title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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ARV-based HIV prevention for women - where we are in 2014. | Women continue to be at special risk for HIV acquisition due to a complex mix of biological, behavioural, structural, cultural and social factors, with unacceptable rates of new infection. Scientific advances over the past decade have highlighted the use of antiretroviral (ARV) drugs as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition (sexually, parenterally and vertically) and ARV treatment (ART) for HIV-positive patients to prevent onward transmission (treatment as prevention - TasP). This paper reviews the evidence base for PrEP and TasP, describes new products in development and the need to translate research findings into programmes with impact at the population level. | 25,224,614 | [
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Reversion of trichostatin A resistance via inhibition of the Wnt signaling pathway in human pancreatic cancer cells. | Drug resistance is a major impediment to successful chemotherapy in pancreatic cancer (PC) patients. We investigated the effect of Wnt/β-catenin signaling inhibition by wnt-c59 on chemoresistance in a trichostatin A-resistant Panc-1 cell line (Panc-1/TSA). Panc-1/TSA cells were treated with the Wnt/β‑catenin signaling inhibitor wnt-c59 (10 µmol · l-1) and/or trichostatin A (TSA; 10 µmol · l-1) for 24 h. CCK-8 assay was utilized to analyze the interactive effect of TSA and wnt-c59 on induction of apoptosis of the Panc-1/TSA cells. Cell apoptosis was measured by flow cytometry. Real-time PCR and western blotting were used to assess Wnt/β-catenin signaling, epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR). Real-time cell analysis (RTCA) was used to detect the cell migration ability. After wnt-c59 treatment for 24 h, relative genes and transcriptional targets of Wnt/β-catenin signaling were downregulated (P<0.05). CCK-8 assay indicated that the combination of TSA and wnt-c59 had a synergistic effect on induction of Panc-1/TSA cell apoptosis. As detected by FACS, cell apoptosis rates increased significantly (P<0.05). The results of RTCA showed that the cell indices of the control group, wnt-c59 group, TSA group and TSA+wnt-c59 combination group were 1.2842±0.0257, 1.2155±0.0282, 1.2533±0.0194 and 0.8541±0.0250, respectively. In accordance, MMP-9 protein in the wnt-c59 treatment groups was decreased compared to the non-wnt-c59 treatment groups. Meanwhile, E-cadherin protein was upregulated and vimentin protein was downregulated, both of which are characteristic markers of EMT. Chemoresistant gene MDR1 and P-glycoprotein (P-gp) in the wnt-c59 treatment groups had a reduced expression compared to the non-wnt-c59 treatment groups. This study revealed that TSA sensitivity, migration ability, and the EMT phenotype in Panc-1/TSA cells were reversed following Wnt/β-catenin signaling inhibition. | 25,224,651 | [
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Multichannel lens-free CMOS sensors for real-time monitoring of cell growth. | A low-cost platform is proposed for the growth and real-time monitoring of biological cells. The main components of the platform include a PMMA cell culture microchip and a multichannel lens-free CMOS (complementary metal-oxide-semiconductor) / LED imaging system. The PMMA microchip comprises a three-layer structure and is fabricated using a low-cost CO2 laser ablation technique. The CMOS / LED monitoring system is controlled using a self-written LabVIEW program. The platform has overall dimensions of just 130 × 104 × 115 mm(3) and can therefore be placed within a commercial incubator. The feasibility of the proposed system is demonstrated using HepG2 cancer cell samples with concentrations of 5000, 10 000, 20 000, and 40 000 cells/mL. In addition, cell cytotoxicity tests are performed using 8, 16, and 32 mM cyclophosphamide. For all of the experiments, the cell growth is observed over a period of 48 h. The cell growth rate is found to vary in the range of 44∼52% under normal conditions and from 17.4∼34.5% under cyclophosphamide-treated conditions. In general, the results confirm the long-term cell growth and real-time monitoring ability of the proposed system. Moreover, the magnification provided by the lens-free CMOS / LED observation system is around 40× that provided by a traditional microscope. Consequently, the proposed system has significant potential for long-term cell proliferation and cytotoxicity evaluation investigations. | 25,224,658 | [
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Surgery for amygdala enlargement with mesial temporal lobe epilepsy: pathological findings and seizure outcome. | Amygdala enlargement (AE) has been suggested to be a subtype of mesial temporal lobe epilepsy (MTLE). However, most reports related to AE have referred to imaging studies, and there have been few reports regarding surgical and pathological findings. The present study was performed to clarify the surgical outcomes and pathology of AE. Eighty patients with drug-resistant MTLE were treated surgically at the Tokyo Metropolitan Neurological Hospital between April 2010 and July 2013. Of these patients, 11 were diagnosed as AE based on presurgical MRI. Nine patients with AE underwent selective amygdalohippocampectomy, while the remaining two patients underwent selective amygdalotomy with hippocampal transection. Intraoperative EEG was routinely performed. The histopathology of the resected amygdala tissue was evaluated and compared with the amygdala tissue of patients with hippocampal sclerosis. Pathological findings indicated that 10 of 11 specimens had closely clustering hypertrophic neurons with vacuolisation of the background matrix. Slight gliosis was seen in nine specimens, while the remaining two showed no gliotic changes. Intraoperative EEG showed abnormal sharp waves that seemed to originate not from the amygdala but from the hippocampus in all cases. Ten patients became seizure-free during the postoperative follow-up period. Histopathologically, clustering hypertrophic neurons and vacuolation with slight gliosis or without gliosis were considered to be pathological characteristics of AE. Amygdalohippocampectomy or hippocampal transection with amygdalotomy is effective for seizure control in patients with AE. | 25,224,675 | [
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A dyf-7 haplotype causes sensory neuron defects and is associated with macrocyclic lactone resistance worldwide in the nematode parasite Haemonchus contortus. | Heavy reliance on macrocyclic lactones to treat parasitic nematodes has resulted in the evolution of widespread drug resistance that threatens human and animal health. Management strategies have been proposed that would slow the rise of resistance, however testing these strategies has been hampered by the lack of identified strong-effect resistance markers in parasites. We show that the Caenorhabditis elegans gene Cel_dyf-7, necessary for amphid sensory neuron development, also confers macrocyclic lactone sensitivity. In the sheep parasite Haemonchus contortus: (i) strains selected for macrocyclic lactone resistance were enriched in a Hco_dyf-7 haplotype that was rare in the drug-naïve population, (ii) the resistant haplotype correlated with the sensory neuron defects, and (iii) the resistant haplotype was associated with decreased Hco_dyf-7 expression. Resistant field isolates of H. contortus from five continents were enriched for the resistant haplotype, demonstrating the relevance of the Hco_dyf-7 haplotype to practise and indicating that it is a locus of strong effect. Hemizygosity resulting from sex linkage of dyf-7 likely contributes to the rise of resistance in treated populations. | 25,224,687 | [
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Postoperative steroids after Kasai portoenterostomy for biliary atresia: a meta-analysis. | The aim of this systematic review and meta-analysis was to determine if adjunct steroids affect jaundice-free, cholangitis, and survival rates after Kasai portoenterostomy. The literature was searched using the following terms: biliary atresia, portoenterostomy, steroids, glucocorticoids, dexamethasone, prednisolone, and hydrocortisone. The primary outcome was the jaundice-free rate. Secondary outcomes were cholangitis and survival rates. Ten studies were included in the systematic review and 8 in the meta-analyses. Steroid treatment regimens were inconsistent between studies. The pooled odds ratio (OR) for the jaundice-free rate did not significantly favor steroid over non-steroid treatment (1.95; 95% confidence interval [CI]: 0.91-4.11; P = 0.087), nor did the pooled OR for the cholangitis rate (0.75; 95% CI: 0.48-1.17; P = 0.202). Overall survival ranged from 58 to 95% in the steroid group and from 36 to 96% in the control group. Native liver survival ranged from 30 to 56% in the steroid group and from 31 to 48% in the control group. The survival data were not suitable for meta-analysis. Although these results imply that adjunct steroids after Kasai portoenterostomy for BA may not improve jaundice-free or cholangitis rates, the quality of available evidence is limited and therefore not definitive. Additional high quality studies are needed. | 25,224,699 | [
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[Application of the diagnosis procedure combination (DPC) data to clinical studies]. | The Diagnosis Procedure Combination (DPC) is a case-mix classification system that is linked with a lump-sum payment system for inpatient care reimbursement. The key objectives of introducing the DPC system are to implement an electronic claim system and to provide transparency of hospital performance. The DPC data include discharge abstract and administrative claims data. The unique advantage of the DPC data is the inclusion of detailed process data and several clinical data that can be applied to clinical studies. In this report, we explain the structure and contents of the DPC database, and discuss the applicability of the DPC data to clinical studies, comparing them with the US Nationwide Inpatient Sample database. | 25,224,711 | [
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A scoping review of risk behaviour interventions in young men. | Young adult males commonly engage in risky behaviours placing them at risk of acute and chronic health conditions. The purpose of this scoping review was to provide an overview of existing literature, describing the interventions targeting risk behaviours in young adult males. A search of seven electronic databases, grey literature and relevant journals reported in English language until May 2013 was conducted. All interventions that promoted healthy behaviours or reductions in risky behaviours to treat or prevent an associated health issue(s) in young adult males (17-35 years) in upper-middle and high-income countries were included. For inclusion the appropriate age range had to be reported and the sample had to be young adult male participants only or the outcomes reported with stratification by age and/or sex to include young adult males. Risk behaviours included: physical inactivity, poor diet, alcohol use, tobacco smoking, recreational drug use, unsafe sexual behaviours, tanning/sun exposure, violence, unsafe vehicle driving, gambling and self-harm. The search strategy identified 16,739 unique citations and the full-text of 1149 studies were retrieved and screened with 100 included studies focussed on: physical inactivity (27%), alcohol use (25%), unsafe sexual behaviour (21%), poor diet (5%), unsafe vehicle driving (5%), tobacco smoking (4%), recreational drug use (2%), and tanning/sun exposure (1%) with no relevant studies targeting violence, gambling or self-harm. Also 10% of the studies targeted multiple risk behaviours. The most common study design was randomized controlled trials (62%). Face-to-face was the most common form of intervention delivery (71%) and the majority were conducted in university/college settings (46%). There were 46 studies (46%) that included young adult male participants only, the remaining studies reported outcomes stratified by age and/or sex. Risk behaviours in young men have been targeted to some extent, but the amount of research varies across risk behaviours. There is a need for more targeted and tailored interventions that seek to promote healthy behaviours or decrease risky behaviours in young men. | 25,224,717 | [
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Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients. | Intracellular cytokine staining (ICS) assay is increasingly used in vaccine clinical trials to measure antigen-specific T-cell mediated immune (CMI) responses in cryopreserved peripheral blood mononuclear cells (PBMCs) and whole blood. However, recent observations indicate that several parameters involved in blood processing can impact PBMC viability and CMI responses, especially in antiretroviral therapy (ART)-naïve HIV-1-infected individuals. In this phase I study (NCT01610427), we collected blood samples from 22 ART-naïve HIV-1-infected adults. PBMCs were isolated and processed for ICS assay. The individual and combined effects of the following parameters were investigated: time between blood collection and PBMC processing (time-to-process: 2, 7 or 24 h); time between PBMC thawing and initiation of in vitro stimulation with HIV-1 antigens (resting-time: 0, 2, 6 and 18 h); and duration of antigen-stimulation in PBMC cultures (stimulation-time: 6h or overnight). The cell recovery after thawing, cell viability after ICS and magnitude of HIV-specific CD8(+) T-cell responses were considered to determine the optimal combination of process conditions. The impact of time-to-process (2 or 4 h) on HIV-specific CD8(+) T-cell responses was also assessed in a whole blood ICS assay. A higher quality of cells in terms of recovery and viability (up to 81% and >80% respectively) was obtained with shorter time-to-process (less than 7 h) and resting-time (less than 2 h) intervals. Longer (overnight) rather than shorter (6 h) stimulation-time intervals increased the frequency of CD8(+)-specific T-cell responses using ICS in PBMCs without change of the functionality. The CD8(+) specific T-cell responses detected using fresh whole blood showed a good correlation with the responses detected using frozen PBMCs. Our results support the need of standardized procedures for the evaluation of CMI responses, especially in HIV-1-infected, ART-naïve patients. | 25,224,748 | [
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Spectroscopic characterization and mechanistic investigation of P-methyl transfer by a radical SAM enzyme from the marine bacterium Shewanella denitrificans OS217. | Natural products containing carbon-phosphorus bonds elicit important bioactivity in many organisms. l-Phosphinothricin contains the only known naturally-occurring carbon-phosphorus-carbon bond linkage. In actinomycetes, the cobalamin-dependent radical S-adenosyl-l-methionine (SAM) methyltransferase PhpK catalyzes the formation of the second C-P bond to generate the complete C-P-C linkage in phosphinothricin. Here we use electron paramagnetic resonance and nuclear magnetic resonance spectroscopies to characterize and demonstrate the activity of a cobalamin-dependent radical SAM methyltransferase denoted SD_1168 from Shewanella denitrificans OS217, a marine bacterium that has not been reported to synthesize phosphinothricin. Recombinant, refolded, and reconstituted SD_1168 binds a four-iron, four-sulfur cluster that interacts with SAM and cobalamin. In the presence of SAM, a reductant, and methylcobalamin, SD_1168 surprisingly catalyzes the P-methylation of N-acetyl-demethylphosphinothricin and demethylphosphinothricin to produce N-acetyl-phosphinothricin and phosphinothricin, respectively. In addition, this enzyme is active in the absence of methylcobalamin if the strong reductant titanium (III) citrate and hydroxocobalamin are provided. When incubated with [methyl-(13)C] cobalamin and titanium citrate, both [methyl-(13)C] and unlabeled N-acetylphosphinothricin are produced. Our results suggest that SD_1168 catalyzes P-methylation using radical SAM-dependent chemistry with cobalamin as a coenzyme. In light of recent genomic information, the discovery of this P-methyltransferase suggests that S. denitrificans produces a phosphinate natural product. | 25,224,746 | [
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Kinetic study of the heterogeneous photocatalysis of porous nanocrystalline TiO₂ assemblies using a continuous random walk simulation. | The continuous time random walk (CTRW) simulation was used to study the photocatalytic kinetics of nanocrystalline (nc)-TiO2 assemblies in this research. nc-TiO2 assemblies, such as nc-TiO2 porous films and nc-TiO2 hierarchical structures, are now widely used in photocatalysis. The nc-TiO2 assemblies have quasi-disordered networks consisting of many tiny nanoparticles, so the charge transport within them can be studied by CTRW simulation. We considered the experimental facts that the holes can be quickly trapped and transferred to organic species just after photogeneration, and the electrons transfer to O2 slowly and accumulate in the conduction band of TiO2, which is believed to be the rate-limiting process of the photocatalysis under low light intensity and low organic concentration. Due to the existence of numerous traps, the electron transport within the nc-TiO2 assemblies follows a multi-trapping (MT) mechanism, which significantly limits the electron diffusion speed. The electrons need to undergo several steps of MT transport before transferring to oxygen, so it is highly important that the electron transport in nc-TiO2 networks is determined for standard photocatalytic reactions. Based on the MT transport model, the transient decays of photocurrents during the photocatalytic oxidation of formic acid were studied by CTRW simulation, and are in good accordance with experiments. The steady state photocatalysis was also simulated. The effects of organic concentration, light intensity, temperature, and nc-TiO2 crystallinity on the photocatalytic kinetics were investigated, and were also consistent with the experimental results. Due to the agreement between the simulation and the experiments for both the transient and the steady state photocatalysis, the MT charge transport should be an important mechanism that controls the kinetics of recombination and photocatalysis in nc-TiO2 assemblies. Also, our research provides a new methodology to study the photocatalytic dynamics from the random event viewpoint, which can be revised to investigate the kinetic processes of other kinds of material. | 25,224,752 | [
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[Predictive factors of contamination in a blood culture with bacterial growth in an Emergency Department]. | The aim of this study is to identify predictive factors of bacterial contamination in positive blood cultures (BC) collected in an emergency department. A prospective, observational and analytical study was conducted on febrile children aged on to 36 months, who had no risk factors of bacterial infection, and had a BC collected in the Emergency Department between November 2011 and October 2013 in which bacterial growth was detected. The potential BC contamination predicting factors analysed were: maximum temperature, time to positivity, initial Gram stain result, white blood cell count, absolute neutrophil count, band count, and C-reactive protein (CRP). Bacteria grew in 169 BC. Thirty (17.8%) were finally considered true positives and 139 (82.2%) false positives. All potential BC contamination predicting factors analysed, except maximum temperature, showed significant differences between true positives and false positives. CRP value, time to positivity, and initial Gram stain result are the best predictors of false positives in BC. The positive predictive values of a CRP value≤30mg/L, BC time to positivity≥16h, and initial Gram stain suggestive of a contaminant in predicting a FP, are 95.1, 96.9 and 97.5%, respectively. When all 3 conditions are applied, their positive predictive value is 100%. Four (8.3%) patients with a false positive BC and discharged to home were revaluated in the Emergency Department. The majority of BC obtained in the Emergency Department that showed positive were finally considered false positives. Initial Gram stain, time to positivity, and CRP results are valuable diagnostic tests in distinguishing between true positives and false positives in BC. The early detection of false positives will allow minimising their negative consequences. | 25,224,758 | [
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An observational study of nasal cavity toxicity in cancer patients treated with bevacizumab. | The nasal cavity is a vulnerable zone which may be damaged by vascular disorders. We systematically assessed the frequency and severity of nasal cavity alterations during bevacizumab treatment, to determine its clinical relevance and factors contributing to its onset. We conducted a hospital-based cohort study in 47 consecutive patients with advanced cancers who were on treatment with chemotherapy and bevacizumab at different doses. All patients underwent otolaryngology (ENT) examination at the time of study initiation. The mean number of cycles at first ENT examination was 16 (standard deviation = 14). A total of 45 patients (96%) showed nose mucosal lesions, of whom 30% had erosions and 62% had grade 1 - 2 epistaxis. One patient had septal perforation. Grades 1 - 4 sinus disorders were noted in 60%. There was a significant trend to a higher risk of grade ≥ 2 nasal events for bevacizumab doses > 7.5 mg/kg, concomitant taxane use and digital nasal self-manipulation. We found a high incidence of nasal cavity lesions in patients receiving bevacizumab, with evidence for a dose-related effect. Most cases were low grade and manageable without drug interruption, but severe toxicity may rarely occur. Oncologists should be aware of this unusual event. | 25,224,760 | [
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Long-term effects of drenches with condensed tannins from Acacia mearnsii on goats naturally infected with gastrointestinal nematodes. | In this study, the long-term effects of exposure to a drench containing condensed tannins (CTs) from Acacia mearnsii on gastrointestinal nematodes in goats were investigated. Male cross-bred Anglo-Nubian goat kids between 3 and 5 months of age were dewormed at the beginning of the experiment. The goat kids were divided into one group that received weekly 24 g oral doses of A. mearnsii bark extract dissolved in water containing 16.7% CTs (GCT group, n = 8) and a second group that did not receive CTs (GC group, n = 8). All of the animals were kept in an Andropogon gayanus pasture and grazed with a herd of 100 naturally infected adult goats. Each animal was supplemented daily with 200 g of a concentrated mixture containing 18% crude protein. Fecal egg counts (FECs) were performed weekly for 192 days, and weight measurements and blood collections were done at two-week intervals in this period. The packed cell volume of the blood was calculated, and the plasma was used to determine the total protein, albumin, and glucose concentrations. After 192 days, the animals were slaughtered and the carcasses evaluated, with nematodes harvested for identification and counting. The FECs of the animals treated with CTs from A. mearnsii (GCT group) remained lower than the FECs of the control group animals for the majority of the first half of the experimental period. An observed increase in the FECs for both groups coincided with increased rainfall in the region where the experiment was conducted. The worm burden, scrotal circumference, carcass weight, leg circumference, carcass size and blood analysis were not significantly different between the groups. The packed cell volume (PCV) was constant in all of the animals throughout the experiment. In conclusion, repeated and prolonged treatment of goats with CTs from A. mearnsii helped to maintain low FECs in a period of low challenge but did not reduce nematode infections in the goats. | 25,224,791 | [
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Characterization of a novel exported esterase Rv3036c from Mycobacterium tuberculosis. | Mycobacterium tuberculosis possesses an unusually high number of genes involved in the metabolism of lipids. Driven by a newly described esterase motif SXXK in the amino acid sequence and a predicted signal peptide, the gene rv3036c from M. tuberculosis was cloned and characterized biochemically. Rv3036c efficiently hydrolyzes soluble p-nitrophenyl esters but not emulsified lipid. The highest activity of this enzyme was observed when p-nitrophenyl acetate (C2) was used as the substrate. Based on the activities, Rv3036c was classified as a nonlipolytic hydrolase. The results of immunoreactivity studies on the subcellular mycobacterial fractions suggested that the enzyme was present in the cell wall and cell membrane in mycobacteria. In summary, Rv3036c was characterized as a novel cell wall-anchored esterase from M. tuberculosis. | 25,224,799 | [
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Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway. | Levofloxacin, a fluoroquinolone, is a widely-used and effective antibiotic. However, various adverse side effects are associated with levofloxacin. The purpose of this study was to further explore the effects of levofloxacin on rat nucleus pulposus cells (NPCs). Inverted phase-contrast microscopy, flow cytometry and caspase-3 activity assays were used and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. Simultaneously, levofloxacin decreased cell binding to type II collagen (COL2). Thus, levofloxacin-induced apoptosis exhibits characteristics of anoikis, the process by which cell death is triggered by separation from the extracellular matrix, which contains COL2. Furthermore, real-time quantitative RT-PCR was used to further confirm that levofloxacin downregulates COL2 expression in a dose-dependent manner. At last, western blot was used to find that levofloxacin increased the ratio of Bax/Bcl-2 and active caspase-3 in a dose-dependent manner. Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating COL2 in rat NPCs in vitro via Bax/Bcl-2/caspase-3 pathway. This research provides a novel insight into the mechanisms of levofloxacin-induced toxicity and may potentially lead to a better understanding of the clinical effects of levofloxacin, especially in terms of intervertebral disc degeneration. | 25,224,805 | [
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What are the health costs of uranium mining? A case study of miners in Grants, New Mexico. | Uranium mining is associated with lung cancer and other health problems among miners. Health impacts are related with miner exposure to radon gas progeny. This study estimates the health costs of excess lung cancer mortality among uranium miners in the largest uranium-producing district in the USA, centered in Grants, New Mexico. Lung cancer mortality rates on miners were used to estimate excess mortality and years of life lost (YLL) among the miner population in Grants from 1955 to 2005. A cost analysis was performed to estimate direct (medical) and indirect (premature mortality) health costs. Total health costs ranged from $2·2 million to $7·7 million per excess death. This amounts to between $22·4 million and $165·8 million in annual health costs over the 1955-1990 mining period. Annual exposure-related lung cancer mortality was estimated at 2185·4 miners per 100 000, with a range of 1419·8-2974·3 per 100 000. Given renewed interest in uranium worldwide, results suggest a re-evaluation of radon exposure standards and inclusion of miner long-term health into mining planning decisions. | 25,224,806 | [
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Prevalence of low back pain among handloom weavers in West Bengal, India. | Handloom is one of the oldest industries in India, particularly in West Bengal, where a considerable number of rural people are engaged in weaving. The purpose of this study was to evaluate the prevalence of low back pain among the handloom weavers in India. A modified Nordic Musculoskeletal Disorder Questionnaire and Oswestry Low Back Pain Disability Questionnaire along with a body part discomfort scale were administered to handloom weavers (n = 175). Working posture of the participants was assessed using the Ovako Working Posture Analysis System (OWAS). Sixty eight per cent of the participants reported suffering from low back pain, making it the most prevalent disorder in our sample. Analysis of the Oswestry Low Back Pain Disability Questionnaire data revealed that among those with low back pain (n = 119), 2% had severe disabilities, 46% had moderate disabilities, and 52% had minimal disabilities. Statistical analyses revealed a positive significant association between the intensity of pain in the lower back and an increased number of years of work experience (P<0·05). The study underlines the need for further research regarding the postural strain of weavers and also suggests the implementation of ergonomic design into weaver workstations to minimize the adverse effect of their current working postures. Improving upon the weaver's work-posture could improve their quality of life. | 25,224,808 | [
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Large animal models and new therapies for glycogen storage disease. | Glycogen storage diseases (GSD), a unique category of inherited metabolic disorders, were first described early in the twentieth century. Since then, the biochemical and genetic bases of these disorders have been determined, and an increasing number of animal models for GSD have become available. At least seven large mammalian models have been developed for laboratory research on GSDs. These models have facilitated the development of new therapies, including gene therapy, which are undergoing clinical translation. For example, gene therapy prolonged survival and prevented hypoglycemia during fasting for greater than one year in dogs with GSD type Ia, and the need for periodic re-administration to maintain efficacy was demonstrated in that dog model. The further development of gene therapy could provide curative therapy for patients with GSD and other inherited metabolic disorders. | 25,224,826 | [
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Sonography of the normal lung: Comparison between young and elderly subjects. | The senile lung undergoes physiologic changes that are well known but have not been investigated with ultrasound (US). Thus, the aim of our study was to compare the US appearances of the lungs in a group of healthy, nonsmoker elderly subjects with those in a group of young subjects. One hundred elderly subjects older than 65 years of age (mean age ± SD, 79 ± 7 years) and 50 younger subjects less than 56 years of age (mean age ± SD, 33 ± 12) underwent US examination of the lungs. We analyzed the anterior, midlateral, and posterobasal surface of each lung to evaluate the presence or absence of A-lines and B-lines. Fisher's exact test and Pearson's χ<sup2</sup test were used to compare the findings in the two groups. A-lines were absent in 94/100 (94%) elderly subjects versus 2/50 (4%) young subjects (p < 0.0001). B-lines were found in 37/100 (37%) elderly subjects: ≤3 lines per field of view in 27/37 (73%); >3 lines in 2/37 (5%); both ≤3 lines and >3 lines (depending on the region scanned) in 8/37 (22%). In contrast, only in 5/50 (10%) young subjects were B-lines visible (≤3 lines per field of view in all cases [p < 0.001]). The majority of the elderly subjects did not have A-lines, and B-lines were observed in a high percentage. The reduction of impedance between lung parenchyma and soft tissues of the chest wall and the increased thickness of interlobular septa might explain these results. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:230-234, 2015. | 25,224,838 | [
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Mechanical thromboembolic prophylaxis with risk stratification in total knee arthroplasty. | The purpose of this study was to determine the rate of thromboembolic and bleeding complications when using mechanical prophylaxis with preoperative risk stratification following total knee arthroplasty (TKA). Between 1994 and 2007, 4037 TKAs were performed on 3144 patients at our institution. Mechanical VTE prophylaxis was used for standard risk patients, which included AV impulse foot pumps, thigh high stockings, and early mobilization. Chemoprophylaxis was only given to patients who were at increased thromboembolic risk. The incidence of DVT identified by ultrasound following TKA was 2.1%. A retrospective review showed 1 patient had a fatal pulmonary embolism, and 5 patients had bleeding complications in the knee. We conclude that mechanical thromboembolic prophylaxis using risk stratification is safe and effective following TKA. | 25,224,874 | [
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Temperature responses of mesophyll conductance differ greatly between species. | The temperature responses of mesophyll conductance (gm ) were investigated for nine species using carbon isotope techniques combining tunable diode laser spectroscopy and gas exchange measurements. Species included the evergreen trees Eucalyptus pauciflora and Quercus engelmannii; the tropical evergreen tree Lophostemon confertus; as well as the herbaceous species Nicotiana tabacum, Oryza sativa, Triticum aestivum, Gossypium hirsutum, Glycine max and Arabidopsis thaliana. Responses varied from a two- to threefold increase in mesophyll conductance between 15 and 40 °C observed for N. tabacum, G. hirsutum, G. max and E. pauciflora to almost no change in L. confertus and T. aestivum. To account for the different temperature responses between species, we suggest that there must be variation in both the activation energy for membrane permeability and the effective pathlength for liquid phase diffusion. Stomatal conductance was relatively independent of increases in leaf temperature and concomitant increases in leaf to air vapour pressure difference. Two exceptions were Eucalyptus and Gossypium, where stomatal conductance increased with temperature up to 35 °C despite increasing leaf to air vapour pressure. For a given species, temperature responses of stomatal and mesophyll conductance were independent of one another. | 25,224,884 | [
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The use of the FACT-H&N (v4) in clinical settings within a developing country: a mixed method study. | In the last decade there has been an increasing awareness about 'quality of life' (QOL) of cancer survivors in developing countries. The study aimed to cross-culturally adapt and validate the FACT-H&N (v4) in Urdu language for Pakistani head and neck cancer patients. In this study the 'same language adaptation method' was used. Cognitive debriefing through in-depth interviews of 25 patients to assess semantic, operational and conceptual equivalence was done. The validation phase included 50 patients to evaluate the psychometric properties. The translated FACT-H&N was easily comprehended (100%). Cronbach's alpha for FACT-G subscales ranged from 0.726 - 0.969. The head and neck subscale and Pakistani questions subscale showed low internal consistency (0.426 and 0.541 respectively). Instrument demonstrated known-group validity in differentiating patients of different clinical stages, treatment status and tumor sites (p < 0.05). Most FACT summary scales correlated strongly with each other (r > 0.75) and showed convergent validity (r > 0.90), with little discriminant validity. Factor analysis revealed 6 factors explaining 85.1% of the total variance with very good (>0.8) Kaiser-Meyer-Olkin and highly significant Bartlett's Test of Sphericity (p < 0.001). The cross-culturally adapted FACT-H&N into Urdu language showed adequate reliability and validity to be incorporated in Pakistani clinical settings for head and neck cancer patients. | 25,224,886 | [
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The question of pro-inflammatory immune activity in schizophrenia and the potential importance of anti-inflammatory drugs. | Throughout the last 20 years, numerous studies have indicated pro-inflammatory activity in patients with an acute schizophrenic episode. In this report, the most relevant findings concerning the cytokine systems in schizophrenia are demonstrated, together with recent studies on gene expression. Findings in humans are supplemented by observations from rodent models of schizophrenia. Furthermore, the current state of both neuroleptic and anti-inflammatory compounds on the immune system is reported, together with clinical data on the effects of anti-inflammatory medications on the course of the acute illness in patients with schizophrenia. | 25,224,894 | [
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Proteomic analysis of human nasal mucosa: different expression profile in rhino-pathologic states. | Rhinitis comprises several diseases with varying causes and different clinical manifestations and pathological features, but treated as a single clinical disorder. As heterogeneous disease, proper differential diagnosis is useful to delineate appropriate therapeutic intervention. Comparative proteomic investigation was aimed to provide information for specific differentially expressed proteins in rhino pathologic state, that could be used for diagnostic purpose and therapeutic monitoring. Proteins extracted from nasal mucosa cells of patients with different features of rhinitis and from control subjects, were separated by 2-DE. Proteins differentially expressed were identified by mass spectrometry (MS). Comparative proteomic analyses led to the identification of eighteen proteins differentially expressed in patients with rhinitis, mainly related to cell defense and innate and acquired immunity. From that, at least one protein can be a possible candidate as biomarker of disease. | 25,224,946 | [
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Phytochemicals increase the antibacterial activity of antibiotics by acting on a drug efflux pump. | Drug efflux pumps confer resistance upon bacteria to a wide range of antibiotics from various classes. The expression of efflux pumps are also implicated in virulence and biofilm formation. Moreover, organisms can only acquire resistance in the presence of active drug efflux pumps. Therefore, efflux pump inhibitors (EPIs) are attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. We investigated the potential of pure compounds isolated from plants to act as EPIs. In silico screening was used to predict the bioactivity of plant compounds and to compare that with the known EPI, phe-arg-β-naphthylamide (PAβN). Subsequently, promising products have been tested for their ability to inhibit efflux. Plumbagin nordihydroguaretic acid (NDGA) and to a lesser degree shikonin, acted as sensitizers of drug-resistant bacteria to currently used antibiotics and were able to inhibit the efflux pump-mediated removal of substrate from cells. We demonstrated the feasibility of in silico screening to identify compounds that potentiate the action of antibiotics against drug-resistant strains and which might be potentially useful lead compounds for an EPI discovery program. | 25,224,951 | [
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Distinct genetic characteristics of Sri Lankan Rattus and Bandicota (Murinae, Rodentia) inferred from mitochondrial and nuclear markers. | We examined genetic variation in black rats (the Rattus rattus complex) from Kandy District, Sri Lanka using mitochondrial cytochrome b (cytb, 1140 bp) and nuclear melanocortin 1 receptor (Mc1r, 954 bp) gene sequences together with database sequences. We confirmed the existence of two divergent mitochondrial lineages in Sri Lankan black rats, with genetic distance of 2.2% and estimated divergence time of 0.3 million years ago. Because one lineage is unique to the island and the other is closely related to R. rattus populations on the Indian subcontinent, two migration events of R. rattus from the subcontinent are inferred, one ancient and one recent. Mc1r analyses revealed 12 haplotypes among the Sri Lankan black rats. A median-joining network together with other available sequences separated the 12 haplotypes into two groups, one unique to the island and the other related to previously reported R. rattus sequences. Notably, most individuals possessed various combinations of both haplotype groups which had no association with the cytb clades. These results imply that old and new R. rattus lineages are now intermingled as a result of hybridization in Sri Lanka. Specimens of the lesser bandicoot rat (Bandicota bengalensis) collected from Sri Lanka (n = 24) were shown to have no genetic variability in the cytb sequence. Our results indicate that the two most abundant groups of commensal rats in Sri Lanka, black rats and lesser bandicoot rats, are the product of contrasting evolutionary histories on different timescales. | 25,224,973 | [
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Validation of the Italian version of the Client Satisfaction with Device module of the Orthotics and Prosthetics Users' Survey. | Information on patient satisfaction with orthosis (PSwO) is crucial for verifying and enhancing orthotic quality, for clinical decision making, and for improving patient's quality of life. To perform the translation and cross-cultural adaptation into Italian of the recently revised version of the Client Satisfaction with Device (CSD) module of the Orthotics and Prosthetics Users' Survey, and then analyze its psychometric properties using factor and Rasch analyses. We translated and cross-culturally adapted the revised CSD into Italian (CDS-It) and assessed it in a convenience sample of orthotic-user patients with orthopedic, neurological and rheumatic conditions (N = 178; 56% men; median age, 62 years). Exploratory factor analysis and Rasch analysis (rating scale model) were used to investigate, respectively, dimensionality and metric properties of the scale. Factor analysis confirmed the substantial unidimensionality of the CSD-It. The rating scale fulfilled the category functioning criteria. All items fitted the Rasch model except #2 ("The weight of my device is manageable") that overfitted the model, and #4 ("It is easy to put on my device") that was underfitting in six stroke patients (i.e. not systematically). The targeting of item difficulty to person ability was out of range. The person separation reliability was 0.70 and Cronbach's alpha 0.73. The residual correlation between items #7 and #8 showed a borderline local dependency. This study confirms the validity of the CSD-It, and provides a useful starting point for further refinement of this outcome measure. | 25,224,984 | [
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Arsenic and fluoride variations in groundwater of an endorheic basin undergoing land-use changes. | The salt content of soil and water in endorheic basins within arid areas greatly restrict agricultural activities. Despite this limitation, these lands are increasingly used to accommodate new settlements and/or agricultural practices. This study focuses on the Laguna El Cuervo closed basin of northern Mexico and its underlying aquifer, which has been found to contain high concentrations of arsenic (As) and fluoride (F). The spatial distribution of As and F, their variations with time, and the impact of drought conditions and land-use changes were investigated using well data collected from a total of 27 wells in 2007, 2010, and 2011 (As data also collected in 2005). Four of these wells were used as monitoring wells. Data also included the As content of 140 surface sediments. Results showed that 54.5 % of the wells surpassed the As limit for drinking water of 0.025 mg L(-1) and that 89.0 % surpassed he F limit of 1.5 mg L(-1). Spatial analyses identified the areas in the center of the basin with the highest content of contaminants. Principal component and correlation analyses showed a co-occurrence of As and F with r = 0.55 for the 2011 data and 0.59 for the combined data. In contrast, the relationship of As and F concentrations to droughts and changes in land use were not as clearly shown, possibly because of the short time this area has been monitored. The high As and F concentrations in the groundwater may be limiting the availability of water within this basin, especially considering the greater groundwater demand foreseen for the future. Water-conservation practices, such as drip irrigation and artificial groundwater recharge, should be considered to maintain groundwater levels supportive of agricultural practices. | 25,224,991 | [
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Impact of instruction in the Creighton model fertilitycare system on time to pregnancy in couples of proven fecundity: results of a randomised trial. | The Creighton Model FertilityCare System (CrMS) teaches women to identify days when intercourse is likely to result in pregnancy. We sought to assess the impact of the CrMS on time to pregnancy (TTP), via per-cycle pregnancy rates (fecundability). We conducted a parallel randomised trial at the University of Utah School of Medicine, 2003-06. Women ages 18-35 years, in a relationship of proven fertility, who desired to conceive, were block-randomised and stratified for age, with allocation concealment by opaque sequentially numbered sealed envelopes. The control group received the advice to have intercourse 2-3 times per week, and the intervention group received CrMS instruction. All women were asked to begin trying to conceive starting the second cycle in the study and were followed actively up to seven cycles, without blinding of research personnel. We calculated descriptive statistics and fecundability, and estimated Cox models for TTP. (Clinicaltrials.gov NCT00161395). There were 143 women randomised: 71 to the control group (all analysed) and 72 to the CrMS group (69 analysed). The adjusted hazard ratio for the influence of CrMS on TTP was 0.86 [95% confidence interval (CI): 0.53, 1.38]. Fecundability in cycles with intent to conceive was 31% in controls and 36% with CrMS (P = 0.32). By the first cycle, fecundability was 17% in controls, and 4% with CrMS (P = 0.02). No adverse events were reported. We found no significant impact of CrMS on TTP or fecundability, but fewer of the women receiving CrMS conceived by the first cycle. | 25,225,008 | [
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Potential neuroimmunological targets in the treatment of anxiety disorders. | In the translation of psychoneuroimmunology research into clinical practice, one critical step is to identify biomarkers for improved diagnosis and targeting of interventions. Inflammatory markers deserve special attention due to their crucial role linking various health conditions and disorders. In this chapter, we discuss the pivotal roles of cytokines in signalling to the brain and leading to behavioural changes. This is followed by a review of recent research findings into neuroimmunology of depression, and immunomodulating effects of antidepressants. The rest of the chapter focuses on neuroinflammatory hypothesis in anxiety disorders, and provides an overview of current research evidence on inflammatory responses in anxious state and anxiety disorders. Research suggestions are recommended, including study design, risk factors, medication effects, and measurement strategies. Clinical and pharmacotherapeutic implications and future research directions are also discussed in the final section. | 25,225,018 | [
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Social determinants of health predict state incidence of HIV and AIDS: a short report. | There are approximately 1.2 million people living with HIV/AIDS (PLWHA) in the USA. Each year, there are roughly 50,000 new HIV diagnoses. The World Health Organization Commission on Social Determinants of Health (CSDH) identified several social determinants of health and health inequity (SDH) including childcare, education, employment, gender equality, health insurance, housing, and income. The CSDH also noted the significant impact the SDH can have on advocacy for social change, social interventions to reduce HIV prevalence, and health monitoring. The current analysis evaluated the predictive ability of five SDH for HIV and AIDS incidence on the state level. The SDH used in the analysis were education, employment, housing, income, and insurance; other SDH were not included because reliable and appropriate state-level data were not available. The results of multiple regression analyses indicate that the use of these five SDH create statistically significant models predicting HIV incidence (adjusted R(2) = .54) and AIDS incidence (adjusted R(2) = .37) and account for a sizable portion of the variance for each. Stepwise variable selection reduced the necessary SDH to two: (1) education and (2) housing. These models are also statistically significant and account for a notable portion of variance in HIV incidence (adjusted R(2) = .55) and AIDS incidence (adjusted R(2) = .40). These outcomes demonstrate that state-level SDH, particularly education and housing, offer significant explanatory power regarding HIV and AIDS incidence rates. Congruent with the recommendations of the CSDH, the results of the current analysis suggest that state-sponsored policy and social interventions should consider and target SDH, especially education and housing, in attempts to reduce HIV and AIDS incidence rates. | 25,225,050 | [
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The role of the antisperm antibodies in male infertility assessment after microsurgical varicocelectomy. | Antisperm antibodies (ASA) are a cause of male infertility. ASA are often found in varicocele patients. The study objective was to assess the ASA role in fertility recovery after varicocelectomy. The longitudinal study involved 99 patients with varicocele. Patients were examined according to the WHO recommendations; ASA level was measured using the direct method of Sperm MAR test: 66 patients were ASA-negative, 33 had MAR-IgG ≥ 10%. All patients underwent microsurgical varicocelectomy. Student's t-test, Wilcoxon test, Chi-squared test and signed rank test were used for data analysis. The retrospective analysis of all operated patients data showed that the patients without spermiogram improvement after varicocelectomy had higher ASA levels. 3 months after the surgery, the initially ASA-negative varicocele patients demonstrated 2.5 times increase in number of progressive motile spermatozoa in the ejaculate (p < 0.001), accompanied by 6% decrease in abnormal sperm count (p < 0.05); the spermiogram parameters improved in 77% of cases (p < 0.01). After the surgery, ASA developed in 16% of cases (Max--MAR-IgG = 12%). The patients who were initially ASA-positive demonstrated ASA decrease only in half of the cases (16 of 33; p > 0.05). The main outcome in this group was a favourable response to the surgery (ASA level decrease) vs. no reduction in autoimmune process. The improvement in the ASA-positive group was demonstrated in the patients with higher varicocele grade (median--2 vs. 1; p < 0.05) and lower ASA level (MAR-IgG = 48% vs. 92%; p < 0.01). The pregnancy rate within a year after surgery was 2.8 times more frequent in couples with ASA-negative men: 39% (25 of 65) in the ASA-negative group compared to 14% (4 of 28) in the ASA-positive group (p < 0.05). Thus, antisperm immune response decreases the varicocelectomy efficacy for reproductive function recovery: the higher percentage of ASA and lower grade of varicocele are associated with an unfavourable prognosis. | 25,225,061 | [
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Contextual Approach to Acculturative Stress Among Latina Immigrants in the U.S. | Based on Family Stress Management theory, we explored the contextual influence on acculturative stress and psychological distress. We included 639 Latinas from the National Latino Asian American Survey. We hypothesized that (a) impact of acculturative stress on psychological distress depends on specific contexts; (b) U.S. climate (i.e., perceived discrimination, happiness with U.S. move, years in the U.S.) impacts acculturative stress and psychological distress the most, and (c) contextual factors interact in impacting acculturative stress. Acculturative stress did not always lead to psychological distress. Perceived discrimination and difficulty visiting family abroad were positively associated with acculturative stress. Years in the U.S. and happiness with the U.S. move were negatively associated with acculturative stress. Years in the U.S. and perceived discrimination interacted in predicting acculturative stress. These results can aid formulation of effective interventions that target contexts likely to impact acculturative stress and psychological distress among Latinas. | 25,225,078 | [
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Co-administration of phospholipid emulsion with first dose bacteriocidal antibiotic may retard progression of the sepsis response in gram negative septicaemia. | Endotoxic lipopolysaccharide (LPS) is a major constituent of the outer membrane of the gram-negative bacillus, and its' release a potent pro-inflammatory stimulus. Unchecked the cytokine cascades unleashed by blood borne LPS leads to clinical manifestations of severe sepsis and septic shock. Experimentally exogenous administration of cell-wall specific bacteriocidal drugs are known to precipitate endotoxin release and contribute to development of the sepsis syndrome. Mitigation of the inflammatory septic response with intravenous infusion of phospholipid emulsion has been demonstrated in vivo, with phospholipid credited with binding and neutralizing circulating endotoxin. We therefore propose co-administration of phospholipid emulsion preparations in conjunction with potent cell wall specific antibacterial agents in gram-negative sepsis - hypothesizing that released LPS may be immediately sequestered by phospholipid thereby blunting the severity of the developing septic response. | 25,225,084 | [
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Astrocytes in endocannabinoid signalling. | Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour. | 25,225,093 | [
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Organization, control and function of extrasynaptic NMDA receptors. | N-methyl D-aspartate receptors (NMDARs) exist in different forms owing to multiple combinations of subunits that can assemble into a functional receptor. In addition, they are located not only at synapses but also at extrasynaptic sites. There has been intense speculation over the past decade about whether specific NMDAR subtypes and/or locations are responsible for inducing synaptic plasticity and excitotoxicity. Here, we review the latest findings on the organization, subunit composition and endogenous control of NMDARs at extrasynaptic sites and consider their putative functions. Because astrocytes are capable of controlling NMDARs through the release of gliotransmitters, we also discuss the role of the glial environment in regulating the activity of these receptors. | 25,225,095 | [
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Volume transmission signalling via astrocytes. | The influence of astrocytes on synaptic function has been increasingly studied, owing to the discovery of both gliotransmission and morphological ensheathment of synapses. While astrocytes exhibit at best modest membrane potential fluctuations, activation of G-protein coupled receptors (GPCRs) leads to a prominent elevation of intracellular calcium which has been reported to correlate with gliotransmission. In this review, the possible role of astrocytic GPCR activation is discussed as a trigger to promote synaptic plasticity, by affecting synaptic receptors through gliotransmitters. Moreover, we suggest that volume transmission of neuromodulators could be a biological mechanism to activate astrocytic GPCRs and thereby to switch synaptic networks to the plastic mode during states of attention in cerebral cortical structures. | 25,225,097 | [
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Five heavy metallic elements and age-related macular degeneration: Korean National Health and Nutrition Examination Survey, 2008-2011. | To investigate the association between age-related macular degeneration (AMD) and 5 heavy metallic elements (lead, mercury, cadmium, manganese, and zinc). A cross-sectional study using a complex, stratified, multistage, probability cluster survey. Participants of the Korean National Health and Nutrition Examination Survey from 2008 to 2011. Using a standardized protocol, AMD was determined by fundus photograph grading. Blood concentrations of lead, mercury, cadmium, manganese, and zinc were measured. Associations between AMD and these 5 elements were estimated using logistic regression analyses (LRAs). The distributions of the 5 metallic elements in blood were analyzed, and the same set of LRAs estimating the association between AMD and logarithmic-transformed blood concentrations of the 5 elements were also conducted. Association between AMD and 5 heavy metals. Lead was positively associated with both early AMD and late AMD in all LRAs. Mercury and cadmium also had a positive association with late AMD in all LRAs, but not with early AMD. In contrast, manganese and zinc had an inverse association with late AMD in all LRAs. Manganese and zinc were not associated with early AMD. Using logarithmic-transformed blood concentrations for each metallic element, the LRAs showed similar results compared with those of the LRAs using nontransformed blood concentrations, despite the skewed distribution of these metallic elements in the blood. This study suggests that the toxic heavy metals (lead, mercury, and cadmium) may negatively influence late AMD, whereas essential heavy metals (manganese and zinc) may favorably influence late AMD. Lead may widely affect the pathogenesis of both early and late AMD. | 25,225,109 | [
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SAGE: String-overlap Assembly of GEnomes. | De novo genome assembly of next-generation sequencing data is one of the most important current problems in bioinformatics, essential in many biological applications. In spite of significant amount of work in this area, better solutions are still very much needed. We present a new program, SAGE, for de novo genome assembly. As opposed to most assemblers, which are de Bruijn graph based, SAGE uses the string-overlap graph. SAGE builds upon great existing work on string-overlap graph and maximum likelihood assembly, bringing an important number of new ideas, such as the efficient computation of the transitive reduction of the string overlap graph, the use of (generalized) edge multiplicity statistics for more accurate estimation of read copy counts, and the improved use of mate pairs and min-cost flow for supporting edge merging. The assemblies produced by SAGE for several short and medium-size genomes compared favourably with those of existing leading assemblers. SAGE benefits from innovations in almost every aspect of the assembly process: error correction of input reads, string-overlap graph construction, read copy counts estimation, overlap graph analysis and reduction, contig extraction, and scaffolding. We hope that these new ideas will help advance the current state-of-the-art in an essential area of research in genomics. | 25,225,118 | [
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Risk factors for and occurrence of postoperative cervical hematoma after thyroid surgery: A single-institution study based on 5156 cases from the past 2 years. | The occurrence of and risk factors for postoperative cervical hematoma remain unclear. We conducted a retrospective analysis of 5156 patients treated at a single institution. The occurrence of postoperative cervical hematoma was 0.85% (44 of 5156 patients). The multivariate analysis showed that male sex, benign pathology, hypertension, and previous thyroid surgery are individual risk factors with odds ratios of 1.906, 2.004, 7.962, and 4.407, respectively. The majority (88.7%) of hematomas occurred within 12 hours after surgery. Obvious bleeding points were detected in 28 cases (73.6%) during reexploration, surface of the strap muscle, superior thyroid vessel, and end of the recurrent laryngeal nerve were the most frequent bleeding sources. Hematoma often occurs within 12 hours after thyroid surgery. Hypertension, previous thyroid surgery, male sex, and benign pathology may increase the risk of hematoma. | 25,225,123 | [
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Molecular characterization of Indian Sugarcane streak mosaic virus isolates reveals recombination and negative selection in the P1 gene. | Sugarcane streak mosaic virus (SCSMV), a member of the genus Poacevirus is an important viral pathogen affecting sugarcane production in India. The P1 gene of ten Indian isolates was sequenced and compared with previously reported SCSMV isolates. Comparative sequence analysis revealed a high level of diversity in the P1 gene (83-98% nucleotide sequence identity; 87-100% amino acid sequence identity), and the Indian SCSMV isolates were found to be the most variable (up to 9% diversity at the amino acid level). Phylogenetic tree analysis showed clustering of 17 SCSMV isolates into two groups: group I included isolates from India (except SCSMV-TPT) and Pakistan, and group II consisted of isolates from Japan, Indonesia, Thailand and SCSMV-TPT. The results obtained from phylogenetic study were further supported by the different in silico analysis viz. SNPs (single nucleotide polymorphism), INDELs (insertion and deletion) and evolutionary distance analysis. A significant proportion of recombination sites were observed at the N terminal region of P1 gene. Analysis of selection pressure indicated that the P1 gene of the Indian SCSMV isolates is under strong negative or purifying selection. It is likely that recombination identified in Indian SCSMV isolates, along with strong purifying selection, enhances the speed of elimination of deleterious mutations in the P1 gene. The evolutionary processes (recombination and selection pressure) together contributed to the observed genetic diversity and population structure of Indian SCSMV isolates. | 25,225,126 | [
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Thermodynamic study of transthyretin association (wild-type and senile forms) with heparan sulfate proteoglycan: pH effect and implication of the reactive histidine residue. | The tetramer destabilization of transthyretin into monomers and its fibrillation are phenomena leading to amyloid deposition. Heparan sulfate proteoglycan (HSPG) has been found in all amyloid deposits. A chromatographic approach was developed to compare binding parameters between wild-type transthyretin (wtTTR) and an amyloidogenic transthyretin (sTTR). Results showed a greater affinity of sTTR for HSPG at pH 7.4 compared with wtTTR owing to the monomeric form of sTTR. Analysis of the thermodynamic parameters showed that van der Waals interactions were involved at the complex interface for both transthyretin forms. For sTTR, results from the plot representing the number of protons exchanged vs pH showed that the binding mechanism was pH-dependent with a critical value at a pH 6.5. This observation was due to the protonation of a histidine residue as an imidazolium cation, which was not accessible when TTR was in its tetrameric structure. At pH >6.5, dehydration at the binding interface and several contacts between nonpolar groups of sTTR and HSPG were also coupled to binding for an optimal hydrogen-bond network. At pH <6.5, the protonation of the His residue from sTTR monomer when pH decreased broke the hydrogen-bond network, leading to its destabilization and thus producing slight conformational changes in the sTTR monomer structure. | 25,225,131 | [
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Selective and ratiometric fluorescent trapping and quantification of protein vicinal dithiols and in situ dynamic tracing in living cells. | Protein vicinal dithiols play fundamental roles in intracellular redox homeostasis due to their involvement in protein synthesis and function through the reversible vicinal dithiol oxidation to disulfide. To provide quantitative information about the global distribution and dynamic changes of protein vicinal dithiols in living cells, we have designed and synthesized a ratiometric fluorescent probe (VTAF) for trapping of vicinal dithiol-containing proteins (VDPs) in living cells. VTAF exhibits a ratiometric fluorescence signal upon single excitation, which enables self-calibration of the fluorescence signal and quantification of endogenous vicinal dithiols of VDPs. Its potential for in situ dynamic tracing of changes of protein vicinal dithiols under different cellular redox conditions was exemplified. VTAF facilitated the direct observation of subcellular distribution of endogenous VDPs via ratiometric fluorescence imaging and colocalization assay. And the results suggested that there are abundant VDPs in mitochondria. Moreover, some redox-sensitive VDPs are also present on cell surface which can respond to redox stimulus. This ratiometric fluorescence technique presents an important extension to previous fluorescence intensity-based probes for trapping and quantifying protein vicinal dithiols in living cells, as well as its visible dynamic tracing of VDPs. | 25,225,148 | [
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Efficacy of Boswellia serrata L. and Cyperus scariosus L. plus pelvic floor muscle training in stress incontinence in women of reproductive age. | To determine the efficacy of combining of Boswellia serrata L. resin and the root of Cyperus scariosus L. plus PFMT in reproductive age women with stress urinary incontinence. A prospective, single-blind, placebo-controlled, randomized trial was conducted. The patients were randomized to receive orally either combination of equal quantity of B. serrata and C. scariosus (2g) (n = 30) or placebo (n = 30) respectively twice daily for 8 weeks in addition to pelvic floor muscle training in both groups. The outcome was one hour pad test. The results were analyzed using parametric and nonparametric test. The improvement in the test and control group was 60% and 37% respectively. Between the group comparison was statistically significant (P = 0.035). The intra group comparison of one hour pad test was statistically significant in both groups (P < 0.001). No adverse effects were noted. The test group was more effective than control group in women with SUI. | 25,225,151 | [
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Dengue in children. | Dengue is a mosquito-borne viral disease of expanding geographical range and increasing incidence. The vast majority of dengue cases are children less than 15 years of age. Dengue causes a spectrum of illness from mild fever to severe disease with plasma leakage and shock. Infants and children with secondary heterologous dengue infections are most at risk for severe dengue disease. Laboratory diagnosis of dengue can be established within five days of disease onset by direct detection of viral components in serum. After day five, serologic diagnosis provides indirect evidence of dengue. Currently, no effective antiviral agents are available to treat dengue infection. Therefore, treatment remains supportive, with emphasis on close hematological monitoring, recognition of warning signs of severe disease and fluid-replacement therapy and/or blood transfusions when required. Development of a dengue vaccine is considered a high public health priority. A safe and efficacious dengue vaccine would also be important for travelers. This review highlights the current understanding of dengue in children, including its clinical manifestations, pathogenesis, diagnostic tests, management and prevention. | 25,225,163 | [
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A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma. | We report four previously undescribed families with germline BRCA1-associated protein-1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family. | 25,225,168 | [
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Improved overall survival and mortality in head and neck cancer with adjuvant concurrent chemoradiotherapy in national databases. | Many studies have demonstrated the advantage of postoperative concurrent chemoradiotherapy (CRT) over radiotherapy (RT) alone in locoregional control, but few have examined overall survival with respect to national databases. The literature was searched for eligible randomized controlled trials. The Surveillance, Epidemiology, and End Results (SEER) Database and National Cancer Data Base (NCDB) were searched for 5-year overall survival data. Twenty-eight studies were examined and demonstrated 44% greater locoregional control (relative risk [RR] = 0.56; 95% confidence interval [CI] = 0.46-0.68) and 12% overall survival benefit (RR = 0.88; 95% CI = 0.81-0.98) with postoperative adjuvant CRT compared to adjuvant RT. Overall SEER survival was 45.0% in 1973, rising to 53.2% in 2005. The NCDB documents a similar increase in overall survival from 45.5% in 1994 to 53.4% in 2005. The literature shows mortality benefit of adjuvant CRT in patients with advanced head and neck cancer, reflected in SEER and NCDB. | 25,225,171 | [
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Association of rs12979860 and rs8099917 polymorphisms near IL28B with SVR in hepatic allograft recipients with HCV recurrence undergoing PEG-IFN/RBV therapy: a meta-analysis. | The association of rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) near IL28B with sustained virological response (SVR) in hepatic allograft recipients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV) for recurrent hepatitis C virus (HCV) infection remains inconclusive. We therefore performed a meta-analysis to estimate this association. A search of the literature published prior to November 1, 2013, was conducted using various databases. Eleven eligible studies were included in the meta-analysis. The pooled results revealed that rs12979860 genotype CC in the recipient, donor, and recipient/donor pair was significantly related to high SVR in the recipients (recipient: odds ratio [OR]=3.06, 95% confidence interval [CI]=2.18-4.30; donor: OR=2.65, 95% CI=1.83-3.85; recipient/donor pair: OR=6.05, 95% CI=3.16-11.58). A similar association was observed with rs8099917 genotype TT (recipient: OR=3.84, 95% CI=2.37-6.22; donor: OR=2.44, 95% CI=1.12-5.28; recipient/donor pair: OR=5.43, 95% CI=2.51-11.75). These results suggest that rs12979860 genotype CC and rs8099917 genotype TT contribute to a high SVR in the recipient after antiviral treatment. | 25,225,180 | [
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ST-elevation myocardial infarction secondary to coronary artery spasm provoked by food. | We describe a patient with recurrent episodes of inferior ST elevation, secondary to coronary artery spasm. Each episode appeared to be provoked by the ingestion of rice and accompanied by a troponin T rise. An inpatient coronary angiogram immediately following an episode of pain demonstrated a focal area of spasm affecting the right coronary artery, which resolved with intracoronary nitrate injection. Although these episodes were self-limiting, cardiac MRI confirmed an acute subendocardial infarct. An association between food substances and coronary artery spasm with subsequent infarction has not been documented previously. Following appropriate advice and titration of antispasmodic medication, the patient has been pain free. | 25,225,191 | [
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Increased levels of copeptin before clinical diagnosis of preeclampsia. | Copeptin, a surrogate biomarker of vasopressin, has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia. We measured serum copeptin using samples collected longitudinally during pregnancy among unaffected controls (n=136) and cases of preeclampsia (n=169), gestational diabetes mellitus (n=92), gestational hypertension (n=101), and preterm birth (n=86) in the Calcium for Preeclampsia Prevention trial (1992-1995). Preeclampsia and gestational hypertension were defined as having a diastolic blood pressure≥90 mm Hg on 2 occasions with and without proteinuria, respectively. The risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age, race, body mass index, insurance status, marital status, current smoking, and clinical site. Baseline copeptin levels, at mean 16 weeks of gestation, were associated with increased preeclampsia risk (adjusted odds ratios and 95% confidence interval being 1.55 per log unit; 1.03-2.31) when compared with controls (P=0.03). The association was stronger among cases diagnosed before 37 weeks (1.86; 1.08-3.20) than those diagnosed later (1.45; 0.91-2.32). Copeptin levels rose with increasing gestational age in both cases and controls but remained significantly higher among those who were diagnosed with preeclampsia. Differences in levels of copeptin between cases and controls became more apparent closer to time of diagnosis. No significant associations were found for gestational hypertension without proteinuria, gestational diabetes mellitus, or preterm birth without preeclampsia. Copeptin levels are elevated in pregnant women before diagnosis of preeclampsia with elevation specific to this pregnancy complication rather than hypertension alone. | 25,225,209 | [
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Disease-associated Neisseria meningitidis isolates inhibit wound repair in respiratory epithelial cells in a type IV pilus-independent manner. | Neisseria meningitidis is the causative agent of meningococcal disease. Onset of meningococcal disease can be extremely rapid and can kill within a matter of hours. However, although a much-feared pathogen, Neisseria meningitidis is frequently found in the nasopharyngeal mucosae of healthy carriers. The bacterial factors that distinguish disease- from carriage-associated meningococci are incompletely understood. Evidence suggesting that disruptions to the nasopharynx may increase the risk of acquiring meningococcal disease led us to evaluate the ability of disease- and carriage-associated meningococcal isolates to inhibit cell migration, using an in vitro assay for wound repair. We found that disease-associated isolates in our collection inhibited wound closure, while carriage-associated isolates were more variable, with many isolates not inhibiting wound repair at all. For isolates selected for further study, we found that actin morphology, such as presence of lamellipodia, correlated with cell migration. We demonstrated that multiple meningococcal virulence factors, including the type IV pili, are dispensable for inhibition of wound repair. Inhibition of wound repair was also shown to be an active process, i.e., requiring live bacteria undergoing active protein synthesis. | 25,225,250 | [
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Methylamine utilization via the N-methylglutamate pathway in Methylobacterium extorquens PA1 involves a novel flow of carbon through C1 assimilation and dissimilation pathways. | Methylotrophs grow on reduced single-carbon compounds like methylamine as the sole source of carbon and energy. In Methylobacterium extorquens AM1, the best-studied aerobic methylotroph, a periplasmic methylamine dehydrogenase that catalyzes the primary oxidation of methylamine to formaldehyde has been examined in great detail. However, recent metagenomic data from natural ecosystems are revealing the abundance and importance of lesser-known routes, such as the N-methylglutamate pathway, for methylamine oxidation. In this study, we used M. extorquens PA1, a strain that is closely related to M. extorquens AM1 but is lacking methylamine dehydrogenase, to dissect the genetics and physiology of the ecologically relevant N-methylglutamate pathway for methylamine oxidation. Phenotypic analyses of mutants with null mutations in genes encoding enzymes of the N-methylglutamate pathway suggested that γ-glutamylmethylamide synthetase is essential for growth on methylamine as a carbon source but not as a nitrogen source. Furthermore, analysis of M. extorquens PA1 mutants with defects in methylotrophy-specific dissimilatory and assimilatory modules suggested that methylamine use via the N-methylglutamate pathway requires the tetrahydromethanopterin (H4MPT)-dependent formaldehyde oxidation pathway but not a complete tetrahydrofolate (H4F)-dependent formate assimilation pathway. Additionally, we present genetic evidence that formaldehyde-activating enzyme (FAE) homologs might be involved in methylotrophy. Null mutants of FAE and homologs revealed that FAE and FAE2 influence the growth rate and FAE3 influences the yield during the growth of M. extorquens PA1 on methylamine. | 25,225,269 | [
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The Arf6 GTPase-activating proteins ARAP2 and ACAP1 define distinct endosomal compartments that regulate integrin α5β1 traffic. | Arf6 and the Arf6 GTPase-activating protein (GAP) ACAP1 are established regulators of integrin traffic important to cell adhesion and migration. However, the function of Arf6 with ACAP1 cannot explain the range of Arf6 effects on integrin-based structures. We propose that Arf6 has different functions determined, in part, by the associated Arf GAP. We tested this idea by comparing the Arf6 GAPs ARAP2 and ACAP1. We found that ARAP2 and ACAP1 had opposing effects on apparent integrin β1 internalization. ARAP2 knockdown slowed, whereas ACAP1 knockdown accelerated, integrin β1 internalization. Integrin β1 association with adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif (APPL)-positive endosomes and EEA1-positive endosomes was affected by ARAP2 knockdown and depended on ARAP2 GAP activity. ARAP2 formed a complex with APPL1 and colocalized with Arf6 and APPL in a compartment distinct from the Arf6/ACAP1 tubular recycling endosome. In addition, although ACAP1 and ARAP2 each colocalized with Arf6, they did not colocalize with each other and had opposing effects on focal adhesions (FAs). ARAP2 overexpression promoted large FAs, but ACAP1 overexpression reduced FAs. Taken together, the data support a model in which Arf6 has at least two sites of opposing action defined by distinct Arf6 GAPs. | 25,225,293 | [
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Beyond the bolus: transgenic tools for investigating the neurophysiology of learning and memory. | Understanding the neural mechanisms underlying learning and memory in the entorhinal-hippocampal circuit is a central challenge of systems neuroscience. For more than 40 years, electrophysiological recordings in awake, behaving animals have been used to relate the receptive fields of neurons in this circuit to learning and memory. However, the vast majority of such studies are purely observational, as electrical, surgical, and pharmacological circuit manipulations are both challenging and relatively coarse, being unable to distinguish between specific classes of neurons. Recent advances in molecular genetic tools can overcome many of these limitations, enabling unprecedented control over neural activity in behaving animals. Expression of pharmaco- or optogenetic transgenes in cell-type-specific "driver" lines provides unparalleled anatomical and cell-type specificity, especially when delivered by viral complementation. Pharmacogenetic transgenes are specially designed neurotransmitter receptors exclusively activated by otherwise inactive synthetic ligands and have kinetics similar to traditional pharmacology. Optogenetic transgenes use light to control the membrane potential, and thereby operate at the millisecond timescale. Thus, activation of pharmacogenetic transgenes in specific neuronal cell types while recording from other parts of the circuit allows investigation of the role of those neurons in the steady state, whereas optogenetic transgenes allow one to determine the immediate network response. | 25,225,296 | [
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Social defeat as an animal model for depression. | Depression is one of the most disabling medical conditions in the world today, yet its etiologies remain unclear and current treatments are not wholly effective. Animal models are a powerful tool to investigate possible causes and treatments for human diseases. We describe an animal model of social defeat as a possible model for human depression. We discuss the paradigm, behavioral correlates to depression, and potential underlying neurobiological mechanisms with an eye toward possible future therapies. | 25,225,302 | [
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Integrative quantitative proteomics unveils proteostasis imbalance in human hepatocellular carcinoma developed on nonfibrotic livers. | Proteomics-based clinical studies represent promising resources for the discovery of novel biomarkers or for unraveling molecular mechanisms underlying particular diseases. Here, we present a discovery study of hepatocellular carcinoma developed on nonfibrotic liver (nfHCC) that combines complementary quantitative iTRAQ-based proteomics and phosphoproteomics approaches. Using both approaches, we compared a set of 24 samples (18 nfHCC versus six nontumor liver tissue). We identified 43 proteins (67 peptides) differentially expressed and 32 peptides differentially phosphorylated between the experimental groups. The functional analysis of the two data sets pointed toward the deregulation of a protein homeostasis (proteostasis) network including the up-regulation of the Endoplasmic Reticulum (ER) resident HSPA5, HSP90B1, PDIA6, and P4HB and of the cytosolic HSPA1B, HSP90AA1, HSPA9, UBC, CNDP2, TXN, and VCP as well as the increased phosphorylation of the ER resident calnexin at Ser583. Antibody-based validation approaches (immunohistochemistry, immunoblot, Alphascreen(®), and AMMP(®)) on independent nfHCC tumor sets (up to 77 samples) confirmed these observations, thereby indicating a common mechanism occurring in nfHCC tumors. Based on these results we propose that adaptation to proteostasis imbalance in nfHCC tumors might confer selective advantages to those tumors. As such, this model could provide an additional therapeutic opportunity for those tumors arising on normal liver by targeting the tumor proteostasis network. Data are available via ProteomeXchange with identifier PXD001253. | 25,225,353 | [
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The benefits of breakfast cereal consumption: a systematic review of the evidence base. | There have been no comprehensive reviews of the relation of breakfast cereal consumption to nutrition and health. This systematic review of all articles on breakfast cereals to October 2013 in the Scopus and Medline databases identified 232 articles with outcomes related to nutrient intake, weight, diabetes, cardiovascular disease, hypertension, digestive health, dental and mental health, and cognition. Sufficient evidence was available to develop 21 summary evidence statements, ranked from A (can be trusted to guide practice) to D (weak and must be applied with caution). Breakfast cereal consumption is associated with diets higher in vitamins and minerals and lower in fat (grade B) but is not associated with increased intakes of total energy or sodium (grade C) or risk of dental caries (grade B). Most studies on the nutritional impact are cross-sectional, with very few intervention studies, so breakfast cereal consumption may be a marker of an overall healthy lifestyle. Oat-, barley-, or psyllium-based cereals can help lower cholesterol concentrations (grade A), and high-fiber, wheat-based cereals can improve bowel function (grade A). Regular breakfast cereal consumption is associated with a lower body mass index and less risk of being overweight or obese (grade B). Presweetened breakfast cereals do not increase the risk of overweight and obesity in children (grade C). Whole-grain or high-fiber breakfast cereals are associated with a lower risk of diabetes (grade B) and cardiovascular disease (grade C). There is emerging evidence of associations with feelings of greater well-being and a lower risk of hypertension (grade D), but more research is required. | 25,225,349 | [
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A "proteomic ruler" for protein copy number and concentration estimation without spike-in standards. | Absolute protein quantification using mass spectrometry (MS)-based proteomics delivers protein concentrations or copy numbers per cell. Existing methodologies typically require a combination of isotope-labeled spike-in references, cell counting, and protein concentration measurements. Here we present a novel method that delivers similar quantitative results directly from deep eukaryotic proteome datasets without any additional experimental steps. We show that the MS signal of histones can be used as a "proteomic ruler" because it is proportional to the amount of DNA in the sample, which in turn depends on the number of cells. As a result, our proteomic ruler approach adds an absolute scale to the MS readout and allows estimation of the copy numbers of individual proteins per cell. We compare our protein quantifications with values derived via the use of stable isotope labeling by amino acids in cell culture and protein epitope signature tags in a method that combines spike-in protein fragment standards with precise isotope label quantification. The proteomic ruler approach yields quantitative readouts that are in remarkably good agreement with results from the precision method. We attribute this surprising result to the fact that the proteomic ruler approach omits error-prone steps such as cell counting or protein concentration measurements. The proteomic ruler approach is readily applicable to any deep eukaryotic proteome dataset-even in retrospective analysis-and we demonstrate its usefulness with a series of mouse organ proteomes. | 25,225,357 | [
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The cultural side of science communication. | The main proposition of this paper is that science communication necessarily involves and includes cultural orientations. There is a substantial body of work showing that cultural differences in values and epistemological frameworks are paralleled with cultural differences reflected in artifacts and public representations. One dimension of cultural difference is the psychological distance between humans and the rest of nature. Another is perspective taking and attention to context and relationships. As an example of distance, most (Western) images of ecosystems do not include human beings, and European American discourse tends to position human beings as being apart from nature. Native American discourse, in contrast, tends to describe humans beings as a part of nature. We trace the correspondences between cultural properties of media, focusing on children's books, and cultural differences in biological cognition. Finally, implications for both science communication and science education are outlined. | 25,225,366 | [
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Using narratives and storytelling to communicate science with nonexpert audiences. | Although storytelling often has negative connotations within science, narrative formats of communication should not be disregarded when communicating science to nonexpert audiences. Narratives offer increased comprehension, interest, and engagement. Nonexperts get most of their science information from mass media content, which is itself already biased toward narrative formats. Narratives are also intrinsically persuasive, which offers science communicators tactics for persuading otherwise resistant audiences, although such use also raises ethical considerations. Future intersections of narrative research with ongoing discussions in science communication are introduced. | 25,225,368 | [
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Ecological and evolutionary significance of genomic GC content diversity in monocots. | Genomic DNA base composition (GC content) is predicted to significantly affect genome functioning and species ecology. Although several hypotheses have been put forward to address the biological impact of GC content variation in microbial and vertebrate organisms, the biological significance of GC content diversity in plants remains unclear because of a lack of sufficiently robust genomic data. Using flow cytometry, we report genomic GC contents for 239 species representing 70 of 78 monocot families and compare them with genomic characters, a suite of life history traits and climatic niche data using phylogeny-based statistics. GC content of monocots varied between 33.6% and 48.9%, with several groups exceeding the GC content known for any other vascular plant group, highlighting their unusual genome architecture and organization. GC content showed a quadratic relationship with genome size, with the decreases in GC content in larger genomes possibly being a consequence of the higher biochemical costs of GC base synthesis. Dramatic decreases in GC content were observed in species with holocentric chromosomes, whereas increased GC content was documented in species able to grow in seasonally cold and/or dry climates, possibly indicating an advantage of GC-rich DNA during cell freezing and desiccation. We also show that genomic adaptations associated with changing GC content might have played a significant role in the evolution of the Earth's contemporary biota, such as the rise of grass-dominated biomes during the mid-Tertiary. One of the major selective advantages of GC-rich DNA is hypothesized to be facilitating more complex gene regulation. | 25,225,383 | [
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Functional biogeography of oceanic islands and the scaling of functional diversity in the Azores. | Analyses of species-diversity patterns of remote islands have been crucial to the development of biogeographic theory, yet little is known about corresponding patterns in functional traits on islands and how, for example, they may be affected by the introduction of exotic species. We collated trait data for spiders and beetles and used a functional diversity index (FRic) to test for nonrandomness in the contribution of endemic, other native (also combined as indigenous), and exotic species to functional-trait space across the nine islands of the Azores. In general, for both taxa and for each distributional category, functional diversity increases with species richness, which, in turn scales with island area. Null simulations support the hypothesis that each distributional group contributes to functional diversity in proportion to their species richness. Exotic spiders have added novel trait space to a greater degree than have exotic beetles, likely indicating greater impact of the reduction of immigration filters and/or differential historical losses of indigenous species. Analyses of species occurring in native-forest remnants provide limited indications of the operation of habitat filtering of exotics for three islands, but only for beetles. Although the general linear (not saturating) pattern of trait-space increase with richness of exotics suggests an ongoing process of functional enrichment and accommodation, further work is urgently needed to determine how estimates of extinction debt of indigenous species should be adjusted in the light of these findings. | 25,225,395 | [
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Predicting species' range limits from functional traits for the tree flora of North America. | Using functional traits to explain species' range limits is a promising approach in functional biogeography. It replaces the idiosyncrasy of species-specific climate ranges with a generic trait-based predictive framework. In addition, it has the potential to shed light on specific filter mechanisms creating large-scale vegetation patterns. However, its application to a continental flora, spanning large climate gradients, has been hampered by a lack of trait data. Here, we explore whether five key plant functional traits (seed mass, wood density, specific leaf area (SLA), maximum height, and longevity of a tree)--indicative of life history, mechanical, and physiological adaptations--explain the climate ranges of 250 North American tree species distributed from the boreal to the subtropics. Although the relationship between traits and the median climate across a species range is weak, quantile regressions revealed strong effects on range limits. Wood density and seed mass were strongly related to the lower but not upper temperature range limits of species. Maximum height affects the species range limits in both dry and humid climates, whereas SLA and longevity do not show clear relationships. These results allow the definition and delineation of climatic "no-go areas" for North American tree species based on key traits. As some of these key traits serve as important parameters in recent vegetation models, the implementation of trait-based climatic constraints has the potential to predict both range shifts and ecosystem consequences on a more functional basis. Moreover, for future trait-based vegetation models our results provide a benchmark for model evaluation. | 25,225,398 | [
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Tectonic-driven climate change and the diversification of angiosperms. | In 1879, Charles Darwin characterized the sudden and unexplained rise of angiosperms during the Cretaceous as an "abominable mystery." The diversification of this clade marked the beginning of a rapid transition among Mesozoic ecosystems and floras formerly dominated by ferns, conifers, and cycads. Although the role of environmental factors has been suggested [Coiffard C, Gómez B (2012) Geol Acta 10(2):181-188], Cretaceous global climate change has barely been considered as a contributor to angiosperm radiation, and focus was put on biotic factors to explain this transition. Here we use a fully coupled climate model driven by Mesozoic paleogeographic maps to quantify and discuss the impact of continental drift on angiosperm expansion and diversification. We show that the decrease of desertic belts between the Triassic and the Cretaceous and the subsequent onset of long-lasting humid conditions during the Late Cretaceous were driven by the breakup of Pangea and were contemporaneous with the first rise of angiosperm diversification. Positioning angiosperm-bearing fossil sites on our paleobioclimatic maps shows a strong match between the location of fossil-rich outcrops and temperate humid zones, indicating that climate change from arid to temperate dominance may have set the stage for the ecological expansion of flowering plants. | 25,225,405 | [
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Ultradian corticosterone pulses balance glutamatergic transmission and synaptic plasticity. | The rodent adrenal hormone corticosterone (CORT) reaches the brain in hourly ultradian pulses, with a steep rise in amplitude before awakening. The impact of a single CORT pulse on glutamatergic transmission is well documented, but it remains poorly understood how consecutive pulses impact on glutamate receptor trafficking and synaptic plasticity. By using high-resolution imaging and electrophysiological approaches, we report that a single pulse of CORT to hippocampal networks causes synaptic enrichment of glutamate receptors and increased responses to spontaneously released glutamatergic vesicles, collectively abrogating the ability to subsequently induce synaptic long-term potentiation. Strikingly, a second pulse of CORT one hour after the first--mimicking ultradian pulses--completely normalizes all aspects of glutamate transmission investigated, restoring the plastic range of the synapse. The effect of the second pulse is precisely timed and depends on a nongenomic glucocorticoid receptor-dependent pathway. This normalizing effect through a sequence of CORT pulses--as seen around awakening--may ensure that hippocampal glutamatergic synapses remain fully responsive and able to encode new stress-related information when daily activities start. | 25,225,407 | [
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Incorporation of pazopanib in maintenance therapy of ovarian cancer. | Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy. Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators. Maintenance pazopanib prolonged progression-free survival compared with placebo (hazard ratio [HR], 0.77; 95% CI, 0.64 to 0.91; P = .0021; median, 17.9 v 12.3 months, respectively). Interim survival analysis based on events in 35.6% of the population did not show any significant difference. Grade 3 or 4 adverse events of hypertension (30.8%), neutropenia (9.9%), liver-related toxicity (9.4%), diarrhea (8.2%), fatigue (2.7%), thrombocytopenia (2.5%), and palmar-plantar erythrodysesthesia (1.9%) were significantly higher in the pazopanib arm. Treatment discontinuation related to adverse events was higher among patients treated with pazopanib (33.3%) compared with placebo (5.6%). Pazopanib maintenance therapy provided a median improvement of 5.6 months (HR, 0.77) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy. Overall survival data to this point did not suggest any benefit. Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity (NCT00866697). | 25,225,436 | [
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Use of blood products in patients with anticoagulant-related major bleeding: an analysis of inhospital outcomes. | The impact of correcting elevated International Normalized Ratio (INR) values on inhospital mortality in patients with warfarin-associated major bleeding is presented. Using patient information from the database of a large U.S. health system, a retrospective analysis was conducted to (1) evaluate inpatient practice patterns in correcting INR elevations among patients hospitalized with warfarin-related intracranial hemorrhage (ICH) or non-ICH bleeding and (2) test the hypothesis that achieving INR correction, defined as an INR of ≤1.5, at any point during the hospital stay is correlated with lower inhospital mortality. Cox proportional hazards models were constructed to assess predictors of inhospital death. Among the 354 patients who met the study selection criteria, INR correction was achieved in 87.9% overall (92.5% and 85.5% of patients with ICH and non-ICH bleeds, respectively). Patients whose elevated INR values were corrected had significantly lower inhospital death rates than those with uncorrected elevations: 15.3% versus 55.6% (p = 0.010) among patients with ICH and 2.0% versus 11.8% (p = 0.017) among those with non-ICH bleeds. After adjusting for baseline demographics and comorbidities, the correlation between failure to correct INR elevations and increased mortality risk was significant only for patients with ICH (hazard ratio, 8.04; 95% confidence interval, 2.07-31.18; p = 0.003). Results of this study indicated that correction of elevated INR values was associated with a lower likelihood of inhospital death among warfarin-treated patients hospitalized for ICH or non-ICH major bleeding. | 25,225,449 | [
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A Learning Based Fiducial-driven Registration Scheme for Evaluating Laser Ablation Changes in Neurological Disorders. | In this work, we present a novel learning based fiducial driven registration (LeFiR) scheme which utilizes a point matching technique to identify the optimal configuration of landmarks to better recover deformation between a target and a moving image. Moreover, we employ the LeFiR scheme to model the localized nature of deformation introduced by a new treatment modality - laser induced interstitial thermal therapy (LITT) for treating neurological disorders. Magnetic resonance (MR) guided LITT has recently emerged as a minimally invasive alternative to craniotomy for local treatment of brain diseases (such as glioblastoma multiforme (GBM), epilepsy). However, LITT is currently only practised as an investigational procedure world-wide due to lack of data on longer term patient outcome following LITT. There is thus a need to quantitatively evaluate treatment related changes between post- and pre-LITT in terms of MR imaging markers. In order to validate LeFiR, we tested the scheme on a synthetic brain dataset (SBD) and in two real clinical scenarios for treating GBM and epilepsy with LITT. Four experiments under different deformation profiles simulating localized ablation effects of LITT on MRI were conducted on 286 pairs of SBD images. The training landmark configurations were obtained through 2000 iterations of registration where the points with consistently best registration performance were selected. The estimated landmarks greatly improved the quality metrics compared to a uniform grid (UniG) placement scheme, a speeded-up robust features (SURF) based method, and a scale-invariant feature transform (SIFT) based method as well as a generic free-form deformation (FFD) approach. The LeFiR method achieved average 90% improvement in recovering the local deformation compared to 82% for the uniform grid placement, 62% for the SURF based approach, and 16% for the generic FFD approach. On the real GBM and epilepsy data, the quantitative results showed that LeFiR outperformed UniG by 28% improvement in average. | 25,225,455 | [
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Feasibility of using the patient-reported outcomes measurement information system in academic health centers: case series design on pain reduction after chiropractic care. | The purpose of this study was to test the utility of Patient-Reported Outcomes Measurement Information System (PROMIS) as a resource for collecting data on patient-reported outcomes (PRO) within academic health centers at a chiropractic college; and, to describe changes in PRO following pragmatic chiropractic care incorporating instrument-assisted soft tissue mobilization (IASTM) on pain symptoms. This was a pre-post intervention design without a control group (case series) involving 25 patients (14 females and 11 males; 40.5 ± 16.39 years, range 20-70 years) who completed their chiropractic care and their baseline and post-treatment pain assessments. The pragmatic chiropractic care intervention included both spinal manipulation and IASTM to treat pain symptoms. PRO's were collected using PROMIS to measure pain behavior, pain interference and pain intensity. The average pre-post assessment interval was 33 ± 22.5 days (95% CI, 23-42 days). The durations of treatments ranged from one week to 10 weeks. The median number of IASTM treatments was six. Pre-post decreases in T-scores for pain behavior and pain interference were 55.5 to 48.4 and 57.7 to 48.4, respectively (P < .05). Only 12 patients had a baseline T-score for pain intensity greater than 50. The pre-post decrease in pain intensity T-scores for these 12 patients was from 53.4 to 40.9. Within the limitations of a case series design, these data provide initial evidence on the utility of PROMIS instruments for clinical and research outcomes in chiropractic patients. | 25,225,465 | [
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Clinical Characteristics and Immediate-Outcome of Children Mechanically Ventilated in PICU of Pakistan. | Back ground and Objective: Mechanical Ventilation (MV) is frequently used as one of the most frequent life-supportive technology in Pediatric Intensive Care Units (PICUs). Very little data is available from Asian countries like Pakistan regarding use of MV in PICUs. Our objective was to assess the frequency, indications and immediate-outcomes in mechanically ventilated pediatric patients in tertiary-care center of developing country. Retrospective cohort study of critically ill pediatric patients admitted in PICU of Aga Khan University Hospital, who required MV for more than 24-hour over two-year period. A total of 605 patients were admitted to PICU, 307 (50.7%) patients required MV support for >24hr. The median age was 3 years (IQR 6 month to 6 yr 2 months), and male was 59.6% (183/307). Common indications for MV was neurological illness 35.8%, followed by respiratory diseases in 20.8% patients and cardiac diseases in 13%; and 30.3 % patients were ventilated for other reasons. The median length of MV was 2.1 days. 9.4% developed complications and atelectasis (4.6%) was the most common. The mortality rate of children mechanically ventilated was 30.3% as compared to the overall mortality rate of in PICU was 16.3%. The long duration (> 10 days) and cardiogenic shock were identified as independent risk factor associated with increased mortality. About half of PICU admission required mechanical ventilation for more than 24 hours. The neurological illness was the most common reason for ventilation. The low incidence of complication rate and relatively high mortality in cardiac cases and long duration of mechanical ventilation were noted in our cohort. | 25,225,500 | [
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Comparison of the analgesic effect of intra-articular and extra-articular injection of morphine and ketamine compound in arthrotomy lower limb surgery under spinal anesthesia. | One of the critical components in the postoperative care is pain. Given that little research has been done regarding the analgesic effects of intra-articular injection of ketamine, this study was aimed to compare the analgesic effect of intra-articular and extra-articular injection of morphine and ketamine compound in arthrotomy surgery under spinal anesthesia. A total of 50 patients were candidate for arthrotomy surgery, aged 18-60 years were divided randomly into two groups. At the end of surgery, the first group was treated with combination of intra-articular morphine and ketamine compound and the second group was treated with combination of extra-articular morphine and ketamine compound. The amount of postoperative pain was recorded in the hours of 2,4,6,12,24 respectively. Also 24 hours consumption of rescue analgesic was recorded. The pain severity (VAS) in the hours of 2, 4, 6, 12 and 24 after surgery in the intra-articular injection group was significantly lower than the extra-articular injection group (P<0.05). Postoperative morphine consumption in intra-articular injection group (3.2±3.78) was significantly less than the extra-articular injection group (6.36±5.22) (p = 0.018). Postoperative pain severity of intra-articular injection of ketamine and morphine in knee surgery is less than extra-articular injection. | 25,225,503 | [
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Estimated costs of the treatment of diabetic foot ulcers in a tertiary hospital in Turkey. | The prevalence of diabetes and its related complications are increasing, and a considerable portion of healthcare expenditures is spent worldwide on diabetes and its complications. In this study, we investigated the estimated treatment costs of diabetic foot ulcers in a tertiary hospital in Turkey. A total of 203 patients with type 2 diabetes mellitus were included in this retrospective study. The study group comprised 91 patients with foot ulcers and the control group comprised 112 patients without any chronic complications. Their demographic characteristics, HbA1c levels and the length of hospital stay were recorded. The patients' bills, received from the hospital billing departments, were analysed. The average cost of diabetes patients with foot ulcers per person was calculated as 976.1±253.6 USD while it was 430.3±144.2 USD for diabetes patients without any chronic complications; thus, there was a significant difference between the average cost of these groups (p<0.001). Similarly, there were significant differences between the groups according to the costs of drugs, equipment and services (p<0.001). The estimated cost of treatment of diabetic foot ulcers is high in Turkey. It will continue to be a heavy economic burden if preventive measures are not taken. | 25,225,508 | [
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Ductus Venosus Doppler Flow Velocity after Transplacental and Non-transplacental Amniocentesis during Midtrimester. | We aimed to evaluate ductus venosus Doppler waveforms before and after amniocentesis in order to investigate any effect of amniocentesis on fetal myocardial hemodynamics. We also evaluated the umbilical artery, uterine artery and fetal mid-cerebral artery Doppler waveforms in order to investigate any relationship with ductus venosus Doppler changes. The study population consisted of 56 singleton pregnancies having genetic amniocentesis. Twenty seven of them had transplacental needle insertion; whereas 29 of them had non-transplacental amniocentesis. Uterine artery, umbilical artery, mid-cerebral artery and ductus venosus pulsatiliy index and resistance index were measured just before and after amniocentesis. Amniocentesis does not cause any significant changes in fetal ductus venosus Doppler waveforms. There is also no significant changes in uterine artery, umbilical artery, mid-cerebral artery pulsatility and resistance index. Amniocentesis-whether transplacental or not- does not cause any significant effect on fetal myocardial hemodynamics. | 25,225,513 | [
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A study of stress response to endotracheal intubation comparing glidescope and flexible fiberoptic bronchoscope. | To compare hemodynamic stress response (HDSR) to ET intubation using Glidescope (GLS) and Flexible fiberoptic laryngoscope (FFB). This prospective randomized comparative study was conducted at King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia from June 2011 - November 2013. Eighty ASA 1 & 2 patients with normal airway undergoing elective surgical procedure requiring ET intubation were included in the study. Patients were randomly assigned in two groups GLS or FFB. General anesthesia was induced with propofol and fentanyl. Muscle relaxation was achieved with cisatracurium and ET intubation was performed using either GLS or FFB. Noninvasive hemodynamic data was recorded (HR, systolic, diastolic and mean blood pressure) as pre-induction, baseline and after ET intubation at one minute intervals for successive five minutes. End tidal Sevoflurane and CO2 at the time of intubation, need of external neck pressure, time to successful intubation and number of attempts were recorded; and rate pressure product was calculated. Induction of anesthesia resulted in significant fall in blood pressure in both the groups. ET intubation resulted in similar rise of BP in both groups (for 3-4 minutes) from their baseline values; however the rise was not significantly different from their respective pre-induction values. Time to intubation was longer with FFB compared to GLS however, need for external neck manipulation was more with GLS. There was no difference in HDSR due to ET intubation using either GLS or FFB in healthy adult patients with normal airway. Rate pressure product remained within the acceptable range. | 25,225,515 | [
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Clinical comparison of propofol-remifentanil TCI with sevoflurane induction/maintenance anesthesia in laparoscopic cholecystectomy. | Objective : We aimed to compare the anesthetic characteristics between total intravenous anesthesia (TIVA) using propofol-remifentanil with target control infusion (TCI) and volatile induction and maintenance anesthesia (VIMA) using sevoflurane and sufentanyl for patients undergoing laparoscopic cholecystectomy. A total of 120 patients undergoing laparoscopic cholecystectomy were randomly assigned to two groups. Patients in group T received TCI of propofol-remifentanil for induction and maintenance. Patients in group S received sevoflurane-sufentanyl for induction and maintenance. Patients in group S had a significantly faster induction time than patients in group T (109s vs.44s). The emergence time in terms of time to extubation was comparable between the two groups, while the time to eyes opening (419s vs.483s, p=0.006) and duration in PACU were longer in group S (44 min vs.53 min, p=0.017). Ten (17.2%) patients in group S were administered an antihypertensive drug when gallbladder issues were present, while only 1(1.7%) patient needed this drug in group T (p=0.004).More patients in group T than in group S received fentanyl for analgesia in PACU (88%vs.70%, p=0.013). The incidence of postoperative nausea and vomiting (PONV) in PACU was higher in group S than in group T (20% vs.38%, p=0.027). Both techniques had advantages and disadvantages in laparoscopic cholecystectomy; none of the techniques studied was superior. | 25,225,518 | [
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Glial Fibrillary Acidic Protein (GFAP) as a Mesenchymal marker of Early Hepatic Stellate Cells Activation in Liver Fibrosis in Chronic Hepatitis C Infection. | This study aims to determine expression of Glial Fibrillary Acidic Protein and of Alpha Smooth Muscle Actin (α-SMA) in hepatic stellate cells of CHC cases and their association with stage of fibrosis. The study was conducted at Ziauddin University, Clifton Campus during the year 2010-2012. Sixty Chronic Hepatitis C cases were immmunostained using anti α-SMA antibody and anti-GFAP antibody. Semi quantitative scoring in pericentral, periportal and perisinusoidal area of each case was done to assess immunoexpression of each marker. Results : Immunoexpression of GFAP showed significant association with α-SMA. GFAP expression was inversely correlated with progression of fibrosis. Conclusion : GFAP could represent a useful marker for early hepatic stellate cells activation. Follow up biopsies showing decline in GFAP levels may help identify the target group requiring aggressive therapy. | 25,225,520 | [
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Comparative evaluation of chromogenic agar medium and conventional culture system for isolation and presumptive identification of uropathogens. | Urine is the most frequent specimen received for culture/sensitivity by clinical laboratories. The microbiological performance of HiCrome UTI agar medium was compared with Blood agar and MacConkey agar for isolation and presumptive identification of bacteria from urine culture. A total of 443 consecutively collected midstream and/or catheter-catch urine samples from patients attending the Islami Bank Medical College Hospital, Rajshahi, Bangladesh during January to December, 2012 were cultured. Urine samples showing pus cells ≥ 5/HPF were inoculated on to Blood agar (BA), MacConkey agar (MAC) and HiCrome UTI agar (CA) media simultaneously and incubated overnight aerobically at 37(0)C. Rate of isolation and presumptive identification of bacterial species were compared for different media. Culture yielded a total of 199 bacterial isolates from 189 (42.67%) positive plates including 179 (40.40%) unimicrobial and 10 (2.26%) polymicrobial (mixed growth of pair of bacteria) growths. Both HiCrome UTI agar and Blood agar media supported 100% growths while 151 (75.88%) growths were observed on MacConkey agar. The rate of presumptive identification was found significantly higher on HiCrome UTI agar (97.49%) than MAC agar (67.34%) (P<0.001) as primary urine culture medium. Of 199 isolates, E. coli was found to be the leading uropathogen isolated from 118 (59.30%) samples with its presumptive identification rate of 95.76%, 93.22% and 5.93% on CA, MAC and BA respectively. All 10 (100%) polymicrobial growths were demonstrated distinctly on CA against only 01(10%) on each BA and MAC. HiCrome UTI agar was found to be more useful as primary urine culture medium in both higher rate of isolation and presumptive identification of uropathogens in comparison to conventional media. Its inherent characteristics in demonstrating polymicrobial growth and ease of rapid identification by distinct colony colour are unique. | 25,225,521 | [
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Diabetes effect on Quality of Life in the long-term after Limb salvage with Infrageniculate Bypasses accompanied with minor amputations. | Objective : To evaluate the quality of life in patients, who had their limbs salvaged with an infrageniculate bypass and minor amputation in the long term and to see if diabetics are prone to worse results. The patients with limb salvage following an infrageniculate bypass and minor amputation were asked to complete Short Form 36 at the last follow-up visit. The mean scores in diabetic and non-diabetic population were compared to each other .The mean follow-up period was 58±8 months. Results : Of 142 patients, 40 patients were eligible to be included in the study. 33 (82.5%) patients were male and 7 (17.5%) patients were female. The mean age at the time of intervention was 57±14 (33-83) years. The mean scores for eight domains of SF-36 evaluation ranged from 44 to 67 out of 100. There were no significant differences concerning the mean scores of any dimension between the diabetic and non-diabetic group. Conclusion : Despite a minor amputation, the functional outcome of limb salvage with an infrageniculate bypass is favorable and diabetes does not seem to have negative effect on the functional outcome and Quality of Life. | 25,225,523 | [
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Demographic factors affecting quality of life of hemodialysis patients - Lahore, Pakistan. | The objective of the study was to determine the demographic factors affecting Quality Of Life (QOL) of hemodialysis (HD) patients. This observational study was conducted at Shalamar Hospital, Lahore. Patients of End Stage Renal Disease (ESRD) and on maintenance HD for more than three months were included during the period March to June 2012. Patient of ESRD not on dialysis and Acute Renal Failure were excluded. One hundred and twenty five patients who fulfilled the criteria were included. Demographic data containing age, sex, residence, socio economic status, education, mode of traveling for dialysis, total time consumed in dialysis were collected by the investigators. QOL index was measured using 26 items, WHO QOL BREF. There were 89(71.2%) male and 36(28.8%) female patients. Environmental domain score was highest (p=0.000) than all other domains in HD Patients. In overall analysis age, marital status and total time consumed in getting HD effect QOL significantly (p=<0.05). In domain wise analysis, male has better QOL in social relationship domain than female. Age has negative relationship with physical health and psychological health domain. QOL of unmarried and literate patients is significantly better (p=<0.05) in physical health domain. Employed patients have better QOL in physical, psychological and social relationship domain (p=<0.05) than unemployed patients. Patients of residence of rural areas have better QOL in physical and environment domain. Financial status of HD patients affect QOL in social domain. Distance covered to reach hospital effect QOL in psychological domain (p=<0.05). Patients traveling in private transport have better QOL in environmental domain (p=<0.05). Total time consumed in getting HD effect social relation in QOL (p=<0.05). According to linear regression model, marital status is positive predictor and unemployment is negative predictor of QOL in physical health domain. Age is negative predictor of QOL in psychological domain, monthly income is positive predictor of QOL in domain. Unemployment is positive predictor of QOL in social relation domain. Monthly income and place of residence is positive predictor of QOL in environment domain. Gender, age, marital status, unemployment, residence of rural area, economical status, distance covered to reach hospital, mode of transport, total time consumed in getting HD, effect QOL in HD patient. Education level is a positive factor for improving QOL of HD patients. | 25,225,539 | [
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'E-learning' modalities in the current era of Medical Education in Pakistan. | There are a number of e-Learning modalities, some or all of which may be used throughout a medical, dental, nursing or any other health related undergraduate curriculum. The purpose of this paper is to briefly describe what e-learning is along with some of the modalities, their common advantages and limitations. This publication ends with practical implications of these modalities for Pakistan. | 25,225,547 | [
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The influence of thread geometry on biomechanical load transfer to bone: A finite element analysis comparing two implant thread designs. | The success of dental implants depends on the manner in which stresses are transferred to the surrounding bone. An important consideration is to design an implant with a geometry that will minimize the peak bone stresses caused by standard loading. The aim of this study was to assess the influence of implant thread geometry on biomechanical load transfer and to compare the difference between two different thread designs. A three-dimensional finite element model of D2 bone representing mandibular premolar region was constructed. Two implants of differing thread geometries, 13-mm length, and 4-mm diameter along with superstructures were simulated. One design featured fourfold microthread of 0.4-mm pitch, 0.25-mm depth in the crestal one-third; 0.8-mm pitch, 0.5-mm depth in the apical two-third. The other design had a single-pitch microthread of 0.8-mm pitch, 0.25-mm depth in the crestal one-third; 0.8-mm pitch, 0.5-mm depth in the apical two-third. A static axial load of 100-N was applied to the occlusal surface of the prosthesis. ANSYS CLASSIC 9.0 (PA,USA)software was used for stress analysis as von Mises stresses. A comparison of von Mises stresses between two thread designs revealed that fourfold microthread allows better stress distribution within the implant body by 43.85%, abutment by 15.68%, its superstructure by 39.70% and 36.30% within cancellous bone as compared to single-pitch microthread. The effective stress transfer to the cortical bone is lowered by 60.47% with single-pitch microthread. Single-pitch microthread dissipates lesser stresses to cortical bone while the implant body, abutment, and superstructure absorb more stress. This will have a positive influence on the bone-implant contact and contribute to preservation of crestal bone. Implant with single pitch microthread will thus be preferable to be used in areas where the amount of cortical bone available is less. | 25,225,563 | [
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Craniofacial polyostotic fibrous dysplasia: A rare case. | Craniofacial fibrous dysplasia (FD) is one of three types of FD which can affect the craniofacial complex. It is the proliferation of cellular fibrous connective tissue intermixed with irregular bony trabecules. It is a developmental tumor-like condition that is characterized by replacement of normal bone. The purpose of this report is to present a rare case of craniofacial polyostotic FD that led to vision loss in the same affected side. | 25,225,568 | [
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The outcome of treatment for anorexia nervosa inpatients who required urgent hospitalization. | This study was done to determine which psychosocial factors are related to the urgent hospitalization of anorexia nervosa patients (AN) due to extremely poor physical condition and to evaluate their outcome after inpatient treatment. 133 hospitalized AN patients were classified into an urgent hospitalization (n = 24) or a planned hospitalization (n = 109) group. Multiple regression analysis was done of clinical features, body mass index (BMI), psychological tests [The Minnesota Multiphasic Personality Inventory (MMPI), alexithymia, relationship with parents, and the Eating Disorder Inventory (EDI)]. The effectiveness of treatment was prospectively determined two years after discharge by the Global Clinical Score (GCS). The hospitalized weight gain and the frequency of outpatient visits were evaluated. Of the factors assessed, only BMI at admission was related to the necessity of urgent hospitalization (β = - 1.063, P = 0.00). The urgent group had significantly more weight loss after discharge and poorer social adaptation on the GCS, even when the patient had a sufficient increase in body weight during inpatient treatment and an equivalent number of outpatient consultations. None of the parameters of the psychosocial tests studied were significantly different between the groups. The outcome of the urgent group was poor. Two years after discharge they had difficulty maintaining weight and continued to have poor social adaptation. | 25,225,574 | [
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Dynamic changes in DNA modification states during late gestation male germ line development in the rat. | Epigenetic reprogramming of fetal germ cells involves the genome-wide erasure and subsequent re-establishment of DNA methylation. Mouse studies indicate that DNA demethylation may be initiated at embryonic day (e) 8 and completed between e11.5 and e12.5. In the male germline, DNA remethylation begins around e15 and continues for the remainder of gestation whilst this process occurs postnatally in female germ cells. Although 5-methylcytosine (5mC) dynamics have been extensively characterised, a role for the more recently described DNA modifications (5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)) remains unclear. Moreover, the extent to which the developmental dynamics of 5mC reprogramming is conserved across species remains largely undetermined. Here, we sought to describe this process during late gestation in the male rat. Using immunofluorescence, we demonstrate that 5mC is re-established between e18.5 and e21.5 in the rat, subsequent to loss of 5hmC, 5fC and 5caC, which are present in germ cells between e14.5 and e16.5. All of the evaluated DNA methyl forms were expressed in testicular somatic cells throughout late gestation. 5fC and 5caC can potentially be excised through Thymine DNA Glycosylase (TDG) and repaired by the base excision repair (BER) pathway, implicating 5mC oxidation in active DNA demethylation. In support of this potential mechanism, we show that TDG expression is coincident with the presence of 5hmC, 5fC and 5caC in male germ cell development. The developmental dependent changes in germ cell DNA methylation patterns suggest that they are linked with key stages of male rat germline progression. | 25,225,576 | [
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Comparison of plasma microRNA-1 and cardiac troponin T in early diagnosis of patients with acute myocardial infarction. | Early reperfusion can effectively treat acute myocardial infarction (AMI) and reduce the mortality significantly. This study aimed to compare the role of plasma microRNA-1 (miR-1) and cardiac troponin T (cTnT) in early diagnosis of AMI patients. From May 2011 to May 2012, plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic (ROC) curve was established to discriminate the AMI patients from the controls. In the present study, the expression of plasma miR-1 was significantly increased in the AMI patients compared with the healthy controls (P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days (P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population (P>0.05). ROC curve analyses demonstrated that miR-1 was specific and sensitive for the early diagnosis of AMI, but not superior to cTnT. Plasma miR-1 could be used in the early diagnosis of AMI, but it is similar to cTnT. | 25,225,581 | [
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The Effects of Alcohol Problems, PTSD, and Combat Exposure on Nonphysical and Physical Aggression Among Iraq and Afghanistan War Veterans. | Aggression among combat veterans is of great concern. Although some studies have found an association between combat exposure and aggressive behavior following deployment, others conclude that aggression is more strongly associated with symptoms of posttraumatic stress disorder (PTSD), and that alcohol misuse may influence this association. Many of these studies have assessed aggression as a single construct, whereas the current study explored both nonphysical aggression only and physical aggression in a sample of Iraq and Afghanistan war veterans (<iN</i = 337; 91% male). We found that alcohol problems interacted with PTSD symptom severity to predict nonphysical aggression only. At low levels of PTSD symptoms, veterans with alcohol problems were more likely to perpetrate nonphysical aggression only, as compared with no aggression, than veterans without an alcohol problem. There was no difference in the likelihood of nonphysical aggression only between those with and without alcohol problems at high levels of PTSD symptoms. The likelihood of nonphysical aggression only, as compared with no aggression, was also greater among younger veterans. Greater combat exposure and PTSD symptom severity were associated with an increased likelihood of perpetrating physical aggression, as compared with no aggression. Ethnic minority status and younger age were also associated with physical aggression, as compared with no aggression. Findings suggest that a more detailed assessment of veterans' aggressive behavior, as well as their alcohol problems and PTSD symptoms, by researchers and clinicians is needed in order to determine how best to intervene. | 25,225,593 | [
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Ulcer dressings and management. | Chronic leg ulcers caused by venous disease, arterial disease or a combination of both need to be clearly identified before treatment can be commenced. Their management will depend on the diagnosis, combining direct management of the ulcer as well as management of patient factors. Other chronic wounds commonly observed in practice include pressure wounds, skin tears, atypical leg ulcers. This paper will outline a simple way to manage people with chronic ulcers. Conclusion The prevalence of chronic wounds is expected to rise given that people are living longer and that the incidence of diabetes is increasing. There is a need is to clearly identify the underlying cause of any wound, including factors that may delay healing, and to treat appropriately. Treatment should address the wound environment, tissue base, presence of bacteria and the level of slough. If there is no improvement in wound healing after 4 weeks then seek help from a wound specialist. The prevalence of chronic ulcers in Australia has been estimated at 2-5%. Comprehensive assessment of the ulcer, the region and the whole person is an important first step in treatment. The aim of management is to promote healing and minimise the impact on the patient. | 25,225,641 | [
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Visions of generalism - what does the future hold? | Support for generalism is underpinned by more than 100 years of writings and these writings point to writers and thinkers who have grappled with the tensions between generalism and specialism since ancient Egyptian times. Taking a historical stance we make the case that generalism is here to stay. But, what does the future hold? We outline some ideas for growing generalism in the wake of smart technologies, personalised medicine and the deluge of ever increasing health information. | 25,225,653 | [
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Functional significance of mononuclear phagocyte populations generated through adult hematopoiesis. | Tissue homeostasis requires a complete repertoire of functional macrophages in peripheral tissues. Recent evidence indicates that many resident tissue macrophages are seeded during embryonic development and persist through adulthood as a consequence of localized proliferation. Mononuclear phagocytes are also produced during adult hematopoiesis; these cells are then recruited to sites throughout the body, where they function in tissue repair and remodeling, resolution of inflammation, maintenance of homeostasis, and disease progression. The focus of this review is on mononuclear phagocytes that comprise the nonresident monocyte/macrophage populations in the body. Key features of monocyte differentiation are presented, focusing primarily on the developmental hierarchy that is established through this process, the markers used to identify discrete cell populations, and novel, functional attributes of these cells. These features are then explored in the context of the tumor microenvironment, where mononuclear phagocytes exhibit extensive plasticity in phenotype and function. | 25,225,678 | [
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Graphene-based nanomaterials as heterogeneous acid catalysts: a comprehensive perspective. | Acid catalysis is quite prevalent and probably one of the most routine operations in both industrial processes and research laboratories worldwide. Recently, "graphene", a two dimensional single-layer carbon sheet with hexagonal packed lattice structure, imitative of nanomaterials, has shown great potential as alternative and eco-friendly solid carbocatalyst for a variety of acid-catalyzed reactions. Owing to their exceptional physical, chemical, and mechanical properties, graphene-based nanomaterials (G-NMs) offer highly stable Brønsted acidic sites, high mass transfer, relatively large surface areas, water tolerant character, and convenient recoverability as well as recyclability, whilst retaining high activity in acid-catalyzed chemical reactions. This comprehensive review focuses on the chemistry of G-NMs, including their synthesis, characterization, properties, functionalization, and up-to-date applications in heterogeneous acid catalysis. In line with this, in certain instances readers may find herein some criticisms that should be taken as constructive and would be of value in understanding the scope and limitations of current approaches utilizing graphene and its derivatives for the same. | 25,225,721 | [
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Estimated infant intake of persistent organic pollutants through breast milk in New Zealand. | To estimate average infant daily intake of chlorinated persistent organic pollutants (POPs) through the consumption of breast milk in New Zealand. Breast milk of 39 first-time mothers aged 20-30 years was collected during 2007-2010 and analysed for persistent organic pollutants including dioxin-like compounds and organochlorine pesticides. The quantity of POPs consumed by infants assuming exclusive breast feeding was estimated by calculating the Estimated Daily Intake (EDI) expressed as amount consumed through breast milk per kilogram of body weight per day. Of all POPs quantified, the EDI of DDT (principally in the form of its metabolite p,p'-DDE) was the highest (1.6 mcg/kg/day), and above the tolerable daily intake (TDI) of 0.5 mcg/kg/day. The mean EDI for dioxin-like compounds (including PCDD/Fs and PCBs) was 19.7 pg TEQ(toxic equivalency)/kg/day, which is among the lowest reported worldwide, yet above the TDI of 1 pg TEQ/kg/day. The EDI of HCH, HCB, dieldrin, heptachlor and mirex were 32.9, 37.9, 39.4, 2.0, and 0.9 ng/kg/day respectively, all of which were below the current TDI. Age of the mother was positively associated with higher EDIs for the infant, particularly for total-TEQ and total-DDT. Infant daily intakes of chlorinated POPs through breast milk estimated for New Zealand are low or average by international comparison, and 5 times lower than 25 years ago. Future breast milk monitoring will determine whether this diminishing trend is continuing as well as providing monitoring information on other POPs. | 25,225,757 | [
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Direct-to-consumer advertising of prescription medication in New Zealand. | The last decade has seen increasing measures aimed at regulating the influence of 'Big Pharma' following a number of scandals relating to unethical marketing. Despite these international trends, New Zealand continues to tolerate direct-to-consumer advertising (DTCA) of prescription medication, a controversial pharmaceutical marketing strategy that has been prohibited in all but two countries in the industrialised world. While the pharmaceutical industry asserts that DTCA is informational and empowers consumers, in this viewpoint article we argue that DTCA is a heavily biased source of health information that favours representation of benefits over harms, and is associated with unnecessary prescribing, iatrogenic harm and increased costs to the taxpayer. In this paper, we show that DTCA provides unbalanced information to consumers who may misconstrue DTCA as public health messages, and fail to recognise inherent commercial bias. We describe how DTCA has been linked with inappropriate prescribing and overtreatment, with evidence indicating that patients request and receive specific medications in response to DTCA, even when treatment is not clinically indicated. This exposes patients to unnecessary adverse effects and iatrogenic harm, and increases costs for the health-care sector through the prescription of expensive branded medication. We use local examples to illustrate these points. New Zealand remains an outlier in allowing DTCA to continue which, in our view, is a controversial and harmful practice. The available evidence suggests that consumers and health care professionals are generally opposed to DTCA. Therefore, we believe that the New Zealand government should review its stance on DTCA. | 25,225,761 | [
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Entrepreneurship by any other name: self-sufficiency versus innovation. | Entrepreneurship has been promoted as an innovative strategy to address the employment of people with disabilities. Research has predominantly focused on the self-sufficiency aspect without fully integrating entrepreneurship literature in the areas of theory, systems change, and demonstration projects. Subsequently there are gaps in services, policies, and research in this field that, in turn, have limited our understanding of the support needs and barriers or facilitators of entrepreneurs with disabilities. A thorough analysis of the literature in these areas led to the development of two core concepts that need to be addressed in integrating entrepreneurship into disability employment research and policy: clarity in operational definitions and better disability statistics and outcome measures. This article interrogates existing research and policy efforts in this regard to argue for a necessary shift in the field from focusing on entrepreneurship as self-sufficiency to understanding entrepreneurship as innovation. | 25,225,770 | [
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Neutrophil mobilization by surface-glycan altered Th17-skewing bacteria mitigates periodontal pathogen persistence and associated alveolar bone loss. | Alveolar bone (tooth-supporting bone) erosion is a hallmark of periodontitis, an inflammatory disease that often leads to tooth loss. Periodontitis is caused by a select group of pathogens that form biofilms in subgingival crevices between the gums and teeth. It is well-recognized that the periodontal pathogen Porphyromonas gingivalis in these biofilms is responsible for modeling a microbial dysbiotic state, which then initiates an inflammatory response destructive to the periodontal tissues and bone. Eradication of this pathogen is thus critical for the treatment of periodontitis. Previous studies have shown that oral inoculation in mice with an attenuated strain of the periodontal pathogen Tannerella forsythia altered in O-glycan surface composition induces a Th17-linked mobilization of neutrophils to the gingival tissues. In this study, we sought to determine if immune priming with such a Th17-biasing strain would elicit a productive neutrophil response against P. gingivalis. Our data show that inoculation with a Th17-biasing T. forsythia strain is effective in blocking P. gingivalis-persistence and associated alveolar bone loss in mice. This work demonstrates the potential of O-glycan modified Tannerella strains or their O-glycan components for harnessing Th17-mediated immunity against periodontal and other mucosal pathogens. | 25,225,799 | [
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Illegal and legal parrot trade shows a long-term, cross-cultural preference for the most attractive species increasing their risk of extinction. | Illegal trade constitutes a major threat for a variety of wildlife. A criminology framework has been recently applied to parrot poaching in Mexico, suggesting an opportunistic crime in which the most abundant and accessible species, and not the rare or highly priced species, were poached more often. We analyzed this information, together with additional long-term data (1981-2005) on both the legal and illegal trade of the 22 Mexican parrot species (n = 31,019 individuals), using multivariate statistics and hypothesis-testing approaches. Our results showed a selective capture of parrot species attending to their attractiveness. Parrot species widely differed in attractiveness to people (as reflected by their combined measures of body size, coloration, and ability to imitate human speech), and their attractiveness strongly correlated with their prices both in the Mexican and US markets. The most attractive and valuable species (amazons and macaws) were disproportionally caught attending to the number of years they were legally trapped. Similar patterns were found for parrots poached for the domestic Mexican market, for those smuggled to the USA, and for those legally exported before or after 1992, when the USA ban led parrot exports to be mostly directed to European countries. Finally, the long-term cross-cultural preference for the most attractive species has led them to be among the most threatened species today. Since current parrot poaching mostly responds to local demand, socio-ecological work is needed to reverse the long-standing pet-keeping tradition that may decimate the most desired species in Neotropical countries. | 25,225,808 | [
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Progress in simulation education: developing an anesthesia curriculum. | Simulation's role in anesthesia education is expanding to include more advanced skills and training for subspecialty practice. This review will provide an overview of many recent studies that expand the simulation curriculum for anesthesia education. Recent studies describe a curriculum that uses a range of simulation modalities, including part-task trainers, mannequin-based simulation, virtual reality, in-situ techniques, screen-based simulations as well as encounters with 'standardized' patients, nurses or physician colleagues. A variety of studies describe the use of task-training devises to more effectively acquire skills, such as fibre-optic intubation, ultrasound-guided regional anesthesia and transthoracic echocardiography as well as expand on a variety of teamwork skills particularly in subspecialty anesthesia practice. A curriculum is emerging that utilizes a variety of simulation modalities as part of a more comprehensive educational strategy for anesthesia specialty training. | 25,225,825 | [
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Shrinking the lymphatic filariasis map: update on diagnostic tools for mapping and transmission monitoring. | Lymphatic filariasis (LF), which is highly endemic in 73 countries worldwide, is targeted for elimination by 2020. The strategy for achieving this goal is based on 4 sequential programmatic steps: mapping, Mass drug administration (MDA) implementation, post-MDA surveillance and verification of LF elimination. All 4 stages of the implementation process are dependent on the availability of user friendly and highly sensitive rapid diagnostic tools. By the end of 2012, 59 countries had completed mapping for LF and Eritrea was the only country yet to start the process. Rolling out new diagnostic tools to facilitate the mapping process will enable an accelerated shrinking of the LF map to zero endemic countries by 2020. When the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, diagnostic tools for LF were limited to clinical examination, detection of microfilaria (MF) by microscopy in night blood samples and detection of antibodies to native-antigen preparations. There has been a significant improvement in the traditional LF diagnostic methods in recent years and some new tools are now available. This paper provides an update on the human diagnostic tests available for LF and their current applications as tools in mapping and transmission monitoring. The values of entomological indicators and parasite detection and speciation methods applied to vector populations are also discussed. | 25,225,828 | [
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Protective effects of proanthocyanidin and vitamin E against toxic effects of formaldehyde in kidney tissue. | We investigated possible effects of proanthocyanidin (PA) and vitamin E on damage to rat kidneys induced by formaldehyde (FA), using biochemical characteristics and light and electron microscopy. Male rats were divided into control, FA, PA and vitamin E treated groups. Kidney tissue was observed by light and electron microscopy. Bcl-2/Bax rate was measured using immunohistochemistry. Malondialdehyde (MDA) and total sialic acid (TSA) levels, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase (CAT) and myeloperoxidase (MPO) activities were measured. We found that FA caused damage to the parietal epithelial layer of the glomerulus, mononuclear cell infiltration, membrane damage in renal tubules, pyknotic nuclei, hypertrophic cells in Henle's loop and tubules, and loss of renal tubule integrity. We also observed invagination of the nuclear membrane, irregularity of chromatin material and loss of mitochondrial cristae. We observed increased Bcl-2 and Bax immunostaining in the FA group, but the Bcl-2/Bax rate remained unchanged in FA, PA and vitamin E groups compared to controls. Tissue MDA and TSA levels, and CAT and Gpx activities were increased, and SOD and MPO activities were decreased by FA toxicity. We observed a protective effect of PA in tissue MDA and TSA levels and SOD activities, because there was no difference in the PA group compared to the control group. We investigated the antioxidant effects of PA and vitamin E and found protective effects of PA against apoptosis. | 25,225,844 | [
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Decision support for redesigning wastewater treatment technologies. | This paper offers a methodology for structuring the design space for innovative process engineering technology development. The methodology is exemplified in the evaluation of a wide variety of treatment technologies for source-separated domestic wastewater within the scope of the Reinvent the Toilet Challenge. It offers a methodology for narrowing down the decision-making field based on a strict interpretation of treatment objectives for undiluted urine and dry feces and macroenvironmental factors (STEEPLED analysis) which influence decision criteria. Such an evaluation identifies promising paths for technology development such as focusing on space-saving processes or the need for more innovation in low-cost, energy-efficient urine treatment methods. Critical macroenvironmental factors, such as housing density, transportation infrastructure, and climate conditions were found to affect technology decisions regarding reactor volume, weight of outputs, energy consumption, atmospheric emissions, investment cost, and net revenue. The analysis also identified a number of qualitative factors that should be carefully weighed when pursuing technology development; such as availability of O&M resources, health and safety goals, and other ethical issues. Use of this methodology allows for coevolution of innovative technology within context constraints; however, for full-scale technology choices in the field, only very mature technologies can be evaluated. | 25,225,855 | [
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