title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Emotion, power and identity. Emotional display of envy when taking on management roles in a professional hierarchy. | Drawing on a previous study of organising processes and the construction of identity in a Swedish geriatric clinic, the impact of emotions is brought to the fore in the interpretation of power relations among professional groups. The purpose of this paper is to find a way to interpret emotions as discursively constructed in organising processes. A sequence of critical events is described where leading positions were negotiated at the clinic. Senior physicians and head nurses are highlighted as opposing forces in a struggle where envious emotions seemed to be a driving force in the political interplay. The empirical material in this paper comes from the previous study. It is a set of participant observations and parts of interviews that took place before and after the implementation of a new organisational plan for the clinic. The envious and regressive undertone in the relationships between the actors made them act for egocentric reasons instead of creating new ways of collaborating and learning new leading roles. The power relations of the medical hierarchy were reproduced, which made new ways of relating threatening and difficult to achieve. The results of the study confirm that people involved and perhaps in conflict with each other have to be able to, or get help to, make sense of their emotional experiences to employ them constructively. Otherwise they fall back into well-known patterns in order to feel secure. A vital part of learning in change processes is the support to individuals and groups in gaining emotional understanding of themselves and others. Leaders and managers who often are initiators of change ought to be aware of the importance of emotional support in change processes. If they are not, they are destined to be a part of the confusion and unable to lead or support their staff in change processes. | 25,241,599 | [
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Effects of low molecular weight agar and Lactobacillus plantarum on growth performance, immunity, and disease resistance of basa fish (Pangasius bocourti, Sauvage 1880). | This study evaluated effects of low molecular weight agar (LMWA) and Lactobacillus plantarum singly or combined on growth performance, immunity and disease resistance of basa fish (Pangasius bocourti). Two hundred forty fish were divided into four treatments, i.e. 0 g kg(-1) LMWA (Control), 2 g kg(-1) LMWA, 10(8) cfu g(-1)L. plantarum, and 2 g kg(-1) LMWA + 10(8) cfu g(-1)L. plantarum. Following 7, 14 and 28 days of the treatment, specific growth rate (SGR), feed conversion ratio (FCR), serum lysozyme, phagocytosis, respiratory burst and alternative complement activity (ACP) were measured. A Completely Randomized Design with four replications was applied. At the end of the feeding trial, five fish were randomly selected for a challenge test against Aeromonas hydrophila. The results showed that fish fed diet of 2 g kg(-1) LMWA and 10(8) cfu g(-1) of L. plantarum singly or combined significantly enhanced SGR, FCR, serum lysozyme, phagocytosis, respiratory burst, alternative complement activities and post-challenge survival rate of P. bocourti. The results inferred that dietary of LMWA and L. plantarum stimulated growth, immunity and disease resistance of the P. bocourti. | 25,241,604 | [
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Variability of DKA Management Among Pediatric Emergency Room and Critical Care Providers: A Call for More Evidence-Based and Cost-Effective Care? | Management protocols have been shown to be effective in the pediatric emergency medicine (PEM) and pediatric critical care (PCC) settings. Treatment protocols define clear goals which are achieved with consistency in implementation. Over the last decade, many new recommendations have been proposed on managing diabetic ketoacidosis (DKA). Although no perfect set of guidelines exist, many institutions are developing DKA treatment protocols. We sought to determine the variability between institutions in implementation of these protocols. | 25,241,617 | [
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Analysis of the intrahepatic ductular reaction and progenitor cell responses in hepatitis C virus recurrence after liver transplantation. | Fibrosis in livers with hepatitis C virus (HCV) recurrence after liver transplantation (LT) can be rapidly progressive, and the mechanisms underlying this process are poorly understood. In livers with HCV infections in the non-LT setting, there is a significant relationship between the development of structures known as the ductular reaction (DR), hepatic progenitor cells (HPCs), and fibrosis. This study characterizes the DR, HPCs, and fibrosis associated with HCV recurrence after LT. Immunohistochemistry and confocal microscopy were used to characterize the DR, HPC, and fibrosis in liver biopsy specimens. Key findings were confirmed in a separate, independent cohort. The initial characterization cohort had 194 biopsy samples from 105 individuals with HCV recurrence after LT. The immunophenotype, morphology, and location of the DR were consistent with an HPC origin. The DR correlated with intrahepatic fibrosis (rs = 0.529, P < 0.001) and the number of activated hepatic stellate cells (HSCs; rs = 0.446, P < 0.001). There was an early occurrence of hepatocyte replicative arrest as well as increased hepatocyte proliferation that correlated with the DR (rs = 0.295, P < 0.001). Replicative arrest preceded hepatocyte proliferation in early-stage injury. Hepatocyte proliferation decreased with advanced fibrosis; in contrast, the extent of the DR and the number of activated HSCs continued to increase. In the second cohort of 37 individuals, the DR and the number of HPCs similarly correlated with fibrosis and inflammation after LT. In conclusion, this is the first characterization of the DR in HCV-associated liver injury after LT. There was a significant correlation between the DR and the development of progressive fibrosis in HCV recurrence. These results suggest a pivotal role for both the DR and the HPC responses in the aggressive fibrosis seen with HCV recurrence after LT. | 25,241,637 | [
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Species-specific defence responses facilitate conspecifics and inhibit heterospecifics in above-belowground herbivore interactions. | Conspecific and heterospecific aboveground and belowground herbivores often occur together in nature and their interactions may determine community structure. Here we show how aboveground adults and belowground larvae of the tallow tree specialist beetle Bikasha collaris and multiple heterospecific aboveground species interact to determine herbivore performance. Conspecific aboveground adults facilitate belowground larvae, but other aboveground damage inhibits larvae or has no effect. Belowground larvae increase conspecific adult feeding, but decrease heterospecific aboveground insect feeding and abundance. Chemical analyses and experiments with plant populations varying in phenolics show that all these positive and negative effects on insects are closely related to root and shoot tannin concentrations. Our results show that specific plant herbivore responses allow herbivore facilitation and inhibition to co-occur, likely shaping diverse aboveground and belowground communities. Considering species-specific responses of plants is critical for teasing apart inter- and intraspecific interactions in aboveground and belowground compartments. | 25,241,651 | [
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The study on the nanomachining property and cutting model of single-crystal sapphire by atomic force microscopy. | This study focused on the nanomachining property and cutting model of single-crystal sapphire during nanomachining. The coated diamond probe is used to as a tool, and the atomic force microscopy (AFM) is as an experimental platform for nanomachining. To understand the effect of normal force on single-crystal sapphire machining, this study tested nano-line machining and nano-rectangular pattern machining at different normal force. In nano-line machining test, the experimental results showed that the normal force increased, the groove depth from nano-line machining also increased. And the trend is logarithmic type. In nano-rectangular pattern machining test, it is found when the normal force increases, the groove depth also increased, but rather the accumulation of small chips. This paper combined the blew by air blower, the cleaning by ultrasonic cleaning machine and using contact mode probe to scan the surface topology after nanomaching, and proposed the "criterion of nanomachining cutting model," in order to determine the cutting model of single-crystal sapphire in the nanomachining is ductile regime cutting model or brittle regime cutting model. After analysis, the single-crystal sapphire substrate is processed in small normal force during nano-linear machining; its cutting modes are ductile regime cutting model. In the nano-rectangular pattern machining, due to the impact of machined zones overlap, the cutting mode is converted into a brittle regime cutting model. | 25,241,676 | [
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Comparison of the detection rates of RT-PCR and virus culture using a combination of specimens from multiple sites for enterovirus-associated encephalomyelitis during enterovirus 71 epidemic. | Enterovirus (EV) 71 may cause severe neurological illness in the pediatric population. The present study aimed to compare the detection rates of reverse transcription-polymerase chain reaction (RT-PCR) with pan-EV/EV71 type- specific primers and virus culture (VC) for the identification of EV and EV71 using specimens from multiple sites. In total, specimens from throat/rectal swabs, cerebrospinal fluid (CSF), and blood from 66 patients diagnosed with EV encephalomyelitis were subjected to both RT-PCR and VC for detecting the presence of pan-EV and EV71. The results revealed that the positive RT-PCR rate was higher in throat swabs (60.6%) and rectum swabs (50.0%) than in CSF (16.7%) and blood (15.6%). The same trend was also observed in case of VC: throat swabs (22.7%), rectum swabs (10.6%), and blood (3.0%). The detection rate of EV encephalomyelitis by RT-PCR was 90.9% for all samples, 63.6% of which were subtyped as EV71. The detection rates of RT-PCR were superior to those of VC, and identification using specimens from throat/rectal swabs yielded higher positive results. These findings may help physicians to identify the etiologies at an early stage during EV71 epidemics and to make emergent medical decisions for minimizing patient morbidity and mortality. | 25,241,681 | [
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Phylogenetic analysis of the oriental-Palearctic-Afrotropical members of Anopheles (Culicidae: Diptera) based on nuclear rDNA and mitochondrial DNA characteristics. | The phylogenetic relationships of Anopheles spp. at the junction of Oriental, Palearctic, and Afrotropical regions in the Iranian plateau were investigated using molecular markers. A 711-bp mitochondrial DNA cytochrome oxidase C subunit I (COI) fragment and the entire second internal transcribed spacer (ITS2) region (286-576 bp) of the nuclear ribosomal DNA (rDNA-ITS2) were sequenced from 14 and 28 taxa, respectively. The analyses included 12 species within Anopheles and 4 within the Myzorhynchus Series of the subgenus Anopheles, 8 within Neocellia, 6 within Myzomyia, 3 within Paramyzomyia, and 1 within the Pyretophorus Series of the subgenus Cellia. The congruent tree topologies of both molecular markers strongly supported monophyly of subgenera Anopheles and Cellia. Phylogenetic trees constructed on the basis of ITS2 sequences could accurately categorize all of the series according to the classical taxonomy but could not distinguish Pyretophorus (Anopheles subpictus) from Paramyzomyia Series. Although sequence data of the COI region were available for only 14 species, the inferred trees revealed good classification among the series but could not show the monophyletic relationship of Cellia spp. Except for a few cases, the tree inferred from ITS2 sequences revealed the best classification for the species studied. The molecular data could significantly improve our understanding of the phylogenetic position of the taxa. | 25,241,686 | [
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Organization of nosocomial infection control measures and local networks for infectious disease control in middle-scale hospitals in Japan. | The aims of this study were to assess nosocomial infection control measures at middle-scale hospitals throughout Japan. Of the 823 hospitals participating in this questionnaire-based survey, more than half of the middle-scale hospitals have implemented nosocomial infection control measures, including infection surveillance or infection control rounds, while acknowledging a shortage of infection control staff. These hospitals most frequently consulted public health centers to obtain information and advice. Improved nosocomial infection control in middle-scale hospitals requires sufficient staffing and a local network, with active participation by public health centers. | 25,241,689 | [
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Oseltamivir-resistant seasonal A(H1N1) and A(H1N1)pdm09 influenza viruses from the 2007/2008 to 2012/2013 season in Nara Prefecture, Japan. | We examined the incidence of oseltamivir-resistant seasonal A(H1N1) and A(H1N1)pdm09 influenza viruses from the 2007/2008 to 2012/2013 season in Nara Prefecture, Japan. To detect the oseltamivir resistance marker in neuraminidase (NA), 365 influenza viruses (60 seasonal A(H1N1) and 305 A(H1N1)pdm09) were sequenced. The H275Y mutation in the NA gene, which confers resistance to oseltamivir, was identified in 93.8% (30/32) of seasonal A(H1N1) viruses that were circulating during the 2008/2009 season. Moreover, the detection rate of oseltamivir-resistant A(H1N1)pdm09 viruses was 4.1% (3/74) and 2.8% (5/180) in the 2009/2010 and 2010/2011 season, respectively. Four cases of oseltamivir-resistant A(H1N1)pdm09 virus infection occurred in the same hematology ward during the 2010/2011 season. Our data show a low frequency of oseltamivir-resistant A(H1N1)pdm09 virus in Nara Prefecture but suggested the possibility of human-to-human transmission of this virus. | 25,241,691 | [
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Decrease in junior resident case volume after 2011 ACGME work hours. | To determine how the new 2011 Accreditation Council for Graduate Medical Education work hours affected case volume across postgraduate year (PGY) levels of surgical trainees. Retrospective review of Accreditation Council for Graduate Medical Education case logs of surgical residents at Beth Israel Deaconess Medical Center from 2006 to 2013. Tertiary care center. All categorical surgical residents from 2006 to 2013. PGY-1 cases decreased from 139 (122.25-172.5) to 111.5 (102.25-117.5) (p = 0.003). PGY-2 case volume decreased as well from 162 (151.5-192) to 126 (95.5-173) (p = 0.011). Only 45% of PGY-2 residents performed more than 250 major cases after the work hours changed compared with 82% of residents before 2011. PGY-3 cases increased from 263 (215-309) to 309 (282-340) (p = 0.0038). Cases performed by PGY-4 and PGY-5 residents were not statistically different. Total cases performed by graduating chiefs, however, has increased from 987 (848.5-1050) to 1090 (1033-1145) (p = 0.0006). Intern and PGY-2 case volume has declined at our institution as new work-hour regulations took effect in 2011. However, PGY-3 case volume increased significantly, and graduating chiefs are graduating with more cases. The work hours do not appear to have had the intended result of improving intern educational experience from a standpoint of case volume. Significant programmatic changes will likely be required to achieve the 250-case minimum by the end of PGY-2 year, as per 2014 American Board of Surgery requirements. | 25,241,704 | [
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Piecewise cause-specific association analyses of multivariate untied or tied competing risks data. | In this paper we extend the bivariate hazard ratio to multivariate competing risks data and show that it is equivalent to the cause-specific cross hazard ratio. Two approaches are proposed to estimate these two equivalent association measures. One extends the plug-in estimator, and the other adapts the pseudo-likelihood estimator for bivariate survival data to multivariate competing risks data. The asymptotic properties of the extended estimators are established by using empirical processes techniques. The extended plug-in and pseudo-likelihood estimators have comparable performance with the existing U-statistic when the data have no tied events. However, in many applications, there are tied events in which all the three estimators are found to produce biased results. To our best knowledge, we are not aware of any association analysis for multivariate competing risks data that has considered tied events. Hence we propose a modified U-statistic to specifically handle tied observations. The modified U-statistic clearly outperforms the other estimators when there are rounding errors. All methods are applied to the Cache County Study to examine mother-child and sibship associations in dementia among this aging population, where the event times are rounded to the nearest integers. The modified U performs consistently with our simulation results and provides more reliable results in the presence of tied events. | 25,241,735 | [
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Methylation and transcripts expression at the imprinted GNAS locus in human embryonic and induced pluripotent stem cells and their derivatives. | Data from the literature indicate that genomic imprint marks are disturbed in human pluripotent stem cells (PSCs). GNAS is an imprinted locus that produces one biallelic (Gsα) and four monoallelic (NESP55, GNAS-AS1, XLsα, and A/B) transcripts due to differential methylation of their promoters (DMR). To document imprinting at the GNAS locus in PSCs, we studied GNAS locus DMR methylation and transcript (NESP55, XLsα, and A/B) expression in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) derived from two human fibroblasts and their progenies. Results showed that (1) methylation at the GNAS locus DMRs is DMR and cell line specific, (2) changes in allelic transcript expression can be independent of a change in allele-specific DNA methylation, and (3) interestingly, methylation at A/B DMR is correlated with A/B transcript expression. These results indicate that these models are valuable to study the mechanisms controlling GNAS methylation, factors involved in transcript expression, and possibly mechanisms involved in the pathophysiology of pseudohypoparathyroidism type 1B. | 25,241,742 | [
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Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). | to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes. | 25,241,753 | [
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Protocol to evaluate the impact of yoga supplementation on cognitive function in schizophrenia: a randomised controlled trial. | Schizophrenia (SZ) is a chronic illness that is treated symptomatically. Cognitive dysfunction is a core feature of SZ that is relatively intractable to pharmacotherapy. Yoga can improve cognitive function among healthy individuals. A recent open trial indicated significant benefits of yoga training (YT) in conjunction with conventional pharmacotherapy among patients with SZ. To describe the protocol for an ongoing randomised controlled trial designed to test whether the reported beneficial effects of YT on cognitive function among SZ patients can be replicated. Secondarily, the effects of YT on daily functioning living skills are evaluated. Consenting patients with SZ receive routine clinical treatment and are randomised to adjunctive YT, adjunctive physical exercise (PE) or treatment as usual (proposed N = 234 total, N = 78 in each group). The trial involves YT or PE 5 days a week and lasts 3 weeks. Participants are evaluated thrice over 6 months. Cognitive functions measured by Trail Making Test, University of Pennsylvania Neurocognitive Computerised Battery were primary outcome measures while clinical severity and daily functioning measured by Independent Living Skills Survey were secondary outcome measures. A total of 309 participants have been randomised as of 31 August 2013, which exceeded beyond 294 proposed after attrition. Once participants begin YT or PE they generally complete the protocol. No injuries have been reported. Short term YT is feasible and acceptable to Indian SZ patients. If beneficial effects of YT are detected, it will provide a novel adjunctive cognitive remediation strategy for SZ patients. | 25,241,756 | [
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Adrenocortical carcinoma in children: first population-based clinicopathological study with long-term follow-up. | Adrenocortical carcinoma (ACC) is rare in both adult and pediatric populations. Literature suggests significant differences between children and adults in presentation, histological properties and outcome. The aim of this first nationwide study on pediatric ACC was to describe the incidence, presentation, pathological characteristics, treatment and survival in The Netherlands. All ACC patients aged <20 years at diagnosis and registered in the population-based Netherlands Cancer Registry between 1993 and 2010 were included. Clinical data were extracted from medical records. Archival histological slides were collected via the Dutch Pathology Registry (PALGA). We compared our findings to all clinical studies on pediatric ACC that were found on PubMed. Based on the results, 12 patients were identified: 8 females and 4 males. The median age was 4.1 years (range 1.1-18.6). The population-based age-standardized incidence rate for patients <20 years was 0.18 per million person-years. Autonomous hormonal secretion was present in 10 patients. Seven patients were aged ≤4 years at diagnosis, 5 presented with localized disease and 2 with locally advanced disease. Five patients were aged ≥5 years, 3 presented with distant metastases and 1 with locally advanced disease. For all patients, histological examination displayed malignant characteristics. All patients aged ≤4 years at diagnosis survived; the median follow-up was 97 months (57-179 months). All patients aged ≥5 years died; the median survival was 6 months (0-38 months). Pediatric ACC is extremely rare in the Western world. The clinical outcome was remarkably better in patients aged ≤4 years. This is in accordance with less advanced stage of disease at presentation, yet contrasts with the presence of adverse histological characteristics. Clinical management in advanced disease is adapted from adult practice in the absence of evidence regarding pediatric ACC. | 25,241,764 | [
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"Are you available for the next 18 months?" - methods and aims of a longitudinal birth cohort study investigating a universal developmental surveillance program: the 'Watch Me Grow' study. | Universal developmental surveillance programs aimed at early identification and targeted early intervention significantly improve short- and long-term outcomes in children at risk of developmental disorders. However, a significant challenge remains in providing sufficiently rigorous research and robust evidence to inform policy and service delivery. This paper describes the methods of the 'Watch Me Grow' study that aims to maximise accurate early detection of children with developmental disorders through a partnership formed between policy makers, service providers and researchers. A mixed methods study design was developed consisting of: (1) a qualitative study of parents and health service providers to investigate barriers and enablers of developmental surveillance; (2) recruitment of a birth cohort and their longitudinal follow-up to 18 months of age to: a) assess risk factors for not accessing existing developmental surveillance programs and b) estimate the prevalence of children identified with developmental risk; (3) comparison of surveillance outcomes with a reference standard at 18 months of age to assess the diagnostic test accuracy of existing and alternative developmental surveillance tools; and (4) comparison of developmental surveillance models to inform policy recommendations. Data linkage will be used to determine the uptake and representativeness of the study participant group versus non-participants. The Watch Me Grow study is expected to provide a collaborative opportunity to enhance universal developmental surveillance for early accurate identification of developmental risk. This will also provide quality evidence about identification of developmental risk and access to services to be embedded in existing practice with linkages to policy development. | 25,241,772 | [
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[Clinicopathological and CT features of mucinous cystic neoplasms of the pancreas]. | To evaluate the clinicopathological and CT features of mucinous cystic neoplasms (MCNs) of the pancreas and analyze the correlative risk factors for malignant pancreatic mucinous cystic neoplasms. Ninety-eight patients who underwent curative resection for mucinous cystic neoplasms of the pancreas at PLA General Hospital from April 1994 to January 2013 were included in this study. All clinicopathological data available were retrospectively analyzed. All patients were divided into benign tumors + premalignant lesion group (70 patients) and malignant tumor group (28 patients). Clinicopathological and CT features of the mucinous cystic neoplasms of the pancreas and risk factors of malignant pancreatic mucinous cystic neoplasms were analyzed. Mucinous cystic neoplasms were seen mostly in perimenopausal women (71.4%, 70/98 cases,), and 51.0% (50/98 cases) of the patients had obvious clinical signs, mostly non-specific abdominal pain, but jaundice was present only in cases of malignant mucinous cystic neoplasms. Benign mucinous cystic neoplasms were mostly located in the distal pancreas (74.3%) and characterized with septa and thin cystic wall, while more malignant mucinous cystic neoplasms were located at the proximal pancreas (57.1%) and characterized with thick cystic wall and solid components. Univariate analysis showed that findings associated with malignancy gender, age ≥ 60, presence of symptoms, jaundice, weight loss, tumor location, margin, wall thickness, solid components and dilation of the main pancreatic duct were significantly correlated with malignant tumor development (P < 0.05 for all). The results of multiple logistic regression analysis showed that thick wall and solid components were independent prognostic factors for malignancy (OR = 31.417 and 34.976, P < 0.05 for both). Gender, age ≥ 60, presence of symptoms, jaundice, weight loss, tumor location, margin, wall thickness, solid components and dilation of the main pancreatic duct are important diagnostic indices of malignant mucinous cystic tumors of the pancreas, while thick wall and solid components are independent risk factors of malignant pancreatic mucinous cystic neoplasms. | 25,241,787 | [
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Serum metabonomic analysis of apoE(-/-) mice reveals progression axes for atherosclerosis based on NMR spectroscopy. | Atherosclerosis is a multifactorial and progressive disease commonly correlated with a high fat diet. The aim of this study was to identify potential biomarkers for the early diagnosis and monitoring of the progression of atherogenesis in apoE(-/-) mice using (1)H NMR-based metabonomics. The apoE(-/-) mice were split into four groups according to the duration of high fat feeding (0 w, 2 w, 4 w and 8 w), and each group possessed different pathological characteristics. Serum (1)H NMR-based metabonomics selectively captured the metabotypes that correlated with the degree of atherosclerosis, showing a time-dependent progression from the physiological to pathophysiological status. It was noted that changes in HDL, choline, taurine, glycine and glucose may be regarded as specific biomarkers of the early stage of atherosclerosis. With the progression of atherosclerosis, disorders in the metabolism of amino acids such as valine, alanine and methionine appeared when large atherosclerotic plaques existed. Multiple biochemical disorders involving lipid metabolism, energy and fatty acid metabolism were observed in the progression of atherosclerosis in apoE(-/-) mice. This study demonstrated that (1)H NMR-based metabonomics can provide biochemical information about the progression of atherogenesis and offer a non-invasive means to discover potential biomarkers for the onset and development of atherosclerosis. | 25,241,798 | [
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Diurnal fluctuations in HPA and neuropeptide Y-ergic systems underlie differences in vulnerability to traumatic stress responses at different zeitgeber times. | The hypothalamic-pituitary-adrenal (HPA) axis displays a characteristic circadian pattern of corticosterone release, with higher levels at the onset of the active phase and lower levels at the onset of the inactive phase. As corticosterone levels modify the response to stress and influence the susceptibility to and/or severity of stress-related sequelae, we examined the effects of an acute psychological trauma applied at different zeitgeber times (ZTs) on behavioral stress responses. Rats were exposed to stress either at the onset of the inactive-(light) phase (ZT=0) or at the onset of the active-(dark) phase (ZT=12). Their behavior in the elevated plus-maze and acoustic startle response paradigms were assessed 7 days post exposure for retrospective classification into behavioral response groups. Serum corticosterone levels and the dexamethasone suppression test were used to assess the stress response and feedback inhibition of the HPA axis. Immunoreactivity for neuropeptide Y (NPY) and NPY-Y1 receptor (Y1R) in the paraventricular (PVN) and arcuate (ARC) hypothalamic nuclei, hippocampus, and basolateral amygdala were measured. The behavioral effects of NPY/Y1R antagonist microinfused into the PVN 30 min before stress exposure during the inactive or active phase, respectively, were evaluated. PVN immunoreactivity for NPY and Y1R was measured 1 day after the behavioral tests. The time of day of the traumatic exposure markedly affected the pattern of the behavioral stress response and the prevalence of rats showing an extreme behavioral response. Rats exposed to the stressor at the onset of their inactive phase displayed a more traumatic behavioral response, faster post-exposure corticosterone decay, and a more pronounced stress-induced decline in NPY and Y1R expression in the PVN and arcuate hypothalamic nuclei. Blocking PVN Y1R before stress applied in the active phase, or administering NPY to the PVN before stress applied in the inactive phase, had a resounding behavioral effect. The time at which stress occurred significantly affected the behavioral stress response. Diurnal variations in HPA and NPY/Y1R significantly affect the behavioral response, conferring more resilience at the onset of the active phase and more vulnerability at the onset of the inactive phase, implying that NPY has a significant role in conferring resilience to stress-related psychopathology. | 25,241,802 | [
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Bilateral subtentorial empyema complicated with nosocomial acinectobacter ventriculitis: a case report. | Subtentorial subdural empyema is a rare and life threatening intracranial suppuration. It is usually an intracranial complication of otogenic infections. Early diagnosis and surgical drainage are the most important factors determining prognosis. The high mortality reported in the literature reflects the severity of subtentorial subdural empyema if proper management is delayed. Intracranial infections usually require between 4 to 6 weeks of intravenous antibiotics therapy. However, the prolonged duration of hospitalization as well as requirement for neurosurgically inserted indwelling devices may predispose these patients to new nosocomial infections. | 25,241,818 | [
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Posterior intraorbital metallic foreign body: a case discussion. | Intraorbital foreign body (IOFB) has been a rare phenomenon in the cases of gunshot wounds and always represents a dilemma in medical management. In Sabah, this scenario is becoming common as there is still certain population in the interiors who owns self made guns for hunting. They either present with self inflicted gunshot injuries or after being mistakenly shot while hunting. There are very few articles on this topic especially when it is located posteriorly in the orbit and occurs without visual impairment. This case reports the challenges faced in the management of the patient with a posteriorly located metallic IOFB. The appropriate management of the patient is discussed based on several international literatures. Author describes a 37 years old male farmer, who was referred from a nearby district hospital after he sustained gunshot injuries to his face and scalp. Urgent computed tomography (CT) scan showed that bullet pellets were at the left orbital floor, the left mandible and the left frontal bone. All bullet pellets were located extracranially only without intracranial involvement. Patient clinically does not have any neurologic deficit and without any visual impairment, thus he refused any surgical intervention. As there is no proper guideline in managing such cases, decision was made based on evidences from international literatures. It was concluded that metallic IOFB located in the posterior orbit may be conservatively managed with observation and regular follow-ups as they are well-tolerated and does not cause much impact on visual deterioration unless inflammation, infection, optic neuropathy or functional deficit occurs. This avoids unnecessary surgery and prevents risk of iatrogenic injury to the eye. | 25,241,819 | [
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Bladder endometriosis: report of 7 new cases and review of the literature. | To describe our experience with bladder endometriosis at the Department of Urology of Complejo Hospitalario Universitario de Santiago de Compostela. We performed a retrospective analysis of the cases of bladder endometriosis diagnosed during the last 11 years in our hospital, from January 2000 to December 2011. A total of 7 women, with a mean age of 32-year-old have been diagnosed by biopsy of bladder endometriosis. The most common symptoms were dysuria, suprapubic pain, urinary urgency and hematuria. All patients have undergone surgery (5 transurethral resection, 2 partial cystectomy), 6 of them were also treated with post-operative LHRH analogues. Endometriosis is a common disease in young women, but the involvement of the urinary tract is unusual. There are multiple therapeutic options; despite this there exists a high probability of recurrence. | 25,241,840 | [
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Physicochemical behaviors of cationic gemini surfactant (14-4-14) based microheterogeneous assemblies. | A comprehensive study of micellization and microemulsion formation of a cationic gemini surfactant (tetramethylene-1,4-bis(dimethyltetradecylammonium bromide; 14-4-14) in the absence or presence of hydrophobically modified polyelectrolyte, sodium carboxymethylcellulose (NaCMC), has been conducted by conductometry, tensiometry, microcalorimetry, and fluorimetry methods at different temperatures. Both critical micelle concentration and degree of ionization of the surfactant have been observed to increase with increasing temperature. The interfacial and thermodynamic parameters were evaluated. The standard Gibbs free energy of micellization (ΔGm°) is negative, which decreases with increase in temperature. Larger entropic contribution is observed compared to the enthalpy. The interaction of 14-4-14 with NaCMC produces coacervates which was determined from turbidimetry method. The pseudoternary phase behavior of the microemulsion systems comprising water (or NaCMC as additive), 14-4-14, isopropanol (IP) or n-butanol (Bu) as cosurfactant, and isopropyl myristate (IPM) were studied at 298 K. Phase diagrams reveal that IP derived microemulsions (in the absence of NaCMC) offer a large isotropic region compared to Bu-derived systems at comparable physicochemical conditions. Increasing the concentration of IP or Bu decreases the isotropic region in the phase diagram. NaCMC influences the microemulsion zone, depending upon its concentration, and type of cosurfactant and surfantant/cosurfactant ratio. Dynamic light scattering and conductometric measurements show the size of the droplet, threshold temperature of percolation, scaling parameters, and activation energy of the percolation process of 14-4-14/IP or Bu derived microemulsion systems without/with NaCMC at various physicochemical conditions. Bu exerts a greater effect to reduce θt than IP as a cosurfactant (in the absence of NaCMC) at comparable ω. On the other hand, IP showed better percolating effect than Bu in the presence of NaCMC. Bu and IP (as cosurfactant) and NaCMC (as additive) influenced the microemulsion droplet size (Dh) to different extents under comparable conditions. Temperature insensitive microemulsions have been reported at the studied temperature range (298–353 K). 14-4-14/IP (1:2)-derived microemulsion showed a fractured surface at fixed ω = 15, where ω is the water and surfactant molar ratio, and temperature (298 K); whereas, large scale mesospheres comprising multiple closely winded nanoslices and spheroid morphology were formed in 14-4-14/IP and 14-4-14/Bu microemulsions, respectively, in the presence of 0.01 g % NaCMC, at comparable conditions. These systems revealed good antimicrobial activity toward the strains of Gram-positive Bacillus subtilis and Gram-negative Escherichia coli bacteria at 298 K, and inhibitory effect was governed by ω, type of cosurfactant, and bacterial strains. | 25,241,843 | [
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Cyclic swelling as a phenomenon inherent to biodegradable polyesters. | The aim of this study is to evaluate and describe the phenomenon and mechanism of the spontaneous cyclic swelling and deswelling of linear and branched aliphatic polyesters in the aqueous medium. The fluctuation of gel volume in one or several cycles as an inherent property of biodegradable and bioerodible materials has not yet been described. We have observed the process at linear and branched polyesters of aliphatic α-hydroxy acids. The period of duration of cycles was in order of hours to days, as influenced by the size of the bodies ranging from 25 to 1000 mg, the temperature in the range of 7°C-42°C, ionic strength, and pH value. The results demonstrated that swelling is accompanied by hydrolysis of ester bonds with the development of small water-soluble osmotically active molecules. After reaching a higher degree of swelling, the obstruction effect of the gel decreases and the diffusion of soluble degradation products from the body to the environment prevails. A decrease in osmotic pressure inside the body and a decrease in the hydrophilic character of the gel matrix result in deswelling by a collapse of the structure, probably due to hydrophobic interactions of nonpolar polyester chains. | 25,241,844 | [
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Low subjective health literacy is associated with adverse health behaviors and worse health-related quality of life among colorectal cancer survivors: results from the profiles registry. | The objectives of the study were to examine the prevalence of health literacy (HL) among colorectal cancer (CRC) survivors and the relation between HL and health behaviors and to explore whether or not HL and health behaviors are independently associated with health-related quality of life (HRQoL) and mental distress. This analysis is part of a longitudinal, population-based survey among CRC survivors diagnosed between 2000 and 2009 and registered by the Eindhoven Cancer Registry. Data collected during the second data wave was used (n = 1643; response rate 83%). Patients filled out a screening question on subjective functional HL, questions on health behaviors, HRQoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), and mental distress (Hospital Anxiety and Depression Scale). Subjective HL was low among 14%, medium among 45%, and high among 42% of the participants. CRC survivors with low HL were more often smokers and did not meet the prescribed physical activity guidelines compared with survivors with medium or high HL. CRC survivors with low HL reported statistically significantly lower levels of mental and physical HRQoL and higher distress levels compared with survivors with medium and high HL. HL, in addition to sociodemographic and clinical characteristics and health behaviors, significantly explained 1.5-6.2% of the variance in HRQoL and mental distress levels. Partial mediation is indicated for HRQoL and feelings of depression, but not for anxiety. Low subjective functional HL among CRC survivors is associated with lower levels of physical activity, higher frequency of smoking, poorer HRQoL, and more mental distress. HL and health behaviors have both a unique as well as an overlapping contribution to the explained variances of HRQoL and mental distress. | 25,241,852 | [
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[Clinical analysis of sinonasal hemangiopericytoma]. | To investigate the clinical features, therapeutic methods and therapeutic effects of sinonasal hemangiopericytoma. Clinical data of 6 patients with sinonasal hemangiopericytoma, diagnosed by pathology and immunohistochemistry between January 1990 and December 2012 were analyzed retrospectively. There were 4 males and 2 females, with a median age of 58 years. Clinical manifestation included epistaxis and nasal obstruction. These patients were operated on by nasal endoscopic surgery or endoscope-assisted surgery, of which 2 cases of tumor located in the nasal cavity underwent nasal endoscopic surgery and 4 cases of tumor located in the nasal cavity and sinuses underwent endoscope-assisted surgery. All the patients were followed up for a period of 6 months to 7 years after operation. Two cases recurred and 4 cases didn't recurred. One case recurred 6 months after operation and underwent second operation, with no recurrence by further one year follow-up. Another case recurred 17 months after operation and underwent second operation, with recurrence by further 9 months follow-up. This patient lived with tumor over two years. Hemangiopericytomas are rarely found in the sinonasal cavity. Nasal endoscopic or endoscope-assisted surgery provides satisfactory effect. | 25,241,860 | [
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[Inhibition of Th2 reaction by thymic stromal lymphopoietin blockade in vitro]. | To explore the effect of thymic stromal lymphopoietin (TSLP) on transformation of dendritic cell (DC) and T cell in vitro. Mouse-derived immature dendritic cells and T lymphocytes were co-cultured in vitro, which were divided into 4 groups (TSLP stimulation group, TSLP stimulation and its receptor blocking group, ovalbumin stimulation group and ovalbumin stimulation and TSLP receptor blocking group). IL-4, IL-8 and IFN-β in cell culture supernatant were detected after 2 days by ELISA. SPSS 13.0 software was used to analyze the data. IL-4 levels of TSLP receptor blocking groups [(48.84 ± 1.56) pg/ml, (52.53 ± 2.36) pg/ml]were significantly lower than those of corresponding TSLP stimulation group and ovalbumin stimulation group [(72.55 ± 7.76) pg/ml, (80.47 ± 21.93) pg/ml;t = 5.994, P < 0.05;t = 2.534, P < 0.05]. However, there were not significant differences of IL-8 and IFN-β expression between corresponding two groups of whether or not TSLP receptor blocking (all P > 0.05). TSLP receptor blockade in vitro can inhibit T lymphocyte transformation to Th2, which may provide a new therapeutic strategy for clinical Th2 dominant diseases such as allergic rhinitis and asthma. | 25,241,867 | [
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Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation. | It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms. | 25,241,887 | [
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Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. | Progesterone (P4) has emerged as an important hormone-regulating mammary stem cell (MaSC) populations. In breast cancer, P4 and synthetic analogs increase the number of stem-like cells within luminal estrogen receptor (ER)- and progesterone receptor (PR)-positive breast cancers. These cells gain expression of de-differentiated cell markers CD44 and cytokeratin 5 (CK5), lose luminal markers ER and PR, and are more therapy resistant. We previously described that P4 downregulation of microRNA (miR)-29a contributes to the expansion of CD44(high) and CK5(+) cells. Here we investigated P4 downregulation of miR-141, a member of the miR-200 family of tumor suppressors, in facilitating an increase in stem-like breast cancer cells. miR-141 was the sole member of the miR-200 family P4-downregulated at the mature miRNA level in luminal breast cancer cell lines. Stable inhibition of miR-141 alone increased the CD44(high) population, and potentiated P4-mediated increases in both CD44(high) and CK5(+) cells. Loss of miR-141 enhanced both mammosphere formation and tumor initiation. miR-141 directly targeted both PR and signal transducer and activator of transcription 5A (Stat5a), transcription factors important for MaSC expansion. miR-141 depletion increased PR protein levels, even in cell lines where PR expression is estrogen dependent. Stat5a suppression via small interfering RNA or a small-molecule inhibitor reduced the P4-dependent increase in CK5(+) and CD44(high) cells. These data support a mechanism by which P4-triggered loss of miR-141 facilitates breast cancer cell de-differentiation through deregulation of PR and Stat5a, two transcription factors important for controlling mammary cell fate. | 25,241,899 | [
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A high performance all-organic flexural piezo-FET and nanogenerator via nanoscale soft-interface strain modulation. | Flexural strain fields are encountered in a wide variety of situations and invite novel device designs for their effective use in sensing, actuating, as well as energy harvesting (nanogenerator) applications. In this work we demonstrate an interesting all-organic device design comprising an electrospun P(VDF-TrFE) fiber-mat built directly on a conducting PANI film, which is also grown on a flexible PET substrate, for flexural piezo-FET and nanogenerator applications. Orders of magnitude stronger modulation of electrical transport in PANI film is realized in this device as compared to the case of a similar device but with a uniform spin-coated P(VDF-TrFE) film. We find that in the flexural mode of operation, the interaction between the laterally modulated nanoscale strain field distributions created by the fibers and the applied coherent strain field strongly influences the carrier transport in PANI. The transport modulation is suggested to occur due to strain-induced conformational changes in P(VDF-TrFE) leading to changes in carrier localization-delocalization. We further show that the fiber-mat based device system also works as an efficient nanogenerator capable of delivering power for low power applications. | 25,241,902 | [
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Supporting clinical decision making during deep brain stimulation surgery by means of a stochastic dynamical model. | During deep brain stimulation (DBS) surgery for the treatment of advanced Parkinson's disease (PD), microelectrode recording (MER) in conjunction with functional stimulation techniques are commonly applied for accurate electrode implantation. However, the development of automatic methods for clinical decision making has to date been characterized by the absence of a robust single-biomarker approach. Moreover, it has only been restricted to the framework of MER without encompassing intraoperative macrostimulation. Here, we propose an integrated series of novel single-biomarker approaches applicable to the entire electrophysiological procedure by means of a stochastic dynamical model. The methods are applied to MER data pertinent to ten DBS procedures. Considering the presence of measurement noise, we initially employ a multivariate phase synchronization index for automatic delineation of the functional boundaries of the subthalamic nucleus (STN) and determination of the acceptable MER trajectories. By introducing the index into a nonlinear stochastic model, appropriately fitted to pre-selected MERs, we simulate the neuronal response to periodic stimuli (130 Hz), and examine the Lyapunov exponent as an indirect indicator of the clinical effectiveness yielded by stimulation at the corresponding sites. Compared with the gold-standard dataset of annotations made intraoperatively by clinical experts, the STN detection methodology demonstrates a false negative rate of 4.8% and a false positive rate of 0%, across all trajectories. Site eligibility for implantation of the DBS electrode, as implicitly determined through the Lyapunov exponent of the proposed stochastic model, displays a sensitivity of 71.43%. The suggested comprehensive method exhibits remarkable performance in automatically determining both the acceptable MER trajectories and the optimal stimulation sites, thereby having the potential to accelerate precise target finalization during DBS surgery for PD. | 25,241,917 | [
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Dental pulp stem cells' secretome enhances pulp repair processes and compensates TEGDMA-induced cytotoxicity. | Aim of this study was to investigate the effects of dental pulp stem cells' (DPSCs) secretome, expressed through their culture conditioned medium (CM), on biological endpoints related to pulp repair and on TEGDMA-induced cytotoxicity. DPSCs cultures were established and characterized for stem cell markers with flow cytometry. CM was collected from DPSCs under serum deprivation conditions (SDC) and normal serum conditions (NSC) at various time-points. CM effects on DPSCs viability, migration and mineralization potential were evaluated by MTT assay, transwell insert and in vitro scratch assay and Alizarin Red staining/quantification respectively. TEGDMA (0.25-2.0mM) cytotoxicity regarding the same biological endpoints was tested in the presence/absence of CM. TGF-β1 and FGF-2 secretion in CM was measured by ELISA. CM collected under SDC (4d) was able to increase cell viability by 20-25% and to reduce TEGDMA cytotoxicity by 20% (p<0.05). CM positive effects were not obvious when collected under NSC. Transwell assay showed significant increase (26%, p<0.05) of DPSCs' migration after CM exposure, whereas both migration assays could not support a migration rate improvement in TEGDMA-treated cultures exposed to CM compared to TEGDMA alone. CM significantly (p<0.01) increased DPSCs mineralization potential and completely counteracted TEGDMA cytotoxicity on this process. ELISA analysis showed a time-dependent increase of TGF-β1 and a TEGDMA concentration-dependent increase of both TGF-β1 and FGF-2 in CM. These findings suggest that DPSCs secretome increases their viability, migration and mineralization potential and counteracts TEGDMA-induced cytotoxicy, revealing a novel mechanism of DPSCs autocrine signaling on pulp repair processes. | 25,241,918 | [
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Porcine intestinal glycosphingolipids recognized by F6-fimbriated enterotoxigenic Escherichia coli. | One important virulence factor of enterotoxigenic Escherichia coli is their ability to adhere via fimbrial adhesins to specific receptors located on the intestinal mucosa. Here, the potential glycosphingolipid receptors of enterotoxigenic F6-fimbriated E. coli were examined by binding of purified F6 fimbriae, and F6-expressing bacteria, to glycosphingolipids on thin-layer chromatograms. When intestinal mucosal non-acid glycosphingolipids from single pigs were assayed for F6 binding capacity, a selective interaction with two glycosphingolipids was observed. The binding-active glycosphingolipids were isolated and characterized as lactotriaosylceramide (GlcNAcβ3Galβ4Glcβ1Cer) and lactotetraosylceramide (Galβ3GlcNAcβ3Galβ4Glcβ1Cer). Further binding assays using a panel of reference glycosphingolipids showed a specific interaction between the F6 fimbriae and a number of neolacto core chain (Galβ4GlcNAc) glycosphingolipids. In addition, an occasional binding of the F6 fimbriae to sulfatide, galactosylceramide, lactosylceramide with phytosphingosine and/or hydroxy fatty acids, isoglobotriaosylceramide, gangliotriaosylceramide, and gangliotetraosylceramide was obtained. From the results we conclude that lactotriaosylceramide and lactotetraosylceramide are major porcine intestinal receptors for F6-fimbriated E. coli. | 25,241,919 | [
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The design and implementation of a generic lipopeptide scanning platform to enable the identification of 'locally acting' agonists for the apelin receptor. | This Letter describes methodology to enable the identification of tool or therapeutic lipopeptides which modulate the function of membrane bound proteins. The choice of lipopeptides as a chemotype is the amalgamation of multiple medicinal chemistry considerations including duration of action, low systemic exposure and access to intracellular components. The 'lipopeptide shuffle' has been applied here to the APJ receptor and has rapidly resulted in the discovery of a 33 nM APJ agonist hit from an initial 369 member lipopeptide synthetic array. | 25,241,924 | [
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Synthesis of novel benzimidazole functionalized chiral thioureas and evaluation of their antibacterial and anticancer activities. | A small library of benzimidazole functionalized chiral thioureas was prepared starting from natural amino acids (S)-alanine, (S)-phenylalanine, (S)-valine and (S)-leucine and also their (R)-isomers and studied their antimicrobial activity against a various Gram-positive and Gram-negative bacterial strains. In this study, compounds 5g and 5j were found to exhibit good antibacterial activity against both Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Klebsiella planticola, Escherichia coli and Pseudomonas aeruginosa. In the cytotoxicity study, thioureas derived from non-natural amino acids 5a-l showed good activity against human cancer cell lines A549, MCF7, DU145, HeLa, and no cytotoxicity was observed with their antipodes 6a-l. | 25,241,926 | [
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Effects of individual and multiple fatty acids (palmitate, oleate and docosahaexenoic acid) on cell viability and lipid metabolism in LO2 human liver cells. | This study was designed to investigate the direct effects of fatty acids (FAs) on the cell viability and the expression levels of genes involved in lipid metabolism in LO2 human liver cells. Palmitate (PA), oleate (OA) and docosahaexenoic acid (DHA) were used to represent saturated, mono-unsaturated and polyunsaturated FAs, respectively. At concentrations of ≤3.2 µg/ml, treatment with single FAs increased the viability of the LO2 cells. At FA concentrations of >3.2 µg/ml, cell viability following OA treatment was increased, but PA or DHA treatment at these concentrations reduced cell viability. Administration of mixtures of these FAs in three ratios (PA:OA:DHA = 1:2:1, 1:1:1 and 1:1:2, respectively) increased the cell viability compared with the control group. The intracellular triglyceride (TG) levels following all types of treatment were significantly increased and the accumulation of TGs was markedly increased with high doses of DHA. In addition, peroxisome proliferator-activated receptor-γ was significantly upregulated in all groups, with the exception of the 1:1:1 group at 3.2 µg/ml and the 1:1:2 group at 12.8 µg/ml. The expression levels of sterol regulatory-element binding protein‑1c, liver X receptor α and apolipoprotein C‑I were significantly reduced in all groups with the exception of the DHA‑treated group and the 1:2:1 groups at 3.2 and 12.8 µg/ml. In conclusion, these results indicate that the type, concentration and mixture ratios of FAs are all important in determining the cell viability and lipid metabolism-related gene expression in LO2 hepatocytes. | 25,241,938 | [
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The meninges: new therapeutic targets for multiple sclerosis. | The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. | 25,241,937 | [
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Phosphoinositides and host-pathogen interactions. | Phosphoinositides control key cellular processes including vesicular trafficking and actin polymerization. Intracellular bacterial pathogens manipulate phosphoinositide metabolism in order to promote their uptake by target cells and to direct in some cases the biogenesis of their replication compartments. In this chapter, we review the molecular strategies that major pathogens including Listeria, Mycobacterium, Shigella, Salmonella, Legionella and Yersinia use to hijack phosphoinositides during infection. This article is part of a Special Issue entitled Phosphoinositides. | 25,241,942 | [
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Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI. | Cellular therapeutics are emerging as a treatment option for a host of serious human diseases. To accelerate clinical translation, noninvasive imaging of cell grafts in clinical trials can potentially be used to assess the initial delivery and behavior of cells. The use of a perfluorocarbon (PFC) tracer agent for clinical fluorine-19 ((19) F) MRI cell detection is described. This technology was used to detect immunotherapeutic dendritic cells (DCs) delivered to colorectal adenocarcinoma patients. Autologous DC vaccines were labeled with a PFC MRI agent ex vivo. Patients received DCs intradermally, and (19) F spin-density-weighted MRI at 3 Tesla (T) was used to observe cells. Spin-density-weighted (19) F images at the injection site displayed DCs as background-free "hot-spot" images. (19) F images were acquired in clinically relevant scan times (<10 min). Apparent DC numbers could be quantified in two patients from the (19) F hot-spots and were observed to decrease by ∼50% at injection site by 24 h. From 3T phantom studies, the sensitivity limit for DC detection is estimated to be on the order of ∼10(5) cells/voxel in this study. These results help to establish a clinically applicable means to track a broad range of cell types used in cell therapy. | 25,241,945 | [
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UV laser radiation alters the embryonic protein profile of adrenal-kidney-gonadal complex and gonadal differentiation in the lizard, Calotes Versicolor. | To examine the impact of ultraviolet (UV) laser radiation on the embryos of Calotes versicolor in terms of its effects on the protein profile of the adrenal-kidney-gonadal complex (AKG), sex determination and differentiation, embryonic development and hatching synchrony. The eggs of C. versicolor, during thermo-sensitive period (TSP), were exposed to third harmonic laser pulses at 355 nm from a Q-switched Nd:YAG laser for 180 sec. Subsequent to the exposure they were incubated at the male-producing temperature (MPT) of 25.5 ± 0.5°C. The AKG of hatchlings was subjected to protein analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and to histology. The UV laser radiation altered the expression of the protein banding pattern in the AKG complex of hatchlings and it also affected the gonadal sex differentiation. SDS-PAGE of AKG of one-day-old hatchlings revealed a total of nine protein bands in the control group whereas UV laser irradiated hatchlings expressed a total of seven protein bands only one of which had the same Rf as a control band. The UV laser treated hatchlings have an ovotestes kind of gonad exhibiting a tendency towards femaleness instead of the typical testes. It is inferred that 355 nm UV laser radiation during TSP induces changes in the expression of proteins as well as their secretions. UV laser radiation had an impact on the gonadal differentiation pathway but no morphological anomalies were noticed. | 25,241,959 | [
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[The correlation study of the expression of VEGF with t-PA and PAI expression in plasma and intraocular tissue in proliferative diabetic retinopathy]. | To evaluate the correlation between the expression of VEGF with t-PA and PAI expression in plasma aqueous humor and vitreous of proliferative diabetic retinopathy (PDR). It was an experimental study. The concentrations of VEGF t-PA and PAI in plasma, aqueous humor and vitreous body in PDR and normal group were detected by ELISA. The levels of VEGF (53.37 ng/L) and PAI (8.00 µg/L) in the plasma of PDR patients were higher than control group, and there was significant statistically difference between them (Z = -3.437, -5.816; P < 0.01). The levels of t-PA (24.32 µg/L) in plasma of PDR patients and control group was no statistically difference between them (Z = -1.715, P = 0.086). The levels of VEGF (335.00 ng/L) t-PA (5.70 µg/L) and PAI (0.63 µg/L) in the aqueous humor of PDR patients were higher than control group, and there was statistically difference between them (Z = -4.805, -1.967, -4.018; P < 0.05). The levels of VEGF (691.69 ng/L) t-PA (13.05 µg/L) and PAI (4.01 µg/L) in the vitreous of PDR patients were higher than control group , and there was statistically difference between them (Z = -2.807, -2.642, -2.230;P < 0.05). Compare the plasma aqueous humor and vitreous of PDR patients. The levels of VEGF is: vitreous>aqueous humor>plasma. The levels of t-PA is: plasma>vitreous>aqueous humor. The levels of PAI is: plasma and vitreous>aqueous humor. The expression of VEGF was highly correlated with t-PA and PAI in plasma aqueous humor and vitreous of PDR (P < 0.05). VEGF PAI in plasma, VEGF t-PA PAI in aqueous humor and vitreous were increases. The expression of VEGF was positive correlated with t-PA and PAI in plasma aqueous humor and vitreous of PDR. | 25,241,978 | [
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Apoptotic activities of thymoquinone, an active ingredient of black seed (Nigella sativa), in cervical cancer cell lines. | Thymoquinone (TQ) is the main constituent of black seed (Nigella sativa, spp) essential oil which shows promising in vitro and in vivo anti-neoplastic activities in different tumor cell lines. However, to date there are only a few reports regarding the apoptotic effects of TQ on cervical cancer cells. Here, we report that TQ stimulated distinct apoptotic pathways in two human cervical cell lines, Siha and C33A. TQ markedly induced apoptosis as demonstrated by cell cycle analysis in both cell lines. Moreover, quantitative PCR revealed that TQ induced apoptosis in Siha cells through p53-dependent pathway as shown by elevated level of p53-mediated apoptosis target genes, whereas apoptosis in C33A cells was mainly associated with the activation of caspase-3. These results support previous findings on TQ as a potential therapeutic agent for human cervical cancer. | 25,241,984 | [
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Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats. | Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P < 0.05, IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR. | 25,241,987 | [
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Relationship between hemoglobin levels and risk for suspected non-alcoholic fatty liver in Taiwanese adults. | Body iron levels have recently been shown to be a strong predictor for non-alcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence of NAFLD in a general adult population, and to investigate the relationship between body iron levels, NAFLD and the metabolic syndrome (MetS). 2186 adults participated in the third National Nutrition and Health Survey in Taiwan (NAHSIT, 2005-2008). The participants underwent anthropometry measurements and phlebotomy after an overnight fast, and those with excessive alcohol intake, iron overload of serum ferritin > 600 ng/ml, hepatitis viral infection and hepatocellular carcinoma were excluded. Suspected NAFLD was diagnosed by three alanine transaminase (ALT) cut-points: cut-point 1: serum ALT > 40 U/l; cut-point 2: ALT ≥ 25 U/l for male and ALT ≥ 17 U/l for female; and cut-point 3: ALT ≥ 35 U/l for male and ALT ≥ 26 U/l for female. The prevalence proportion of suspected NAFLD among Taiwanese adults was 6.6% (cut-point 1), 36% (cut-point 2); and 14.3% (cut-point 3). Body iron levels were significantly higher in individuals with suspected NAFLD compared with those without. Distribution of hemoglobin levels, but not serum ferritin levels, by decade of age showed strong correlation with the prevalence of suspected NAFLD in individuals with MetS. Multivariate adjusted odds ratio (OR) showed that the best predictors for suspected NAFLD with the MetS were hemoglobin [OR 1.43 (1.21-1.68); P < 0.0001] and hyperlipidemia [OR 1.52 (1.19-1.94); P = 0.0007]. In individuals without MetS, the adjusted OR of suspected NAFLD was markedly higher for hemoglobin [OR 1.25 (1.12-1.41); P < 0.0001]. In conclusion, adults with high hemoglobin levels (14.4 μg/dl for male and 13.2 μg/dl for female) are at the greatest risk for developing abnormal liver function. Hemoglobin test should be considered as a part of clinical evaluation for patients with NAFLD. | 25,241,989 | [
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Incidental parathyroidectomy as a cause of postoperative hypocalcemia after thyroid surgery: reality or illusion? | We aimed to investigate the incidence and clinical relevance of incidental parathyroidectomy (IPT) following thyroid surgery. A retrospective review of thyroid operations was performed between January 2013 and January 2014. Pathology and operative reports were analyzed to identify the specimens which included parathyroid tissue. Information related to diagnosis, operative details and postoperative complications were collected. Calcium levels of ≤8 mg/dL was defined as biochemical hypocalcemia and those presenting with classic findings of acute hypocalcemia, were classified as clinical hypocalcemia. Two hundred and forty-five thyroid procedures were performed during study period. IPT was found in 34 (13.8%) cases: 25 were benign and 9 were malignant. Parathyroid tissue was found intrathyroidal in 6 patients (17.6%); lobar locations were right lobe in 19 (55.8%) and left lobe in 13 (38.2%) and isthmus in 2 cases (5.8%). The frequency of biochemical and clinical hypocalcemia were 50% (N.=17) and 8.8% (N.=3), respectively. Neither surgical type (lobectomy or thyroidectomy) nor malignancy (benign or malign) was not found associated with biochemical hypocalcemia. In those with biochemical hypocalcemia, left location of both dominant nodule and extracted parathyroid gland were significantly higher (P=0.01 and 0.04, respectively). Incidental parathyroidectomy which is not uncommon (13.8%) after thyroidectomy is not associated with postoperative biochemical hypocalcemia. Neither the type of surgical procedure (lobectomy or thyroidectomy) nor the pathology but adjacent dominant nodule location may increase the risk of IPT. | 25,242,004 | [
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Insects recycle endosymbionts when the benefit is over. | Symbiotic associations are widespread in nature and represent a driving force in evolution. They are known to impact fitness, and thereby shape the host phenotype. Insects subsisting on nutritionally poor substrates have evolved mutualistic relationships with intracellular symbiotic bacteria (endosymbionts) that supply them with metabolic components lacking in their diet. In many species, endosymbionts are hosted within specialized host cells, called the bacteriocytes, and transmitted vertically across host generations. How hosts balance the costs and benefits of having endosymbionts, and whether and how they adjust symbiont load to their physiological needs, remains largely unexplored. By investigating the cereal weevil Sitophilus association with the Sodalis pierantonius endosymbiont, we discover that endosymbiont populations intensively multiply in young adults, before being rapidly eliminated within few days. We show that young adults strongly depend on endosymbionts and that endosymbiont proliferation after metamorphosis matches a drastic host physiological need for the tyrosine (Tyr) and phenylalanine (Phe) amino acids to rapidly build their protective exoskeleton. Tyr and Phe are precursors of the dihydroxyphenylalanine (DOPA) molecule that is an essential component for the cuticle synthesis. Once the cuticle is achieved, DOPA reaches high amounts in insects, which triggers endosymbiont elimination. This elimination relies on apoptosis and autophagy activation, allowing digestion and recycling of the endosymbiont material. Thus, the weevil-endosymbiont association reveals an adaptive interplay between metabolic and cellular functions that minimizes the cost of symbiosis and speeds up the exoskeleton formation during a critical phase when emerging adults are especially vulnerable. | 25,242,028 | [
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Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice. | Mammalian karyotypes (number and structure of chromosomes) can vary dramatically over short evolutionary time frames. There are examples of massive karyotype conversion, from mostly telocentric (centromere terminal) to mostly metacentric (centromere internal), in 10(2)-10(5) years. These changes typically reflect rapid fixation of Robertsonian (Rb) fusions, a common chromosomal rearrangement that joins two telocentric chromosomes at their centromeres to create one metacentric. Fixation of Rb fusions can be explained by meiotic drive: biased chromosome segregation during female meiosis in violation of Mendel's first law. However, there is no mechanistic explanation of why fusions would preferentially segregate to the egg in some populations, leading to fixation and karyotype change, while other populations preferentially eliminate the fusions and maintain a telocentric karyotype. Here we show, using both laboratory models and wild mice, that differences in centromere strength predict the direction of drive. Stronger centromeres, manifested by increased kinetochore protein levels and altered interactions with spindle microtubules, are preferentially retained in the egg. We find that fusions preferentially segregate to the polar body in laboratory mouse strains when the fusion centromeres are weaker than those of telocentrics. Conversely, fusion centromeres are stronger relative to telocentrics in natural house mouse populations that have changed karyotype by accumulating metacentric fusions. Our findings suggest that natural variation in centromere strength explains how the direction of drive can switch between populations. They also provide a cell biological basis of centromere drive and karyotype evolution. | 25,242,031 | [
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Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS. | The casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage, whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the nondeleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target. | 25,242,043 | [
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Ferric citrate spans mineral metabolism and anemia domains in ESRD: a review of efficacy and safety data. | Ferric citrate (Zerenex™, Keryx Biopharmaceuticals, Inc.), a phosphate binder drug candidate, recently completed a Phase III program confirming efficacy and demonstrating safety when used to treat hyperphosphatemia in patients with end-stage renal disease. Results of these trials demonstrate that ferric citrate effectively controls serum phosphorus and is well tolerated. Additionally, these studies demonstrate that ferric citrate improves iron parameters and reduces IV iron and erythropoietin stimulating agent utilization while maintaining hemoglobin levels. These unique features may further benefit the management of end-stage renal disease-related anemia. | 25,242,077 | [
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Role of inositol-1,4,5-trisphosphate receptor in the regulation of calcium transients in neonatal rat ventricular myocytes. | This study determined the regulatory effect of inositol 1,4,5-trisphosphate receptors (IP3Rs) on the basal Ca(2+) transients in cardiomyocytes. In cultured neonatal rat ventricular myocytes (NRVMs) at different densities, we used confocal microscopy to assess the effect of IP3Rs on the endogenous spontaneous Ca(2+) oscillations through specific activation of IP3Rs with myo-IP3 hexakis (butyryloxymethyl) ester (IP3BM), a membrane permeable IP3, and interference of IP3R expression with shRNA. We found that NRVMs at the monolayer state displayed coordinated Ca(2+) transients with less rate, shorter duration, and higher amplitude compared to single NRVMs. In addition, monolayer NRVMs exhibited 4 or 10 times more increased Ca(2+) transients in response to phenylephrine, an α-adrenergic receptor agonist, or IP3BM than single NRVMs did, while the transient pattern remained unaltered, suggesting that the sensitivity of intracellular Ca(2+) response to IP3R activation is different between single and monolayer NRVMs. However, interference of IP3R expression with shRNA reduced the frequency and amplitude of the spontaneous Ca(2+) fluctuates similarly in both densities of NRVMs, resembling the effects of ryanodine receptor inhibition by ryanodine or tetracaine. Our findings suggest that IP3Rs are involved, in part, in the regulation of native Ca(2+) transients, in profiles of their initiation and Ca(2+) release extent, in developing cardiomyocytes. In addition, caution should be paid in evaluating the behavior of Ca(2+) signaling in primary cultured cardiomyocytes at different densities. | 25,242,084 | [
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Surface plasmon coupling dynamics in InGaN/GaN quantum-well structures and radiative efficiency improvement. | Surface plasmonics from metal nanoparticles have been demonstrated as an effective way of improving the performance of low-efficiency light emitters. However, reducing the inherent losses of the metal nanoparticles remains a challenge. Here we study the enhancement properties by Ag nanoparticles for InGaN/GaN quantum-well structures. By using a thin SiN dielectric layer between Ag and GaN we manage to modify and improve surface plasmon coupling effects, and we attribute this to the improved scattering of the nanoparticles at the quantum-well emission wavelength. The results are interpreted using numerical simulations, where absorption and scattering cross-sections are studied for different sized particles on GaN and GaN/SiN substrates. | 25,242,090 | [
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Soy but not bisphenol A (BPA) induces hallmarks of polycystic ovary syndrome (PCOS) and related metabolic co-morbidities in rats. | Polycystic ovarian syndrome (PCOS) is the most common female endocrine disorder with a prevalence as high as 8-15% depending on ethnicity and the diagnostic criteria employed. The basic pathophysiology and mode of inheritance remain unclear, but environmental factors such as diet, stress and chemical exposures are thought to be contributory. Developmental exposure to endocrine disrupting compounds (EDCs) have been hypothesized to exacerbate risk, in part because PCOS hallmarks and associated metabolic co-morbidities can be reliably induced in animal models by perinatal androgen exposure. Here we show that lifetime exposure to a soy diet, containing endocrine active phytoestrogens, but not developmental exposure (gestational day 6-lactational day 40) to the endocrine disrupting monomer bisphenol A (BPA), can induce key features of PCOS in the rat; results which support the hypothesis that hormonally active diets may contribute to risk when consumed throughout gestation and post-natal life. | 25,242,113 | [
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Evaluation of the mechanical behaviour and estimation of the elastic properties of porcine zonular fibres. | The mechanical behaviour of zonular fibres greatly affects the accommodation process in mammalian eyes. This paper introduces a detailed measurement procedure for the purpose of obtaining the force-displacement diagram necessary to evaluate the mechanical properties of porcine zonular fibres in situ. It is a complex technique, keeping the integrity of the zonular bundles between the crystalline lens and the ciliary muscle cells. We present a brief description of the measurement procedure both in theory and in practice, along with the force-displacement diagrams acquired from a porcine sample group. The strengths of this newly developed method are the unequivocal force transmission between the sample and the transducer, and the intact connection between the ciliary body and the crystalline lens via zonular fibres. With the aid of these measurements, we define an estimated material model for the zonular apparatus both analytically and using the finite element method. The two different evaluation methods show close agreement in the calculated Young's modulus for the zonular fibres. The range of the calculated elastic modulus is 200-250 kPa. This new measuring method is adaptable to human specimens. Despite its complexity, the entire procedure and the evaluation part are reproducible. The constitutive model aims to shed light on the mechanics of the accommodation process. | 25,242,131 | [
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Noninvasive metabolic syndrome model using an extremely small minipig, the microminipig. | Metabolic syndrome (MetS) induces serious complications; therefore, we developed a noninvasive MetS model using an extremely small minipig, the Microminipig. For 8 weeks, Microminipigs were administrated a high-fat and high-cholesterol diet (HFCD) for atherosclerosis and N(G)-nitro-l-arginine methyl ester (l-NAME) for inhibiting nitric oxide synthase. HFCD significantly increased serum low-density lipoprotein levels, l-NAME increased blood pressure and cardiac hypertrophy, and HFCD-induced aortal arteriosclerosis was accelerated by l-NAME administration. Endothelium-dependent relaxation of the coronary artery was remarkably decreased by l-NAME administration. This model may be useful for elucidating the mechanisms of MetS and developing new therapeutic medicines for its treatment. | 25,242,170 | [
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Complete mitochondrial DNA sequence of Lepus sinensis (Leporidae: Lepus). | In the present study, we determined the complete nucleotide sequence of the mitochondrial (mt) genome of Chinese hare, Lepus sinensis (Leporidae: Lepus) by using polymerase chain reaction (PCR) technique. The entire mtDNA sequence is 17438 nucleotides long and contains 13 protein-coding genes, 2 ribosomal tRNA 22 transfer RNA gens and one long non-coding region known as the control region. The mt gene arrangement of L. sinensis is identical to those typical for vertebrates. | 25,242,179 | [
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The complete mitochondrial genome of G3 genotype of Echinococcus granulosus (Cestoda: Taeniidae). | As a cryptic species complex, the taxonomy of Echinococcus granulosus has long been controversial. The complete mitochondrial (mt) genome of the E. granulosus G3 genotype was sequenced and characterized. The G3 mt genome was 13,607 bp in length, and contained 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and 12 protein-coding genes, with a gene order identical to those of other reported genotypes. The overall nucleotide composition (coding strand) for the mt genome sequence of G3 was 19.1% A, 47.8% T, 25.0% G, and 8.1% C, with T being the most common base and C the least common. | 25,242,186 | [
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The complete mitochondrial genome of Holland's spinibarbel Spinibarbus hollandi Oshima (Cypriniformes, Cyprinidae). | In this study, the complete mitogenome sequence of cyprinid fish, Holland's spinibarbel Spinibarbus hollandi Oshima (1919) (Cypriniformes, Cyprinidae, Barbinae) has been amplified and sequenced by employing long polymerase chain reaction method. The mitogenome, consisting of 16,523 base pairs (bp), had the typical vertebrate mitochondrial gene arrangement, including 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes, and a non-coding control region (CR). CR of 867 bp length is located between tRNA(Pro) and tRNA(Phe). The overall base composition of S. hollandi is 31.87% for A, 26.56% for C, 25.89% for T, and 15.68% for G, with a slight AT bias of 57.76%. The complete mitogenome may provide rather essential and important DNA molecular data for further phylogenetic analysis for not only congeneric species but also higher different taxa of Cyprinid fishes. | 25,242,188 | [
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Comparisons of increases in knee and ankle joint moments following an increase in running speed from 8 to 12 to 16km·h(-1.). | Knowledge regarding knee and ankle joint load across a range of running speeds is important, if running related injuries are to be prevented. The purpose of the present study was to test the hypothesis that peak plantar flexion moment increases relatively more than peak knee extension moment when running speed is increased. Kinematic and ground reaction force data were collected from 33 recreational runners during steady-state running at three different speeds: 7.96km·h(-1) (SD 0.18), 11.92km·h(-1) (SD 0.25) and 15.91km·h(-1) (SD 0.36). Peak plantar flexion moment and peak knee extension moment were calculated using a standard three-dimensional inverse dynamics approach. There was a significant interaction between the joint location and the running speed (P=0.03): When running speed increased from 7.96 to 15.91km·h(-1), mean peak plantar flexion moment increased by 0.74N·m·kg(-1) (95% CI: 0.64; 0.85) which was more than the 0.52N·m·kg(-1) (95% CI: 0.42; 0.63) increase in mean peak knee extension moment. A greater increase in biomechanical load occurs for the plantar flexors of the ankle joint than for the extensors of the knee joint when running speed increases. This may indicate that at an excessive running speed, the structures at the posterior part of the lower leg and underneath the foot are relatively more vulnerable to injury compared with the structures at the anterior part of the knee. As a considerable load reduction is achieved, a decrease in running speed may benefit rearfoot striking recreational runners experiencing pain in the posterior lower leg or underneath the foot. | 25,242,200 | [
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The evolution of pregnancy. | Although viviparity has evolved many times in the animal kingdom, it remains relatively uncommon-scorpions and therian mammals being rare examples of entirely viviparous major taxa. Viviparity is a specialised form of intra-species parasitism which biases parental investment towards fertilised eggs, temporally spreads that investment, and also temporarily protects offspring from many selection pressures. Importantly, the mammalian viviparity appeared at a relatively late stage in the process of vertebrate evolution. Because of this, viviparity was 'superimposed' on complex pre-existing cardiovascular, respiratory, metabolic and immune systems, and has altered them dramatically. Also, pregnancy has exerted pervasive effects on gene expression in mammals, including genetic imprinting, X inactivation, sex determination, and the ectopic expression in the extra-embryonic membranes of many genes previously expressed in the gonads, brain, pituitary and immune system. Finally, although lactation probably pre-dated viviparity in mammalian evolution, the two have co-evolved as alternative strategies of offspring nutrition ever since. | 25,242,206 | [
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A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the lower limbs. | No prior studies have identified which patients with deep vein thrombosis in the lower limbs are at a low risk for adverse events within the first week of therapy. We used data from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) to identify patients at low risk for the composite outcome of pulmonary embolism, major bleeding, or death within the first week. We built a prognostic score and compared it with the decision to treat patients at home. As of December 2013, 15,280 outpatients with deep vein thrombosis had been enrolled. Overall, 5164 patients (34%) were treated at home. Of these, 12 (0.23%) had pulmonary embolism, 8 (0.15%) bled, and 4 (0.08%) died. On multivariable analysis, chronic heart failure, recent immobility, recent bleeding, cancer, renal insufficiency, and abnormal platelet count independently predicted the risk for the composite outcome. Among 11,430 patients (75%) considered to be at low risk, 15 (0.13%) suffered pulmonary embolism, 22 (0.19%) bled, and 8 (0.07%) died. The C-statistic was 0.61 (95% confidence interval [CI], 0.57-0.65) for the decision to treat patients at home and 0.76 (95% CI, 0.72-0.79) for the score (P = .003). Net reclassification improvement was 41% (P < .001). Integrated discrimination improvement was 0.034 for the score and 0.015 for the clinical decision (P < .001). Using 6 easily available variables, we identified outpatients with deep vein thrombosis at low risk for adverse events within the first week. These data may help to safely treat more patients at home. This score, however, should be validated. | 25,242,230 | [
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Laparoscopic supracervical hysterectomy with morcellation: should it stay or should it go? | To establish the risk of unidentified neoplasia and subsequent adverse outcomes of laparoscopic supracervical hysterectomy (SCH) with morcellation. Retrospective review (Canadian Task Force classification II-2). University community hospital. Consecutive women who had undergone SCH with morcellation between January 2002 and December 2008. Medical records were assessed for patient characteristics and outcomes. We identified 808 women who had undergone planned laparoscopic SCH with morcellation. Their median age was 44.1 years (range, 23.4-79.8 years). The most common indications were menorrhagia in 472 patients (58.4%) and leiomyomas in 400 patients (49.5%). Of the 30 patients in whom laparoscopy was converted to an open procedure before morcellation, 1 had leiomyosarcoma at final pathologic analysis. Of the 778 patients who underwent laparoscopic SCH with morcellation, 16 (2.0%) had endometrial hyperplasia and 3 (0.4%) had cancer at final pathologic analysis. Abnormal pathologic findings were more likely in women older than age 50 years with abnormal bleeding. Of the 778 patients, 189 were younger than 40 years, and 4 of these 189 women (2.1%) had hyperplasia at final pathologic analysis; none had cancer. Of the 433 patients aged 40 to 49 years, 8 (1.8%) had hyperplasia or cancer. Of the 156 patients aged 50 years or older, 7 (4.5%) had hyperplasia (p = .18); none had cancer. No patient with hyperplasia or morcellated cancer experienced adverse sequelae after a median follow-up of 90.4 months. In this cohort of patients who underwent laparoscopic SCH, the risk of hyperplasia or malignancy was low. Laparoscopic SCH with morcellation seems to be a low-risk procedure. | 25,242,233 | [
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Inherited ADAMTS13 deficiency (Upshaw-Schulman syndrome): a short review. | Congenital thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is associated with an inherited deficiency of ADAMTS13, a von Willebrand factor-cleaving protease. It is a rare, life-threatening disorder characterized by thrombocytopenia, hemolytic anemia, neurological symptoms, renal dysfunction, and fever resulting from formation of platelet thrombi within the microvasculature. Patients have initial episodes mainly during infancy or early childhood, and are conventionally treated with fresh frozen plasma. However, a more appropriate approach based on recombinant ADAMTS13 is slated to begin shortly. Mutations throughout the ADAMTS13 have been identified in congenital TTP patients. The prevalence of this entity is probably underestimated because it is often not suspected, the clinical course is usually heterogeneous and most of the symptoms are common to other diseases. The present review summarizes our current knowledge about Upshaw-Schulman syndrome. | 25,242,241 | [
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Comparison between alkali heat treatment and sprayed hydroxyapatite coating on thermally-sprayed rough Ti surface in rabbit model: Effects on bone-bonding ability and osteoconductivity. | In this study, we investigated the effect of different surface treatments (hydroxyapatite (HA) coating, alkali heat treatment, and no treatment) on the ability of bone to bond to a rough arc-sprayed Ti metal surface, using rabbit models. The bone-to-implant contacts for untreated, HA-coated, and alkali heat-treated implants were 21.2%, 72.1%, and 33.8% at 4 weeks, 21.8%, 70.9%, and 30.0% at 8 weeks, and 16.3%, 70.2%, and 29.9% at 16 weeks, respectively (n = 8). HA -coated implants showed significantly higher bone-to-implant contacts than the untreated and alkali heat-treated implants at all the time point, whereas alkali heat-treated implants showed significantly higher bone-to-implant contacts than untreated implants at 4 and 16 weeks. The failure loads in a mechanical test for untreated, HA coated, alkali heat-treated plates were 65.4 N, 70.7 N, and 90.8 N at 4 weeks, 76.1 N, 64.7 N, and 104.8 N at 8 weeks and 88.7 N, 92.6 N, and 118.5 N at 16 weeks, respectively (n = 8). The alkali heat-treated plates showed significantly higher failure loads than HA-coated plates at 8 and 16 weeks. The difference between HA-coated plates and untreated plates were not statistically significant at any time point. Thus HA coating, although it enables high bone-to-implant contact, may not enhance the bone-bonding properties of thermally-sprayed rough Ti metal surfaces. In contrast, alkali heat treatment can be successfully applied to thermally-sprayed Ti metal to enhance both bone-to-implant contact and bone-bonding strength. | 25,242,248 | [
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Controllable pulse parameter transcranial magnetic stimulator with enhanced circuit topology and pulse shaping. | This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with a lower voltage rating than prior cTMS devices. cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (< 10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in ten healthy volunteers. The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool. | 25,242,286 | [
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Small molecule inhibitor of myogenic microRNAs leads to a discovery of miR-221/222-myoD-myomiRs regulatory pathway. | Myogenic microRNAs (myomiRs) that are specifically expressed in cardiac and skeletal muscle are highly relevant to myogenic development and diseases. Discovery and elucidation of unknown myomiRs-involved regulatory pathways in muscle cells are important, but challenging due to the lack of proper molecular tools. We report here a miR-221/222-myoD-myomiRs regulatory pathway revealed by using a small-molecule probe that selectively inhibits myomiRs including miR-1, miR-133a, and miR-206. The small-molecule inhibitor screened from luciferase assay systems was found to inhibit myomiRs and differentiation of C2C12 cells. Using the small molecule as a probe, we found that the transcriptional factor myoD, which is upstream of myomiRs, was further regulated by miR-221/222. This miR-221/222-myoD-myomiRs regulatory pathway was confirmed by over-expressing or knockdown miR-221/222 in muscle cells, which respectively led to the inhibition or enhancement of myoD protein expression and subsequent downregulation or upregulation of myomiR expression. | 25,242,288 | [
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Associations between measures of gait stability, leg strength and fear of falling. | Fear of falling (FoF) in elderly frequently leads to decreased quality of life. FoF is suggested to be associated with changes in gait quality and muscle strength with aging. The aim of this study was to determine whether gait quality and maximal voluntary torque (MVT) of knee extensor muscles are associated with FoF. We hypothesized that high between-stride variability and local divergence exponent (LDE) of trunk kinematics in gait are associated with higher FoF in non-fallers, but not in fallers. Moreover, we hypothesized that knee extensor muscle strength is associated with a high variability and LDE of trunk kinematics during gait. 134 four adults, aged 62.4 (SD 6.2) years agreed to participate. FoF was assessed on a 10-point numerical rating scale. Subjects with at least one fall in the past 12 months were considered as fallers. LDE and variability were calculated from data of a trunk-mounted inertial-sensor collected during several minutes of treadmill walking. Maximal voluntary knee extension torque (MVT) was assessed isometrically. Fall history was an effect modifier in the association between LDE and FoF only, i.e. only subjects without fall history and a high LDE had a five times higher chance of reporting FoF. Gait variability was not associated with FoF. Low MVT was associated with FoF. Multivariate analysis demonstrated that LDE was more strongly associated with FoF than MVT. Decreased stability of gait as reflected in a high LDE and low muscle strength are associated with and a potential cause of FoF in subjects without fall history. | 25,242,294 | [
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Single rodent mesohabenular axons release glutamate and GABA. | The lateral habenula (LHb) is involved in reward, aversion, addiction and depression through descending interactions with several brain structures, including the ventral tegmental area (VTA). The VTA provides reciprocal inputs to LHb, but their actions are unclear. Here we show that the majority of rat and mouse VTA neurons innervating LHb coexpress markers for both glutamate signaling (vesicular glutamate transporter 2; VGluT2) and GABA signaling (glutamic acid decarboxylase; GAD, and vesicular GABA transporter; VGaT). A single axon from these mesohabenular neurons coexpresses VGluT2 protein and VGaT protein and, surprisingly, establishes symmetric and asymmetric synapses on LHb neurons. In LHb slices, light activation of mesohabenular fibers expressing channelrhodopsin2 driven by VGluT2 (Slc17a6) or VGaT (Slc32a1) promoters elicits release of both glutamate and GABA onto single LHb neurons. In vivo light activation of mesohabenular terminals inhibits or excites LHb neurons. Our findings reveal an unanticipated type of VTA neuron that cotransmits glutamate and GABA and provides the majority of mesohabenular inputs. | 25,242,304 | [
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Citrobacter koseri septicaemia in a holstein calf. | A 4-day-old male Holstein calf with dull mentation, nystagmus and blindness was humanely destroyed and subject to necropsy examination. Gross lesions included severe suppurative meningitis characterized by diffuse cloudy thickening of the meninges, bilateral hypopyon and fibrinosuppurative polyarthritis affecting the hocks. Citrobacter koseri was isolated from the meninges, ocular fluid, synovial fluid, spleen and small intestine. Microscopically, there was neutrophilic and histiocytic meningitis with intralesional bacilli, endophthalmitis, neutrophilic splenitis and multiple renal microabscesses. Failure of passive transfer of colostrum was confirmed. This appears to be the first characterization of septicaemia in a calf caused by C. koseri, with lesions comparable with those described in human neonates. | 25,242,308 | [
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Bacterial contamination of blood components: Norwegian strategies in identifying donors with higher risk of inducing septic transfusion reactions in recipients. | Bacterial contamination of blood and its cellular components remains the most common microbiological cause of transfusion associated morbidity and mortality, even in developed countries. This yet unresolved complication is seen more often in platelet transfusions, as platelet concentrates are stored at room temperature, in gas permeable containers with constant agitation, which support bacterial proliferation from relatively low undetectable levels, at the beginning of storage time, to relatively high virulent bacteria titers and endotoxin generation, at the end of shelf life. Accordingly, several combined strategies are introduced and implemented to at least reduce the potential risk of bacterial contaminated products for transfusion. These embody: improved donors arms cleaning; bacterial avoidance by diversion of the first portion of collection; reducing bacterial growth through development of newer storage media for longer platelet shelf life; bacterial load reduction by leucoreduction/viral inactivation, in some countries and eliminating the use potentially contaminated units through screening, through current available testing procedures, though none are not yet fully secure. We have not seen the same reduction in bacterial associated transfusion infections as we have observed for the sharp drop in transfusion associated transmission rates of HIV and hepatitis B and C. This great viral reduction is not only caused by the introduction of newer and more sensitive and specific detection methods for different viruses, but also the identification of donor risk groups through questionnaires and personal interviews. While search for more efficient methods for identifying potential blood donors with asymptomatic bacteremia, as well as a better way for detecting bacteria in stored blood components will be continuing, it is necessary to establish more standardized guidelines for the recognition the adverse reactions in recipients of potentially contaminated units. Efforts also should be also directed to identify blood donors with significant risk of bacteremia, at the time of donation in the first place as a high priority. The goal of this review is to highlights strategies for identifying both the sources of bacterial contamination of blood components in Norway and identifying donors with a higher risk of bacteremia at the time of donation. The key to achieving this goal is initiating continual revising and upgrading the Norwegian transfusion guidelines, based on the transfusion legislation and by introducing a relevant specialized donor bacterial questionnaire. | 25,242,310 | [
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Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance. | Colorectal cancer (CRC) initiation and growth is often attributed to stem cells, yet little is known about the regulation of these cells. We show here that a subpopulation of Prox1-transcription-factor-expressing cells have stem cell activity in intestinal adenomas, but not in the normal intestine. Using in vivo models and 3D ex vivo organoid cultures of mouse adenomas and human CRC, we found that Prox1 deletion reduced the number of stem cells and cell proliferation and decreased intestinal tumor growth via induction of annexin A1 and reduction of the actin-binding protein filamin A, which has been implicated as a prognostic marker in CRC. Loss of Prox1 also decreased autophagy and the survival of hypoxic tumor cells in tumor transplants. Thus, Prox1 is essential for the expansion of the stem cell pool in intestinal adenomas and CRC without being critical for the normal functions of the gut. | 25,242,330 | [
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A cell engineering strategy to enhance the safety of stem cell therapies. | The long-term risk of malignancy associated with stem cell therapies is a significant concern in the clinical application of this exciting technology. We report a cancer-selective strategy to enhance the safety of stem cell therapies. Briefly, using a cell engineering approach, we show that aggressive cancers derived from human or murine induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are strikingly sensitive to temporary MYC blockade. On the other hand, differentiated tissues derived from human or mouse iPSCs can readily tolerate temporary MYC inactivation. In cancer cells, endogenous MYC is required to maintain the metabolic and epigenetic functions of the embryonic and cancer-specific pyruvate kinase M2 isoform (PKM2). In summary, our results implicate PKM2 in cancer's increased MYC dependence and indicate dominant MYC inhibition as a cancer-selective fail-safe for stem cell therapies. | 25,242,333 | [
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The importance of cytokines and autoantibodies in depression. | The relationship between depression and immunity has been widely discussed. Cytokines, such as TNF-α, play an important role in immune system; these cytokines interact with virtually every pathophysiologic domain relevant to depression, including neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. Antibodies have also been implicated in the pathophysiology of depression. The association between decreased serotonin levels and excessive glutamatergic activity forms the first biochemical basis for cytokine-induced depression. Cytokines and antibodies (anti-ribosomal-P and anti-N-methyl-D-aspartate receptor antibodies) are deeply related to pathogenesis of neurodevelopmental disorders, especially depression. Tumor necrosis factor alpha (TNF-α) may underlie the mechanism of depression by an activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, an activation of neuronal serotonin transporters and the stimulation of the indoleamine 2,3-dioxygenase which leads to tryptophan depletion. In the last 20 years since the initial reports of neural-immune interactions in depression, studies have shown a clear association between activation of the immune system mediated by proinflammatory cytokines. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. To date, there are only few studies that investigated the relationship between depression and proinflammatory cytokines in patients with autoimmune diseases. Although an associative link between neuroinflammation and mood disorders is widely accepted, further studies are necessary to establish the cause-effect relationship. In this paper, we review the role of cytokines, focusing on TNF-α and antibodies in the depression and hypothesize how TNF-α may underlie and mediate the inflammatory process depression in patients with autoimmune disease. | 25,242,344 | [
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In vitro antioxidant and mineral-chelating properties of natural and autocleaved ovotransferrin. | Egg white proteins can be excellent substrates for the development of functional foods and nutraceuticals. In this study, several in vitro antioxidant methods, namely the β-carotene linoleate model system, the ferric thiocyanate method, the 2-thiobarbituric acid-reactive substances (TBARS) method and copper/calcium ion chelation, were used to determine the antioxidant capacity of natural and autocleaved ovotransferrin. Autocleaved ovotransferrin was prepared by reducing natural ovotransferrin with tris(2-carboxyethyl)phosphine (TCEP) for 6 h at 37 °C. Autocleaved ovotransferrin suppressed the discoloration of β-carotene effectively and prevented the oxidation of linoleic acid during 5 days of storage at 4 °C. However, the concentration of autocleaved ovotransferrin had no influence on its antioxidant effect. Similarly, the highest TBARS values were obtained from autocleaved ovotransferrin (>90%) and the lowest value in natural ovotransferrin (24%) during incubation at 37 °C for 48 h. The hydrolysates obtained from autocleaved ovotranferrin showed better copper/calcium-solublilizing activity than those from natural ovotransferrin. The results indicated that autocleaved ovotransferrin has the potential to be used as a natural antioxidant in foods. | 25,242,349 | [
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Fufang Kushen injection inhibits sarcoma growth and tumor-induced hyperalgesia via TRPV1 signaling pathways. | Cancer pain is a deleterious consequence of tumor growth and related inflammation. Opioids and anti-inflammatory drugs provide first line treatment for cancer pain, but both are limited by side effects. Fufang Kushen injection (FKI) is GMP produced, traditional Chinese medicine used alone or with chemotherapy to reduce cancer-associated pain. FKI limited mouse sarcoma growth both in vivo and in vitro, in part, by reducing the phosphorylation of ERK and AKT kinases and BAD. FKI inhibited TRPV1 mediated capsaicin-induced ERK phosphorylation and reduced tumor-induced proinflammatory cytokine production. Thus, FKI limited cancer pain both directly by blocking TRPV1 signaling and indirectly by reducing tumor growth. | 25,242,356 | [
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Potential impact of 18F-FDG PET/CT on patients selection for neoadjuvant chemotherapy before radical cystectomy. | The detection of lymph node metastases in bladder cancer has a major impact on treatment decisions and patients prognosis. Due to limited value of conventional imaging, the place of molecular and functional imaging needs to be precised, particularly in the neoadjuvant setting. From June 2011 to June 2013, 102 patients with clinically localized BCa were simultaneously staged with (18)F-FDG PET/CT before RC. This study assessed the diagnostic accuracy of (18)F-FDG PET/CT for the detection of metastases in normal-sized lymph nodes using extended pelvic lymph node dissection and histopathology as the reference standard. A total of 1211 LNs were examined histopathologically. Sixty-seven (5.5%) metastatic nodes were found in 26/102 patients (25.5%). Lymph node density was 22%. On patient-based analysis, sensitivity, specificity, predictive positive value (PPV), negative positive value (NPV) and accuracy for (18)F-FDG PET/CT were calculated as 50%, 96.2%, 80%, 86.2% and 85.3% respectively. On a field-based analysis, sensitivity, specificity, PPV, NPV and accuracy for (18)F-FDG PET/CT were calculated as 50.0%, 99.0%, 71.9%, 97.4%, and 96.5% respectively. The majority of missed metastases were micrometastasis <5 mm in long axis diameter. (18)F-FDG PET/CT improves diagnostic efficacy for lymph node staging in patients staged N0 with conventional cross-sectional imaging. (18)F-FDG PET/CT could be used as a surrogate marker for detection of metastases in non-enlarged pelvic lymph nodes and enhances management strategy guiding patients selection for neoadjuvant chemotherapy. | 25,242,381 | [
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Grape seed proanthocyanidins inhibit H2O2-induced osteoblastic MC3T3-E1 cell apoptosis via ameliorating H2O2-induced mitochondrial dysfunction. | Oxidative stress represents a major cause of cellular damage and death in pathological conditions including osteoporosis, in which oxidative stress is associated with increased bone resorption and low bone mass. And grape seed proanthocyanidins are a group of polyphenolic bioflavonoids which are known to possess broad pharmacological activity and therapeutic potential, exerting a protective role against oxidant injury. The aim of our study was to investigate whether proanthocyanidins exert an anti-apoptosis effect in osteoblastic MC3T3-E1 cells, via their antioxidant activity. Firstly, we determined the anti-apoptosis effect of proanthocyanidins in osteoblastic MC3T3-E1 cells, which were subject to H2O2 treatment, then we determined the association of the antioxidant activity exerted by proanthocyanidins with their anti-apoptosis effect. Results demonstrated that proanthocyanidins inhibit H2O2-promoted apoptosis in MC3T3-E1 cells, via ameliorating the viability of MC3T3-E1 cells post H2O2 treatment and reducing the apoptotic cell numbers. And the proanthocyanidins treatment also ameliorates the H2O2-induced mitochondrial dysfunction via promoting the mitochondrial membrane potential (MMP) and respiratory chain complex IV, and reducing the mitochondrial free radical production, ROS and mitochondrial superoxide. Moreover, the proanthocyanidins inhibit H2O2-induced apoptosis signaling which is mediated by p53. This study implied a possible anti-osteoporosis effect of proanthocyanidins via their antioxidant and anti-apoptosis activity. | 25,242,411 | [
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Meta-analysis of lactation performance in dairy cows receiving supplemental dietary methionine sources or postruminal infusion of methionine. | The objectives of our study were to evaluate the productive response to methionine supplementation in lactating dairy cows and to define a relationship between metabolizable Met (MP Met) intake and production. A database of 64 papers meeting the selection criteria was developed evaluating postruminally infused dl-methionine (9 papers with 18 control diets and 35 treatment comparisons), 2-hydroxy-4-methylthio butanoic acid (HMTBa) provided as either a liquid or Ca salt form (17 papers with 34 control diets and 46 treatment comparisons), Mepron (Evonik Industries, Essen, Germany; 18 papers with 35 control diets and 42 treatment comparisons), and Smartamine (Adisseo Inc., Antony, France; 20 papers with 30 control diets and 39 treatment comparisons). Dietary ingredients and their accompanying nutritional compositions as described in the reports were entered into the Cornell-Penn-Miner software to model the diets and to predict nutrients that were not reported in the original publication. Data were analyzed using a weighted analysis of response to supplementation compared with the intraexperiment control, as well as through a regression analysis to changing dietary MP Met. Data included in the analysis were from experiments published between 1970 and 2011 with cows supplemented with between 3.5 and 67.9 g of Met or its equivalent from HMTBa. Cows supplemented with Smartamine consumed more, whereas cows supplemented with Mepron consumed less DM compared with controls. Milk yield did not significantly respond to Met supplementation, although it tended to increase for cows supplemented with HMTBa and Mepron. Milk protein yield was increased due to supplementation from all sources or from infusion, and protein concentration was greater for all supplements or infusion of dl-Met, except for cows supplemented with HMTBa. Irrespective of Met source, milk protein yield increased 2.23 g of protein/g of MP Met until reaching the breakpoint. Milk fat yield was increased for Mepron and HMTBa, whereas milk fat concentration was increased for infused dl-Met and for cows supplemented with HMTBa. Based on regression analysis, response of milk fat yield to Met supplementation was not different for infused dl-Met, Mepron, and Smartamine (1.87 g of fat/g of MP Met), whereas the response to HMTBa was significantly greater at 5.38 g of fat/g of MP Met. | 25,242,429 | [
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Mood dependence of perceived criticism: a significant null finding. | Five decades of research have shown that the quality of one׳s interactions with significant others, as captured in the expressed emotion (EE) concept, affects the course of various psychiatric and medical complaints. The key EE-component, interpersonal criticism, is increasingly assessed with the single-item Perceived Criticism Measure (PCM). The measure is highly practical and has shown good concurrent and predictive validity. Because the PCM relies on respondents׳ memories, ratings may be subject to mood bias. In this study we examined to what extent PCM-ratings are mood dependent. College students (N=150) provided data on mood and PCM before and after the induction of either a positive or negative mood. Although the mood induction was highly successful, PCM-ratings remained stable and appeared unaffected by changes in mood. This finding contradicts the robust mood-congruency-effect finding that the valence of one's mood enhances the recollection of similarly valenced memories. This apparent stability bolsters the PCM's construct validity and makes it less likely that high PCM-ratings simply reflect the negatively biased perceptions of distressed individuals. | 25,242,433 | [
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[How to select the spermatozoon in ICSI?]. | The selection of the individual spermatozoon in ICSI is routinely performed by the observation of its motility and morphology. However, in case of severe oligoasthenozoospermia or non-obstructive azoospermia needing the use of testicular sperm, other methods are necessary to help the embryologist making this choice. According to some authors, sperm processing before ICSI seems to limit the DNA fragmentation index, and in this way improve ICSI outcomes. Moreover, IMSI is potentially a good option in some specific indications such as severe teratozoospermia, or repeated ICSI failures. Other methods based on sperm structure, as sperm head birefringence observation, or based on its function, like the hyaluronic acid or zona pellucida binding capacity, could be of interest, but still need to be confirmed. Finally, in case of akinetozoospermia, the use of functional tests, such as pentoxifylline test, HOS-test, or to a lesser extent laser touch, makes the selection of viable spermatozoa easier. Nevertheless, studies on larger series have to be conducted to evaluate and precise the interest of each of these methods and their indications, before considering an application on larger scale. | 25,242,440 | [
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Hetero-oligomerization of C2 domains of phospholipase C-related but catalytically inactive protein and synaptotagmin-1. | The C2 domain is a protein module often found in molecules that regulate exocytosis. C2 domains mediate interactions between the parental molecule and Ca(2+), phospholipids, and proteins. Although various molecules have been shown to interact with several C2 domains, no interactions between the C2 domains from different molecules have yet been reported. In the present study, we identified direct interactions between the C2 domain of PRIP (phospholipase C-related but catalytically inactive protein) and the C2 domains of other molecules. Among the C2 domains examined, those of synaptotagmin-1 (Syt1-C2A and Syt1-C2B) and phospholipase C δ-1 bound to the C2 domain of PRIP. We investigated the interactions between the C2 domain of PRIP (PRIP-C2) with Syt1-C2A and Syt1-C2B, and the mode of binding of each was Ca(2+)-dependent and -independent, respectively. We further demonstrated that the Ca(2+) dependence of the interaction between PRIP-C2 and Syt1-C2A was attributed to Ca(2+) binding with Syt1-C2A, but not PRIP-C2, using a series of mutants prepared from both C2 domains. We previously reported that the interaction between PRIP-C2 and the membrane fusion machinery suggested a critical role for PRIP in exocytosis; therefore, the results of the present study further support the importance of PRIP-C2 in the inhibitory function of PRIP in regulating exocytosis. | 25,242,442 | [
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Radiation-induced epithelial-myoepithelial carcinoma in a patient previously treated with mantle-field radiation therapy for Hodgkin lymphoma. | Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands. We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period. Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population. | 25,242,451 | [
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Microparticles in multiple sclerosis and clinically isolated syndrome: effect on endothelial barrier function. | Cell-derived microparticles are secreted in response to cell damage or dysfunction. Endothelial and platelet dysfunction are thought to contribute to the development of multiple sclerosis (MS). Our aim here is, first, to compare the presence of microparticles of endothelial and platelet origin in plasma from patients with different clinical forms of MS and with clinically isolated syndrome. Second, to investigate the effect of microparticles on endothelial barrier function. Platelet-poor plasma from 95 patients (12 with clinically isolated syndrome, 51 relapsing-remitting, 23 secondary progressive, 9 primary progressive) and 49 healthy controls were analyzed for the presence of platelet-derived and endothelium-derived microparticles by flow cytometry. The plasma concentration of platelet-derived and endothelium-derived microparticles increased in all clinical forms of MS and in clinically isolated syndrome versus controls. The response of endothelial barriers to purified microparticles was measured by electric cell-substrate impedance sensing. Microparticles from relapsing-remitting MS patients induced, at equivalent concentrations, a stronger disruption of endothelial barriers than those from healthy donors or from patients with clinically isolated syndrome. MS microparticles acted synergistically with the inflammatory mediator thrombin to disrupt the endothelial barrier function. Plasma microparticles should be considered not only as markers of early stages of MS, but also as pathological factors with the potential to increase endothelial permeability and leukocyte infiltration. | 25,242,463 | [
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Influence of grape maturity on the foaming properties of base wines and sparkling wines (Cava). | The aim of this paper is to determine the main factors that influence the foaming properties of base wines and sparkling wines and, in particular, the role played by the maturity of the grapes in the controlled designation of origin (CDO) Cava. Macabeo, Xarel.lo, Parellada and Chardonnay grapes were harvested at two different maturity levels in two vintages. The first harvest was selected because of its desirable titratable acidity and the second because of its optimal sugar concentration. The mono-varietal base wines and standard blends were transformed into sparkling wines and aged for 14 months. The results indicate that the main factors affecting foam properties are ethanol content, high molecular weight polysaccharides and gluconic acid (which have a negative effect), and proteins (which have a positive effect). The main conclusion of this study is that the foaming properties of wines can be improved if harvest dates are advanced. | 25,242,464 | [
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miR‑96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer. | microRNA-96 (miR-96) is known to be downregulated in pancreatic cancer. The overexpression of miR-96 in MIA PaCa-2 pancreatic cancer cells has been shown to inhibit cell proliferation, migration and invasion; however, the mechanisms involved have not yet been fully elucidated. Novel (nua) kinase family 1 (NUAK1) functions as an oncogene in non‑small cell lung cancer (NSCLC), melanoma, glioma, breast cancer, hepatocellular carcinoma and pancreatic cancer. In this study, firstly, we demonstrate that NUAK1 expression is specifically upregulated in pancreatic cancer and that it promotes the proliferation, migration and invasion of MIA PaCa-2 pancreatic cancer cells. Secondly, we performed an analysis of potential microRNA (miRNA) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-96 targets the 3' untranslated region (3' UTR) of NUAK1. Further experiments confirmed this prediction, namely that miR-96 suppresses the expression of NUAK1 by targeting its 3' UTR. Finally, we demonstrate that the introduction of NUAK1 cDNA lacking predicted sites of the 3' UTR abrogates miR-96 cellular function. | 25,242,509 | [
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Mutations of rat surfactant protein A have distinct effects on its glycosylation, secretion, aggregation and degradation. | Surfactant protein A (SP-A) plays critical roles in the innate immune system and surfactant homeostasis of the lung. Mutations in SP-A2 of the carbohydrate recognition domain (CRD) impair its glycosylation and are associated with pulmonary fibrosis in humans. We aim to examine how mutations in SP-A that impair its glycosylation affect its biological properties and lead to disease. We generated rat SP-A constructs with two types of mutations that impair its glycosylation: N-glycosylation site mutations (N21T, N207S and N21T/N207S) and disease-associated CRD mutations (G231V, F198S). We transfected these constructs into Chinese hamster ovary (CHO)-K1 cells and assessed biochemical differences in cellular and secreted wild-type and mutant SP-As by western blot, immunofluorescence, and sensitivity to enzymatic digestion. Mutations of the CRD completely impaired SP-A secretion, whereas mutations of N-glycosylation sites had little effect. Both types of mutations formed nonidet p-40 (NP-40) insoluble aggregates, but the aggregates only from CRD mutations could be partially rescued by a chemical chaperone, 4-phenylbutyrate acid (4-PBA). The majority of CRD mutant SP-A was retained in the endoplasmic reticulum. Moreover, both types of mutations reduced SP-A stability, with CRD mutant SP-A being more sensitive to chymotrypsin digestion. Both types of soluble mutant SP-A could be degraded by the proteasome pathway, while insoluble aggregates could be additionally degraded by the lysosomal pathway. Our data provide evidence that the differential glycosylation of SP-A may play distinct roles in SP-A secretion, aggregation and degradation which may contribute to familial pulmonary fibrosis caused by SP-A2 mutations. | 25,242,514 | [
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The effectiveness of spent coffee grounds and its biochar on the amelioration of heavy metals-contaminated water and soil using chemical and biological assessments. | Spent coffee grounds (SCG) and charred spent coffee grounds (SCG-char) have been widely used to adsorb or to amend heavy metals that contaminate water or soil and their success is usually assessed by chemical analysis. In this work, the effects of SCG and SCG-char on metal-contaminated water and soil were evaluated using chemical and biological assessments; a phytotoxicity test using bok choy (Brassica campestris L. ssp. chinensis Jusl.) was conducted for the biological assessment. When SCG and SCG-char were applied to acid mine drainage, the heavy metal concentrations were decreased and the pH was increased. However, for SCG, the phytotoxicity increased because a massive amount of dissolved organic carbon was released from SCG. In contrast, SCG-char did not exhibit this phenomenon because any easily released organic matter was removed during pyrolysis. While the bioavailable heavy metal content decreased in soils treated with SCG or SCG-char, the phytotoxicity only rose after SCG treatment. According to our statistical methodology, bioavailable Pb, Cu and As, as well as the electrical conductivity representing an increase in organic content, affected the phytotoxicity of soil. Therefore, applying SCG during environment remediation requires careful biological assessments and evaluations of the efficiency of this remediation technology. | 25,242,543 | [
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A multi-center population-based case-control study of ovarian cancer in African-American women: the African American Cancer Epidemiology Study (AACES). | Ovarian cancer (OVCA) is the leading cause of death from gynecological cancer, with poorer survival for African American (AA) women compared to whites. However, little is known about risk factors for OVCA in AA. To study the epidemiology of OVCA in this population, we started a collaborative effort in 10 sites in the US. Here we describe the study and highlight the challenges of conducting a study of a lethal disease in a minority population. The African American Cancer Epidemiology Study (AACES) is an ongoing, population-based case-control study of OVCA in AA in 10 geographic locations, aiming to recruit 850 women with invasive epithelial OVCA and 850 controls age- and geographically-matched to cases. Rapid case ascertainment and random-digit-dialing systems are in place to ascertain cases and controls, respectively. A telephone survey focuses on risk factors as well as factors of particular relevance for AAs. Food-frequency questionnaires, follow-up surveys, biospecimens and medical records are also obtained. Current accrual of 403 AA OVCA cases and 639 controls exceeds that of any existing study to date. We observed a high proportion (15%) of deceased non-responders among the cases that in part is explained by advanced stage at diagnosis. A logistic regression model did not support that socio-economic status was a factor in advanced stage at diagnosis. Most risk factor associations were in the expected direction and magnitude. High BMI was associated with ovarian cancer risk, with multivariable adjusted ORs and 95% CIs of 1.50 (0.99-2.27) for obese and 1.27 (0.85- 1.91) for morbidly obese women compared to normal/underweight women. AACES targets a rare tumor in AAs and addresses issues most relevant to this population. The importance of the study is accentuated by the high proportion of OVCA cases ascertained as deceased. Our analyses indicated that obesity, highly prevalent in this population (>60% of the cases), was associated with increased OVCA risk. While these findings need to be replicated, they suggest the potential for an effective intervention on the risk in AAs. Upon completion of enrollment, AACES will be the largest epidemiologic study of OVCA in AA women. | 25,242,549 | [
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Acute aortic dissection caused by Clostridium septicum aortitis. | Clostridium septicum aortitis is a rare cause of aortic dissection. So far, only 28 cases have been described in literature before. Most of these cases occurred in elderly patients and an association to colonic neoplasms and/or atherosclerosis has been witnessed frequently. Here we report the case of a 32-year-old man with fatal aortic dissection due to aortic infection with C. septicum. Beside a case of a 22-year-old man who died of aortic dissection due to C. septicum aortitis this is the second case of C. septicum aortitis in a young individual with no signs of colonic neoplasms or atherosclerosis. | 25,242,573 | [
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Retinal projections into the Zona Incerta of the rock cavy (Kerodon rupestris): a CTb study. | The Zona Incerta is a key neural substrate of higher brain functions. A neural population in the caudal ZI projects into the superior colliculus. This recently has been identified as an important structure for the saccades. Applying CTb, we describe a retinal projection into the caudal ZI and the distribution of its terminal varicosities in the rock cavy, a Brazilian rodent, which has been used as an anatomical model to enhance the comprehension about the phylogeny of the nervous system. Contrary to other investigated rodents, the retinal fibers in the rock cavy lie in the caudal Zona Incerta (ZIc), suggesting a functional specialization in the rock cavy. The high resolution and qualitative analysis of retinal fibers in the present work provide a substrate to interpretation of the visual system, and its phylogenetic pathways among species. | 25,242,576 | [
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Photocatalytic degradation and reactor modeling of 17α-ethynylestradiol employing titanium dioxide-incorporated foam concrete. | Photocatalytic degradation of 17α-ethynylestradiol (EE2) using TiO2 photocatalysts incorporated with foam concrete (TiO2/FC) was investigated for the first time. Scanning electron microscopy (SEM) study of the samples revealed a narrow air void size distribution on the surface of FC cubes on with 5 wt% addition of P25 TiO2, and TiO2 particles were distributed heterogeneously on the surface of TiO2/FC samples. The sorption and photocatalytic degradation of EE2 with UV-light irradiation by TiO2/FC cubes were investigated. Adsorption capacity of EE2 by the TiO2/FC and blank foam concrete (FC) samples were similar, while the degradation rates showed a great difference. More than 50 % of EE2 was removed by TiO2/FC within 3.5 h, compared with 5 % by blank FC. The EE2 removal process was then studied in a photoreactor modified from ultraviolet disinfection pool and constructed with TiO2/FC materials. An integrated model including a plate adsorption-scattering model and a modified flow diffusion model was established to simulate the photocatalytic degradation process with different radiation fields, contaminant load, and flow velocity. A satisfactory agreement was observed between the model simulations and experimental results, showing a potential for the design and scale-up of the modified photocatalytic reactor. | 25,242,591 | [
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... |
Development and evaluation of the US Healthy Food Diversity index. | Varied diets are diverse with respect to diet quality, and existing dietary variety indices do not capture this heterogeneity. We developed and evaluated the multidimensional US Healthy Food Diversity (HFD) index, which measures dietary variety, dietary quality and proportionality according to the 2010 Dietary Guidelines for Americans (DGA). In the present study, two 24 h dietary recalls from the 2003-6 National Health and Nutrition Examination Survey (NHANES) were used to estimate the intake of twenty-six food groups and health weights for each food group were informed by the 2010 DGA. The US HFD index can range between 0 (poor) and 1 - 1/n, where n is the number of foods; the score is maximised by consuming a variety of foods in proportions recommended by the 2010 DGA. Energy-adjusted Pearson's correlations were computed between the US HFD index and each food group and the probability of adequacy for fifteen nutrients. Linear regression was run to test whether the index differentiated between subpopulations with differences in dietary quality commonly reported in the literature. The observed mean index score was 0·36, indicating that participants did not consume a variety of healthful foods. The index positively correlated with nutrient-dense foods including whole grains, fruits, orange vegetables and low-fat dairy (r 0·12 to 0·64) and negatively correlated with added sugars and lean meats (r - 0·14 to - 0·23). The index also positively correlated with the mean probability of nutrient adequacy (r 0·41; P< 0·0001) and identified non-smokers, women and older adults as subpopulations with better dietary qualities. The US HFD index may be used to inform national dietary guidance and investigate whether healthful dietary variety promotes weight control. | 25,242,619 | [
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The blood-brain barrier-permeable catechol-O-methyltransferase inhibitor dinitrocatechol suppresses experimental autoimmune encephalomyelitis. | Reduced levels of noradrenaline (NA) in CNS of multiple sclerosis patients could be due to metabolism by catechol-O-methyltransferase (COMT). In mice immunized with myelin oligodendrocyte glycoprotein peptide, the BBB-permeable COMT inhibitor dinitrocatechol (DNC) reduced clinical signs, while entacapone, a non-BBB-permeable inhibitor, had no effect. Spinal cord NA levels were slightly increased by DNC, and there was an inverse correlation between NA levels and average clinical signs. Spinal cord COMT mRNA levels were not increased during EAE, but were found increased in the frontal cortex of MS patients. These results suggest that COMT inhibitors could provide benefit to MS patients. | 25,242,632 | [
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Cardiovascular disease risk factors in the Hispanic/Latino population: lessons from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). | Cardiovascular disease (CVD) is one of the leading causes of mortality among Hispanics/Latinos residing in the United States (US), yet despite the rapid growth of this diverse population, there has been a dearth of objective, comprehensive data on prevalence of risk factors for CVD and other chronic diseases. The Hispanic Community Health Study/SOL) is the largest and most comprehensive cohort study to date/SOL) was initiated to address this gap in knowledge. This article reviews existing research on CVD risk factors among Hispanic/Latino adults of diverse background residing in the US, compares findings from HCHS/SOL with other representative samples on prevalence of major CVD risk factors in this population, and discusses the lessons learned thus far from HCHS/SOL. Baseline findings from this study demonstrate that sizeable burdens in CVD risk exist among all major Hispanic/Latino background groups in the US. At the same time, there are marked variations in rates of individual risk factors by Hispanic/Latino background groups. Comprehensive public health policies to lower CVD risk among those who have adverse levels of one or more risk factors, and to prevent development of CVD risk factors in the small proportion free of CVD risk are urgently needed to lower the future burden of CVD among the US Hispanic/Latino population. | 25,242,694 | [
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Neglect: failure to thrive and obesity. | Medical providers need to monitor growth at every visit. Weight status is influenced by genetics, medical conditions, socioeconomic status, and family environment. Screening for food security and psychosocial risk factors is an integral tool to identify families at risk for nutritional deficits and child maltreatment. Nutritional rehabilitation is best accomplished in an outpatient, multidisciplinary setting. Medical neglect should be considered in failure to thrive and obesity when there is a serious risk of harm from identified medical complications, additional or worsening medical complications occurring despite a multidisciplinary approach, and/or non-adherence with the treatment plan. | 25,242,707 | [
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Working with child protective services and law enforcement: what to expect. | The process whereby a clinician decides that child abuse is a diagnostic possibility is often marked with doubt and fear. Abusive parents can present convincing lies, and children with suspicious injuries can have unusual accidents. Personal thresholds for reporting suspected abuse vary considerably. Clinicians may mistrust or misunderstand the roles and responsibilities of the investigators and legal professionals involved. This article aims to improve understanding of the community responses to a report of child abuse, and enable the clinician to work effectively with child protective services, law enforcement agencies, and legal professionals to ensure child safety and family integrity when appropriate. | 25,242,714 | [
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Complicated diverticulitis in kidney transplanted patients: analysis of 717 cases. | This study aims to investigate possible risk factors for diverticulitis in kidney transplant recipients affected by colonic diverticulosis. We investigated 717 patients transplanted between 2000 and 2010. Diverticular disease was endoscopically diagnosed in 17 of 717 examined patients. Eight patients were diagnosed with autosomal dominant polycystic kidney disease (ADPKD); 9 of 17 patients underwent emergency surgery. We performed Hartmann's procedure on all patients, with a second stage performed at least 6 months later. Although the incidence of colonic diverticular perforation in kidney transplanted patients is similar to that observed in the general population, perforation in immunosuppressed patients is associated with a higher morbidity/mortality rate. In our study, the incidence of perforation is 1.25% (9 of 717), with almost half of the cases observed in patients with ADPKD (4 of 9). Such an observation is consistent with published data, in which patients with ADPKD are reported to more frequently develop colonic diverticulosis and its complications. One possible explanation might be related to a belated diagnosis of diverticulitis, which could initially simulate an inflammatory disease as a consequence of renal cysts. Also, steroids seem to be a predisposing factor for colonic perforation in these patients. A timely surgery can significantly reduce mortality. In cases of elective surgery, mortality and morbidity are similar to those of immunocompetent patients; accordingly, this is the goal to be pursued. Early signs and symptoms are often masked by immunosuppressive therapy. In these patients, surgeons should always perform (1) abdominal computed tomography scanning and, in the presence of diverticulitis, reduce or withdraw immunosuppressive therapy; and (2) early surgery, with Hartmann's procedure being, in our opinion, the best choice. Before transplantation, elective surgery for colonic resection should be considered in patients with ADPKD or with a history of 1 or more episodes of acute diverticulitis who then regressed with medical therapy. | 25,242,762 | [
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Placental, lipid, and glucidic effects of mammalian target of rapamycin inhibitors: impact on fetal growth and metabolic disorders during pregnancy after solid organ transplantation. | Mammalian target of rapamycin inhibitors (mTORi) are a promising new family of immunosuppressive drugs. No teratogenic effects have been reported to date. Their lipid and glucidic effects should not be underestimated, however, especially during pregnancy. Moreover, mTORi may affect fetal growth by mTOR placental activity. Our purpose was to highlight mTORi placental impact and metabolic implications to detect possible maternal or fetal effects and define management guidelines in pregnant women after solid organ transplantation. A literature search was performed for articles from the Medline and Pubmed databases with the use of the following keywords: mTOR inhibitors, pregnancy, placental transport, lipid metabolism, glucose metabolism. mTOR works as a positive regulator of system A, system L, and taurine placental amino acid transporter activity, which are critical for the transport of amino acids to the fetus. Exposing trophoblast cells to rapamycin reduces system L activity; therefore, treatment with rapamycin in human pregnancies could alter fetal growth with intrauterine growth restriction (IUGR). Regarding the metabolic effects mTORi increase lipolysis, impair insulin's antilipolytic effect and reduce lipid storage, which may potentially contribute to dyslipidemia. Chronic rapamycin treatment reduces adipose tissue size and β-cell mass/function, causes hyperlipidemia, severe insulin resistance, and glucose intolerance, and promotes hepatic gluconeogenesis. The studies on mTORi treatment in transplanted pregnant women have not focused to date on the potential metabolic and placental effects. Selection of women at high risk for metabolic disorders could be needed and consideration of switching to another immunosuppressive drug required if diabetes and abnormal blood lipids have been diagnosed in prepregnancy counseling. It seems to be mandatory to encourage prompt reporting of any additional cases of pregnancy during mTORi exposure to provide a better understanding of the placental effects and safety profile of these immunosuppressive drugs. | 25,242,764 | [
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Predictability and survival in liver replantransplantation: monocentric experience. | Liver retransplantation is the only treatment for patients with hepatic graft failure. Due to the shortage of organs, it is essential to optimize its use. Between 1998-2010, our center performed retransplantations on 48 (12.8%) patients (re-OLT). The data are compared with those for a group of 374 patients who did not receive retransplantations (NO re-OLT). The re-OLT vs NO re-OLT groups did not significantly differ in mean age of recipients (47 vs 51 years), indications for transplantation (hepatitis C virus cirrhosis 54% vs 56%, alcoholic cirrhosis 25% vs 17%, hepatocellular carcinoma 14% vs 22%), mean Model for End-stage Liver Disease (25 vs 20), mean total cold ischemia time (385 vs 379 minutes), or mean age of donors (52 vs 49 years). The main causes of retransplantation were primary graft nonfunction (64%), arterial thrombosis (8%), biliary complications (6%), and hepatitis C virus recurrence (4%). The difference in overall patient survival was not statistically significant. The patient's survival at 1, 3, 5, and 10 years for RE-OLT vs NO-reOLT was 56% vs 63%, 53% vs 60%, 46% vs 57%, and 44% vs 53%, respectively. Multivariate analysis identified Model for End-stage Liver Disease≥23 as a predictor factor of retransplantation (P=.04). Other variables predicting outcome included age of donors (≥65 years vs younger group), age of recipients (≥50 years vs younger group), cold ischemia (≥600 vs <600 minutes), and transplantation indications (hepatitis C virus, hepatitis B virus, alcohol, and others). The retransplantation performed between 8-15 days appeared to have worse results than those in other periods (0-7 days, 16-30 days, 1-6 months, >6 months). The incidence of re-OLT in the series (12.8%) was comparable to that in the literature, and primary graft nonfunction in the study represents the main cause of retransplantation. Our analysis showed that the indication of the first transplant and the age of the donor were not risk factors for re-OLT. Liver retransplantation is a concrete alternative lifesaver for patients with graft failure. | 25,242,771 | [
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Telbivudine prophylaxis for hepatitis B virus recurrence after liver transplantation improves renal function. | Renal impairment after liver transplantation represents an important issue in the management of transplantation patients, particularly when those subjects may need prophylaxis for fungal or viral infection. Herein we report our experience with 12 transplantation patients receiving telbivudine 600 mg/d while on the waiting list, followed by treatment for 18 months after liver transplantation, showing an improvement on their renal function during the follow-up period. Our series consisted of men with hepatitis B virus (HBV)-related end-stage liver disease. The viral load decreased rapidly while on the waiting list once the patient was started on antiviral treatment. Those subjects were compared with 12 patients on lamivudine prophylaxis. All patients were evaluated for liver and renal function, immunosuppression trough levels, and creatine phosphokinase (CPK) before liver transplantation (T0) and at 3, 6, 12, and 18 months (T3, T6, T12, T18). All patients received a calcineurin inhibitor immunosuppression-based regimen. Creatinine clearance (Modification of Diet in Renal Disease) was 67 mL/min at T0, with a statistically significant improvement after month 6 compared with those on lamivudine and with the value at the beginning of the prophylaxis (Mann-Whitney U test P<.05). Neither CPK nor transaminase serum levels increased throughout the study period. Once HBV DNA was cleared while on the waiting list, it remained negative throughout the follow-up period. Telbivudine prophylaxis for HBV is safe and effective, without any significant deleterious effect on the liver; on the contrary, it seems to improve renal function after liver transplantation through 18 months. Further studies and larger series are warranted to confirm these findings. | 25,242,778 | [
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