor in infants and accounts for 15% of all pediatric cancer deaths. Several risk factors predict NBL outcome: age at the time of diagnosis, stage, chromosome alterations and MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-Derived Homolog) amplification, which characterizes the subset of the most aggressive NBLs with an overall survival below 30%. MYCN-amplified tumors develop exceptional chemoresistance and metastatic capacity. These properties have been linked to defects in the apoptotic machinery, either by silencing components of the extrinsic apoptotic pathway (e.g. caspase-8) or by overexpression of antiapoptotic regulators (e.g. Bcl-2, Mcl-1 or FLIP). Very little is known on the implication of death receptors and their antagonists in NBL. In this work, the expression levels of several death receptor antagonists were analyzed in multiple human NBL data sets. We report that Lifeguard (LFG/FAIM2 (Fas apoptosis inhibitory molecule 2)/NMP35) is downregulated in the most aggressive and undifferentiated tumors. Intringuingly, although LFG has been initially characterized as an antiapoptotic protein, we have found a new association with NBL differentiation. Moreover, LFG repression resulted in reduced cell adhesion, increased sphere growth and enhanced migration, thus conferring a higher metastatic capacity to NBL cells. Furthermore, LFG expression was found to be directly repressed by MYCN at the transcriptional level. Our data, which support a new functional role for a hitherto undiscovered MYCN target, provide a new link between MYCN overexpression and increased NBL metastatic properties. | 25,188,511 | [
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Correction: AKT Inhibitors Promote Cell Death in Cervical Cancer through Disruption of mTOR Signaling and Glucose Uptake. | [This corrects the article DOI: 10.1371/journal.pone.0092948.]. | 25,188,521 | [
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Challenges in defining and categorizing falls on diverse unit types: lessons from expansion of the NDNQI Falls Indicator. | In 2012, the National Database of Nursing Quality Indicators launched a project to expand its falls indicator for use on pediatric, neonatal, and psychiatric units. We discuss challenges encountered, argue that schemes for categorizing falls by cause or supposed preventability are not suitable for large-scale efforts to track and prevent falls, express concern about the growing burden of collecting increasingly granular quality data, and discuss limitations of total and injurious fall rates as quality measures. | 25,188,525 | [
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Ophthalmic patients' utilization of technology and social media: an assessment to improve quality of care. | E-health tools have the potential to improve the quality of care for ophthalmic patients, many of whom have chronic conditions. However, little research has assessed ophthalmic patients' use or acceptance of technological devices and social media platforms for health-related purposes. The present study evaluated utilization of technological devices and social media platforms by eye clinic patients, as well as their willingness to receive health reminders through these technologies. A 31-item paper questionnaire was administered to eye clinic patients (n=843) at an urban, tertiary-care center. Questions focused on technology ownership, comfort levels, frequency of use, and preferences for receiving health reminders. Demographic data were also recorded. Eye clinic patients most commonly owned cellular phones (90%), landline phones (81%), and computers (80%). Overall, eye clinic patients preferred to receive health reminders through phone calls and e-mail and used these technologies frequently and with a high level of comfort. Less than 3% of patients preferred using social networking to receive health reminders. In addition, age was significantly associated with technology ownership, comfort level, and frequency of use (p<0.05). The majority of patients 18-45 years of age preferred to receive appointment reminders via text message (57%) and e-mail (53%). This age group also used these technologies more frequently and with a higher comfort level (p<0.001). These data support the proposal that e-mail and text-messaging e-health tools are likely to be immediately adopted by eye clinic patients and therefore have the greatest potential to improve health outcomes and increase quality of care. Eye clinic patients are interested in these technologies for appointment reminders, general eye and vision health information, asking urgent medical questions, and requesting prescription refills. Future controlled trials could further explore the efficacy of e-health tools for these purposes. | 25,188,532 | [
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Role of fat and adipokines in intestinal inflammation. | This review summarizes current knowledge on the contribution of mesenteric adipose tissue in intestinal inflammation. We will describe the cellular and humoral characteristics of creeping fat, their potential impact for Crohn's disease and propose a working model for the critical interplay between the creeping fat and the inflamed intestine. Creeping fat can be distinguished from healthy adipose tissue by its distinctively small adipocytes, by a specific microenvironment defined by high levels of adipokines and by a dominant immune cell infiltration. In Crohn's disease transmural inflammation facilitates increased bacterial translocation into the creeping fat. Translocalizing antigens can directly activate (pre)adipocytes via innate receptors. Adipocyte-derived mediators modulate phenotype and function of innate and adaptive immune cells. Activated (pre)adipocytes and adipokine-modulated immune cells might support a degree of inflammatory activation within the creeping fat that allows competent immune defense against exogenous factors while preventing systemic inflammation. Fat tissue as an active organ in health and disease has been ignored for too long. The last few years of research provided evidence for the complex metabolic and immunological functions of adipose tissue. On the basis of the available data, creeping fat in Crohn's disease exerts a protective function by a localized anti-inflammatory effect, thus preventing a systemic inflammatory response. | 25,188,546 | [
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Emerging medical informatics research trends detection based on MeSH terms. | The aim of this study is to analyze the research trends of medical informatics over the last 12 years. A new method based on MeSH terms was proposed to identify emerging topics and trends of medical informatics research. Informetric methods and visualization technologies were applied to investigate research trends of medical informatics. The metric of perspective factor (PF) embedding MeSH terms was appropriately employed to assess the perspective quality for journals. The emerging MeSH terms have changed dramatically over the last 12 years, identifying two stages of medical informatics: the "medical imaging stage" and the "medical informatics stage". The focus of medical informatics has shifted from acquisition and storage of healthcare data by integrating computational, informational, cognitive and organizational sciences to semantic analysis for problem solving and clinical decision-making. About 30 core journals were determined by Bradford's Law in the last 3 years in this area. These journals, with high PF values, have relative high perspective quality and lead the trend of medical informatics. | 25,188,551 | [
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Therapeutic effect of dynamic interpersonal group psychotherapy for taiwanese patients with depressive disorder. | This study investigated the therapeutic effects of dynamic interpersonal group psychotherapy (DIGP) for the depressed in Taiwan. A 16-session DIGP was held weekly, and participants were evaluated with the Hamilton Depression Rating Scale, Taiwanese Depression Questionnaire, and World Health Organization Quality of Life-BREF before and after DIGP. Compared with control group, the patients treated with DIGP showed significant improvement in severity of their depression, especially in the somatic subscale and quality of life regarding psychological health. We found that focusing on repairing interpersonal interaction in DIGP would improve the social interaction problems of Chinese with depressive disorder. | 25,188,566 | [
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RNA graph partitioning for the discovery of RNA modularity: a novel application of graph partition algorithm to biology. | Graph representations have been widely used to analyze and design various economic, social, military, political, and biological networks. In systems biology, networks of cells and organs are useful for understanding disease and medical treatments and, in structural biology, structures of molecules can be described, including RNA structures. In our RNA-As-Graphs (RAG) framework, we represent RNA structures as tree graphs by translating unpaired regions into vertices and helices into edges. Here we explore the modularity of RNA structures by applying graph partitioning known in graph theory to divide an RNA graph into subgraphs. To our knowledge, this is the first application of graph partitioning to biology, and the results suggest a systematic approach for modular design in general. The graph partitioning algorithms utilize mathematical properties of the Laplacian eigenvector (µ2) corresponding to the second eigenvalues (λ2) associated with the topology matrix defining the graph: λ2 describes the overall topology, and the sum of µ2's components is zero. The three types of algorithms, termed median, sign, and gap cuts, divide a graph by determining nodes of cut by median, zero, and largest gap of µ2's components, respectively. We apply these algorithms to 45 graphs corresponding to all solved RNA structures up through 11 vertices (∼ 220 nucleotides). While we observe that the median cut divides a graph into two similar-sized subgraphs, the sign and gap cuts partition a graph into two topologically-distinct subgraphs. We find that the gap cut produces the best biologically-relevant partitioning for RNA because it divides RNAs at less stable connections while maintaining junctions intact. The iterative gap cuts suggest basic modules and assembly protocols to design large RNA structures. Our graph substructuring thus suggests a systematic approach to explore the modularity of biological networks. In our applications to RNA structures, subgraphs also suggest design strategies for novel RNA motifs. | 25,188,578 | [
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Preoperative anemia does not predict complications after single-level lumbar fusion: a propensity score-matched multicenter study. | Multicenter retrospective cohort study. To estimate the impact of preoperative anemia on 30-day complications in patients undergoing single-level lumbar fusion. Anemia has been widely implicated as a risk factor in various surgical procedures including elective spine surgery. No large-scale study has been performed to examine this relationship in single-level lumbar fusion surgery. The American College of Surgeons National Surgical Quality Improvement Program database was retrospectively reviewed to identify all patients who underwent single-level lumbar fusion procedures during 2006 to 2011. A propensity score-matching algorithm was used to match scores of anemic patients with that of nonanemic patients. Multivariate logistic regression analysis of unadjusted and propensity score-matched cohorts was performed to examine the effect of preoperative anemia on 30-day postoperative complication rates and length of hospital stay. A total of 2960 patients met inclusion criteria. The propensity score-matching procedure yielded scores of 491 pairs of well-matched nonanemic and anemic patients. The multivariate analysis of propensity score-matched population found preoperative anemia to carry no significant association with any of the complications analyzed, including overall complications, medical complications, surgical complications, reoperation, mortality, or length of total hospital stay. For patients undergoing single-level lumbar fusion, preoperative anemia is not independently associated with increased risk of 30-day complications or increased length of stay. Further studies are needed to independently validate this relationship in other spine surgical procedures. 3. | 25,188,593 | [
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Simulation of the progression of intervertebral disc degeneration due to decreased nutritional supply. | Simulate the progression of human disc degeneration. The objective of this study was to quantitatively analyze and simulate the changes in cell density, nutritional level, proteoglycan (PG) content, water content, and volume during human disc degeneration using a numerical method. Understanding the cause and progression of intervertebral disc degeneration is crucial for developing effective treatment strategies for intervertebral disc degeneration-related diseases. During tissue degeneration, the disc undergoes losses of cell viability and activities, changes in extracellular matrix composition and structure, and compromise of the tissue-level integrity and function, which is significantly influenced by the intercoupled biological, chemical, electrical, and mechanical signals in the disc. Characterizing these signals in human discs in vivo is difficult. A realistic 3-dimensional finite element model of the human intervertebral disc was developed on the basis of biomechanoelectrochemical continuum mixture theory. The theoretical framework and the constitutive relationships were all biophysics based. All the material properties were obtained from experimental results. The cell-mediated disc degeneration process caused by lowered nutritional levels at disc boundaries was simulated and validated by comparing with experimental results. Cell density reached equilibrium state in 30 days after reduced nutritional supply at the disc boundary, whereas the PG and water contents reached a new equilibrium state in 55 years. The simulated results for the distributions of PG and water contents within the disc were consistent with the results measured in the literature, except for the distribution of PG content in the sagittal direction. Poor nutritional supply has a long-term effect on disc degeneration. | 25,188,596 | [
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The 5-year cost-effectiveness of anterior cervical discectomy and fusion and cervical disc replacement: a Markov analysis. | A Markov state-transition model was developed to evaluate the cost-effectiveness of anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) at 5 years. To determine the cost-effectiveness of ACDF and CDR at 5 years. ACDF and CDR are surgical options for the treatment of an acute cervical disc herniation with associated myelopathy/radiculopathy. Cost-effectiveness analysis provides valuable information regarding which intervention will lead to a more efficient utilization of health care resources. Outcome and complication probabilities were obtained from existing literature. Physician costs were based on a fixed percentage of 140% of 2010 Medicare reimbursement. Hospital costs were determined from the Nationwide Inpatient Sample. Utilities were derived from responses to health state surveys (Short Form 36) at baseline and at 5 years from the treatment arms of the ProDisc-C trial. Incremental cost-effectiveness ratios were used to compare treatments. One-way sensitivity analyses were performed on all parameters within the model. CDR generated a total 5-year cost of $102,274, whereas ACDF resulted in a 5-year cost of $119,814. CDR resulted in a generation of 2.84 quality-adjusted life years, whereas ACDF resulted in 2.81. The incremental cost-effectiveness ratio was -$557,849 per quality-adjusted life year gained. CDR remained the dominant strategy below a cost of $20,486. ACDF was found to be a cost-effective strategy below a cost of $18,607. CDR was the dominant strategy when the utility value was above 0.713. CDR remained the dominant strategy assuming an annual complication rate less than 4.37%. ACDF and CDR were both shown to be cost-effective strategies at 5 years. CDR was found to be the dominant treatment strategy in our model. Further long-term studies evaluating the clinical and quality-of-life outcomes of these 2 treatments are needed to further validate the model. 5. | 25,188,602 | [
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Copper-mediated intramolecular oxidative C-H/N-H cross-coupling of α-alkenoyl ketene N,S-acetals to synthesize pyrrolone derivatives. | CuCl2 and CuBr2-mediated intramolecular oxidative C-H/N-H cross-coupling/halogenation of β-thioalkyl-substituted α-alkenoyl ketene N,S-acetals occurred efficiently, affording 4-halo-5-thioalkyl-3-pyrrolones. Tunable C-S and C-halo bond transformations of the resultant pyrrolone derivatives led to highly functionalized N-heterocyclic compounds. | 25,188,605 | [
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Synergistic antitumor effect of α-pinene and β-pinene with paclitaxel against non-small-cell lung carcinoma (NSCLC). | The objective of the present research work was to evaluate the synergistic interactions between Paclitaxel (PAC) with α-pinene and β-pinene using isobolographic method against non-small-cell lung cancer cells (NSCLC). This type of interaction between an established drug and a new compound is expected to enhance the efficacy of paclitaxel in combination as compared in isolation. Further, cell cycle analysis was carried out using flow cytometric analysis. Phase contrast microscopy was used to assess the effect of paclitaxel, α-pinene and β-pinene alone and in combination with each other in order to evaluate the effect of combination on cell apoptosis. Further, mitochondrial membrane potential was monitored in non-small-cell lung cancer cells (NSCLC) when treated with paclitaxel, α-pinene and β-pinene alone and in combination. The results revealed that the combination of PAC with α-pinene or with β-pinene showed a plotted curve below the straight line, generating a substantial synergistic effect. The effects of the following combinations were examined utilizing isobolograms: PAC and α-pinene and PAC and β-pinene. The combination of PAC and α-pinene as well as of PAC and β-pinene actually generated a synergistic effect. We also examined the effects of these compounds on the cell cycle distributions of A549 cells by flow cytometric analysis. The percentage of sub-G0/G1-phase cells was decreased on the addition of α-pinene to PAC, while the population of G0/G1 cells was increased. The morphological changes characteristic of apoptosis like chromatin condensation and fragmentation of the nucleus were seen in PAC+α-pinene and PAC+β-pinene treated NSCLC cells. | 25,188,609 | [
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Incidence and hospitalisation rates of Lyme borreliosis, France, 2004 to 2012. | Lyme borreliosis (LB) has become a major concern recently, as trends in several epidemiological studies indicate that there has been an increase in this disease in Europe and America over the last decade. This work provides estimates of LB incidence and hospitalisation rates in France. LB data was obtained from the Sentinelles general practitioner surveillance network (2009–2012) and from the Programme de Médicalisation des Systèmes d’Information (PMSI) data processing centre for hospital discharges (2004–09). The yearly LB incidence rate averaged 42 per 100,000 inhabitants (95% confidence interval (CI): 37–48), ranging from 0 to 184 per 100,000 depending on the region. The annual hospitalisation rate due to LB averaged 1.55 per 100,000 inhabitants (95% CI: 1.42–1.70). Both rates peaked during the summer and fall and had a bimodal age distribution (5–10 years and 50–70 years). Healthcare providers should continue to invest attention to prompt recognition and early therapy for LB, whereas public health strategies should keep promoting use of repellent, daily checks for ticks and their prompt removal. | 25,188,613 | [
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Effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand, in 2013. | This study reports the first vaccine effectiveness (VE) estimates for the prevention of general practice visits and hospitalisations for laboratory-confirmed influenza from an urban population in Auckland, New Zealand, in the same influenza season (2013). A case test-negative design was used to estimate propensity-adjusted VE in both hospital and community settings. Patients with a severe acute respiratory infection (SARI) or influenza-like illness (ILI) were defined as requiring hospitalisation (SARI) or attending a general practice (ILI) with a history of fever or measured temperature ≥38 °C, cough and onset within the past 10 days. Those who tested positive for influenza virus were cases while those who tested negative were controls. Results were analysed to 7 days post symptom onset and adjusted for the propensity to be vaccinated and the timing during the influenza season. Influenza vaccination provided 52% (95% CI: 32 to 66) protection against laboratory-confirmed influenza hospitalisation and 56% (95% CI: 34 to 70) against presenting to general practice with influenza. VE estimates were similar for all types and subtypes. This study found moderate effectiveness of influenza vaccine against medically attended and hospitalised influenza in New Zealand, a temperate, southern hemisphere country during the 2013 winter season. | 25,188,614 | [
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Depression, somatic symptoms, and perceived neighborhood environments among US-born and non-US-born free clinic patients. | The study's purpose was to examine the impact of somatic symptoms and perceived neighborhood environment on depression using a comparison among US-born and non-US-born free clinic patients. US-born English speakers (n = 99), non-US-born English speakers (n = 89), and non-US-born Spanish speakers (n = 158) 18 years old or older (N = 346) were surveyed at a free clinic that provides primary care to people without health insurance. Depression, somatic symptoms, and perceived neighborhood environment were measured using standardized instruments. US-born English speakers reported higher levels of depression and a greater number of somatic symptoms than non-US-born Spanish speakers and non-US-born English speakers. Non-US born English speakers reported lower levels of depression and fewer somatic symptoms than Spanish speakers. Somatic symptoms and perceived neighborhood satisfaction were related to depression. Developing mental health services for patients in a free clinic setting is needed; however, because of limited financial and human resources, providing mental health services in a free clinic setting often is difficult. Community-based health promotion programs as supplements to efforts within clinical settings would be valuable in improving the mental health of free clinic patients. Future studies should implement collaborative pilot programs and evaluate health outcomes. | 25,188,626 | [
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Tips for a physician in getting the right job, part XVI: Assessing the relationship between the group and the hospital(s). | For those job seekers seeking a position with a group of physicians, it is critical to assess the relationship of the hospital administration to the group, and also to physicians generally. Ideally, the relationship should be one of partnership, with mutual cooperation and seeking to understand and help each other. A hostile association could be due to 1 or both parties. An antagonistic relationship could mean that the group will be forced out or that its practice will not thrive, or that the hospital will not do well, or all 3. | 25,188,642 | [
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Alcohol intake and risk of injury. | Injuries constitute a leading cause of morbidity and mortality in the world, with intentional injuries and those related to traffic most important, due to their social impact and high prevalence. Although alcohol consumption has been identified as a risk factor for injuries, few studies have assessed risk separately for intentional injuries and unintentional injuries caused by traffic, and by other causes. The objective of this paper was to estimate the risk of injuries after acute alcohol consumption for intentional injuries and unintentional traffic and non-traffic injuries, using, alternatively, two exposure measures: self-reported drinking prior to the event and blood alcohol concentration. A probability sample was collected of 540 patients from the emergency department of a hospital in Argentina. Logistic regressions were performed, with and without adjusting for gender, age and drinking pattern. Higher risks were found when blood alcohol concentration was used as a measure of consumption, compared to self-report. The highest risk estimates were obtained for intentional injuries, followed by unintentional traffic and, lastly, by unintentional non-traffic injuries. After controlling for confounders, risks for intentional and unintentional traffic injuries appeared similar for those above and below the legal limit. Results point to a significant involvement of alcohol in the regional context. | 25,188,654 | [
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[Treatment of pulmonary vein stenosis secondary to radiofrequency ablation]. | Isolation of the pulmonary veins by applying radiofrequency is an effective treatment for atrial fibrillation. One of the potential complications with higher clinical compromise utilizing this invasive technique is the occurrence of stenosis of one or more pulmonary veins. This complication can be treated by angioplasty with or without stent implantation, with an adequate clinical improvement, but with a high rate of restenosis. | 25,188,658 | [
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[Nevoid basal cell carcinoma syndrome with corpus callosum agenesis, PTCH1 mutation and absence of basal cell carcinoma]. | Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin-Goltz syndrome is a rare autosomal dominant disorder, mainly due to PTCH1 gene mutations, that comprises a broad spectrum of clinical manifestations. The presence of multiple basal cell carcinomas (BCCs) is a cardinal sign in NBCCS, therefore cases in which BCCs are absent entails a delay in the diagnosis.We present a 14 years old boy with a clinical diagnosis of NBCCS by the presence of odontogenic cysts, hypertelorism, macrocephaly, and corpus callosum agenesia, but with absence of skin lesions. His 43 years old mother has NBCCS diagnosis and no history of BCCs. For a deeper study, PTCH1 mutation screening from peripheral blood samples were performed by both bidirectional sequencing and multiplex ligation dependent probe amplification (MLPA) techniques. The proband and his mother carry 25 pb duplication in exon 10 (c.1375dupl25bp) that causes a reading frameshift with a premature stop codon. Bioinformatics analysis predicted that this mutation results in a truncated protein shorter than normal. Our results suggest that complete clinical and genealogical studies accompanied by genetic analysis are essential in the early detection of the NBCCS cases such the one presented here. | 25,188,659 | [
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Dual glutathione-S-transferase-θ1 and -μ1 gene deletions determine imatinib failure in chronic myeloid leukemia. | Approximately 40% of patients with chronic myeloid leukemia (CML) receiving imatinib fail treatment. There is an increased risk of CML in subjects with (i) deletions of genes encoding glutathione-S-transferase (GST)-θ1 (GSTT1) and -μ1, (GSTM1) and (ii) the GST-π1 (GSTP1) single-nucleotide polymorphism (SNP) Ile105Val (GSTP1*B; rs1695); however, their effects on imatinib treatment outcome are not known. Here, we assess the role of these GSTs in relation to imatinib treatment outcome in 193 CML patients. Deletion of GSTT1 alone, or in combination with deletion of the GSTM1 gene, significantly increased the likelihood of imatinib failure (P = 0.021 and P < 0.001, respectively). The GSTP1*B SNP was not associated with time to imatinib failure. Losses of the GSTT1 and GSTM1 genes are therefore important determinants of imatinib failure in CML. Screening for GSTT1 and GSTM1 gene deletions during diagnosis may identify patients who may be better treated using an alternative therapy. | 25,188,725 | [
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Enhanced Raman and luminescence spectra from co-encapsulated silicon quantum dots and Au-Ag nanoalloys. | We report an approach to enhance simultaneously luminescence and SERS signals with a single excitation wavelength by co-encapsulating silicon quantum dots and Au-Ag alloy nanoparticles encoded with Raman reporter molecules inside polymeric nanoparticles. The SERS-luminescence enhancement exploits the large Stokes shift of silicon quantum dots, which allows 'room' for the display of a Raman spectrum. | 25,188,727 | [
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Postnatal development and LPS responsiveness of pulmonary adenosine receptor expression and of adenosine-metabolizing enzymes in mice. | Adenosine levels are regulated by ecto-5'-nucleotidase/CD73 and adenosine deaminase (ADA). Adenosine regulates endothelial permeability and anti-inflammatory responses via adenosine receptors. Here, the adenosine receptors and purine-converting enzymes were studied during postnatal development and inflammation. Newborn, 1-, 10-, 14-d-old and adult C57BL/6 mice were challenged intraperitoneally (i.p.) with lipopolysaccharide (LPS) for 6 h. The inflammatory response was evaluated by histochemistry. Expression levels of adenosine receptors (A1, A2A, A2B, and A3), CD73, and ADA were measured by quantitative reverse transcription polymerase chain reaction. A1 was studied by immunohistochemistry, and enzyme activities were analyzed by thin-layer chromatography. LPS caused respiratory distress in newborns within 24 h. LPS induced neutrophils at the basal stage and alveolar congestion. Low activity and expression of CD73 increased after birth. Expression of ADA after LPS increased 16-fold in adults and 2-fold in newborns (P < 0.05). A1 expression was high in newborns and increased after LPS (P < 0.05). A1 was localized to endothelial membranes. A2A decreased after LPS in newborns and increased in adults (P < 0.05). The expression of A3 increased in newborns and adults after LPS. Low pulmonary CD73 expression, LPS-induced suppression of A2A, LPS-induced increase of A1 expression, and severe respiratory distress were distinguishing responses in the newborns from those in the adults. | 25,188,742 | [
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Conceptualizing the impact of special events on community health service levels: an operational analysis. | Mass gatherings (MG) impact their host and surrounding communities and with inadequate planning, may impair baseline emergency health services. Mass gatherings do not occur in a vacuum; they have both consumptive and disruptive effects that extend beyond the event itself. Mass gatherings occur in real geographic locations that include not only the event site, but also the surrounding neighborhoods and communities. In addition, the impact of small, medium, or large special events may be felt for days, or even months, prior to and following the actual events. Current MG reports tend to focus on the events themselves during published event dates and may underestimate the full impact of a given MG on its host community. In order to account for, and mitigate, the full effects of MGs on community health services, researchers would benefit from a common model of community impact. Using an operations lens, two concepts are presented, the "vortex" and the "ripple," as metaphors and a theoretical model for exploring the broader impact of MGs on host communities. Special events and MGs impact host communities by drawing upon resources (vortex) and by disrupting normal, baseline services (ripple). These effects are felt with diminishing impact as one moves geographically further from the event center, and can be felt before, during, and after the event dates. Well executed medical and safety plans for events with appropriate, comprehensive risk assessments and stakeholder engagement have the best chance of ameliorating the potential negative impact of MGs on communities. | 25,188,753 | [
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Distinguishable Zn(II) and Pb(II) template effects on forming pendant-armed Schiff-base macrocyclic complexes including a remarkable Pb(II)-π macrocyclic complex. | 36-Membered [2 + 2] half-fold Schiff-base macrocyclic dinuclear Zn(II) complexes (1a and 1b) and 18-membered [1 + 1] Schiff-base macrocyclic mononuclear Pb(II) complexes (2 and 3) are produced from the condensation between 1,3-propanediamine and a pair of extended dialdehydes with different functional pendant arms (H2hpdd and H2pdd) because of the distinguishable cationic template effects. It is very interesting to mention that a unique intramolecular Pb(II)-π macrocyclic complex 2 with an uncommon η(3)-coordination type is achieved under ambient conditions and it can remain stable both in the solid state and in solution. The subtle variations of pendant-arms in the macrocyclic ligands H2hpdd and H2pdd yield different Pb(II) complexes, where the competition between Pb(II)-π and Pb(II)-NO3(-) electrostatic interactions as well as the combination of steric and electronic effects of pendant arms are believed to play important roles. | 25,188,754 | [
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Reliability and validity of the Turkish form of the eight-item Morisky medication adherence scale in hypertensive patients. | The aim of this study is to evaluate the reliability and validity of the Turkish version of the 8-item Morisky medication adherence scale. The study was conducted as a methodological design. The study included 196 patients with hypertension who applied to the Family Health Centers in three different regions of Turkey. Data were collected from February-June 2012. Methods used in the analysis included factor analysis, assessment of Cronbach's α test and item-total correlation in order to perform psychometric measurements. Variables influencing scores of medication adherence were determined using logistic regression analysis. Factor loadings of all items in the scale were above 0.40, and the variation explained was determined to be 42.4. The Turkish form consisted of a single domain. The Cronbach's α coefficient of the items in the scale was 0.79. Item-total correlations of items in the scale were between 0. 30 and 0. 62. Scores of medication adherence were observed to be affected by low economic condition and city where said individuals reside. It was determined that levels of reliability and validity of Turkish version of 8-item Morisky medication adherence scale is acceptable. | 25,188,758 | [
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Mid-term assessment of cardiac autonomic functions in children with transposition of the great arteries after arterial switch operation. | It has been documented that impaired heart rate variability (HRV) is related to life threatening arrhythmias in children with surgically repaired congenital heart disease. We aimed to analyze the balance of the cardiac autonomic functions by assessing HRV in children with arterial switch operation (ASO). In this observational cohort study, HRV analysis using 24-h Holter electrocardiography recordings was examined in 22 patients (mean age: 59.5±38.7 months, 18 male, 4 female) who had undergone ASO during the newborn period and 22 healthy children (mean age: 65.1±39.4 months, 18 male, 4 female). After Kolmogorov-Smirnov testing for normality, Student t-test and Mann-Whitney U test were used when appropriate. Chi-square was used for categorical data. In 24-h HRV analysis showed that SDANN and VLF were significantly higher in patient group. Awake SDNN, rMSSD, pNN50, TP and VLF levels of patient group were significantly higher than those of control subjects. Awake LF/HF ratio in patient group was significantly higher than their counterpart in asleep group. In the patient group, awake rMSSD, pNN50, TP, LF and HF were significantly lower than their counterpart in the asleep group. Children with transposition of the great arteries (TGA) following ASO have not decreased levels of time and frequency HRV parameters in the mid-term follow-up period. All HRV parameters reflecting vagal tone were increased in the patient group. It is suggested that vagal tone is more predominant than sympathetic tone for children with ASO. | 25,188,763 | [
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Ceramic ware waste as coarse aggregate for structural concrete production. | The manufacture of any kind of product inevitably entails the production of waste. The quantity of waste generated by the ceramic industry, a very important sector in Spain, is between 5% and 8% of the final output and it is therefore necessary to find an effective waste recovery method. The aim of the study reported in the present article was to seek a sustainable means of managing waste from the ceramic industry through the incorporation of this type of waste in the total replacement of conventional aggregate (gravel) used in structural concrete. Having verified that the recycled ceramic aggregates met all the technical requirements imposed by current Spanish legislation, established in the Code on Structural Concrete (EHE-08), then it is prepared a control concrete mix and the recycled concrete mix using 100% recycled ceramic aggregate instead of coarse natural aggregate. The concretes obtained were subjected to the appropriate tests in order to conduct a comparison of their mechanical properties. The results show that the concretes made using ceramic sanitary ware aggregate possessed the same mechanical properties as those made with conventional aggregate. It is therefore possible to conclude that the reuse of recycled ceramic aggregate to produce recycled concrete is a feasible alternative for the sustainable management of this waste. | 25,188,783 | [
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Tacrolimus for the treatment of subepithelial infiltrates resistant to topical steroids after adenoviral keratoconjunctivitis. | To describe the use of topical 0.03% tacrolimus in patients with symptomatic corneal subepithelial infiltrates (SEIs) secondary to adenoviral keratoconjunctivitis (AK) that were resistant to tapering of corticosteroid eye drops. This was a prospective, nonrandomized, noncomparative interventional case series that included consecutive patients treated with tacrolimus for resistant SEIs after AK. The patients had active SEIs and corrected distance visual acuity (CDVA) of 20/25 or worse when treatment was initiated. The recorded data included age, sex, CDVA, intraocular pressure, duration and intensity of symptoms, biomicroscopy findings, and duration of therapy. The treatment was considered successful if there was a reduction in SEIs, as well as CDVA stabilization or improvement. The treatment was considered unsuccessful if the patient could not tolerate tacrolimus or if there was an increase in SEIs. Seven patients were included (10 eyes). The mean age was 36.7 ± 12.3 years. The mean duration of tacrolimus therapy was 8.8 ± 2.4 months, and the mean duration of follow-up was 13.6 ± 10.7 months. Treatment was successful in 8 eyes of 6 patients. One patient could not tolerate the medication. Statistically significant improvement in the CDVA was observed (from a mean of 0.29 to 0.07) (P = 0.001). No statistically significant changes in the intraocular pressure were observed (P = 0.574). SEI scores showed a significant reduction from 2.20 ± 0.92 to 0.25 ± 0.46 (P = 0.011). All patients who completed treatment had improvement in ocular symptoms. Topical 0.03% tacrolimus seemed to be an effective corticosteroid-sparing agent for the treatment of SEIs after AK. | 25,188,789 | [
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N-heterocyclic carbene-promoted annulation reaction of allenals with chalcones: synthesis of polysubstituted pyranyl aldehydes. | A general N-heterocyclic carbene (NHC)-promoted annulation reaction of allenals with chalcones affording polysubstituted pyranyl aldehydes has been developed. Three mechanistic possible pathways have been proposed. The NHC attacks the center carbon of allenals or acts as a base for deprotonation and then undergoes a 1,4-addition with chalcones, followed by sequential reactions giving the final products. | 25,188,791 | [
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Stimuli-responsive conformational conversion of peptide gatekeepers for controlled release of guests from mesoporous silica nanocontainers. | The use of peptides as gatekeepers for payloads of mesoporous silica nanoparticles would allow triggering the release of guests by various biological stimuli. We investigated the effect of peptide conformation on their gatekeeping capability by employing two model peptides with a turn or a random structure. The conformation-dependent gatekeeping properties provided an opportunity to utilize the conformational conversion of peptides as a valuable motif for stimuli-responsive gatekeepers. Based on that investigation, we demonstrated that Fmoc-CGGC-SS-Si, which exhibited a zero-release property without any stimuli due to a turn-like conformation induced by the intramolecular disulfide bond, can be triggered to release guests by converting its conformation to a random structure, induced by reduction of the disulfide bond upon addition of glutathione. We further demonstrated that the conformational conversion of Fmoc-CGGC by Zn(II) ion can also be utilized as a triggering motif. | 25,188,823 | [
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Isolation and characterization of Vibrio cholerae isolates from seafood in Hat Yai City, Songkhla, Thailand. | Seafood has been identified as an important source of Vibrio cholerae in Thailand, especially in the Southern coastal region. In this study, we isolated and characterized V. cholerae from seafood obtained from several markets in Hat Yai city, Southern Thailand. A total of 100 V. cholerae isolates were obtained from 55 of 125 seafood samples. The dominant serotype was non-O1/non-O139. Polymerase chain reaction (PCR) analysis was used to detect the presence of pathogenesis-related genes. The stn/sto and hlyA El Tor virulence genes were detected in 20% and 96% of the isolates, respectively. None of the isolates were positive for the ctxA, tcpA, zot, and ace genes. Only 6% of the isolates carried the T3SS gene (vcsV2); however, the majority of the isolates (96%) carried the T6SS gene (vasH). Representative isolates (n=35) that exhibited various virulence gene patterns were randomly selected and analyzed for their hemolytic activity, antibiotic susceptibility, biofilm formation, and genotype. Hemolytic activity using sheep red blood cells was detected in only one of the hlyA-negative isolates. Apart from ampicillin, all isolates were pansusceptible to five test antibiotics. Biofilm production was observed in most of the isolates, and there was no difference in the presence of a biofilm between the smooth and rugose isolates. Using the enterobacterial repetitive intergenic consensus-PCR method, clonal relationships were observed among the isolates that exhibited identical virulence gene patterns. | 25,188,839 | [
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Engineering bacterial transcription regulation to create a synthetic in vitro two-hybrid system for protein interaction assays. | Transcriptional activation of σ(54)-RNA polymerase holoenzyme (σ(54)-RNAP) in bacteria is dependent on a cis-acting DNA element (bacterial enhancer), which recruits the bacterial enhancer-binding protein to contact the holoenzyme via DNA looping. Using a constructive synthetic biology approach, we recapitulated such process of transcriptional activation by recruitment in a reconstituted cell-free system, assembled entirely from a defined number of purified components. We further engineered the bacterial enhancer-binding protein PspF to create an in vitro two-hybrid system (IVT2H), capable of carrying out gene regulation in response to expressed protein interactions. Compared with genetic systems and other in vitro methods, IVT2H not only allows detection of different types of protein interactions in just a few hours without involving cells but also provides a general correlation of the relative binding strength of the protein interaction with the IVT2H signal. Due to its reconstituted nature, IVT2H provides a biochemical assay platform with a clean and defined background. We demonstrated the proof-of-concept of using IVT2H as an alternative assay for high throughput screening of small-molecule inhibitors of protein-protein interaction. | 25,188,838 | [
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Corrosivity of paper mill effluent and corrosion performance of stainless steel. | Present study relates to the corrosivity of paper mill effluent and corrosion performance of stainless steel (SS) as a construction material for the effluent treatment plant (ETP). Accordingly, immersion test and electrochemical polarization tests were performed on SS 304 L, 316 L and duplex 2205 in paper mill effluent and synthetic effluent. This paper presents electrochemical polarization measurements, performed for the first time to the best of the authors' information, to see the influence of chlorophenols on the corrosivity of effluents. The corrosivity of the effluent was observed to increase with the decrease in pH and increase in Cl- content while the addition of SO4- tends to inhibit corrosion. Mill effluent was found to be more corrosive as compared to synthetic effluent and has been attributed to the presence of various chlorophenols. Corrosion performance of SS was observed to govern by the presence of Cr, Mo and N contents. | 25,188,842 | [
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HBV and HIV coinfections among intending blood donors in Port Harcourt, Nigeria. | HBV is a major public health concern as it afflicts an estimated 350 million people worldwide. Studies are crucial and necessary to give us a better understanding of the epidemiology of the diseases in developing countries. A clearer picture of HBV/HIV prevalence in Africa is important in order to better educate the population and control these epidemics. This study estimated the seroprevalence of HBV/HIV coinfections among intending blood donors in Port Harcourt, Nigeria. In this cohort study, we collected blood samples from 178 intending blood donors who were confirmed to be HIV-seropositive at the University of Port Harcourt Teaching Hospital (UPTH) from September 2012 to June 2013. Commercial ELISA was used to assay for the presence of HBsAg among these subjects. The overall prevalence was found to be 6.7%. Sex and education (P < 0.05) were the main correlates in this study. Age was not statistically correlated (P > 0.05) in this study. We also observed a high overall HBV/HIV co-infection seronegativity of 93.3% among these blood donors. Group-specific seronegativity was also high ranging from 86.4-100.0%. Although the age groups (13-20, 21-35, and 36-66 years) insignificantly differed, none of their variables showed statistical association with the seronegativity. Our findings underscore the importance of screening for HBV/HIV among blood donors in developing countries, and particularly in sub-Saharan Africa, where the epidemics are still growing and a major public health concern. | 25,188,859 | [
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BRAF mutation is associated with a specific cell type with features suggestive of senescence in ovarian serous borderline (atypical proliferative) tumors. | Serous borderline tumor also known as atypical proliferative serous tumor (APST) is the precursor of ovarian low-grade serous carcinoma (LGSC). In this study, we correlated the morphologic and immunohistochemical phenotypes of 71 APSTs and 18 LGSCs with the mutational status of KRAS and BRAF, the most common molecular genetic changes in these neoplasms. A subset of cells characterized by abundant eosinophilic cytoplasm (EC), discrete cell borders, and bland nuclei was identified in all (100%) 25 BRAF-mutated APSTs but in only 5 (10%) of 46 APSTs without BRAF mutations (P<0.0001). Among the 18 LGSCs, EC cells were found in only 2, and both contained BRAF mutations. The EC cells were present admixed with cuboidal and columnar cells lining the papillae and appeared to be budding from the surface, resulting in individual cells and clusters of detached cells "floating" above the papillae. Immunohistochemistry showed that the EC cells always expressed p16, a senescence-associated marker, and had a significantly lower Ki-67 labeling index than adjacent cuboidal and columnar cells (P=0.02). In vitro studies supported the interpretation that these cells were undergoing senescence, as the same morphologic features could be reproduced in cultured epithelial cells by ectopic expression of BRAF(V600E). Senescence was further established by markers such as SA-β-gal staining, expression of p16 and p21, and reduction in DNA synthesis. In conclusion, this study sheds light on the pathogenesis of this unique group of ovarian tumors by showing that BRAF mutation is associated with cellular senescence and the presence of a specific cell type characterized by abundant EC. This "oncogene-induced senescence" phenotype may represent a mechanism that impedes progression of APSTs to LGSC. | 25,188,864 | [
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Facilitating the Cope rearrangement by partial protonation: implications for synthesis and biosynthesis. | The theoretical investigation of concerted and stepwise Cope rearrangements of natural products led to the prediction that some concerted Cope rearrangements can be promoted by noncovalent association of their transition state structures with ammonium cations. | 25,188,876 | [
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Use of imiquimod for residual acral melanoma. | Recent reports suggest that topical imiquimod cream is an effective treatment option for certain types of melanomas. No reports exist on the efficacy of using imiquimod cream to treat melanoma located on the plantar surface of the foot. We present two patients with a melanoma of the foot who had residual melanoma following surgical excision with acceptable margins. The patients were then treated with topical imiquimod for 8 weeks after which a repeat biopsy of the affected region showed no evidence of residual melanoma in situ. The use of topical imiquimod cream should be considered in the management of residual melanoma in situ of the plantar surface of the foot. | 25,188,932 | [
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Multiple territory watershed infarcts following spinal anaesthesia. | Hypotension is one of the most common complications of spinal anaesthesia (SA). The intraoperative drop in the blood pressure is clearly associated with increased morbidity and mortality. In order to increase the awareness of this complication, we report a case of devastating stroke following an SA in a previously well woman with risk factors for vascular diseases. The patient developed multiple territory watershed infarcts and she eventually died from aspiration pneumonia 14 days after hospitalisation. The case highlights the risk of hypotension complicating SA. | 25,188,933 | [
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Getting the priorities right in end-of-life care. | The Leadership Alliance for the Care of Dying People has drawn up five priorities for the care of dying people. The priorities replace the Liverpool Care Pathway, which was widely criticised for promoting a tick-box approach to the care of the dying. The five priorities focus on: recognising that someone is dying; communicating sensitively with them and their family; involving them in decisions; supporting them and their family; and creating an individual plan of care that includes adequate nutrition and hydration. The alliance has outlined the duties and responsibilities of nurses and other health professionals when caring for people at the end of their lives, with an emphasis on compassionate care. | 25,188,966 | [
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["Purified empiricism": Johann Christian Reil's (1759-1813) attempts at a foundation of medicine in relation to its tradition, kantianism, and speculative philosophy]. | Johann Christian Reil's (1759-1813) importance lies in his theoretical approach to medicine. Following Kant in his early work, he attempts to combine medical experience with an underlying conceptual structure. This attempt is directed against both the chaotic empiricism of traditional medicine and speculative theories such as vitalism. The paper starts from his early reflections on the concept of a life force, which he interprets in the way of a non-reductive materialism. In the following, the basic outlines of his Theory of Fever will be shown. The Theory is a systematic attempt at finding a new foundation for diagnosis and therapy on the basis of the concept of fever, which is understood as modification of vital processes. The paper ends with a discussion of his later work, which has remained controversial so far. It shows that the combination of practical empiricism and scientific theory remained rather unstable in this early phase of the development of modern medicine. | 25,188,999 | [
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[Who should undergo atrial fibrillation ablation?]. | Atrial fibrillation is the most common sustained arrhythmia and its prevalence increases significantly with age. This editorial discusses the review by Laish-Farkash et al. regarding ablation of atrial fibrillation, especially in the elderly, as well as new ablation modalities. | 25,189,029 | [
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[Education and training system in child and adolescent psychiatry with view to carry-over towards adulthood psychiatry]. | The aim of our study was to develop and establish a training system in child and adolescent psychiatry in Japan, especially in light of the continuity and integration with general psychiatry. The Japanese authors surveyed the situation of training in child and adolescent psychiatry (CAP training) through the literature and conducted collaborative and consensus meetings with the authors in the UK, with its long history of training system development. A comparison was made between Japan and CAP training in the UK and other countries. A recent survey of psychiatric education in Japan clarified the current situation and called attention to parts of the education and training system where development is required. A systematic curriculum has not been established. For the elimination of disparities of competencies and skills among multidisciplinary staff, the CAP training curriculum needs to be comprehensive and fundamental, as shown in the Competency-based Curriculum for Specialists developed by the Royal College of Psychiatrists. CAP training and general psychiatry must be integrated into a comprehensive curriculum in the postgraduate education and training system, with an adequate time and place for training and supervision. | 25,189,043 | [
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[The role of psychiatrists in cooperative activity with school staff in school mental health]. | Although it was started some ten years ago in Japan that psychiatrists should be involved as specialists in mental health activity in schools, what was expected at most was to give some therapeutic suggestions on inquiry by teachers in relation to desirable solutions to reduce problem behaviors as pathological symptoms. However, it is now beginning to be acknowledged by psychiatrists that they should not only help to reduce the already appearing severe symptoms, but also to maintain and even promote the mental health conditions of all school children and adolescents irrespective of whether symptoms are already present or not. The most useful activity for school teachers to be engaged in regarding both therapeutic and preventive mental health activities with certain positive results is to learn from case consultation in schools that they belong to with the attendance of psychiatrists about single symptoms after identifying them by themselves, and to know whether the single symptom really exists alone or is a component of a certain disorder, and also the cause of the symptom or the disorder. This activity is called "case consultation activity in school with the attendance of both a psychiatrist as a consultant and teachers as consultees". We are now proceeding to the next stage for the purpose of promoting cooperation in school mental health after nearly 30 years establishing a relationship with school teachers in Nishinomiya City, Japan. In the next stage of school mental health, we expect teachers to identify necessary and useful ways of cooperation with school children by themselves. We, as psychiatrists, can only help teachers proceed with this goal. | 25,189,048 | [
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Land use effects on leaf litter breakdown in low-order streams draining a rapidly developing tropical watershed in Puerto Rico. | Land use has an important role influencing stream ecosystem processes, such as leaf litter breakdown. Here, we assessed rates of leaf litter breakdown in low-order tropical streams draining forest, agriculture, and urban land uses in Puerto Rico. To measure leaf breakdown rates, we placed litter bags made of coarse mesh in nine streams, three for each land use type. At each stream, we measured changes in leaf mass over time, leaf breakdown rates, macroinvertebrate assemblages, and stream physicochemistry. Streams differed in their water physicochemistry, with urban streams showing high values for most variables. Stream physical habitat was evaluated using a visual assessment protocol, which indicated that agricultural and urban streams were more degraded than forested streams. Leaf breakdown rates were fast in all streams (k values ranging 0.006-0.024). Breakdown rates were significantly related to the physical conditions of the stream channel (e.g., visual protocol scores), with fastest rates in forested streams. Invertebrates colonizing leaves were mainly mayflies (Leptophlebiidae, Baetidae, and Caenidae), dipterans (Chironomidae), caddisflies (Polycentropodidae), and beetles (Elmidae and Gyrinidae). Our streams lacked large decapod populations, contrasting with other Puerto Rican streams. We found little evidence for an insect effect on leaf breakdown. Results suggest that land use is an important factor affecting leaf litter processing in streams. In contrast to studies in temperate regions, we found little evidence for a positive nutrient related effect of agricultural land use on decomposition rates. Changes in the physical characteristics of streams appear to be the main drivers behind observed decomposition patterns. | 25,189,074 | [
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Cost-effectiveness of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK. | The introduction of routine childhood vaccination with pneumococcal conjugate vaccines (PCVs) has led to a decrease in the overall incidence of pneumococcal disease in all ages and a change in the serotype distribution of the remaining disease. This study assessed the cost-effectiveness of vaccinating ≥65 years and at risk adults with either the 23-valent pneumococcal polysaccharide vaccine (PPV23) or the 13-valent conjugate vaccine (PCV13) in the UK, accounting for epidemiological changes. A population-based Markov model was used to track one UK-based cohort of individuals assuming PPV23, PCV13 or no vaccination until death. The ICER was estimated at £8413 when PPV23 was compared to no vaccination. PPV23 dominated PCV13. This model suggests that vaccinating with PPV23 is cost-effective when compared to both PCV13 and no vaccination. As PPV23 covers 80-90% in the UK of all serotypes causing invasive pneumococcal diseases, it remains cost-effective despite recent reductions in invasive pneumococcal diseases incidence in adults. | 25,189,087 | [
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Fibroblast phenotypes in different lung diseases. | The "seed and soil" hypothesis emphasizes the importance of interactions between tumor cells and their microenvironment. CAFs (Cancer associated fibroblasts) are important components of the tumor microenvironment. They were widely involved in cancer cells growth and metastasis. Fibroblasts may also play a role in inflammatory disease. The phenotype conversion of fibroblasts in lung diseases has not been investigated previously. We hypothesized that fibroblasts phenotypes may vary among different types of lung disease. The study included six types of lung tissues, ranging from normal lung to lung adenocarcinoma with lymphatic metastasis. Para-carcinoma tissues which were 2-cm-away from the tumor focus were also included in the analysis. The expression of target proteins including alpha-SMA (smooth muscle actin), FAP (fibroblast activation protein), vimentin, E-cadherin, and CK-19 (cytokeratin-19) were examined by immunohistochemistry. TGF-beta(transforming growth factor) and Twist were detected simultaneously in all samples. A progressive increase in the levels of alpha-SMA, vimentin and CK-19 was observed in correlation to the degree of malignancy from normal lung tissue to lung adenocarcinoma with lymphatic metastasis, whereas E-cadherin expression showed the opposite trend. TGF-beta and Twist were detected in cancer tissues and inflammatory pseudotumors. None of the proteins were detected in para-carcinoma tissues. Fibroblast phenotypes varied according to the type and degree of lung malignancy and fibroblasts phenotypic conversion occurs as a gradual process with specific spatiotemporal characteristics. Similar fibroblast phenotypes in inflammatory diseases and cancer tissues suggested a correlation between inflammation and cancer and implied a common mechanism underlying the formation of fibroblasts in inflammatory diseases and lung cancer. | 25,189,096 | [
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Duhuo Jisheng Decoction‑containing serum promotes proliferation of interleukin‑1β‑induced chondrocytes through the p16‑cyclin D1/CDK4‑Rb pathway. | Duhuo Jisheng Decoction (DHJSD) is a traditional Chinese herbal medicine that has multiple uses, including as a treatment for osteoarthritis (OA). However, the molecular mechanisms underlying the therapeutic effects of DHJSD on OA remain unknown. In the present study, a serum pharmacological method was applied to investigate the effects of DHJSD on the proliferation of chondrocytes treated with interleukin‑1β (IL‑1β) in vitro. This is a cell model commonly used to reproduce the mechanisms involved in degenerative arthropathies, including OA. The most effective intervention conditions of DHJSD serum were examined by MTT assay. The degenerative chondrocyte model was established by IL‑1β‑culture for 24 h, and was verified by optical microscopy and immunohistochemical analyses. Following the successful establishment of the degenerative chondrocyte model, the chondrocytes were subsequently randomly divided into two groups: The blank serum group and the DHJSD treatment group. Subsequent to treatment with the corresponding serum, cell proliferation was detected by MTT assay and DNA staining followed by FACS analysis, and the mRNA and protein expression levels of cyclin D1, cyclin‑dependent kinase 4 (CDK4), retinoblastoma tumor suppressor protein (Rb) and p16 were measured by reverse transcription polymerase chain reaction and western blotting, respectively. The results indicated that the most effective condition for the promotion of chondrocyte proliferation was 10% concentration of DHJSD 2‑h serum, and the degenerative chondrocyte model was successfully reproduced by IL‑1β‑treatment for 24 h. The mRNA and protein expression levels of cyclin D1, CDK4 and Rb in the DHJSD serum‑treated cells were significantly increased compared with those in the blank serum group, whereas p16 expression was significantly downregulated. These results indicate that treatment of cells with DHJSD‑containing serum is able to promote IL‑1β‑induced chondrocyte proliferation by promoting G1/S phase transition via modulating the expressions of cyclin D1, CDK4, Rb and p16, which contribute to the clinical efficacy of DHJSD in OA. | 25,189,115 | [
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Constituents of Vigna angularis and their in vitro anti-inflammatory activity. | Nine non-phenolic compounds, including four furanylmethyl glycosides, angularides A-D, one ent-kaurane diterpene glycoside, angularin A, and four triterpenoid saponins, angulasaponins A-D, were isolated from seeds of Vigna angularis, together with eight known compounds. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic analysis as well as chemical methods. Angularin A, angulasaponins A-C, and azukisaponins III and VI showed inhibition of nitric oxide production in LPS-activated RAW264.7 macrophages, with IC50 values ranging from 13μM to 24μM. | 25,189,119 | [
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Isolation of α-glucosidase inhibitors including a new flavonol glycoside from Dendrobium devonianum. | From the whole plant of Dendrobium devonianum, a new flavonol glycoside, 5-hydroxy-3-methoxy-flavone-7-O-[β-D-apiosyl-(1 → 6)]-β-D-glucoside, as well as 13 known compounds, was isolated. Their structures were identified based on extensive spectroscopic studies including HR-EI-MS, (1)H, (13)C NMR, DEPT, H-H COSY, HSQC, HMBC and NOESY spectra. The new compound and gigantol were evaluated for their α-glucosidase inhibitory activity, and both displayed more potent α-glucosidase inhibitory activity than acarbose, one of the most potent α-glucosidase inhibitor drugs, with the inhibition rate of 43.4% and 36.7%, respectively, in the concentration of 437.5 μmol/L. | 25,189,122 | [
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Enhancing protein-vitamin binding residues prediction by multiple heterogeneous subspace SVMs ensemble. | Vitamins are typical ligands that play critical roles in various metabolic processes. The accurate identification of the vitamin-binding residues solely based on a protein sequence is of significant importance for the functional annotation of proteins, especially in the post-genomic era, when large volumes of protein sequences are accumulating quickly without being functionally annotated. In this paper, a new predictor called TargetVita is designed and implemented for predicting protein-vitamin binding residues using protein sequences. In TargetVita, features derived from the position-specific scoring matrix (PSSM), predicted protein secondary structure, and vitamin binding propensity are combined to form the original feature space; then, several feature subspaces are selected by performing different feature selection methods. Finally, based on the selected feature subspaces, heterogeneous SVMs are trained and then ensembled for performing prediction. The experimental results obtained with four separate vitamin-binding benchmark datasets demonstrate that the proposed TargetVita is superior to the state-of-the-art vitamin-specific predictor, and an average improvement of 10% in terms of the Matthews correlation coefficient (MCC) was achieved over independent validation tests. The TargetVita web server and the datasets used are freely available for academic use at http://csbio.njust.edu.cn/bioinf/TargetVita or http://www.csbio.sjtu.edu.cn/bioinf/TargetVita. | 25,189,131 | [
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The journey to psychosis: an exploration of specific psychological pathways. | Recent models of psychosis have implicated specific psychological processes in the aetiology of this disorder, and these factors may form a route to later symptoms-either directly or via a mediating pathway after exposure to adversity. Researchers are beginning to bring together findings that look into specific pathways between early experiences of adversity and different symptoms of psychosis, including thought disorder, hallucinations and persecutory delusions. The adversity-specific pathways include parental communication deviance, source monitoring biases, and insecure attachment. Researchers have also begun to utilise specific psychological factors as targets for treatment, and these include a focus on a worrying thinking style, negative beliefs about the self, interpersonal sensitivity, sleep disturbance, anomalous internal experience, and reasoning biases. Research on the impact of psychological processes is beginning to mount and is likely to improve our understanding of aetiology and lead to significant advances in the treatment of psychotic symptoms and disorders. | 25,189,139 | [
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Validity and Reliability Analysis of the 'SayangKU' (MyLove) in Intervention for Addressing Adolescents Involved in Free Sex. | A module entitled 'SayangKU' (MyLove), based on the Islamic perspective, was developed as an instrument to assist adolescents that involved in premarital sexual activity. The module comprises four phases: Love of God (Allah), Love of the Prophet, Love of Oneself, and Love of the Ummah (world). From analysis of Rasch, the value of item reliability was .80 and an individual reliability was .95. Dimensionality value was more than 40 % variance explained by measures, and level of agreement among experts was 86.88 %. The posttest shows the better result from pretest and proves the effectiveness of the module. | 25,189,148 | [
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Strategy for development of clinically useful glyco-biomarkers. | Recent advancements in proteomics technology have stimulated the widespread research and development in the area of biomarker discovery using mass spectrometry (MS). The final goal of biomarker discovery and development is to establish clinically useful and reliable diagnostic methods for various diseases. Specific alterations in the nature and composition of glycans attached to proteins are seen during the development and progression of a number of diseases and disorders. Therefore, development of glyco-biomarkers, which detect disease-specific glycoproteins and changes in glycoforms, is gaining much attention. The combined use of multiple technologies, not solely MS, is the key to the discovery of clinically significant and reliable biomarkers. We have employed the combination of quantitative real-time polymerase chain reaction (PCR), lectin microarray, liquid chromatography/mass spectrometry-based technique with isotope-coded glycosylation site-specific tagging (IGOT-LC/MS), and bioinformatics to successfully develop a novel diagnostic kit for the quantitative evaluation of liver fibrosis. Efforts to develop highly effective glyco-biomarkers for other diseases are also currently underway. | 25,189,155 | [
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A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T. | Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from three randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442; n = 512), D9901 (NCT00005947; n = 127), and D9902A (NCT01133704; n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory and if data were available from baseline and ≥ 1 posttreatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105 of 377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival [HR, 0.713; 95% confidence interval (CI), 0.525-0.970; P = 0.031], and a trend in overall survival (HR, 0.753; 95% CI, 0.563-1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this finding did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials. | 25,189,164 | [
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Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety. | Dengue shock syndrome (DSS) fluid resuscitation by following the World Health Organization (WHO) guideline usually required large volumes of Ringer lactate (RL) that might induce secondary fluid overload. Our objective was to compare the effectiveness of the recommended volume of RL versus a smaller volume of a hypertonic sodium lactate solution (HSL) in children with DSS. The primary end point was to evaluate the effect of HSL on endothelial cell inflammation, assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1) measurements. Secondarily, we considered the effectiveness of HSL in restoring hemodynamic fluid balance, acid-base status, and sodium and chloride balances, as well as in-hospital survival. A prospective randomized single-blind clinical trial including 50 DSS children was conducted in the Pediatrics Department of Hasan Sadikin Hospital, Bandung, Indonesia. Only pediatric patients (2 to 14 years old) fulfilling the WHO criteria for DSS and new to resuscitation treatments were eligible. Patients were resuscitated with either HSL (5 ml/kg/BW in 15 minutes followed by 1 ml/kg/BW/h for 12 hours), or RL (20 ml/kg/BW in 15 minutes followed by decreasing doses of 10, 7, 5, and 3 ml/kg BW/h for 12 hours). In total, 50 patients were randomized and included in outcome and adverse-event analysis; 46 patients (8.2 ± 0.5 years; 24.9 ± 1.9 kg; mean ± SEM) completed the protocol and were fully analyzed (24 and 22 subjects in the HSL and RL groups, respectively). Baseline (prebolus) data were similar in both groups. Hemodynamic recovery, plasma expansion, clinical outcome, and survival rate were not significantly different in the two groups, whereas fluid accumulation was one third lower in the HSL than in the RL group. Moreover, HSL was responsible for a partial recovery from endothelial dysfunction, as indicated by the significant decrease in sVCAM-1. Similar hemodynamic shock recovery and plasma expansion were achieved in both groups despite much lower fluid intake and fluid accumulation in the HSL group. ClinicalTrials.gov NCT00966628. Registered 26 August 2009. | 25,189,175 | [
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Capturing needles in haystacks: a comparison of B-cell receptor sequencing methods. | Deep-sequencing methods are rapidly developing in the field of B-cell receptor (BCR) and T-cell receptor (TCR) diversity. These promise to revolutionise our understanding of adaptive immune dynamics, identify novel antibodies, and allow monitoring of minimal residual disease. However, different methods for BCR and TCR enrichment and amplification have been proposed. Here we perform the first systematic comparison between different methods of enrichment, amplification and sequencing for generating BCR and TCR repertoires using large sample numbers. Resampling from the same RNA or cDNA pool results in highly correlated and reproducible repertoires, but resampling low frequency clones leads to stochastic variance. Repertoires generated by different sequencing methods (454 Roche and Illumina MiSeq) and amplification methods (multiplex PCR, 5' Rapid amplification of cDNA ends (5'RACE), and RNA-capture) are highly correlated, and resulting IgHV gene frequencies between the different methods were not significantly different. Read length has an impact on captured repertoire structure, and ultimately full-length BCR sequences are most informative for repertoire analysis as diversity outside of the CDR is very useful for phylogenetic analysis. Additionally, we show RNA-based BCR repertoires are more informative than using DNA. Repertoires generated by different sequencing and amplification methods are consistent, but we show that read lengths, depths and error profiles should be considered in experimental design, and multiple sampling approaches could be employed to minimise stochastic sampling variation. This detailed investigation of immune repertoire sequencing methods is essential for informing basic and clinical research. | 25,189,176 | [
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The relapsing fever spirochete Borrelia miyamotoi is cultivable in a modified Kelly-Pettenkofer medium, and is resistant to human complement. | Borrelia miyamotoi is a relapsing fever spirochete found in Ixodes ticks in North America, Europe, and Asia, and has recently been found to be invasive in humans. Cultivation of this spirochete has not yet been described, but is important for patient diagnostics and scientific purposes. Host specificity of Borrelia species is dependent on resistance to host complement (serum resistance), and since B. miyamotoi has been identified as a human pathogen we were interested whether B. miyamotoi is resistant to human complement. We inoculated B. miyamotoi strains LB-2001 and HT31 in modified-Kelly-Pettenkofer medium with 10% fetal calf serum (MKP-F), and used standard non-laborious Borrelia culture methods to culture the spirochetes. Next, we assessed serum sensitivity by a direct killing assay and a growth inhibition assay. We were able to passage B. miyamotoi over 10 times using a standard culture method in MKP-F medium, and found B. miyamotoi to be resistant to human complement. In contrast to B. miyamotoi, Borrelia anserina--a relapsing fever spirochete unrelated to human infection--was serum sensitive. Using a variation on MKP medium we were able to culture B. miyamotoi, opening the door to in vitro research into this spirochete. In addition, we describe that B. miyamotoi is resistant to human complement, which might play an important role in pathogenesis. We have also found B. anserina to be sensitive to human complement, which might explain why it is not related to human infection. Summarizing, we describe a novel culture method for B. miyamotoi and show it is resistant to human complement. | 25,189,195 | [
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A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants. | The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days). Analysis of data with mixed-model methods (EMMAX, GEMMA, GenABEL) and PLINK showed a low positional concordance between trait-associated regions (TARs) for serum lipids at 45 and 190 days. Besides, the proportion of phenotypic variance explained by SNPs at these two time points was also substantially different. The four analyses consistently detected two regions on SSC3 (124 Mb, CHOL and LDL at 190 days) and SSC6 (135 Mb, CHOL and TRIG at 190 days) with highly significant effects on the porcine blood lipid profile. Moreover, we have found that SNP variation within SSC3, SSC6, SSC10, SSC13 and SSC16 TARs is associated with the expression of several genes mapping to other chromosomes and related to lipid metabolism. Our data demonstrate that the effects of genomic determinants influencing lipid concentrations in pigs, as well as the amount of phenotypic variance they explain, are influenced by age-related factors. | 25,189,197 | [
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Large-scale generation of cell-derived nanovesicles. | Exosomes are enclosed compartments that are released from cells and that can transport biological contents for the purpose of intercellular communications. Research into exosomes is hindered by their rarity. In this article, we introduce a device that uses centrifugal force and a filter with micro-sized pores to generate a large quantity of cell-derived nanovesicles. The device has a simple polycarbonate structure to hold the filter, and operates in a common centrifuge. Nanovesicles are similar in size and membrane structure to exosomes. Nanovesicles contain intracellular RNAs ranging from microRNA to mRNA, intracellular proteins, and plasma membrane proteins. The quantity of nanovesicles produced using the device is 250 times the quantity of naturally secreted exosomes. Also, the quantity of intracellular contents in nanovesicles is twice that in exosomes. Nanovesicles generated from murine embryonic stem cells can transfer RNAs to target cells. Therefore, this novel device and the nanovesicles that it generates are expected to be used in exosome-related research, and can be applied in various applications such as drug delivery and cell-based therapy. | 25,189,198 | [
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Is prophylactic psychiatry around the corner? combating adolescent oxidative stress for adult psychosis and schizophrenia. | Early detection and intervention are key principles in clinical medicine and psychiatry. In this issue of Neuron, Cabungcal et al. (2014) demonstrate that prophylactic treatment with antioxidants in adolescence prevents adult deficits in a rat model relevant to schizophrenia. | 25,189,204 | [
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Same-Sex Domestic Violence: Prevalence, Unique Aspects, and Clinical Implications. | Domestic violence is a significant public health issue. Prevalence rates for same-sex domestic violence vary because of methodological issues related to recruitment and definitions of sexual orientation. However, such prevalence rates are currently considered to be similar to slightly greater than other-sex prevalence rates. Research has identified differences between same-sex domestic violence and other-sex domestic violence, including internalized and externalized stressors associated with being a sexual minority that interact with domestic violence to create or exacerbate vulnerabilities, higher risk for complex trauma experiences, and difficulties accessing services. This review provides a critical review of the literature, focusing upon empirical findings regarding same-sex domestic violence. | 25,189,218 | [
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Procalcitonin guidance for reduction of antibiotic use in patients hospitalized with severe acute exacerbations of asthma: a randomized controlled study with 12-month follow-up. | Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma. In this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard (control group) antimicrobial therapy. In the control group, patients received antibiotics according to the attending physician's discretion; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary end point was antibiotic exposure; secondary end points were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma. PCT guidance reduced antibiotic prescription (48.9% versus 87.8%, respectively; P < 0.001) and antibiotic exposure (relative risk, 0.56; 95% confidence interval, 0.44 to 0.70; P < 0.001) compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay or clinical, laboratory and spirometry outcomes in both groups. Number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period. A PCT-guided strategy allows antibiotic exposure to be reduced in patients with severe acute exacerbation of asthma without apparent harm. Chinese Clinical Trial Register ChiCTR-TRC-12002534 (registered 26 September 2012). | 25,189,222 | [
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Detection of parent-of-origin effects for quantitative traits using general pedigree data. | Genomic imprinting is a genetic phenomenon in which certain alleles are differentially expressed in a parent-of-origin-specific manner, and plays an important role in the study of complex traits. For a diallelic marker locus in human, the parentalasymmetry tests Q-PAT(c) with any constant c were developed to detect parent-of-origin effects for quantitative traits. However, these methods can only be applied to deal with nuclear families and thus are not suitable for extended pedigrees. In this study, by making no assumption about the distribution of the quantitative trait, we first propose the pedigree parentalasymmetry tests Q-PPAT(c) with any constant c for quantitative traits to test for parent-of-origin effects based on nuclear families with complete information from general pedigree data, in the presence of association between marker alleles under study and quantitative traits. When there are any genotypes missing in pedigrees, we utilize Monte Carlo (MC) sampling and estimation and develop the Q-MCPPAT(c) statistics to test for parent-of-origin effects. Various simulation studies are conducted to assess the performance of the proposed methods, for different sample sizes, genotype missing rates, degrees of imprinting effects and population models. Simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects and Q-PPAT(c) are robust to population stratification. In addition, the power comparison demonstrates that Q-PPAT(c) and Q-MCPPAT(c) for pedigree data are much more powerful than Q-PAT(c) only using two-generation nuclear families selected from extended pedigrees. | 25,189,228 | [
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Patterns of microsatellite evolution inferred from the Helianthus annuus (Asteraceae) transcriptome. | The distribution of microsatellites in exons, and their association with gene ontology (GO) terms is explored to elucidate patterns of microsatellite evolution in the common sunflower, Helianthus annuus. The relative position, motif, size and level of impurity were estimated for each microsatellite in the unigene database available from the Compositae Genome Project (CGP), and statistical analyses were performed to determine if differences in microsatellite distributions and enrichment within certain GO terms were significant. There are more translated than untranslated microsatellites, implying that many bring about structural changes in proteins. However, the greatest density is observed within the UTRs, particularly 5'UTRs. Further, UTR microsatellites are purer and longer than coding region microsatellites. This suggests that UTR microsatellites are either younger and under more relaxed constraints, or that purifying selection limits impurities, and directional selection favours their expansion. GOs associated with response to various environmental stimuli including water deprivation and salt stress were significantly enriched with microsatellites. This may suggest that these GOs are more labile in plant genomes, or that selection has favoured the maintenance of microsatellites in these genes over others. This study shows that the distribution of transcribed microsatellites in H. annuus is nonrandom, the coding region microsatellites are under greater constraint compared to the UTR microsatellites, and that these sequences are enriched within genes that regulate plant responses to environmental stress and stimuli. | 25,189,238 | [
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High-risk human papillomavirus in Galicia, Spain: prevalence and evaluation of the sample representativeness. | The prevalence of high-risk genotypes of the human papillomavirus (HR-HPV) in Galicia remained unknown before the introduction of the HPV vaccine. The objective of this study was to estimate this prevalence in non-vaccinated women when vaccination against HR-HPV started. Sample representativeness was also evaluated. Female volunteers aged 16-64 years, residents in Galicia, Spain, completed a questionnaire and provided biological samples for a virological study and for cytology. The sample was weighted; prevalence rates were estimated and are shown with 95% confidence intervals. Virological results were available for 1703 women. HR-HPV prevalence was 10.1%, decreasing notably at ages above 30 years. HPV-16 was the most frequent genotype and 3.6% of women were infected by more than one genotype. No adjustment was necessary to generalize the results of the study. In Galicia in 2009 there would be 96 400 women aged 16-64 years infected with HR-HPV. It is possible to estimate HR-HPV prevalence in a population starting from a volunteer sample. | 25,189,272 | [
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Stressful life events and the perpetration of adolescent dating abuse. | Theoretical and empirical evidence suggests that stressful life events are associated with the perpetration of intimate partner violence among adults, but little attention has been given to the relationship between stressful life events and adolescent dating abuse, a prevalent form of violence that results in serious and long-lasting consequences. The current study addresses this gap by examining associations between family-, peer-, school-, and health-related stressful life events and the perpetration of both psychological and physical forms of dating abuse in a sample of 1,125 adolescents (54.6% female, 18% Black), and determining whether these associations are moderated by attributes of the family (closeness to parent) and the adolescent (sex and self-esteem). The total number of stressful events and school-related events were positively associated with the perpetration of psychological dating abuse and family-related events were related to the perpetration of psychological dating abuse for boys, but not girls. Closeness to parent buffered the effect of stressful health-related events on the perpetration of physical dating abuse, but exacerbated the effect of stressful family-related events on the perpetration of physical dating abuse. Health-related events were associated with physical perpetration for those with high, but not low self-esteem. Finally, the total number of stressful events and family-related events were related to the perpetration of physical dating abuse by boys, but not by girls. Taken together, these findings suggest that stressful life events play an important role in adolescent dating abuse, and should be taken into consideration when developing adolescent dating abuse prevention programs. | 25,189,287 | [
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Optical detection of CO and CO2 temperature dependent desorption from carbon nanotube clusters. | The development of new materials relies on high precision methods to quantify adsorption/desorption of gases from surfaces. One commonly used approach is temperature programmed desorption spectroscopy. While this approach is very accurate, it requires complex instrumentation, and it is limited to performing experiments under high vacuum, thus restricting experimental scope. An alternative approach is to integrate the surface of interest directly onto a detector face, creating an active substrate. One surface that has applications in numerous areas is the carbon nanotube (CNT). As such, an active substrate that integrates a CNT surface on a sensor and is able to perform measurements in ambient environments will have significant impact. In the present work, we have developed an active substrate that combines an optical sensor with a CNT cluster substrate. The optical sensor is able to accurately probe the temperature dependent desorption of carbon monoxide and carbon dioxide gases from the CNT cluster surface. This active substrate will enable a wide range of temperature dependent desorption measurements to be performed from a scientifically interesting material system. | 25,189,292 | [
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Academy of Medicine-Ministry of Health clinical practice guidelines: attention deficit hyperactivity disorder. | The Academy of Medicine (AMS) and the Ministry of Health (MOH) have developed the clinical practice guidelines on Attention Deficit Hyperactivity Disorder (ADHD) to provide doctors and patients in Singapore with evidence-based treatment for ADHD. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on ADHD, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html.The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines. | 25,189,301 | [
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Attitudes and perceptions of the general Malaysian public regarding family presence during resuscitation. | Family presence (FP) during resuscitation is an increasingly favoured trend, as it affords many benefits to the critically ill patient's family members. However, a previously conducted study showed that only 15.8% of surveyed Malaysian healthcare staff supported FP during resuscitation. This cross-sectional study used a bilingual self-administered questionnaire to examine the attitudes and perceptions of the general Malaysian public toward the presence of family members during resuscitation of their loved ones. The questionnaires were randomly distributed to Malaysians in three different states and in the federal territory of Kuala Lumpur. Out of a total of 190 survey forms distributed, 184 responses were included for analysis. Of the 184 respondents, 140 (76.1%) indicated that they favoured FP during resuscitation. The most common reason cited was that FP during resuscitation provides family members with the assurance that everything possible had been done for their loved ones (n = 157, 85.3%). Respondents who had terminal illnesses were more likely to favour FP during resuscitation than those who did not, and this was statistically significant (95.0% vs. 73.8%; p = 0.04). FP during resuscitation was favoured by a higher percentage of the general Malaysian public as compared to Malaysian healthcare staff. This could be due to differences in concerns regarding the resuscitation process between members of the public and healthcare staff. | 25,189,307 | [
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The Absent Interpreter in Administrative Detention Center Medical Units. | The particular situation of the French administrative detention center (ADC) medical units appears to be an exemplary case to study the difficulties facing medical practice. Indeed, the starting point of our inquiry was an amazing observation that needed to be addressed and understood: why are professional interpreters so seldom requested in ADC medical units, where one would expect that they would be "naturally" present? Aiming to fully explore the meanings of the "absent interpreter", this article takes into account the possible meanings of this situation: the recourse to professional interpreters in France is far from expected given cumulative evidence of its benefits; perceptions of illegal immigrants and medical habitus itself may both hamper the use of a third party; the ADCs are a very stressful place for healthcare professionals, with conflicting missions, political issues enmeshed with medical goals, and heavy affective burden that may lead to self-protection. Silencing voices of suffering others might be seen as the hidden indecent truth of the "absent interpreter". These reflections open a window to a larger issue with regard to the full range of medicine: what are the place, the role and the function of patient's words and narratives in contemporary medicine? The highly invested somatic perspective and its political corollary giving primacy to bare life harbor potential risks of obscuring speeches and undervaluing narratives. | 25,189,317 | [
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Bilateral Achilles Tendon Ruptures Associated With Ciprofloxacin Use in the Setting of Minimal Change Disease: Case Report and Review of the Literature. | Fluoroquinolones are widely used antibiotics; however, numerous side effects have been reported in published studies, including a spectrum of tendinopathies, affecting numerous anatomic sites. Several risk factors have been identified, including advanced age (>60 years), corticosteroid use, renal failure or dialysis, female sex, and nonobesity. We present the case of an elderly male with minimal change disease treated with glucocorticoids and acute kidney injury, who sustained spontaneous nontraumatic bilateral Achilles tendon tears 4 days after initiating ciprofloxacin. | 25,189,336 | [
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Loss of keratinocytic RXRα combined with activated CDK4 or oncogenic NRAS generates UVB-induced melanomas via loss of p53 and PTEN in the tumor microenvironment. | Understanding the molecular mechanisms behind formation of melanoma, the deadliest form of skin cancer, is crucial for improved diagnosis and treatment. One key is to better understand the cross-talk between epidermal keratinocytes and pigment-producing melanocytes. Here, using a bigenic mouse model system combining mutant oncogenic NRAS(Q61K) (constitutively active RAS) or mutant activated CDK4(R24C/R24C) (prevents binding of CDK4 by kinase inhibitor p16(INK4A)) with an epidermis-specific knockout of the nuclear retinoid X receptor alpha (RXRα(ep-/-)) results in increased melanoma formation after chronic ultraviolet-B (UVB) irradiation compared with control mice with functional RXRα. Melanomas from both groups of bigenic RXRα(ep-/-) mice are larger in size with higher proliferative capacity, and exhibit enhanced angiogenic properties and increased expression of malignant melanoma markers. Analysis of tumor adjacent normal skin from these mice revealed altered expression of several biomarkers indicative of enhanced melanoma susceptibility, including reduced expression of tumor suppressor p53 and loss of PTEN, with concomitant increase in activated AKT. Loss of epidermal RXRα in combination with UVB significantly enhances invasion of melanocytic cells to draining lymph nodes in bigenic mice expressing oncogenic NRAS(Q61K) compared with controls with functional RXRα. These results suggest a crucial role of keratinocytic RXRα to suppress formation of UVB-induced melanomas and their progression to malignant cancers in the context of driver mutations such as activated CDK4(R24C/R24C) or oncogenic NRAS(Q61K). These findings suggest that RXRα may serve as a clinical diagnostic marker and therapeutic target in melanoma progression and metastasis. | 25,189,354 | [
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Computer-aided detection of exophytic renal lesions on non-contrast CT images. | Renal lesions are important extracolonic findings on computed tomographic colonography (CTC). They are difficult to detect on non-contrast CTC images due to low image contrast with surrounding objects. In this paper, we developed a novel computer-aided diagnosis system to detect a subset of renal lesions, exophytic lesions, by (1) exploiting efficient belief propagation to segment kidneys, (2) establishing an intrinsic manifold diffusion on kidney surface, (3) searching for potential lesion-caused protrusions with local maximum diffusion response, and (4) exploring novel shape descriptors, including multi-scale diffusion response, with machine learning to classify exophytic renal lesions. Experimental results on the validation dataset with 167 patients revealed that manifold diffusion significantly outperformed conventional shape features (p<1e-3) and resulted in 95% sensitivity with 15 false positives per patient for detecting exophytic renal lesions. Fivefold cross-validation also demonstrated that our method could stably detect exophytic renal lesions. These encouraging results demonstrated that manifold diffusion is a key means to enable accurate computer-aided diagnosis of renal lesions. | 25,189,363 | [
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Tanshinol protects human umbilical vein endothelial cells against hydrogen peroxide‑induced apoptosis. | The present study was designed to investigate the effect of tanshinol on hydrogen peroxide (H2O2)‑induced apoptosis in human umbilical vein endothelial cells (HUVECs), and to determine the underlying mechanisms. HUVECs were pre‑incubated with tanshinol (25‑200 µM) for 24 h, followed by an incubation with 600 µM H2O2 for 6 h. The cell viability was assessed using MTT reagent and the level of cell death was determined by measuring lactate dehydrogenase (LDH) activity. Superoxide dismutase (SOD) activity, levels of malondialdehyde (MDA), reactive oxygen species (ROS) production and NADPH oxidase activity were measured spectrophotometrically using commercially available kits. The apoptotic rate of the HUVECs was detected using Annexin‑V/propidium iodide (PI) staining, followed by flow cytometry analysis using a fluorescence microscope. The protein expression of SOD‑1, SOD‑2, B‑cell lymphoma‑2 (Bcl‑2), cytochrome c and caspase‑3 was determined by western blot analysis. Pretreatment with tanshinol resulted in a significant increase in the cellular viability of HUVECs and SOD activity, and a decrease of cell apoptosis, MDA levels and ROS production, induced by H2O2. These findings were accompanied by the upregulation of Bcl‑2 protein expression, reduction in the release of cytochrome c from the mitochondria to the cytosol and a downregulation of caspase‑3 protein expression. This study showed that tanshinol protects against atherosclerosis by preventing H2O2‑induced apoptosis of HUVECs. These effects appear to be mediated by enhancing the antioxidant defenses and preserving the mitochondrial function of the cells. | 25,189,379 | [
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Comparative secretome analysis of cholangiocarcinoma cell line in three-dimensional culture. | Cholangiocarcinoma (CCA) is a lethal malignancy which occurs with relatively high incidence in Thailand. This cancer is often difficult to diagnose and associated with high mortality. The secretome, containing the secreted proteins from cells, are potentially useful as biomarkers of cancers. Since three-dimensional (3D) cell culture may mimic growth characteristics and microenvironment of solid tumors in vivo better than monolayer culture, we have developed culture of CCA in natural collagen-based scaffold, to enable analysis of the secretome by 2DE. Our results indicated that CCA growth in 3D environment alters cell shape significantly and enhances extracellular matrix deposition. Interestingly, more secreted proteins were detected from 3D culture compared to monolayer culture. Secretome analysis using 2DE coupled with LC-MS/MS demonstrated 10 secreted proteins uniquely found in 3D culture. Moreover, 25 proteins were enriched in 3D culture compared to monolayer culture, including 14-3-3 σ, triosephosphate isomerase, phosphoglycerate mutase 1, α-enolase, and L-plastin. Immunoblotting was used to confirm the presence of L-plastin in conditioned media of CCA and of hepatocellular carcinoma (HCC) cell lines. The results revealed that L-plastin, an actin bundling protein, was uniquely expressed only in the CCA cell line and could be a promising biomarker for differential diagnosis of CCA compared to HCC. | 25,189,380 | [
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0.279261... |
Dual effect of interferon (IFNγ)-induced nitric oxide on tumorigenesis and intracellular bacteria. | Nitric oxide (NO) is a key messenger involved in numerous physiological functions including inflammatory and immune responses. The functions of NO and their underlying mechanisms have been elucidated by extensive studies over the past 10 years. However, the complexity of the interactions between different levels of NO and multiple aspects of tumor development/progression as well as bacterial pathogenesis has led to apparently conflicting findings. The precise role of NO in bacterial and tumor pathogenesis involves a multitude of inter- and intracellular signaling pathways in which interferon gamma signaling and L-arginine metabolism are the major pathways involved in NO synthesis and regulation. The availability of the amino acid L-Arg can be a key factor to control the expression of inducible nitric oxide synthase (NOS2) and cellular NO levels. The role played by the NOS2/NO system both in bacterial pathogenesis and in tumor development is complex due to the dual role these molecules can play promoting or inhibiting infections and cancer. This duality brings to the table a double challenge to determine the net impact of NO on cancer or bacterial behavior and to define the therapeutic role of NO-centered anticancer or antibacterial strategies. We believe that a comprehensive and dynamic understanding of the cascade of molecular and cellular events underlying tumor biology and bacterial pathogenesis that are affected by NO will allow researchers to exploit the potential antitumor and antibacterial properties of drugs interfering with NO metabolism. The contrasting roles of NO/NOS2 in these processes are clarified in this chapter. | 25,189,392 | [
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Antiobesogenic role of endothelial nitric oxide synthase. | The prevalence of obesity has increased remarkably in the past four decades. Because obesity can promote the development of type 2 diabetes and cardiovascular disease, understanding the mechanisms that engender weight gain and discovering safe antiobesity therapies are of critical importance. In particular, the gaseous signaling molecule, nitric oxide (NO), appears to be a central factor regulating adiposity and systemic metabolism. Obese and diabetic states are characterized by a deficit in bioavailable NO, with such decreases commonly attributed to downregulation of endothelial NO synthase (eNOS), loss of eNOS activity, or quenching of NO by its reaction with oxygen radicals. Gain-of-function studies, in which vascular-derived NO has been increased pharmacologically or genetically, reveal remarkable actions of NO on body composition and systemic metabolism. This review addresses the metabolic actions of eNOS and the potential therapeutic utility of harnessing its antiobesogenic effects. | 25,189,393 | [
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Characterization of β-glucosidase produced by the white rot fungus Flammulina velutipes. | β-Glucosidase production by the white rot fungus Flammulina velutipes CFK 3111 was evaluated using different carbon and nitrogen sources under submerged fermentation. Maximal extracellular enzyme production was 1.6 U/ml, corresponding to a culture grown in sucrose 40 g/l and asparagine 10 g/l. High production yield was also obtained with glucose 10 g/l and asparagine 4 g/l medium (0.5 U/ml). Parameters affecting the enzyme activity were studied using p-nitrophenyl-β-D-glucopyranoside as the substrate. Optimal activity was found at 50°C and pHs 5.0 to 6.0. Under these conditions, β-glucosidase retained 25% of its initial activity after 12 h of incubation and exhibited a half-life of 5 h. The addition of MgCl2, urea, and ethanol enhanced the β-glucosidase activity up to 47%, whereas FeCl2, CuSO4, Cd(NO3)2, and cetyltrimethylammonium bromide inflicted a strong inhibitory effect. Glucose and cellobiose also showed an inhibitory effect on the β-glucosidase activity in a concentration-dependent manner. The enzyme had an estimated molecular mass of 75 kDa. To the best of our knowledge, F. velutipes CFK 3111 β-glucosidase production is amongst the highest reported to date, in a basidiomycetous fungus. | 25,189,408 | [
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Phylogenetic diversity of dominant bacterial and archaeal communities in plant-microbial fuel cells using rice plants. | In this study, the phylogenetic diversities of bacterial and archaeal communities in a plantmicrobial fuel cell (P-MFC) were investigated together with the environmental parameters, affecting its performance by using rice as a model plant. The beneficial effect of the plant appeared only during a certain period of the rice-growing season, at which point the maximum power density was approximately 3-fold higher with rice plants. The temperature, electrical conductivity (EC), and pH in the cathodic and anodic compartments changed considerably during the rice-growing season, and a higher temperature, reduced difference in pH between the cathodic and anodic compartments, and higher EC were advantageous to the performance of the P-MFC. A 16S rRNA pyrosequencing analysis showed that the 16S rRNAs of Deltaproteobacteria and those of Gammaproteobacteria were enriched on the anodes and the cathodes, respectively, when the electrical circuit was connected. At the species level, the operational taxonomic units (OTUs) related to Rhizobiales, Geobacter, Myxococcus, Deferrisoma, and Desulfobulbus were enriched on the anodes, while an OTU related to Acidiferrobacter thiooxydans occupied the highest proportion on the cathodes and occurred only when the circuit was connected. Furthermore, the connection of the electrical circuit decreased the abundance of 16S rRNAs of acetotrophic methanogens and increased that of hydrogenotrophic methanogens. The control of these physicochemical and microbiological factors is expected to be able to improve the performance of P-MFCs. | 25,189,409 | [
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Simultaneous adsorption of SO2 and NO from flue gas over mesoporous alumina. | Mesoporous alumina (MA) with a higher ability to simultaneously remove SO2 and NO was prepared by the evaporation-induced self-assembly process. The adsorption capacities of MA are 1.79 and 0.702 mmol/g for SO2 and NO, respectively. The Brunauer-Emmett-Teller method was used to characterize the adsorbent. Simultaneous adsorption of SO2 and NO from flue gas over MA in different operating conditions had been studied in a fixed bed reactor. The effects of temperature, oxygen concentration and water vapour were investigated. The experimental results showed that the optimum temperature for MA to simultaneously remove SO2 and NO was 90°C. The simultaneous adsorption capacities of SO2 and NO could be enhanced by increasing O2 when its concentration was below 5%. The changes of simultaneous adsorption capacities were not obvious when O2 concentration was above 5%. The increase in relative humidity results in an increase after dropping of SO2 adsorption capacity, whereas the adsorption capacity of NO showed an opposite trend. The results suggest that MA is a great adsorbent for simultaneous removal of SO2 and NO from flue gas. | 25,189,414 | [
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Preparation of multi-shelled conductive polymer hollow microspheres by using Fe₃O₄ hollow spheres as sacrificial templates. | Multi-shelled conductive polymer hollow microspheres were successfully generated by using Fe3O4 hollow microspheres as sacrificial templates via a programmed reaction-temperature process. Moreover, the multi-shelled PEDOT microspheres exhibited superb microwave absorption performance. | 25,189,419 | [
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Electrocatalytic activity of Pt subnano/nanoclusters stabilized by pristine graphene nanosheets. | Downsizing the Pt particle to the atomic level in the electro-catalysts is highly desirable to enhance its utilization efficiency in fuel cells. In this study, Pt subnano/nanoclusters were stabilized by the pristine graphene nanosheets (GNSs) derived from chemical vapor deposition and the resulting Pt/GNS hybrids were examined as catalysts for electro-oxidation of alcohols (methanol, ethanol, ethylene glycol and glycerol). In spite of the strong hydrophobic surface, the GNS was proved to be a promising catalyst support because the edges and defects in the GNS could effectively anchor and stabilize the Pt subnano/nanoclusters. The Pt/GNS catalyst showed an extremely high electrochemical active surface area and superior catalytic activity for alcohol oxidation compared with the commercial Pt/carbon black catalyst. The enhanced catalytic performance was attributed to the presence of the discrete Pt subnano/nanoclusters as well as the modulation of the electronic properties of Pt nanoparticles through the chemical interaction of Pt atoms with the edges and defects of the GNS support. | 25,189,421 | [
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Menstrual pain and epithelial ovarian cancer risk. | Menstrual pain is associated with increased production of inflammatory molecules, such as prostaglandins. Inflammation is involved in pathogenesis of several cancers, including ovarian cancer. In this study, we examined the association between menstrual pain and risk of ovarian cancer. We conducted a case-control study with 2,028 cases of epithelial ovarian cancer and 2,091 age- and study center-matched controls. Women were asked to report the severity of menstrual pain during their twenties and thirties, when not using oral contraceptives or breastfeeding. We used an unconditional logistic regression to evaluate the association between menstrual pain and epithelial ovarian cancer risk overall, and polytomous logistic regression to evaluate whether the association differed across tumor subtypes. Risk of ovarian cancer was increased in women with moderate (OR 1.22, 95 % CI 1.05-1.42) and severe pain (OR 1.34, 95 % CI 1.09-1.65) compared to women with no or mild pain during menstrual period. The association differed by histologic subtypes, with significant associations for severe pain with endometrioid (OR 1.64, 95 % CI 1.15-2.34) and clear cell tumors (OR 1.91, 95 % CI 1.11-3.28). Our data suggest that moderate and severe pain during menstrual period are associated with increased risk of epithelial ovarian cancer. Due to high prevalence of menstrual pain in women of reproductive age, this observation warrants further studies. | 25,189,423 | [
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Microvascular dysfunction in the context of diabetic neuropathy. | Microvascular dysfunction in diabetes plays a crucial role in the development of diabetic complications. The skin, as one of the most accessible organs, serves as a model for the investigation of microvascular dysfunction. Several non-invasive, mostly laser-Doppler-based methods have been developed lately to assess microvascular function in the skin. Microvascular functional changes occur even in the prediabetic state and become more complex with overt diabetes, being exacerbated by the presence of peripheral and/or autonomic diabetic neuropathy. The present article aims at shedding light on the implication of endothelial and neurovascular dysfunction in microvascular changes in diabetes, highlighting the contribution of different forms of diabetic neuropathy. | 25,189,434 | [
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0.06677... |
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