title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Long-term outcome after overlapping anterior anal sphincter repair for fecal incontinence. | The aim was to assess long-term results and quality of life following anterior anal sphincter repair for anal incontinence. Twenty-three female patients underwent anterior anal sphincteroplasty over a 10-year period between January 1999 and January 2009 in a gynecological surgery department. Patients were asked to complete pre- and postoperative questionnaires comprising the Jorge and Wexner incontinence score. The secondary objective was to assess pre- and post-sphincteroplasty symptom severity and sexual quality of life. Mean follow-up was 87 months (median, 91.5 months). Kaplan-Meier time-to-event analysis was applied. Mean age was 52 years (±15.2), and mean postoperative Jorge and Wexner score, 7.5/20 (±4.1). Seventeen patients (85 %) declared themselves satisfied by the repair; 12 (60 %) showed good fecal continence. Fecal incontinence had a negative impact on quality of life for 15 % and on sexuality for 50 % of patients. Kaplan-Meier analysis showed 85 % conservation of anal continence correction at 1 year, 74 % at 48 months, 67 % at 60 months, and 48 % at 84 months. Overlapping anterior anal sphincter repair provided lasting improvement in fecal incontinence, with satisfactory long-term functional results. At 84 months' follow-up, 48 % of patients maintained good fecal continence, with a satisfaction rate of 85 %. Anal sphincteroplasty may be a first-line attitude in young female fecal incontinence patients with a recent sphincter defect following initially undiagnosed obstetric trauma and also restores perineal comfort. | 25,185,844 | [
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Hyperthyroidism during pregnancy--the role of measuring maternal TSH receptor antibodies and foetal ultrasound monitoring. | To evaluate the usefulness of measuring maternal anti-TSH receptor antibodies (TRAbs) and foetal ultrasound (US) monitoring in cases of current or past maternal hyperthyroidism. 77 pregnant women suffering from hyperthyroidism or with a history of Graves' hyperthyroidism were observed prospectively. Maternal serum TSH, fT4, fT3, TRAbs, and foetal US were performed at baseline and repeated every 2-4 weeks when needed. Neonatal thyroid status was assessed based on serum TSH, fT4 and fT3 obtained in the first days of life. 35 women were diagnosed with gestational hyperthyroidism and 42 with Graves' disease; among them 26 had current and 16 past hyperthyroidism. Foetal and neonatal thyroid dysfunction occurred only in cases of maternal Graves' disease: nine (21%) and three (7%), respectively. Active maternal Graves' hyperthyroidism and TRAbs elevated at least five times above the upper normal limit predisposed to foetal hyperthyroidism. Maternal anti-thyroid drug therapy (ATD) and low TRAbs and fT4 were the risk factors of foetal hypothyroidism. Abnormal foetal thyroid sonogram was the only sign of foetal thyroid dysfunction. Four patients (9.5%) had high TRAbs in the 3rd trimester (10.8-29.9 IU/mL), but neither foetal nor neonatal thyroid dysfunctions were noted. In the cases of maternal Graves' disease, foetal thyroid dysfunction occurs more often than commonly assumed. Foetal thyroid US is a valuable tool in early diagnosis and monitoring of the foetal thyroid status in pregnancy complicated by maternal Graves' disease. The evaluation of biological activity of maternal TRAbs may be helpful in prenatal diagnosis in some cases. | 25,185,847 | [
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The effect of short-term combined treatment with simvastatin and ezetimibe on circulating adipokine levels in patients with isolated hypercholesterolemia. | Although several studies have assessed plasma adipokines in patients treated with hypolipidemic agents, these studies have provided contrasting results. This study included 19 high-risk patients with elevated total and LDL cholesterol levels treated with simvastatin (40 mg daily) and ezetimibe (10 mg daily). Plasma levels of leptin, adiponectin, visfatin, tumour necrosis factor-α, free fatty acids as well as C-reactive protein were measured before and after 30 days of treatment. High-risk hypercholesterolemic patients were compared with 17 age-, sex- and weight-matched healthy subjects who did not receive any treatment. Compared to the healthy subjects, hypercholesterolemic patients exhibited lower plasma levels of adiponectin, as well as higher plasma levels of the remaining adipokines. Administration of simvastatin and ezetimibe for 30 days reduced plasma levels of leptin, visfatin, TNF-α, as well as increased plasma levels of adiponectin. The treatment also reduced free fatty acids and C-reactive protein. High-risk hypercholesterolemic patients with elevated cholesterol levels are characterised by abnormal production of adipose tissue hormones. Short-term treatment with simvastatin and ezetimibe partially restores adipokine production and inhibits low-grade inflammation. | 25,185,849 | [
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Activated protein C to heal pressure ulcers. | Pressure ulcers present a major clinical challenge, are physically debilitating and place the patient at risk of serious comorbidities such as septic shock. Recombinant human activated protein C (APC) is an anticoagulant with anti-inflammatory, cytoprotective and angiogenic effects that promote rapid wound healing. Topical negative pressure wound therapy (TNP) has become widely used as a treatment modality in wounds although its efficacy has not been proven through randomised controlled trials. The aim of this study was to determine the preliminary efficacy and safety of treatment with APC for severe chronic pressure sores with and without TNP. This case presentation describes the history, management and outcome of two patients each with a severe chronic non-healing pressure ulcer that had failed to respond to conventional therapy. TNP was added to conservative management of both ulcers with no improvement seen. Then local application of small doses of APC was added to TNP and with conservative management, resulted in significant clinical improvement and rapid healing of both ulcers, displaying rapid growth of vascular granulation tissue with subsequent epithelialisation. Patients tolerated the treatment well and improvements suggested by long-term follow-up were provided. Randomised placebo-controlled double blind trials are needed to quantify the efficacy, safety, cost-effectiveness, optimal dose and quality of life changes seen from treatment with APC. | 25,185,858 | [
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Plasma levels of fibroblast growth factor-23 are associated with muscle mass in haemodialysis patients. | Malnutrition is highly prevalent in haemodialysis (HD) patients, and it contributes to morbidity and mortality. Fibroblast growth factor-23 (FGF-23) and Klotho contribute to chronic kidney disease-mineral and bone disorder (CKD-MBD) in HD patients, but the role that these molecules play in determining nutritional status is currently unknown. A cross-sectional study examining 77 HD patients was performed. The plasma concentrations of FGF-23 and soluble Klotho (s-Klotho) were studied to evaluate their association with muscle mass, which was investigated by abdominal muscle areas measured using computed tomography and by creatinine (Cr) production estimated using the Cr kinetic model. Plasma FGF-23 concentrations were significantly and positively correlated with abdominal muscle areas and Cr production (rho = 0.301, P < 0.01 and rho = 0.345, P < 0.01, respectively). In contrast, s-Klotho was not significantly correlated with these muscle mass indices and plasma FGF-23 concentrations. Multiple regression analyses showed that FGF-23 was a significant independent predictor of both muscle mass indices (P < 0.01 and P < 0.05, respectively). Plasma FGF-23 concentrations were associated with muscle mass indices in HD patients. Our findings suggest that FGF-23 and nutritional status are linked and this link is most likely independent of s-Klotho. | 25,185,859 | [
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Gyrodactylus gasterostei a difficult meal to swallow for the three-spined sticklebacks, Gasterosteus aculeatus L. | This study examines the transmission strategies employed by parasites in order to colonize new hosts. Three-spined sticklebacks, Gasterosteus aculeatus L., were challenged with Gyrodactylus gasterostei Gläser, 1974 in a chamber and the colonization of new hosts was observed. Live-video recording indicates that gyrodactylid transmission possibly maximizes the chances of contact with an alternatively feeding response from dead parasitized hosts to predatory stickleback. It is proposed that host scavenge feeding may comprise an additional route for gyrodactylid transmission, although its relative importance with respect to other recognized routes remains uncertain. Although it was clearly demonstrated that G. gasterostei can reside in the mouth of its host, the study revealed that scavenging-feeding upon dead parasitized hosts did not contribute significantly to the level of infection in 3 h and parasite transmission observed on the feeding fish. A series of experimental exposures and scanning electron microscope images suggest that once ingested, the parasites can attach to the lining of the buccal cavity and then migrate to their preferred colonization site on the outer surface of the fish. In addition to the direct contact infection pathway normally associated with many. This study highlights that diagnosticians should be aware of the fact that the oral cavity may act as temporary transmission location for gyrodactylid fauna. | 25,185,879 | [
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The complete mitochondrial genome of malbrouck monkey, Chlorocebus cynosuros (Chlorocebus, Cercopithecinae). | In this study, the complete mitochondrial genome sequence of malbrouck monkey, Chlorocebus cynosuros, with the total length of 16,334 bp, is reported for the first time. Similar to other monkeys, it contains a typically conserved structure including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). The base composition was A (32.1%), G (12.4%), C (30.1%), and T (25.4%), so the percentage of A and T (57.5%) was higher than that of G and C. Most of the genes are encoded on H-strand, except for the ND6 subunit gene and 8 tRNA genes. The complete mitochondrial genome sequence provided here would be useful for further phylogenetic analysis and population genetic studies in C. cynosuros. | 25,185,937 | [
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Transparent nickel selenide alloy counter electrodes for bifacial dye-sensitized solar cells exceeding 10% efficiency. | In the current work, we report a series of bifacial dye-sensitized solar cells (DSSCs) that provide power conversion efficiencies of more than 10% from bifacial irradiation. The device comprises an N719-sensitized TiO2 anode, a transparent nickel selenide (Ni-Se) alloy counter electrode (CE), and liquid electrolyte containing I(-)/I3(-) redox couples. Because of the high optical transparency, electron conduction ability, electrocatalytic activity of Ni-Se CEs, as well as dye illumination, electron excitation and power conversion efficiency have been remarkably enhanced. Results indicate that incident light from a transparent CE has a compensation effect to the light from the anode. The impressive efficiency along with simple preparation of the cost-effective Ni-Se alloy CEs highlights the potential application of bifacial illumination technique in robust DSSCs. | 25,185,939 | [
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Detection of occult hepatitis C virus among healthy spouses of patients with HCV infection. | The criterion standard for the diagnosis of occult hepatitis C virus (HCV) infection is detection of HCV-RNA in liver cells. However, because of the invasive nature of liver biopsy, other methods have been studied. The present study aimed to identify subjects with occult HCV-4 infection among healthy sexual partners of patients with chronic HCV-4 infection by detecting HCV-RNA in peripheral blood mononuclear cells (PBMCs) using real-time polymerase chain reaction (PCR). Fifty healthy Egyptian spouses of patients with chronic HCV-4 infection were included in this study. Real-time PCR was used to detect HCV-RNA in PBMCs in all the study subjects. The prevalence of occult HCV-4 infection was 4%, and a statistically significant higher prevalence was found among patients with a history of sexually transmitted infection. The results of the present study indicate the importance of intra-spousal transmission of HCV-4 infection, especially in subjects with a history of sexually transmitted infection. | 25,185,940 | [
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Modification of silicone elastomer with zwitterionic silane for durable antifouling properties. | Biofouling on medical devices generally causes adverse complications, such as thrombosis, infection, and pathogenic calcification. Silicone is a widely used material for medical applications. Its surface modification typically encounters undesirable "hydrophobic recovery", leading to deterioration of surface engineering. In this study, we developed a stable superhydrophilic zwitterionic interface on polydimethylsiloxane (PDMS) elastomer by covalent silanization of sulfobetaine silane (SBSi) to resist nonspecific adsorption of bacteria, proteins, and lipids. SBSi is a zwitterionic organosilane assembly, enabling resisting surface reconstruction by forming a cross-linked network and polar segregation. Surface elemental composition was confirmed by X-ray photoelectron spectroscopy (XPS), and the long-term stability of modification was accessed using a contact angle goniometer. The biofouling tests were carried out by exposing substrates to bacterial, protein, and lipid solutions, revealing the excellent bioinertness of SBSi-tailored PDMS, even after 30 day storage in ambient. For the real-world application, we modified commercially available silicone hydrogel contact lenses with developed zwitterionic silane, presenting its antibacterial adhesion property. Moreover, the cytotoxicity of SBSi was accessed with NIH-3T3 fibroblast by the MTT assay, showing negligible cytotoxicity up to a concentration of 5 mM. Consequently, the strategy of surface engineering in this work can effectively retard the "hydrophobic recovery" occurrence and can be applied to other silicone-based medical devices in a facile way. | 25,185,951 | [
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Predicting well-being longitudinally for mothers rearing offspring with intellectual and developmental disabilities. | Well-being outcomes for parents of children with intellectual and developmental disabilities (IDD) may vary from positive to negative at different times and for different measures of well-being. Predicting and explaining this variability has been a major focus of family research for reasons that have both theoretical and applied implications. The current study used data from a 23-year longitudinal investigation of adoptive and birth parents of children with IDD to determine which early child, mother and family characteristics would predict the variance in maternal outcomes 20 years after their original measurement. Using hierarchical regression analyses, we tested the predictive power of variables measured when children were 7 years old on outcomes of maternal well-being when children were 26 years old. Outcome variables included maternal self-report measures of depression and well-being. Final models of well-being accounted for 20% to 34% of variance. For most outcomes, Family Accord and/or the personality variable of Neuroticism (emotional stability/instability) were significant predictors, but some variables demonstrated a different pattern. These findings confirm that (1) characteristics of the child, mother and family during childhood can predict outcomes of maternal well-being 20 years later; and (2) different predictor-outcome relationships can vary substantially, highlighting the importance of using multiple measures to gain a more comprehensive understanding of maternal well-being. These results have implications for refining prognoses for parents and for tailoring service delivery to individual child, parent and family characteristics. | 25,185,956 | [
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Impact of age on early outcome after coronary bypass graft surgery using minimized versus conventional extracorporeal circulation. | Objective of this study was to evaluate the impact of age on comparative early outcomes after coronary artery bypass graft surgery (CABG) with minimized (MECC) and conventional extracorporeal circulation (CECC). A retrospective age-, gender- and operation-matched cohort analysis between January 2005 and December 2010 with a total of 2274 patients undergoing CABG with MECC (n = 1137; 50%) or CECC was performed. Patients were stratified into 4 groups according to age: <59 years, 60-69 years, 70-79 years, and 80 years of age or older. Outcomes were compared within each age group. Patients with preoperative dialysis were excluded from analysis. Primary endpoint was 30-day mortality. Patients treated with CECC had a significantly higher mean logistic EuroSCORE (6.3% vs. 5.0%; p < 0.001), a slightly lower rate of preoperative myocardial infarction (46% vs. 51%; p = 0.01) and a higher rate of impaired renal function (eGFR < 60 mL/min/1.73 m2: 24% vs. 20%; p = 0.01) compared to MECC-patients. Left internal mammary artery was significantly used more often in MECC patients (93% vs. 86%; p < 0.001). Cardiopulmonary bypass and aortic-cross clamping time were significantly lower in the MECC group (p < 0.001). Overall 30-day mortality was significantly higher in patients treated with CECC (4.4% vs. 2.2%; p = 0.002). Within the different age groups mortality rates were not significantly different except for patients aged 60-69 years (4.5% vs. 1.8%; p = 0.03). Postoperative requirement of renal replacement therapy (4% vs. 2.2%; p = 0.01), respiratory insufficiency (9.9% vs. 6.6%; P = 0.004) and incidence of low cardiac output syndrome (3% vs. 1.2%; p = 0.003) were significantly increased in patients with CECC. Multivariate analysis identified age (p = 0.005; 95% CI 1.01 to 1.08; OR 1.05) among other parameters as an independent risk factor, whereas conventional extracorporeal circulation itself did not present as an independent risk factor for 30-day mortality. In this matched study sample early outcome was significantly better in patients with MECC compared to CECC, irrespective of age. Prior myocardial infarction estimated GFR < 60 mL and waiving the use of LIMA were independent risk factors for 30-day mortality, which were more present in the CECC group. | 25,185,963 | [
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Diabetes mellitus type 2 and functional foods of plant origin. | Diabetes is the common, exponentially growing, serious human health problem existing globally. Risk factors like genetic predisposition, lack of balanced diet, inappropriate and lethargic lifestyle, overweight, obesity, stress including emotional and oxidative and lack of probiotics in gut are found to be the causing factors either in isolation or in synergy predisposing Diabetes. High blood sugar is a common symptom in all types of diabetes mellitus and the physiological cause of diabetes is lack of hormone Insulin or resistance in function faced by insulin. Low levels of Insulin causes decreased utilization of glucose by body cells, increased mobilization of fats from fat storage cells and depletion of proteins in the tissues of the body, keeping the body in crisis. The functional foods help achieving optimal physiological metabolism and cellular functions helping the body to come out of these crises. The mechanism of the functional foods is envisaged to act via optimizing vitamins, minerals, essential amino acids, prebiotics and probiotics. This paper reviews role of functional foods of plant origin in the regulation of blood sugar in type 2 diabetes mellitus and also discusses some vital patents in this area. The article aims at creating awareness about key food ingredients in order to prevent most acute effects of diabetes mellitus and to greatly delay the chronic effects as well. | 25,185,980 | [
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Patents in therapeutic recombinant protein production using mammalian cells. | The industrial production of recombinant proteins preferentially requires the generation of stable cell lines expressing proteins in a quick, relatively facile, and a reproducible manner. Different methods are used to insert exogenous DNA into the host cell, and choosing the appropriate producing cell is of paramount importance for the efficient production and quality of the recombinant protein. This review addresses the advances in recombinant protein production in mammalian cell lines, according to key patents from the last 30 years. | 25,185,983 | [
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Pharmacogenomic considerations in the treatment of the pediatric cardiomyopathy called Barth syndrome. | Barth syndrome (BTHS) is a genetic, X-linked, rare but often fatal, pediatric skeletal- and cardiomyopathy occurring due to mutations in the tafazzin gene (TAZ). TAZ encodes a transacylase involved in phospholipid biosynthesis, also called tafazzin, which is responsible for remodeling the inner mitochondrial membrane phospholipid, cardiolipin (CL). Tafazzin mutations lead to compositional alterations in CL molecular species, causing extensive mitochondrial aberrations and ultrastructural muscle damage. There are no specific treatments or cure for BTHS. Current therapy is largely palliative and aimed at treatment of organ-specific complications during disease progression. Polypharmacy frequently occurs during treatment and may lead to severe adverse events. Adverse reactions may originate from exogenous factors such as the inadvertent co-administration of contraindicated drugs. Theoretically, endogenous factors such as polymorphic variations in genes encoding drug metabolizing enzymes may also precipitate fatal toxicity. Investigation of the consequences of pharmacogenomic variations on BTHS therapy is lacking. To our knowledge, this review presents the first examination of the possible sources of pharmacogenomic variations that may affect BTHS therapy. We also explore BTHSspecific patents for possible treatment options. The patents discussed suggest innovative strategies for treatment, including feeding linoleic acid to patients to overcome compositional CL deficiency; or the use of 2S,4R ketoconazole formulations to augment CL levels; or the delivery of mitochondrial stabilizing cargo. Future research directions are also discussed. | 25,185,984 | [
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Pharmacogenomics in psychiatry: implications for practice. | Psychotropic medications are used for numerous psychiatric and neurologic disorders, and are associated with in some cases life-threatening adverse effects, high acquisition costs, stringent monitoring requirements, and potential interactions with other medications. Because of the risks of adverse effects and need for adherence, risk mitigation strategies are being implemented to protect consumers. An understanding of receptor activities, cytochrome P450 2D6 and 2C19 metabolism, overlapping pharmacology, and polymorphic biomarkers for the dopamine 2 D2 receptor gene (DRD2) and dopamine 3 D3 receptor gene (DRD3), serotonin 2A and 2C receptor genes (5HTR2A and 5HTR2C), and human leukocyte antigen (HLA) variants creates opportunities for the integration of pharmacogenomics, and can assist in the application of personalized medicine in this arena. In this review, we discuss the current impression of pharmacogenomic principles pertaining to select psychotropics, with attention given to the atypical antipsychotics, due to their wide use across a broad spectrum of psychiatric disorders (e.g. bipolar disorder, depression, schizophrenia). Patents involving aripiprazole, clozapine, olanzapine, and risperidone will be discussed. | 25,185,985 | [
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Obstacles to precision oncology: confronting current factors affecting the successful introduction of biomarkers to the clinic. | Tailoring treatment strategies to individual patients requires the availability of reliable biomarkers. Despite important investment in biomarker research, few examples of successful biomarker-drug co-development are currently seen in clinical practice. The validity of a biomarker measurement may be affected by different pre-analytical, analytical and post-analytical factors. The lack of control or oversight of any of these factors may ultimately lead to failure in translating a promising research finding into clinical practice. In the present review, we put into perspective some of the obstacles to "precision" oncology, focusing on the technical and biological hurdles that may affect the validity of a biomarker result and, ultimately, the likelihood of a new targeted agent to reach the clinic. Biomarker application in precision oncology must consider the evolution of neoplastic disease, evaluate strengths and limitations of the platform used for the determination, and efficiently address specimen type and handling issues. In-depth analytical validation of a new biomarker test that includes evaluation of target stability should be performed before the test is used in clinical samples. More efficient sampling and use of high-sensitivity methodologies may overcome the influence of tumor heterogeneity on biomarker measurement. Clinical trials with biomarker endpoints may only be successful when multidisciplinary academic study teams are involved and results meet the highest quality standards. | 25,185,990 | [
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Final thermal conditions override the effects of temperature history and dispersal in experimental communities. | Predicting the effect of climate change on biodiversity is a multifactorial problem that is complicated by potentially interactive effects with habitat properties and altered species interactions. In a microcosm experiment with communities of microalgae, we analysed whether the effect of rising temperature on diversity depended on the initial or the final temperature of the habitat, on the rate of change, on dispersal and on landscape heterogeneity. We also tested whether the response of species to temperature measured in monoculture allowed prediction of the composition of communities under rising temperature. We found that the final temperature of the habitat was the primary driver of diversity in our experimental communities. Species richness declined faster at higher temperatures. The negative effect of warming was not alleviated by a slower rate of warming or by dispersal among habitats and did not depend on the initial temperature. The response of evenness, however, did depend on the rate of change and on the initial temperature. Community composition was not predictable from monoculture assays, but higher fitness inequality (as seen by larger variance in growth rate among species in monoculture at higher temperatures) explained the faster loss of biodiversity with rising temperature. | 25,186,000 | [
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Human embryonic stem cells prevent T-cell activation by suppressing dendritic cells function via TGF-beta signaling pathway. | Human embryonic stem cells (hESCs) represent a potential source of transplantable cells for regenerative medicine, but development of teratoma even in syngenic recipients represents a critical obstacle to safe stem cell-based therapies. We hypothesized that hESCs escape the immune surveillance by regulating the environmental immune system. Using cocultures of hESCs with allogenic peripheral blood mononuclear cells, we demonstrated that hESCs prevent proliferation and activation of human CD4+ T lymphocytes, an effect dependent upon monocytes. Altered expression of key signaling molecules responsible for the crosstalk of monocytes with T cells was detected in the presence of hESCs. Analyzing the mechanism of action, we demonstrated that hESCs were able to downregulate intracellular glutathione levels in both monocytes and CD4+ cells by suppressing glutamate cysteine ligase expression and to alter MHCII and CD80 expression in monocytes. These effects were achieved at least partially via TGF-beta signaling, and both monocyte phenotype and GCLC expression were affected by Caspase-3 proteolytic activity. Altogether, our results demonstrate a novel immune-suppressive mechanism used by hESCs. | 25,186,014 | [
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Numerical modelling of the groundwater inflow to an advancing open pit mine: Kolahdarvazeh pit, Central Iran. | The groundwater inflow into a mine during its life and after ceasing operations is one of the most important concerns of the mining industry. This paper presents a hydrogeological assessment of the Irankuh Zn-Pb mine at 20 km south of Esfahan and 1 km northeast of Abnil in west-Central Iran. During mine excavation, the upper impervious bed of a confined aquifer was broken and water at high-pressure flowed into an open pit mine associated with the Kolahdarvazeh deposit. The inflow rates were 6.7 and 1.4 m(3)/s at the maximum and minimum quantities, respectively. Permeability, storage coefficient, thickness and initial head of the fully saturated confined aquifer were 3.5 × 10(-4) m/s, 0.2, 30 m and 60 m, respectively. The hydraulic heads as a function of time were monitored at four observation wells in the vicinity of the pit over 19 weeks and at an observation well near a test well over 21 h. In addition, by measuring the rate of pumping out from the pit sump, at a constant head (usually equal to height of the pit floor), the real inflow rates to the pit were monitored. The main innovations of this work were to make comparison between numerical modelling using a finite element software called SEEP/W and actual data related to inflow and extend the applicability of the numerical model. This model was further used to estimate the hydraulic heads at the observation wells around the pit over 19 weeks during mining operations. Data from a pump-out test and observation wells were used for model calibration and verification. In order to evaluate the model efficiency, the modelling results of inflow quantity and hydraulic heads were compared to those from analytical solutions, as well as the field data. The mean percent error in relation to field data for the inflow quantity was 0.108. It varied between 1.16 and 1.46 for hydraulic head predictions, which are much lower values than the mean percent errors resulted from the analytical solutions (from 1.8 to 5.3 for inflow and from 2.16 to 3.5 for hydraulic head predictions). The analytical solutions underestimated the inflow compared to the numerical model for the time period of 2-19 weeks. The results presented in this paper can be used for developing an effective dewatering program. | 25,186,026 | [
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Evaluation and validation of biochip multi-array technology for the screening of six families of antibiotics in honey according to the European guideline for the validation of screening methods for residues of veterinary medicines. | The main chemicals used against varoa are acaricides, and the antibiotics used for the control of bee bacterial diseases are mainly tetracyclines, streptomycins, sulfonamides and chloramphenicol. No maximum residue limits (MRLs) have been set for any antibiotics in honey. Therefore, in the European Union, minimum recommended concentrations (RC) for the analytical performance of methods to control a certain set of these non-authorised chemicals in honey were published by the European Union Reference Laboratory (EU-RL) in 2007. Concerning the strategy for the control for antibiotic residues in honey, there is still a great need for a cheap and single multi-residue method. Biochip array technology is an innovative assay technology for the multi-analyte screening of biological samples in a rapid and easy-to-use format. A multi-array system, called Evidence Investigator™ (Randox, Crumlin, Co., Antrim, UK), was evaluated in our laboratory. It is a semi-automated biochip system designed for research, clinical applications and veterinary use. A competitive chemiluminescent immunoassay is employed for the detection of antimicrobials. The MicroArray II kit (AM II) dedicated to the screening of six different families of antibiotic residues was validated according to the European guideline for the validation of screening methods for residues of veterinary medicines. The specificity was proven to be very satisfactory, and applicability to different kinds of honey was demonstrated. The detection capabilities (CCβ) of six antibiotic residues were determined and were below the RCs when exist. The AM II kit could detect at least six quinolones, four tetracyclines and three epimers, three aminoglycosides, three macrolides, thiamphenicol, florfenicol and ceftiofur along with one of its stabilised metabolites, the desfuroylceftiofurcysteine disulfide (DCCD). | 25,186,037 | [
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Evaluation of the formation of volatiles and sensory characteristics of persimmon (Diospyros kaki L.f.) fruit wines using different commercial yeast strains of Saccharomyces cerevisiae. | This study evaluated the effects of five strains (IFFI 1346, IFFI 1363, CICC 31482, D254 and CGMCC2.346) of the yeast Saccharomyces cerevisiae on the aromatic profiles of fermented persimmon (Diospyros kaki L.f.) musts. A total of 50 and 60 compounds were identified in persimmon wine by stir bar sorptive extraction coupled with gas chromatography-mass spectrometry. According to odour activity values (OAVs), 26 detected compounds showed an OAV above 1. Principal component analysis explained the distribution of these persimmon wines on the basis of volatile compounds with OAV>1. The volatile compounds with high OAV included ethyl hexanoate, ethyl octanoate, methyl decanoate, linalool and geraniol. Quantitative descriptive analysis was employed. The result showed that persimmon wines fermented with strains IFFI 1363 and D254 were strongly correlated with persimmon, aroma harmony, fruity, fusel and taste balanced, fullness, hedonic scale. Therefore, the two yeast strains could be used as starter culture for persimmon wine production. | 25,186,058 | [
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The effectiveness of skeletal imaging for quality assessment in posterior cruciate ligament reconstruction: reliability and validity of radiographs and computed tomography. | For intra- and postoperative evaluation of precise and anatomic graft tunnel position, radiographs (XR) and computed tomography (CT) scans have been suggested. The purpose of this study was to evaluate the reliability and validity of XR and CT for quality assessment following PCL reconstruction. Postoperative radiographs and CT scans were obtained in 45 consecutive patients following a standard single-bundle PCL reconstruction. Femoral and tibial tunnel apertures were correlated to femoral and tibial measurement grid systems. To assess the reliability and validity of XR and CT scans three independent observers evaluated radiographic and CT images for the position of femoral and tibial tunnel apertures. Almost perfect inter- and intra observer agreement (0.79-0.99) was found for all CT measurements except for the distance of the tunnel position to the previous physis line. Almost perfect and strong inter- and intraobserver agreement (0.70-0.98) was found for all tibial measurements on XR which tended to increase with repeated interpretation and to decrease with low levels of observer qualification. Femoral measurements yielded only poor-to-moderate reliability (0.02-0.5) between raters on XR but strong intraagreement within experienced observers (0.45-0.86). Specificity for XR was calculated with 75.7 % for P2 and P3 and with 71 % for femoral tunnel depth and height. XR and CT represent complementary imaging modalities and both offer considerable accuracy and precision for the determination of femoral and tibial tunnel apertures following PCL reconstruction and can be recommended for intra- and postoperative quality assessment. | 25,186,075 | [
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Postoperative wound dealing and superficial surgical site infection in open radical prostatectomy. | The number of open radical prostatectomy (RP) surgeries has been decreasing owing to the spread of laparoscopic and robotic surgery, which has implications for postoperative wound healing. The purpose of this study was to investigate and document the current status of postoperative wound healing and superficial surgical site infection (SSI) in open RPs. One hundred and seventy-five antegrade RPs with the same or similar kinds of prophylactic antibiotic administration were divided into two groups: (i) 'no intervention' (wound covering group) and (ii) 'washing', using a washing solution from the second postoperative day to the day of skin staple removal (wound washing group). We compared these groups for the occurrence of superficial SSI. The wound covering group had three (3·03%) cases of superficial SSI, with one case caused by methicillin sensitive Staphylococcus aureus (MSSA). The wound washing group had nine (11·8%) cases of superficial SSI, with three cases caused by MSSA, two cases caused by methicillin resistant Staphylococcus aureus (MRSA) and one by Pseudomonas aeruginosa. The wound covering group showed a significantly lower ratio of superficial SSI (P = 0·0472). In conclusion, the postoperative wound status data in this study suggests that no wound intervention after RP resulted in a comparatively lower ratio of superficial SSI than in the wound washing group. | 25,186,077 | [
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Matriptase and MET are prominently expressed at the site of bone metastasis in renal cell carcinoma: immunohistochemical analysis. | High MET expression in renal cell carcinoma (RCC) and MET activation in bone metastases are reportedly important in progression of several cancers. To find new treatment targets in bone metastasis, we immunohistochemically analyzed expression levels of MET and matriptase (specific cellular activator of hepatocyte growth factor). We obtained nephrectomy specimens from 17 RCC patients with metastasis, and bone metastases specimens from 7 RCC patients who underwent metastasectomies, and who were treated at our hospital between 2008 and 2012. We tested the samples with anti-human MET polyclonal antibody and anti-human matriptase polyclonal antibody, and compared postoperative overall survival (OS) rates between positive and negative groups. High MET expression was seen at primary sites in 8/17 (47%) nephrectomy specimens, and 6/7 (86%) bone specimens. Matriptase was expressed in 6/17 (35%) nephrectomy specimens, and all 7 (100%) bone specimens. Interestingly, matriptase was strongly expressed in osteoclasts of 5/7 bone specimens. Postoperative OS rate was significantly higher in the MET(-) group than the MET(+) group. The high MET and matriptase expression seen in RCC cells in bone metastasis accompanied by matriptase expression in osteoclasts indicates their importance in bone metastasis. | 25,186,085 | [
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Prognostic value of liver fibrosis and steatosis biomarkers in type-2 diabetes and dyslipidaemia. | In cardiometabolic disorders, non-alcoholic fatty liver disease is frequent and presumably associated with increased mortality and cardiovascular risk. To evaluate the prognostic value of non-invasive biomarkers of liver fibrosis (FibroTest) and steatosis (SteatoTest) in patients with type-2 diabetes and/or dyslipidaemia. A total of 2312 patients with type-2 diabetes and/or dyslipidaemia were included and prospectively followed up for 5-15 years. The cardiovascular Framingham-risk score was calculated; advanced fibrosis and severe steatosis, were defined by FibroTest >0.48 and SteatoTest >0.69, respectively, as previously established. During a median follow-up of 12 years, 172 patients (7.4%) died. The leading causes of mortality were cancer (31%) and cardiovascular-related death (20%). The presence of advanced fibrosis [HR (95% CI)] [2.98 (95% CI 1.78-4.99); P < 0.0001] or severe steatosis [1.86 (1.34-2.58); P = 0.0002] was associated with an increased risk of mortality. In a multivariate Cox model adjusted for confounders: the presence of advanced fibrosis was associated with overall mortality [1.95 (1.12-3.41); P = 0.02]; advanced fibrosis at baseline [n = 50/677; 1.92 (1.04-3.55); P = 0.04] and progression to advanced fibrosis during follow-up [n = 16/127; 4.8 (1.5-14.9); P = 0.007] were predictors of cardiovascular events in patients with type-2 diabetes. In patients with a Framingham-risk score ≥20%, the presence of advanced fibrosis was predictive of cardiovascular events [2.24 (1.16-4.33); P < 0.05]. Liver biomarkers, such as FibroTest and SteatoTest, have prognostic values in patients with metabolic disorders. FibroTest has prognostic value for predicting overall survival in patients with type-2 diabetes and/or dyslipidaemia. In type-2 diabetes, FibroTest predicted cardiovascular events and improved the Framingham-risk score. | 25,186,086 | [
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Gamma Knife radiosurgery for meningiomas arising from the tentorium: a 22-year experience. | In order to evaluate long term clinical and imaging outcomes, the authors retrospectively reviewed our 22-year experience using stereotactic radiosurgery (SRS) for tentorial meningiomas. Thirty-nine patients with tentorial meningiomas underwent SRS using various Gamma Knife technologies between 1988 and 2010. The most common presenting symptoms were headache, dizziness or disequilibrium, and ataxia. The median tumor volume was 4.6 cm(3) (range 0.5-36.6 cm(3)) and the median radiation dose to the tumor margin was 14 Gy (range 8.9-18 Gy). The median follow-up period was 41 months (range 6-183 months). At the last imaging follow-up, tumor volumes decreased in 22 patients (57 %), remained stable in 13 patients (33 %), and increased in 4 patients (10 %). The progression-free survival after SRS was 97 % at 1 year, and 92 % at 5 years. At the last clinical follow-up, 35 patients (90 %) showed no change in symptoms, 1 patient (2 %) showed improvement of their neurologic symptom, and 3 patients (8 %) demonstrated worsening symptoms. The rate of symptom worsening after SRS was 5 % at 1 year, and 10 % at 5 years. Asymptomatic peritumoral edema after SRS occurred in 2 patients (5 %). Symptomatic adverse radiation effect developed in 2 patients (5 %). SRS for tentorial meningiomas provided long-term effective tumor control and a low risk of radiation related complications. | 25,186,087 | [
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Immunophenotyping does not improve predictivity of the local lymph node assay in mice. | The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry-based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I-A(κ) and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non-irritating sensitizers and non-sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA. | 25,186,098 | [
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Immunohistochemical evidence for the association between attenuated mTOR signaling and diffuse alveolar damage, a fatal lung complication. | Targeted anticancer therapies have been developed to interfere with specific target molecules including those of downstream pathways required for tumor growth and progression. Mammalian target of rapamycin (mTOR) has been considered as one of the target molecules of cancer growth, and its inhibitors have been reported to exert an anticancer effect in various malignant tumors. The pulmonary disorder is one of the major side effects of anticancer drugs including mTOR inhibitor (mTORi), and the diagnosis of lung injury induced by medication is difficult because of non-specific nature of the radiological findings. In this study, we present the detailed autopsy findings of a patient who developed diffuse alveolar damage (DAD) following mTORi treatment for metastatic renal cell carcinoma. We also studied 19 cases of DAD derived from other diseases and 9 cases with non-pathological lung. Of interest, pneumocytes of the patients with DAD, who received other anticancer drugs or contacted bacteria, demonstrated significantly lower mTOR activities than pneumocytes of those with non-pathological lung tissue, as judged by the immunohistochemical analysis. In contrast, both pneumocytes and T cells in DAD tissues of the patient treated with mTORi showed higher mTOR activities than those of patients with DAD of other causes, suggesting that the enhanced mTOR signaling may be involved in the development of DAD after mTORi treatment. This unexpected finding needs to be confirmed in other patients treated with mTORi. In conclusion, the attenuated mTOR signaling in pneumocytes may contribute to the pathogenesis of DAD in patients without mTORi treatment. | 25,186,104 | [
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Uricaemia and left ventricular mass in hypertensive patients. | Both hyperuricaemia and left ventricular (LV) hypertrophy are associated with the metabolic syndrome and increased cardiovascular risk. The relationship between uric acid levels and left ventricular mass in hypertension, however, is unclear. In this study, we have investigated this relationship in hypertensive patients without the metabolic syndrome. In a cross-sectional study, 367 nondiabetic, essential hypertensive patients (age 52 ± 14; 194 males and 173 females) free of clinically relevant cardiovascular complications and without the metabolic syndrome were consecutively recruited at a university hypertension clinic. In these patients, we measured plasma levels of uric acid, lipids, glucose and insulin at fast and after an oral glucose load (OGTT), renal function and performed both conventional and tissue Doppler echocardiography. Hypertensive patients with LV hypertrophy had higher uric acid levels and greater prevalence of hyperuricemia than patients with normal left ventricular mass. Uric acid levels were directly related with fasting and post-OGTT plasma insulin and with the HOMA index and inversely with 24-h creatinine clearance. Uric acid was also significantly and directly related with the left ventricular mass and multivariate regression analysis showed that this relationship was independent from components of the metabolic syndrome and renal function in women, but not in men. Elevated uric acid levels are independently related to the left ventricular mass in hypertensive women without the metabolic syndrome. In these patients with a low cardiovascular risk profile, uric acid might contribute to the development of subclinical cardiac damage. | 25,186,106 | [
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The threat of Asian dust storms on asthma patients: a population-based study in Taiwan. | This study explores the relationship between Asian dust storms (ADSs), asthma hospital admissions and average medical cost discharge. We adopt the hospitalisation data from the Taiwan National Health Insurance research database covering the period from 2000 to 2009. The autoregressive integrated moving average with exogenous variables (ARIMAX) analyses were performed to explore the relationship between ADS and asthma hospital admissions, adjusting for temperature, air pollutants and season dummy. The results show that ADS events do generate a critical influence upon the occurrences of asthma on post-ADS events from days 1 through 3, with an average of 17-20 more hospitalised admissions, and have stronger effects on preschool children, middle-aged people and the elderly. From the perspective of medical expenses, the cost of hospitalised admissions for asthma substantially rises daily, on average, by NT$634,698 to NT$787,407 during ADS event days. This study suggests that government should establish a forecast and alert system and release warnings about dust storms, so that the individuals predisposed to asthma can take precautionary measures to reduce their outdoor exposure. Consequently, personal risk and medical expenditure could be reduced significantly, especially for preschool children, middle-aged people and the elderly with asthma. | 25,186,129 | [
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0.2243795,
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Variation in the recording of common health conditions in routine hospital data: study using linked survey and administrative data in New South Wales, Australia. | To investigate the nature and potential implications of under-reporting of morbidity information in administrative hospital data. Retrospective analysis of linked self-report and administrative hospital data for 32,832 participants in the large-scale cohort study (45 and Up Study), who joined the study from 2006 to 2009 and who were admitted to 313 hospitals in New South Wales, Australia, for at least an overnight stay, up to a year prior to study entry. Agreement between self-report and recording of six morbidities in administrative hospital data, and between-hospital variation and predictors of positive agreement between the two data sources. Agreement between data sources was good for diabetes (κ=0.79); moderate for smoking (κ=0.59); fair for heart disease, stroke and hypertension (κ=0.40, κ=0.30 and κ =0.24, respectively); and poor for obesity (κ=0.09), indicating that a large number of individuals with self-reported morbidities did not have a corresponding diagnosis coded in their hospital records. Significant between-hospital variation was found (ranging from 8% of unexplained variation for diabetes to 22% for heart disease), with higher agreement in public and large hospitals, and hospitals with greater depth of coding. The recording of six common health conditions in administrative hospital data is highly variable, and for some conditions, very poor. To support more valid performance comparisons, it is important to stratify or control for factors that predict the completeness of recording, including hospital depth of coding and hospital type (public/private), and to increase efforts to standardise recording across hospitals. Studies using these conditions for risk adjustment should also be cautious of their use in smaller hospitals. | 25,186,157 | [
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Expression of tomato SlTIP2;2 enhances the tolerance to salt stress in the transgenic Arabidopsis and interacts with target proteins. | Three independent transgenic Arabidopsis lines expressing SlTIP2;2 from Solanum lycopersicum L. cv. Lichun under the control of its endogenous promoter were used to analyze the expression of SlTIP2;2 and the salt stress tolerance under NaCl concentration gradient treatment. The expression patterns of SlTIP2;2 were shown to be tissue-specific and NaCl dose-dependent under salt stress. SlTIP2;2-transformed Arabidopsis plants exhibited enhanced salt stress tolerance, and the physiological parameters suggested that SlTIP2;2 has close links with the ion homeostasis and antioxidant enzymes activities in salt-stressed transgenic Arabidopsis. Moreover, SlTIP2;2 expression significantly affected the Na(+) and K(+) fluxes from the root meristematic zones and resulted in remarkable changes in the morphology of the pith ray cells in the inflorescence stems of transgenic Arabidopsis. Based on the yeast growth assay, β-galactosidase activity testing and bimolecular fluorescence complementation, SlTIP1;1, SlTIP2;1 and an UDP-galactose transporter were confirmed to interact with SlTIP2;2, which may greatly broaden our understanding of the physiological functions of aquaporins. | 25,186,161 | [
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Factors associated with the timing and onset of cannabis use and cannabis use disorder: results from the 2007 Australian National Survey of Mental Health and Well-Being. | To investigate the predictors of both initiation of cannabis use and transition to cannabis use disorder (CUD) in a nationally representative sample using discrete-time survival analyses. Data from a nationally representative sample of 6935 Australian adults. Retrospective data on age of first cannabis use and onset of CUD were used to construct pseudo-longitudinal datasets and survival models used to evaluate factors associated with age of first use and time from first use to onset of CUD. The oldest cohort (born 1942-1951) had lower cannabis use than younger cohorts, with first use also occurring at an older age. Multivariable discrete-time survival models showed other substance use, tobacco and alcohol use at very young ages, and mental disorders were associated with increased risk of cannabis use. There were 7.5% of those <65 years old at interview who had a lifetime CUD; mean time from first use to the onset of CUD was 3.3 years, with 90% of cases within eight years. Younger age of initiation and other substance use were strong predictors of the transition from use to CUD. Women with depression were more likely to develop a CUD; social phobia and panic disorder were also associated with transition from cannabis use to CUD. Patterns of cannabis use differ across birth cohorts. There are multiple factors associated with use and transition to CUD, with other substance use a strong predictor. Mental disorders also predict initiation and progression to CUD. | 25,186,194 | [
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The interaction of N-trifluoroacetylgalactosamine and its derivatives with winged bean (Psophocarpus tetragonolobus) basic agglutinin reveals differential mechanism of their recognition: a fluorine-19 nuclear magnetic resonance study. | Here, we show the binding results of a leguminosae lectin, winged bean basic agglutinin (WBA I) to N-trifluoroacetylgalactosamine (NTFAGalN), methyl-α-N-trifluoroacetylgalactosamine (MeαNTFAGalN) and methyl-β-tifluoroacetylgalactosamine (MeβNTFAGalN) using (19) F NMR spectroscopy. No chemical shift difference between the free and bound states for NTFAGalN and MeβNTFAGalN, and 0.01-ppm chemical shift change for MeαNTFAGalN, demonstrate that the MeαNTFAGalN has a sufficiently long residence time on the protein binding site as compared to MeβNTFAGalN and the free anomers of NTFAGalN. The sugar anomers were found in slow exchange with the binding site of agglutinin. Consequently, we obtained their binding parameters to the protein using line shape analyses. Aforementioned analyses of the activation parameters for the interactions of these saccharides indicate that the binding of α and β anomers of NTFAGalN and MeαNTFAGalN is controlled enthalpically, while that of MeβNTFAGalN is controlled entropically. This asserts the sterically constrained nature of the interaction of the MeβNTFAGalN with WBA I. These studies thus highlight a significant role of the conformation of the monosaccharide ligands for their recognition by WBA I. | 25,186,197 | [
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Mitochondrial tRNAThr 15891C>G mutation was not associated with Leber's hereditary optic neuropathy in Han Chinese patients. | Mutations in mitochondrial DNA (mtDNA) were the most important causes of Leber's hereditary optic neuropathy (LHON). To date, approximately 25 LHON-associated mtDNA mutations have been identified in various ethnic populations. Three primary mutations, the 3460G > A, 11778G > A and 14484T > C, in genes encoding the subunits of respiratory chain complex I, were the most common LHON-associated mtDNA mutations. Moreover, secondary mutations in mt-tRNA genes have been reported increasingly to be associated with LHON, simply due to the high mutation rates of mt-tRNAs. There is a lack of functional analysis and a poor genetic evaluation of a certain mt-tRNA mutation, which failed to meet the classic pathogenicity scoring system. As a result, how to classify a pathogenic mutation in mt-tRNA gene became important for both geneticist and clinician to diagnosis the LHON or the suspicious of LHON. In this study, we reassessed the role of a point mutation in mt-tRNA(Thr) gene which had been reported to be a mutation associated with LHON, the pathogenicity of this mutation has been discussed in this context. | 25,186,221 | [
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Modern network science of neurological disorders. | Modern network science has revealed fundamental aspects of normal brain-network organization, such as small-world and scale-free patterns, hierarchical modularity, hubs and rich clubs. The next challenge is to use this knowledge to gain a better understanding of brain disease. Recent developments in the application of network science to conditions such as Alzheimer's disease, multiple sclerosis, traumatic brain injury and epilepsy have challenged the classical concept of neurological disorders being either 'local' or 'global', and have pointed to the overload and failure of hubs as a possible final common pathway in neurological disorders. | 25,186,238 | [
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Improved bioethanol production in an engineered Kluyveromyces lactis strain shifted from respiratory to fermentative metabolism by deletion of NDI1. | In this paper, we report the metabolic engineering of the respiratory yeast Kluyveromyces lactis by construction and characterization of a null mutant (Δklndi1) in the single gene encoding a mitochondrial alternative internal dehydrogenase. Isolated mitochondria of the Δklndi1 mutant show unaffected rate of oxidation of exogenous NADH, but no oxidation of matrix NADH; this confirms that KlNdi1p is the only internal NADH dehydrogenase in K. lactis mitochondria. Permeabilized cells of the Δklndi1 mutant do not show oxidation of matrix NADH, which suggests that shuttle systems to transfer the NADH from mitochondrial matrix to cytosol, for being oxidized by external dehydrogenases, are not functional. The Δklndi1 mutation decreases the chronological life span in absence of nutrients. The expression of KlNDI1 is increased by glutathione reductase depletion. The Δklndi1 mutation shifts the K. lactis metabolism from respiratory to fermentative: the Δklndi1 strain shows reduced respiration rate and increased ethanol production from glucose, while it does not grow in non-fermentable carbon sources such as lactate. The biotechnological benefit of the Δklndi1 mutant for bioethanol production from waste cheese whey lactose was proved. | 25,186,243 | [
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Current situation and challenge of registry in China. | Increasing emphasis has been placed on registries for an organized system used in developing clinical research to improve health care. China has sufficient data that can be applied broadly, but the heterogeneity and irregularity of registries limit their applicability. This article aims to describe the status of registries in China and the related challenges. Patient registries for observational studies were retrieved from the International Clinical Trials Registry to quantitatively evaluate the number of comparatively high-quality registries in China. A literature search was also performed to provide support and updates. A total of 64 patient registries were retrieved from ClinicalTrials.gov using disease, product, and health service as criteria. The sample sizes ranged from 15 to 30,400, with only 12 registries marked as completed. This article describes and compares the detailed information in many aspects. The efficient use of registries has already made considerable progress in China; however, registries still require standardization, high-quality transition, and coordinated development. | 25,186,248 | [
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Diagnosis of subarachnoid haemorrhage: a survey of Australasian emergency physicians and trainees. | This study aims to establish current practice among Australasian emergency physicians and trainees on several aspects of the investigation of suspected subarachnoid haemorrhage (SAH). An electronic questionnaire (SurveyMonkey™) was distributed to emergency physicians and trainees by email through the ACEM. Survey recipients were asked about demographics, followed by a series of questions relating to the investigation of SAH. There were 878 survey respondents (response rate 24%). Our data showed that 47.3% of respondents agreed or strongly agreed that a CT brain within 6 h of headache onset is sufficient to exclude a diagnosis of SAH. For a CT performed within 12 h of ictus, 14.4% were satisfied that SAH could be excluded. After a negative CT scan, for further investigation of SAH, 88% of respondents preferred lumbar puncture to CT angiography. For detection of xanthochromia in the cerebrospinal fluid, 57.7% of respondents felt that spectrophotometry (vs visual inspection) is necessary to accurately diagnose SAH. A range of information was collected regarding the investigation of suspected SAH. We report significant differences in the diagnostic approach of Australasian emergency physicians and trainees to this condition, in particular the utility of CT within 6 h for exclusion of SAH. | 25,186,282 | [
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Health & Demographic Surveillance System profile: the Muzaffarpur-TMRC Health and Demographic Surveillance System. | The Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS), established in 2007, was developed as an enlargement of the scope of a research collaboration on the project Visceral Leishmaniasis in Bihar, which had been ongoing since 2005. The HDSS is located in a visceral leishmaniasis (VL)-endemic area in the Muzaffarpur district of Bihar state in India. It is the only HDSS conducting research on VL, which is a vector-borne infectious disease transmitted by female phlebotomine sandflies and is fatal if left untreated. Currently the HDSS serves a population of over 105,000 in 66 villages. The HDSS collects data on vital events including pregnancies, births, deaths, migration and marriages, as well as other socio-economic indicators, at regular intervals. Incident VL cases are identified. The HDSS team is experienced in conducting both qualitative and quantitative studies, sample collection and rapid diagnostic tests in the field. In each village, volunteers connect the HDSS team with the community members. The Muzaffarpur-TMRC HDSS provides opportunities for studies on VL and other neglected tropical diseases (NTDs) and their interaction with demographic events such as migration. Queries related to research collaborations and data sharing can be sent to Dr Shyam Sundar at [drshyamsundar@hotmail.com]. | 25,186,307 | [
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The kynurenine pathway of tryptophan degradation is activated during osteoblastogenesis. | The mechanisms involved in the anabolic effect of interferon gamma (IFNγ) on bone have not been carefully examined. Using microarray expression analysis, we found that IFNγ upregulates a set of genes associated with a tryptophan degradation pathway, known as the kynurenine pathway, in osteogenic differentiating human mesenchymal stem cells (hMSC). We, therefore, hypothesized that activation of the kynurenine pathway plays a role in osteoblastogenesis even in the absence of IFNγ. Initially, we observed a strong increase in tryptophan degradation during osteoblastogenesis with and without IFNγ in the media. We next blocked indoleamine 2,3-dioxygenase-1 (IDO1), the most important enzyme in the kynurenine pathway, using a siRNA and pharmacological approach and observed a strong inhibition of osteoblastogenesis with a concomitant decrease in osteogenic factors. We next examined the bone phenotype of Ido1 knockout (Ido1(-/-)) mice. Compared to their wild-type littermates, Ido1(-/-) mice exhibited osteopenia associated with low osteoblast and high osteoclast numbers. Finally, we tested whether the end products of the kynurenine pathway have an osteogenic effect on hMSC. We identified that picolinic acid had a strong and dose-dependent osteogenic effect in vitro. In summary, we demonstrate that the activation of the kynurenine pathway plays an important role during the commitment of hMSC into the osteoblast lineage in vitro, and that this process can be accelerated by exogenous addition of IFNγ. In addition, we found that mice lacking IDO1 activity are osteopenic. These data therefore support a new role for the kynurenine pathway and picolinic acid as essential regulators of osteoblastogenesis and as potential new targets of bone-forming cells in vivo. | 25,186,311 | [
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Schedule Control and Nursing Home Quality: Exploratory Evidence of a Psychosocial Predictor of Resident Care. | To examine whether nursing homes' quality of care was predicted by schedule control (workers' ability to decide work hours), independently of other staffing characteristics. Prospective ecological study of 30 nursing homes in New England. Schedule control was self-reported via survey in 2011-2012 (N = 1,045). Quality measures included the prevalence of decline in activities of daily living, residents' weight loss, and pressure ulcers, indicators systematically linked with staffing characteristics. Outcomes data for 2012 were retrieved from Medicare.gov. Robust Linear Regressions showed that higher schedule control predicted lower prevalence of pressure ulcers (β = -0.51, p < .05). This association was independent of staff mix, staffing ratios, job satisfaction, and turnover intentions. Higher schedule control might enhance the planning and delivery of strategies to prevent or cure pressure ulcers. Further research is needed to identify potential causal mechanisms by which schedule control could improve quality of care. | 25,186,313 | [
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Ocular pulse amplitude and retinal vessel caliber changes after intravitreal ranibizumab. | The purpose of the present study was to examine the effects of intravitreal ranibizumab on ocular pulse amplitude (OPA) and retinal vessel caliber (RVC) in wet age-related macular degeneration (AMD). Thirty-two eyes of 32 wet AMD patients were included in this case series. Three consecutive monthly injections of ranibizumab were performed. The OPA was measured with the Pascal dynamic contour tonometer. RVC measurements were taken with spectral-domain optical coherence tomography. Pre-injection mean OPA value was 2.55 ± 0.76 mmHg and post-injections mean OPA value was 2.79 ± 0.88 mmHg at the last visit (p = 0.10). Pre-injection mean arteriole and venule RVC were 96.7 ± 9.4 and 125.9 ± 8.4 µm; while post-injections arteriole and venule RVC were 96.0 ± 8.7 and 125.6 ± 8.9 µm, respectively (p > 0.05). OPA and RVC are unchanged after triple intravitreal ranibizumab injections, indicating that this treatment does not significantly alter gross retina-choroidal vasculature and hemodynamics. | 25,186,317 | [
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Image-guided transorbital procedures with endoscopic video augmentation. | Surgical interventions to the orbital space behind the eyeball are limited to highly invasive procedures due to the confined nature of the region along with the presence of several intricate soft tissue structures. A minimally invasive approach to orbital surgery would enable several therapeutic options, particularly new treatment protocols for optic neuropathies such as glaucoma. The authors have developed an image-guided system for the purpose of navigating a thin flexible endoscope to a specified target region behind the eyeball. Navigation within the orbit is particularly challenging despite its small volume, as the presence of fat tissue occludes the endoscopic visual field while the surgeon must constantly be aware of optic nerve position. This research investigates the impact of endoscopic video augmentation to targeted image-guided navigation in a series of anthropomorphic phantom experiments. A group of 16 surgeons performed a target identification task within the orbits of four skull phantoms. The task consisted of identifying the correct target, indicated by the augmented video and the preoperative imaging frames, out of four possibilities. For each skull, one orbital intervention was performed with video augmentation, while the other was done with the standard image guidance technique, in random order. The authors measured a target identification accuracy of 95.3% and 85.9% for the augmented and standard cases, respectively, with statistically significant improvement in procedure time (Z=-2.044, p=0.041) and intraoperator mean procedure time (Z=2.456, p=0.014) when augmentation was used. Improvements in both target identification accuracy and interventional procedure time suggest that endoscopic video augmentation provides valuable additional orientation and trajectory information in an image-guided procedure. Utilization of video augmentation in transorbital interventions could further minimize complication risk and enhance surgeon comfort and confidence in the procedure. | 25,186,388 | [
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Characteristic performance evaluation of a photon counting Si strip detector for low dose spectral breast CT imaging. | The possible clinical applications which can be performed using a newly developed detector depend on the detector's characteristic performance in a number of metrics including the dynamic range, resolution, uniformity, and stability. The authors have evaluated a prototype energy resolved fast photon counting x-ray detector based on a silicon (Si) strip sensor used in an edge-on geometry with an application specific integrated circuit to record the number of x-rays and their energies at high flux and fast frame rates. The investigated detector was integrated with a dedicated breast spectral computed tomography (CT) system to make use of the detector's high spatial and energy resolution and low noise performance under conditions suitable for clinical breast imaging. The aim of this article is to investigate the intrinsic characteristics of the detector, in terms of maximum output count rate, spatial and energy resolution, and noise performance of the imaging system. The maximum output count rate was obtained with a 50 W x-ray tube with a maximum continuous output of 50 kVp at 1.0 mA. A109Cd source, with a characteristic x-ray peak at 22 keV from Ag, was used to measure the energy resolution of the detector. The axial plane modulation transfer function (MTF) was measured using a 67 μm diameter tungsten wire. The two-dimensional (2D) noise power spectrum (NPS) was measured using flat field images and noise equivalent quanta (NEQ) were calculated using the MTF and NPS results. The image quality parameters were studied as a function of various radiation doses and reconstruction filters. The one-dimensional (1D) NPS was used to investigate the effect of electronic noise elimination by varying the minimum energy threshold. A maximum output count rate of 100 million counts per second per square millimeter (cps/mm2) has been obtained (1 million cps per 100×100 μm pixel). The electrical noise floor was less than 4 keV. The energy resolution measured with the 22 keV photons from a 109Cd source was less than 9%. A reduction of image noise was shown in all the spatial frequencies in 1D NPS as a result of the elimination of the electronic noise. The spatial resolution was measured just above 5 line pairs per mm (lp/mm) where 10% of MTF corresponded to 5.4 mm(-1). The 2D NPS and NEQ shows a low noise floor and a linear dependence on dose. The reconstruction filter choice affected both of the MTF and NPS results, but had a weak effect on the NEQ. The prototype energy resolved photon counting Si strip detector can offer superior imaging performance for dedicated breast CT as compared to a conventional energy-integrating detector due to its high output count rate, high spatial and energy resolution, and low noise characteristics, which are essential characteristics for spectral breast CT imaging. | 25,186,390 | [
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Reduction of ring artifacts in CBCT: detection and correction of pixel gain variations in flat panel detectors. | In using flat panel detectors (FPD) for cone beam computed tomography (CBCT), pixel gain variations may lead to structured nonuniformities in projections and ring artifacts in CBCT images. Such gain variations can be caused by change in detector entrance exposure levels or beam hardening, and they are not accounted by conventional flat field correction methods. In this work, the authors presented a method to identify isolated pixel clusters that exhibit gain variations and proposed a pixel gain correction (PGC) method to suppress both beam hardening and exposure level dependent gain variations. To modulate both beam spectrum and entrance exposure, flood field FPD projections were acquired using beam filters with varying thicknesses. "Ideal" pixel values were estimated by performing polynomial fits in both raw and flat field corrected projections. Residuals were calculated by taking the difference between measured and ideal pixel values to identify clustered image and FPD artifacts in flat field corrected and raw images, respectively. To correct clustered image artifacts, the ratio of ideal to measured pixel values in filtered images were utilized as pixel-specific gain correction factors, referred as PGC method, and they were tabulated as a function of pixel value in a look-up table. 0.035% of detector pixels lead to clustered image artifacts in flat field corrected projections, where 80% of these pixels were traced back and linked to artifacts in the FPD. The performance of PGC method was tested in variety of imaging conditions and phantoms. The PGC method reduced clustered image artifacts and fixed pattern noise in projections, and ring artifacts in CBCT images. Clustered projection image artifacts that lead to ring artifacts in CBCT can be better identified with our artifact detection approach. When compared to the conventional flat field correction method, the proposed PGC method enables characterization of nonlinear pixel gain variations as a function of change in x-ray spectrum and intensity. Hence, it can better suppress image artifacts due to beam hardening as well as artifacts that arise from detector entrance exposure variation. | 25,186,400 | [
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Dose response of selected solid state detectors in applied homogeneous transverse and longitudinal magnetic fields. | MR-Linac devices under development worldwide will require standard calibration, commissioning, and quality assurance. Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is therefore evaluated in varying transverse and longitudinal magnetic fields for this purpose. The Monte Carlo code PENELOPE was used to model irradiation of a PTW 60003 diamond detector and IBA PFD diode detector in the presence of a magnetic field. The field itself was varied in strength, and oriented both transversely and longitudinally with respect to the incident photon beam. The long axis of the detectors was oriented either parallel or perpendicular to the photon beam. The dose to the active volume of each detector in air was scored, and its ratio to dose with zero magnetic field strength was determined as the "dose response" in magnetic field. Measurements at low fields for both detectors in transverse magnetic fields were taken to evaluate the accuracy of the simulations. Additional simulations were performed in a water phantom to obtain few representative points for beam profile and percent depth dose measurements. Simulations show significant dose response as a function of magnetic field in transverse field geometries. This response can be near 20% at 1.5 T, and it is highly dependent on the detectors' relative orientation to the magnetic field, the energy of the photon beam, and detector composition. Measurements at low transverse magnetic fields verify the simulations for both detectors in their relative orientations to radiation beam. Longitudinal magnetic fields, in contrast, show little dose response, rising slowly with magnetic field, and reaching 0.5%-1% at 1.5 T regardless of detector orientation. Water tank and in air simulation results were the same within simulation uncertainty where lateral electronic equilibrium is present and expectedly differed at the beam edge in transverse field orientations only. Due to the difference in design, the two detectors behaved differently. When transverse magnetic fields are present, great care must be taken when using diamond or diode detectors. Dose response varies with relative detector orientation, magnetic field strength, and between detectors. This response can be considerable (∼20% for both detectors). Both detectors in longitudinal fields exhibit little to no dose response as a function of magnetic field. Water tank simulations seem to suggest that the diode detector is better suited to general beam commissioning, and each detector must be investigated separately. | 25,186,403 | [
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A mapping of people's positions regarding the breaking of bad news to patients. | The objective of this study was to map people's positions regarding the breaking of bad news to patients. One hundred forty adults who had in the past received bad medical news or whose elderly relatives had in the past received bad news, 25 nurses, and 28 nurse's aides indicated the acceptability of physicians' conduct in 72 vignettes of giving bad news to elderly patients. Vignettes were all combinations of five factors: (a) the severity of the disease (severe but not lethal, extremely severe and possibly lethal, or incurable), (b) the patient's wishes (insists on knowing the full truth vs. does not insist), (c) the level of social support during hospitalization, (d) the patient's psychological robustness, and (e) the physician's decision about communicating bad news (tell the patient that the illness is not severe and minimize the severity of the illness when talking to the patient's relatives, tell the full truth to her relatives, or tell the full truth to both the elderly patient and her relatives). Four qualitatively different positions were found. Twenty-eight percent of participants preferred the full truth to be told; 36% preferred the truth to be told but understood that the physician would inform the family first; 13% did not think that telling the full truth is best for patients; and 23% understood that the full truth would be told in some cases and not in others, depending on the physician's perception of the situation. The present mapping could be used to detect the position held by each patient and act accordingly. This would be made easier if breaking bad news was conceived as a communication process involving a range of health care professionals, rather than as a single occurrence in time. | 25,186,427 | [
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11C-Choline PET/pathology image coregistration in primary localized prostate cancer. | The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of (11)C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). In 28 PC patients, (11)C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71% of patients, and complete overlap in 4%. PET/pathology image coregistration can be used for evaluation of different imaging modalities. (11)C-Choline PET failed to distinguish tumour from nontumour tissue. | 25,186,430 | [
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Influence of valve size, orientation and downstream geometry of an aortic BMHV on leaflet motion and clinically used valve performance parameters. | The aim of this study was to reconcile some of our own previous work and the work of others to generate a physiologically realistic numerical simulation environment that allows to virtually assess the performance of BMHVs. The model incorporates: (i) a left ventricular deformable model to generate a physiological inflow to the aortic valve; (ii) a patient-specific aortic geometry (root, arch and descending aorta); (iii) physiological pressure and flow boundary conditions. We particularly studied the influence of downstream geometry, valve size and orientation on leaflet kinematics and functional indices used in clinical routine. Compared to the straight tube geometry, the patient-specific aorta leads to a significant asynchronous movement of the valve, especially during the closing of the valve. The anterior leaflet starts to close first, impacts the casing at the closed position and remains in this position. At the same time, the posterior leaflet impacts the pivoting mechanisms at the fully open position. At the end of systole, this leaflet subsequently accelerates to the closed position, impacting the casing with an angular velocity of approximately -477 rad/s. The valve size greatly influences the transvalvular pressure gradient (TPG), but does not change the overall leaflet kinematics. This is in contrast to changes in valve orientation, where changing valve orientation induces large differences in leaflet kinematics, but the TPG remains approximately the same. | 25,186,435 | [
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Model-based approach to early predict prolonged high grade neutropenia in carboplatin-treated patients and guide G-CSF prophylactic treatment. | Neutropenia is a major dose-limiting side effect of chemotherapy and is closely related to febrile neutropenia which mainly occurs during the first cycle. Our objectives were to establish model-based decision rules from early absolute neutrophil counts (ANC) to anticipate prolonged high grade neutropenia at cycle 1 and to prevent it through delayed granulocyte colony stimulating factor (G-CSF) administration in carboplatin-treated patients. The decision rules were built from Monte Carlo simulations performed with a previously published semi-mechanistic model describing ANC time-course in carboplatin-treated patients with or without concomitant G-CSF therapy. ANC measured at day 0 (D0, baseline), D4 and D5 were good predictors of prolonged high grade neutropenia at cycle 1. Pegfilgrastim administration on D5 was as effective as the conventional pegfilgrastim administration on D1 but none avoided prolonged high grade neutropenia in all patients. Additional decision rules were thus derived, using the same ANC combination, to identify patients for whom G-CSF was beneficial. All decision rules showed good performances (sensitivity/specificity). We propose an innovative approach to guide oncologist in their clinical practice. The next step is to perform prospective studies to implement, validate and possibly refine the proposed decision rules. | 25,186,439 | [
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Diagnostic angiography skill acquisition with a secondary curve catheter: phase 2 of a curriculum-based endovascular simulation program. | We have previously reported the efficacy of a simulator-based training paradigm for residents in neurosurgery with little or no prior experience in diagnostic cerebral angiography with straightfoward arch anatomy. This study investigates the utility of a simulation-based training curriculum for the acquisition of skills employing a secondary curve catheter to navigate more complex arch anatomy. Residents at the Medical University of South Carolina (MUSC) with moderate exposure to diagnostic angiography enrolled into a standardized Institutional Review Board-approved training protocol using SimSuite Compass and Simbionix simulators. The task involved (in order) forming the Simmons catheter in the left subclavian artery and then selecting the brachiocephalic, left common carotid and left vertebral arteries. All participants improved their total time to complete the task over the course from the first to last trial. Each milestone within the overall task also demonstrated an improvement across trials for each participant. Following the hands-on experience, participants' rating of their knowledge of arch anatomy and vessel selection technique improved to that between competence and high competence (values of 3.3±0.49 (p<0.005) and 3.1±0.38 (p<0.01), respectively). Comfort with use of the Simmons catheter improved to a value of 2.9±0.38 (p<0.001), between an experienced learner and competence. Participants rated the usefulness of the training environment as very high (4.1±0.90 out of maximum 5). Residents became more proficient at vessel selection in a type II and bovine arch over a relatively compressed time period, with both objective and subjective data demonstrating acquisition of skill sets and increased confidence. | 25,186,445 | [
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Genetic covariance between components of male reproductive success: within-pair vs. extra-pair paternity in song sparrows. | The evolutionary trajectories of reproductive systems, including both male and female multiple mating and hence polygyny and polyandry, are expected to depend on the additive genetic variances and covariances in and among components of male reproductive success achieved through different reproductive tactics. However, genetic covariances among key components of male reproductive success have not been estimated in wild populations. We used comprehensive paternity data from socially monogamous but genetically polygynandrous song sparrows (Melospiza melodia) to estimate additive genetic variance and covariance in the total number of offspring a male sired per year outside his social pairings (i.e. his total extra-pair reproductive success achieved through multiple mating) and his liability to sire offspring produced by his socially paired female (i.e. his success in defending within-pair paternity). Both components of male fitness showed nonzero additive genetic variance, and the estimated genetic covariance was positive, implying that males with high additive genetic value for extra-pair reproduction also have high additive genetic propensity to sire their socially paired female's offspring. There was consequently no evidence of a genetic or phenotypic trade-off between male within-pair paternity success and extra-pair reproductive success. Such positive genetic covariance might be expected to facilitate ongoing evolution of polygyny and could also shape the ongoing evolution of polyandry through indirect selection. | 25,186,454 | [
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Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice. | The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice. | 25,186,490 | [
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Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug-induced liver injury in rats. | Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug-induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver-operating characteristic (ROC) curve, using a free-access database where 142 hepatotoxic or non-hepatotoxic compounds were administrated to male rats (n=5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in-house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. | 25,186,495 | [
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Influence of substrate steps on the catalytic properties of Pt layers: the ethanol electrooxidation reaction. | The ethanol oxidation reaction (EOR) is investigated on Pt/Au(hkl) electrodes. The Au(hkl) single crystals used belong to the [n(111)x(110)] family of planes. Pt is deposited following the galvanic exchange of a previously deposited Cu monolayer using a Pt(2+) solution. Deposition is not epitaxial and the defects on the underlying Au(hkl) substrates are partially transferred to the Pt films. Moreover, an additional (100)-step-like defect is formed, probably as a result of the strain resulting from the Pt and Au lattice mismatch. Regarding the EOR, both vicinal Pt/Au(hkl) surfaces exhibit a behavior that differs from that expected for stepped Pt; for instance, the smaller the step density on the underlying Au substrate, the greater the ability to break the CC bond in the ethanol molecule, as determined by in situ Fourier transform infrared spectroscopy measurements. Also, we found that the acetic acid production is favored as the terrace width decreases, thus reflecting the inefficiency of the surface array to cleave the ethanol molecule. | 25,186,523 | [
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Are personality traits associated with white-coat and masked hypertension? | Anxiety and other psychological dispositions are thought to be associated with blood pressure. This study tests whether personality traits have long-term associations with masked and white-coat effects. A community-based sample of 2838 adults from Sardinia (Italy) completed the Revised NEO Personality Inventory, and 7 years later, blood pressure was assessed in the clinic and with ambulatory monitoring. Logistic regressions were used to test whether anxiety, neuroticism, extraversion, openness, agreeableness, and conscientiousness predicted the white-coat and masked hypertension phenomena. Age, sex, and antihypertensive medication use were tested as moderators. Significant interactions were found between personality traits and antihypertensive medications in predicting masked and white-coat effects. Only among those taking antihypertensive medication, higher anxiety was associated with a higher risk of pseudo-resistant hypertension due to white-coat effect (odds ratio 1.39, 95% confidence interval 1.01-1.91) and higher conscientiousness was associated with a lower risk of masked uncontrolled hypertension (odds ratio 0.70, 95% confidence interval 0.49-0.99). There were no significant interactions with age or sex. Among those on antihypertensive medications, anxious individuals were more likely to have pseudo-resistant hypertension due to white-coat effect and less conscientious individuals were at increased risk of masked uncontrolled hypertension. Particularly among anxious and less conscientious individuals, ambulatory monitoring may improve the tailoring of pharmacological treatments. | 25,186,529 | [
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Use of biomarker S100B for traumatic brain damage in the emergency department may change observation strategy. | The revised Scandinavian Neurotrauma Committee (SNC) guidelines on management of patients with head trauma include an option for measurement of S100B in peripheral blood with 100% sensitivity for neurosurgical intervention. A medical technology assessment was conducted to evaluate any impact of using S100B on the use of computed tomographies (CT) of the brain and admission for observation. Patients referred for assessment of head injury over a period of 1.5 months had their blood sampled for measurement of S100B in serum. Results were not available to the treating physician and treatment was conducted according to existing practice. Patient records were reviewed retrospectively and post hoc divided into two groups depending on whether the SNC criteria for taking the blood sample were met. The use of CT and admission was analysed. A total of 39 patients had their blood sampled for analysis. In all, 12 patients were excluded in pursuance of SNC guidelines, which left 27 patients for analysis. A total of 15 patients had abnormally high S100B levels. Using the SNC criteria, only eight of these qualified a priori for blood sampling. Furthermore, seven of the 11 patients who were admitted had normal S100B levels. The number of patients with an above-threshold concentration of S100B was almost equally distributed between those fulfilling the SNC criteria for S100B assessment and those who could have been discharged without further evaluation. Using S100B as a screening tool may lead to an increase in the use of CTs of the brain. In relation to admission, measurement of S100B may contribute to the adoption of an appropriate observation strategy. not relevant. not relevant. | 25,186,536 | [
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Almost half of women with malignant mesothelioma were exposed to asbestos at home through their husbands or sons. | Women often develop malignant mesothelioma (MM) without occupational asbestos exposure. Northern Jutland has a high prevalence of MM due to previously high occupational exposures to asbestos. The aim of this study was to elucidate a possible domestic exposure to asbestos through first-degree relatives in women who develop MM. This was a retrospective study in women with MM of the pleura. A total of 30 women were diagnosed with and treated for MM in Northern Jutland from 1996 to 2012. In all, 24 women were included. Demographic data, subtype of MM, time from first hospital contact to diagnosis, survival and information on occupational and domestic exposure to asbestos were obtained from hospital records. A total of 12.5% of the study population were primarily exposed to asbestos. 46% had domestic exposure to asbestos through their husbands or sons. The median age of the study population was 66.5 years. In all, 75% suffered from the epitheloid subtype, 12.5% from the biphasic and 8.4% from the sarcomatoid subtype. Time from first hospital contact to diagnosis was one month and the median survival time was 12 months. The 1- and 5- year-survival were 58% and 0%, respectively. Nearly 50% of the women affected by MM have been domestically exposed to asbestos through first-degree relatives. not relevant. not relevant. | 25,186,542 | [
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Seckel syndrome with severe sinus bradycardia. | Seckel syndrome is an uncommon form of microcephalic dwarfism. The authors report a young boy with Seckel syndrome who presented with severe sinus bradycardia with symptoms of syncope and presyncope. Implantation of a permanent pacemaker was necessary in view of the severe symptoms. Although uncommon, cardiac abnormalities have been rarely reported in Seckel syndrome. This is the one of the few reports of rhythm abnormalities in this condition. | 25,186,569 | [
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Therapeutic effects of the long-term use of PAN membrane dialyzer in hemodialysis patients: efficacy in old dialysis patients with mild PAD. | AN69 dialyzer, a plate type dialyzer with a polyacrylonitrile membrane (PAN membrane) is reported to reduce symptoms in hemodialysis (HD) patients with complications such as poor nutritional status and peripheral arterial disease (PAD). Yet very few studies have investigated the long-term use of the PAN membrane or compared the solute-removal properties of the PAN membrane with those of the Type IV polysulfone membrane (PS membrane), the dialysis membrane most widely used. In the present study we compared the contaminant-removal properties of the AN69 membrane dialyzer with those of a Type IV PS membrane dialyzer and investigated the clinical effects of the long-term use of the former for elderly hemodialysis patients with mild PAD. Cross-over trials with 2 week intervals for solute were conducted in 6 patients to compare the performance of the membranes in removing small molecular weight substances, β2 microglobulin (β2MG), amino acid (AA), and serum albumin (Alb). Next, the AN69 membrane was used for dialysis over a period of 72 weeks in 8 patients. The time course changes of Alb, the geriatric nutritional risk index (GNRI), the % creatinine generation rate (%CGR), the normalized protein catabolic rate (nPCR) and the dry weight (DW) were observed to evaluate the nutritional status. The time course changes of β2MG, C-reactive proteins (CRP), LDL cholesterol (LDL), fibrinogens (Fib), nitrogen oxide (NOx), hemoglobin (Hb), ferritins, transferrin saturation (TSAT), dose of erythropoiesis-stimulating agents (ESA), and dose of iron were observed to evaluate the therapeutic effects of long-term use. Skin perfusion pressure (SPP) was measured at two points: once at the switchover to the AN69 membrane and once 72 weeks later. In cross-over trials, the AN69 membrane showed basically the same dialysis efficiency as the PS membrane in removing small molecular weight substances, but it removed significantly lower amounts of β2MG. The AN69 membrane also showed significantly lower rates of AA removal rate and Alb leakage. The nutritional status was stably maintained during long-term use after the switchover to the AN69 membrane, and no significant increase of β2MG was observed. Fib and NOx were both reduced, the latter to a significant degree. The Hb values showed a good time course, with relatively high TSAT levels and low ferritin levels overall. SPP remained generally stable for 72 weeks. The cross-over trial show the AN69 membrane eliminates less AA and Alb compared with the PS membrane. Judging from the therapeutic effects of the long-term use of the AN69 membrane, the membrane is effective for dialysis and has good biocompatibility in the treatment of elderly HD patients with mild PAD. | 25,186,576 | [
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Flexor pollicis longus rupture in a trigger thumb after intrasheath triamcinolone injections: a case report with literature review. | We report an unusual case of a rupture of the flexor pollicis longus tendon after two intrasheath triamcinolone injections for left trigger thumb in a 56-year-old woman. Tendon grafting from proximal to the wrist to the fingertip was carried out using the palmaris longus tendon. The clinical result was evaluated as good according to Strickland's criteria. Recently, intrasheath triamcinolone injection has been thought of as a mainstay of the treatment for trigger digits. However, flexor tendon ruptures have been reported as a serious, rare complication following the injections suspected to be the result of intratendinous injection. To avoid this complication, it is considered important to perform correct injection into the tendon sheath. Moreover, it is recommended that the number of injections should be once or twice, that a dose of triamcinolone should be less than 10 mg, and that, for preventing the flexor tendon rupture, intervals between injections should be more than three months. Given the potential for tendon rupture, surgeons should certainly recognize and alert patients to the risk of tendon ruptures even after only a few steroid injections. | 25,186,581 | [
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Peptides and peptidomimetics as immunomodulators. | Peptides and peptidomimetics can function as immunomodulating agents by either blocking the immune response or stimulating the immune response to generate tolerance. Knowledge of B- or T-cell epitopes along with conformational constraints is important in the design of peptide-based immunomodulating agents. Work on the conformational aspects of peptides, synthesis and modified amino acid side chains have contributed to the development of a new generation of therapeutic agents for autoimmune diseases and cancer. The design of peptides/peptidomimetics for immunomodulation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus and HIV infection is reviewed. In cancer therapy, peptide epitopes are used in such a way that the body is trained to recognize and fight the cancer cells locally as well as systemically. | 25,186,605 | [
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Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases. | To review the pharmacology, efficacy, and safety of vedolizumab in the treatment of patients with ulcerative colitis (UC) and Crohn's disease (CD). A literature search through clinicialtrials.gov, EMBASE and MEDLINE was conducted (January 1966-June 2014) using the terms vedolizumab and MLN0002. References from retrieved articles were reviewed for any additional material. Additionally, the prescribing information was retrieved. Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of vedolizumab were identified. Vedolizumab, an α4β7 integrin inhibitor, was recently approved for adult patients with moderate to severe active UC or CD who are refractory or intolerant to standard therapies or who are dependent on corticosteroids. Trial data have demonstrated that vedolizumab 300 mg at weeks 0, 2, and 6 followed by every 8 weeks is effective at inducing and maintaining clinical response and remission, improving mucosal appearance, and achieving corticosteroid-free remission in patients with UC. This regimen is also effective at achieving clinical response, remission, and corticosteroid-free remission in patients with CD. Patients treated with vedolizumab, unadjusted for exposure, reported experiencing nasopharyngitis, headache, nausea, arthralgias, pyrexia, upper-respiratory-tract infections, fatigue, and cough. Vedolizumab is an effective agent at inducing and maintaining remission in patients with UC or CD. Vedolizumab is generally well tolerated and has not been associated with progressive multifocal leukoencephalopathy. | 25,186,623 | [
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Is there a right to access innovative surgery? | Demands for access to experimental therapies are frequently framed in the language of rights. This article examines the justifiability of such demands in the specific context of surgical innovations, these being promising but non-validated and potentially risky departures from standard surgical practices. I argue that there is a right to access innovative surgery, drawing analogies with other generally accepted rights in medicine, such as the right not to be forcibly treated, to buy contraceptives, and to choose to have an abortion, including a post-viability abortion where the mother's life or health is threatened by the pregnancy. I argue that we accept these rights because we believe that people are entitled to try to preserve their lives and health and to make choices of an important and intensely personal kind, and I suggest that a person's choice of medical treatment should be seen in the same light. However, since few rights are absolute, I also consider the circumstances in which it may be justifiable to limit the right to access innovative surgery. In discussing this question, I apply the human rights standard of proportionality, comparing the importance of the reasons for limiting the right with the severity of the invasion on liberty. | 25,186,629 | [
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Stable isotopic analysis of porcine, bovine, and ovine heparins. | The assessment of provenance of heparin is becoming a major concern for the pharmaceutical industry and its regulatory bodies. Batch-specific [carbon (δ(13) C), nitrogen (δ(15) N), oxygen (δ(18) O), sulfur (δ(34) S), and hydrogen (δD)] stable isotopic compositions of five different animal-derived heparins were performed. Measurements readily allowed their differentiation into groups and/or subgroups based on their isotopic provenance. Principle component analysis showed that a bivariate plot of δ(13) C and δ(18) O is the best single, bivariate plot that results in the maximum discrimination ability when only two stable isotopes are used to describe the variation in the data set. Stable isotopic analyses revealed that (1) stable isotope measurements on these highly sulfated polysaccharide (molecular weight ∼15 kDa) natural products ("biologics") were feasible; (2) in bivariate plots, the δ(13) C versus δ(18) O plot reveals a well-defined relationship for source differentiation of hogs raised in the United States from hogs raised in Europe and China; (3) the δD versus δ(18) O plot revealed the most well-defined relationship for source differentiation based on the hydrologic environmental isotopes of water (D/H and (18) O/(16) O); and (4) the δ(15) N versus δ(18) O and δ(34) S versus δ(18) O relationships are both very similar, possibly reflecting the food sources used by the different heparin producers. | 25,186,630 | [
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Inoculation of drought-stressed strawberry with a mixed inoculum of two arbuscular mycorrhizal fungi: effects on population dynamics of fungal species in roots and consequential plant tolerance to water deficiency. | The effect of inoculation with two arbuscular mycorrhizal fungi (AMF) on growth and drought tolerance of cultivated strawberry (Fragaria × ananassa) was studied. Three treatments (a single treatment either of Funneliformis mosseae BEG25, Funneliformis geosporus BEG11 or a 50:50 mixed inoculation treatment of both species) were compared to uninoculated plants. Species-specific primers for qPCR quantification of F. geosporus and F. mosseae DNA were developed to quantify the relative abundance of each fungus in roots of strawberry under different conditions of water stress. Co-occupation of the same root by both species was shown to commonly occur, but their relative abundance varied with water stress (reduced irrigation of up to 40%). Greater root colonisation was observed microscopically under water stress, but this increased colonisation was often accompanied with decreased amounts of fungal DNA in the root. F. mosseae tended to become more abundant under water stress relative to F. geosporus. There was significant correlation in the fungal colonisation measurements from the microscopic and qPCR methods under some conditions, but the nature of this relationship varied greatly with AMF inoculum and abiotic conditions. Single-species inoculation treatments gave similar benefits to the host to the mixed inoculation treatment regardless of irrigation regime; here, amount of colonisation was of greater importance than functional diversity. The addition of AMF inocula to plants subjected to reduced irrigation restored plant growth to the same or higher values as the non-mycorrhizal, fully-watered plants. The water use efficiency of plants was greater under the regulated deficit irrigation (RDI) regime and in AMF-inoculated plants, but there were no significant differences between plants inoculated with the single or combined inoculum. This study demonstrated that the increase in plant growth was directly influenced by an increase in root colonisation by AMF when individual plants were examined. | 25,186,649 | [
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A neuron model of stochastic resonance using rectangular pulse trains. | Stochastic resonance (SR) is the enhanced representation of a weak input signal by the addition of an optimal level of broadband noise to a nonlinear (threshold) system. Since its discovery in the 1980s the domain of input signals shown to be applicable to SR has greatly expanded, from strictly periodic inputs to now nearly any aperiodic forcing function. The perturbations (noise) used to generate SR have also expanded, from white noise to now colored noise or vibrational forcing. This study demonstrates that a new class of perturbations can achieve SR, namely, series of stochastically generated biphasic pulse trains. Using these pulse trains as 'noise' we show that a Hodgkin Huxley model neuron exhibits SR behavior when detecting weak input signals. This result is of particular interest to neuroscience because nearly all artificial neural stimulation is implemented with square current or voltage pulses rather than broadband noise, and this new method may facilitate the translation of the performance gains achievable through SR to neural prosthetics. | 25,186,655 | [
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A public health and budget impact analysis of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK. | Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits. | 25,186,657 | [
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Voltage-driven photoluminescence modulation of liquid-crystalline hybridized ZnO nanoparticles. | Liquid-crystalline hybrid nanomaterials have been obtained by grafting mesogenic units around luminescent ZnO nanocrystals of 5 nm in diameter. Modifying the mesogenic density around the inorganic core allows the modulation of the liquid-crystalline behavior and its miscibility in commercial liquid crystal (LC). The strong blue photoluminescence observed for the hybrids can be modulated by applying a voltage on a LC cell containing commercial LC and 10 wt % of hybrid. | 25,186,659 | [
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Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. | The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml(-1). The median IC50 of neutralized viruses was 0.033 μg ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design. | 25,186,731 | [
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An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. | The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain. | 25,186,741 | [
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Form-cue invariant second-order neuronal responses to contrast modulation in primate area V2. | A fundamental task of the visual system is to extract figure-ground boundaries between images of objects, which in natural scenes are often defined not only by luminance differences but also by "second-order" contrast or texture differences. Responses to contrast modulation (CM) and other second-order stimuli have been extensively studied in human psychophysics, but the neuronal substrates of second-order responses in nonhuman primates remain poorly understood. In this study, we have recorded single neurons in area V2 of macaque monkeys, using both CM patterns as well as conventional luminance modulation (LM) gratings. CM stimuli were constructed from stationary sine wave grating carrier patterns, which were modulated by drifting envelope gratings of a lower spatial frequency. We found approximately one-third of visually responsive V2 neurons responded to CM stimuli with a pronounced selectivity to carrier spatial frequencies, and often orientations, that were clearly outside the neurons' passbands for LM gratings. These neurons were "form-cue invariant" in that their tuning to CM envelope spatial frequency and orientation was very similar to that for LM gratings. Neurons were tuned to carrier spatial frequencies that were typically 2-4 octaves higher than their optimal envelope spatial frequencies, similar to results from human psychophysics. These results are distinct from CM responses arising from surround suppression, but could be understood in terms of a filter-rectify-filter model. Such neurons could provide a functionally useful and explicit representation of segmentation boundaries as well as a plausible neural substrate for human perception of second-order boundaries. | 25,186,753 | [
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TDP-43 toxicity proceeds via calcium dysregulation and necrosis in aging Caenorhabditis elegans motor neurons. | Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with either sporadic or genetic origins characterized by the progressive degeneration of motor neurons. At the cellular level, ALS neurons show protein misfolding and aggregation phenotypes. Transactive response DNA-binding protein 43 (TDP-43) has recently been shown to be associated with ALS, but the early pathophysiological deficits causing impairment in motor function are unknown. Here we used Caenorhabditis elegans expressing mutant TDP-43(A315T) in motor neurons and explored the potential influences of calcium (Ca(2+)). Using chemical and genetic approaches to manipulate the release of endoplasmic reticulum (ER) Ca(2+)stores, we observed that the reduction of intracellular Ca(2+) ([Ca(2+)]i) rescued age-dependent paralysis and prevented the neurodegeneration of GABAergic motor neurons. Our data implicate elevated [Ca(2+)]i as a driver of TDP-43-mediated neuronal toxicity. Furthermore, we discovered that neuronal degeneration is independent of the executioner caspase CED-3, but instead requires the activity of the Ca(2+)-regulated calpain protease TRA-3, and the aspartyl protease ASP-4. Finally, chemically blocking protease activity protected against mutant TDP-43(A315T)-associated neuronal toxicity. This work both underscores the potential of the C. elegans system to identify key targets for therapeutic intervention and suggests that a focused effort to regulate ER Ca(2+) release and necrosis-like degeneration consequent to neuronal injury may be of clinical importance. | 25,186,754 | [
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Linking macroscale graph analytical organization to microscale neuroarchitectonics in the macaque connectome. | Macroscale connectivity of the mammalian brain has been shown to display several characteristics of an efficient communication network architecture. In parallel, at the microscopic scale, histological studies have extensively revealed large interregional variation in cortical neural architectonics. However, how these two "scales" of cerebrum organization are linked remains an open question. Collating and combining data across multiple studies on the cortical cytoarchitecture of the macaque cortex with information on macroscale anatomical wiring derived from tract tracing studies, this study focuses on examining the interplay between macroscale organization of the macaque connectome and microscale cortical neuronal architecture. Our findings show that both macroscale degree as well as the topological role in the overall network are related to the level of neuronal complexity of cortical regions at the microscale, showing (among several effects) a positive overall association between macroscale degree and metrics of microscale pyramidal complexity. Macroscale hub regions, together forming a densely interconnected "rich club," are noted to display a high level of neuronal complexity, findings supportive of a high level of integrative neuronal processes to occur in these regions. Together, we report on cross-scale observations that jointly suggest that a region's microscale neuronal architecture is tuned to its role in the global brain network. | 25,186,762 | [
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Dual nanoparticle amplified surface plasmon resonance detection of thrombin at subattomolar concentrations. | A novel dual nanoparticle amplification approach is introduced for the enhanced surface plasmon resonance (SPR) detection of a target protein at subattomolar concentrations. Thrombin was used as a model target protein as part of a sandwich assay involving an antithrombin (anti-Th) modified SPR chip surface and a thrombin specific DNA aptamer (Th-aptamer) whose sequence also includes a polyadenine (A30) tail. Dual nanoparticle (NP) enhancement was achieved with the controlled hybridization adsorption of first polythymine-NP conjugates (T20-NPs) followed by polyadenine-NPs (A30-NPs). Two different nanoparticle shapes (nanorod and quasi-spherical) were explored resulting in four different NP pair combinations being directly compared. It was found that both the order and NP shape were important in optimizing the assay performance. The use of real-time SPR measurements to detect target concentrations as low as 0.1 aM is a 10-fold improvement compared to single NP-enhanced SPR detection methods. | 25,186,782 | [
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Fluid shear stress stimulates osteogenic differentiation of human periodontal ligament cells via the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase signaling pathways. | Fluid shear stress (FSS) is a major type of mechanical stress that is loaded on human periodontal ligament cells (hPDLCs) during mastication and orthodontic tooth movement. This study aims to clarify the effect of FSS on the osteogenic differentiation of hPDLCs and to further verify the involvement of mitogen-activated protein kinase (MAPK) signaling in this process. After isolation and characterization, hPDLCs were subjected to 2-hour FSS at 12 dynes/cm(2), and cell viability, osteogenic gene mRNA expression, alkaline phosphatase (ALP) activity, secretion of Type I collagen (COL-I), and calcium deposition were assayed. The levels of phosphorylated p38 and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) in response to FSS were detected by Western blot, and the involvement of ERK1/2 and p38 MAPK signaling pathways in hPDLC osteogenesis under FSS was investigated using the specific MAPK inhibitors U0126 (2Z,3Z)-2,3-bis[amino(2-aminophenylthio)methylene]succinonitrile,ethanol) and SB203580 (4-[4-(4-fluorophenyl)-2-(4-[methylsulfinyl]phenyl)-1H-imidazol-5-yl]pyridine). The application of FSS on hPDLCs induced an early morphologic change and rearrangement of filamentous actin. ALP activity, messenger RNA (mRNA) levels of osteogenic genes, COL-I, and osteoid nodules were significantly increased by FSS. Moreover, ERK1/2 and p38 were activated in different ways after FSS exposure. U0126 and SB203580 completely blocked the FSS-induced increases in ALP activity and osteogenic gene mRNA expression and osteoid nodules formation. FSS is an effective approach for stimulating osteogenic differentiation of hPDLCs. The ERK1/2 and p38 MAPK signaling pathways are involved in this cellular process. | 25,186,781 | [
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"My YAP Family": Analysis of a Facebook Group for Young Adults Living with HIV. | Little research exists regarding the use of social networking sites, like Facebook, for improving patient well-being. The aim of this study was to evaluate a private Facebook group established for members of an HIV clinic's young adult program. This study employed directed content analysis to examine the types and frequencies of interactions observable in the 3,838 posts and comments that appeared on the Facebook group page between March 1, 2011 and July 1, 2012. Analysis revealed that a large percentage (41.7 %) of the content was classified as "administrative/engagement in group" and functioned to enhance the operations of the program as a whole. Additionally, positive interactions were frequently observed, especially socializing (24.8 %), banter (20.2 %), and offers of social support (15.1 %). Emotional support was the most frequent type of support requested, while esteem support was the most commonly provided form of support. The results of this study demonstrate that a Facebook group can be a means of providing patients with social support and positive social interaction and can improve services for young adults with HIV. | 25,186,783 | [
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Disclosure of their status to youth with human immunodeficiency virus infection in the Dominican Republic: a mixed-methods study. | A mixed-methods study was conducted to determine the proportion of HIV-infected children who knew their status, identify characteristics associated with children's knowledge of their status, and describe caregivers' and adolescents' experiences relevant to disclosure in the Dominican Republic (DR). Of 327 patients aged 6-18 years treated in the principal DR pediatric HIV facilities, 74 (22.6 %) knew their status. Patients aged 13 years or older and/or who had participated in non-clinical activities for HIV-infected children were more likely to know their status. Caregivers who had disclosed cited healthcare providers' advice, children's desire to know and concerns that children might initiate sexual activity before knowing or discover their status by accidental or malicious disclosure. Non-disclosing caregivers worried that children would be traumatized by disclosure and/or stigmatized if they revealed it to others. Adolescents supported disclosure by 10-12 years of age, considered withholding of children's HIV diagnosis ill-advised, and recommended a disclosure process focused initially on promoting non-stigmatizing attitudes about HIV. | 25,186,784 | [
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An autopsy case of Balamuthia mandrillaris amoebic encephalitis, a rare emerging infectious disease, with a brief review of the cases reported in Japan. | Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10-60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature. | 25,186,798 | [
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Two-dimensional motility of a macrophage cell line on microcontact-printed fibronectin. | The ability of macrophages to migrate to sites of infection and inflammation is critical for their role in the innate immune response. Macrophage cell lines have made it possible to study the roles of individual proteins responsible for migration using molecular biology, but it has not been possible to reliably elicit the motility of macrophage cell lines in two dimensions. In the past, measurements of the motility of macrophage cell lines have been largely limited to transwell assays which provide limited quantitative information on motility and limited ability to visualize cell morphology. We used microcontact printing to create polydimethylsiloxane (PDMS) surfaces functionalized with fibronectin that otherwise support little macrophage adhesion. We used these surfaces to measure macrophage migration in two dimensions and found that these cells migrate efficiently in a uniform field of colony-stimulating factor-1, CSF-1. Knockdown of Cdc42 led to a nonstatistically significant reduction in motility, whereas chemical inhibition of PI3K activity led to a complete loss of motility. Inhibition of the RhoA kinase, ROCK, did not abolish the motility of these cells but caused a quantitative change in motility, reducing motility significantly on high concentrations of fibronectin but not on low concentrations. This study illustrates the importance of studying cell motility on well controlled materials to better understand the exact roles of specific proteins on cell migration. © 2014 Wiley Periodicals, Inc. | 25,186,818 | [
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Current techniques for pediatric liver transplantation. | Orthotopic liver transplantation in the pediatric population is a technically challenging undertaking, requiring highly specialized surgical techniques unique to this group. This review describes the most current method of transplantation for these patients. Pediatric liver transplantation employs multiple modifications of standard transplant technique, including alternative methods of vascular and biliary anastomoses as well as technical variant grafts. We herein describe how these methods are employed in procurement, back-table preparation, hepatectomy, and allograft implantation. This review provides concise direction of surgical technique for pediatric liver transplant recipients. | 25,186,822 | [
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Deltoid ligament repair versus syndesmotic fixation in bimalleolar equivalent ankle fractures. | To compare the outcomes of bimalleolar equivalent ankle fractures treated with lateral malleolus open reduction and internal fixation (ORIF) with transsyndesmotic fixation versus lateral malleolus ORIF with deltoid ligament repair. Retrospective design. Single level I trauma center. Subjects with bimalleolar equivalent ankle fractures were eligible for enrollment. Patients with posterior or medial malleolar fractures and age <16 years were excluded. Twenty-seven total subjects met inclusion criteria. Fifteen patients were treated with lateral malleolus ORIF with transsyndesmotic fixation, whereas 12 were treated with lateral malleolus ORIF with deltoid ligament repair. Lateral malleolus ORIF with transsyndesmotic fixation versus lateral malleolus ORIF with deltoid ligament repair. Lower Extremity Function Scale, Foot and Ankle Disability Index, Short Musculoskeletal Function Assessment, Foot and Ankle Outcome Score, American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Visual Analog Pain Scale, and overall function of lower extremity. Univariate analysis of the outcome questionnaire variables demonstrated no statistically significant differences between the 2 groups. All patients in the syndesmotic fixation group underwent a subsequent procedure for removal of the syndesmotic implant. Additionally, there were 2 complications in the syndesmotic group that required repeat operative intervention. Repairing the deltoid ligament at the time of lateral malleolus fixation demonstrates subjective, functional, and radiologic outcomes that are comparable with lateral malleolus fixation with syndesmotic fixation for bimalleolar equivalent ankle fractures. The former avoids the costs and inherits surgical risks that occur during a subsequent operation for removal of the syndesmotic implant. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. | 25,186,845 | [
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Vaccination strategies to improve outcome of hematopoietic stem cell transplant in leukemia patients: early evidence and future prospects. | Allogeneic hematopoietic stem cell transplantation (HSCT) has largely improved the prognosis of leukemia patients. However, relapse is still a major concern. One promising option for the prevention of relapse is vaccination therapy. The post allogeneic HSCT period provides a unique platform for vaccination, because tumor burden is minimal, lymphopenic condition allows for rapid expansion of cytotoxic T cells (CTLs), donor-derived CTLs are not exhausted and inflammatory condition is caused by allo reactions. Tumor cells, dendritic cells and peptides have been used as vaccines targeting leukemia-associated antigens or minor histocompatibility antigens. Clinical trials with several types of vaccines for post-HSCT patients showed that the vaccination induced immunological response and might benefit patients with minimal residual disease, while their effect in patients with advanced disease were limited. To enhance the effect, vaccination in combination with other immune-modulatory drugs such as checkpoint antibodies is now being considered. | 25,186,852 | [
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RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. | Receptor interacting protein kinase 1 (RIPK1) has an essential role in the signalling triggered by death receptors and pattern recognition receptors. RIPK1 is believed to function as a node driving NF-κB-mediated cell survival and inflammation as well as caspase-8 (CASP8)-dependent apoptotic or RIPK3/MLKL-dependent necroptotic cell death. The physiological relevance of this dual function has remained elusive because of the perinatal death of RIPK1 full knockout mice. To circumvent this problem, we generated RIPK1 conditional knockout mice, and show that mice lacking RIPK1 in intestinal epithelial cells (IECs) spontaneously develop severe intestinal inflammation associated with IEC apoptosis leading to early death. This early lethality was rescued by antibiotic treatment, MYD88 deficiency or tumour-necrosis factor (TNF) receptor 1 deficiency, demonstrating the importance of commensal bacteria and TNF in the IEC Ripk1 knockout phenotype. CASP8 deficiency, but not RIPK3 deficiency, rescued the inflammatory phenotype completely, indicating the indispensable role of RIPK1 in suppressing CASP8-dependent apoptosis but not RIPK3-dependent necroptosis in the intestine. RIPK1 kinase-dead knock-in mice did not exhibit any sign of inflammation, suggesting that RIPK1-mediated protection resides in its kinase-independent platform function. Depletion of RIPK1 in intestinal organoid cultures sensitized them to TNF-induced apoptosis, confirming the in vivo observations. Unexpectedly, TNF-mediated NF-κB activation remained intact in these organoids. Our results demonstrate that RIPK1 is essential for survival of IECs, ensuring epithelial homeostasis by protecting the epithelium from CASP8-mediated IEC apoptosis independently of its kinase activity and NF-κB activation. | 25,186,904 | [
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Development and application of aromatic [(13)C, (1)H] SOFAST-HMQC NMR experiment for nucleic acids. | Higher sensitivity of NMR spectrometers and novel isotopic labeling schemes have ushered the development of rapid data acquisition methodologies, improving the time resolution with which NMR data can be acquired. For nucleic acids, longitudinal relaxation optimization in conjunction with Ernst angle excitation (SOFAST-HMQC) for imino protons, in addition to rendering rapid pulsing, has been demonstrated to yield significant improvements in sensitivity per unit time. Extending such methodology to other spins offers a viable prospect to measure additional chemical shifts, thereby broadening their utilization for various applications. Here, we introduce the 2D [(13)C, (1)H] aromatic SOFAST-HMQC that results in overall sensitivity gain of 1.4- to 1.7-fold relative to the conventional HMQC and can also be extended to yield long-range heteronuclear chemical shifts such as the adenine imino nitrogens N1, N3, N7 and N9. The applications of these experiments range from monitoring real-time biochemical processes, drug/ligand screening, and to collecting data at very low sample concentration and/or in cases where isotopic enrichment cannot be achieved. | 25,186,910 | [
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Differences between rosuvastatin and atorvastatin in lipid-lowering action and effect on glucose metabolism in Japanese hypercholesterolemic patients with concurrent diabetes. Lipid-lowering with highly potent statins in hyperlipidemia with type 2 diabetes patients (LISTEN) study –. | Little is known about the differences between standard-dose statins effects on glucose level and lipids in Japanese patients with diabetes mellitus (DM). The 1,049 patients were randomly assigned to either the rosuvastatin group or atorvastatin group. There were no significant differences between the 2 groups in the effect on non-high-density lipoprotein cholesterol (non-HDL-C) and HbA1c at 12 months. However, physicians tended to switch to more intensive therapy for DM in the atorvastatin group. Rosuvastatin 5 mg and atorvastatin 10 mg have a similar lowering effect on non-HDL-C, but might be different in terms of adverse effect on glucose levels. | 25,186,922 | [
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Effects of Visual Information on Wind-Evoked Escape Behavior of the Cricket, Gryllus bimaculatus. | We investigated the effects of visual information on wind-evoked escape behavior in the cricket, Gryllus bimaculatus. Most agitated crickets were found to retreat into a shelter made of cardboard installed in the test arena within a short time. As this behavior was thought to be a type of escape, we confirmed how a visual image of a shelter affected wind-evoked escape behavior. Irrespective of the brightness of the visual background (black or white) or the absence or presence of a shelter, escape jumps were oriented almost 180° opposite to the source of the air puff stimulus. Therefore, the direction of wind-evoked escape depends solely depended on the direction of the stimulus air puff. In contrast, the turning direction of the crickets during the escape was affected by the position of the visual image of the shelter. During the wind-evoked escape jump, most crickets turned in the direction in which a shelter was presented. This behavioral nature is presumably necessary for crickets to retreat into a shelter within a short time after their escape jump. | 25,186,926 | [
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Assembling multiporphyrin stacks inside the DNA double helix. | Double stranded DNA hybrids containing up to four consecutive, face-to-face stacked porphyrins are described. Non-nucleosidic, 5,15-bisphenyl-substituted porphyrin building blocks were incorporated into complementary oligonucleotide strands. Upon hybridization multiple porphyrins are well accommodated inside the DNA scaffold without disturbing the overall B-DNA structure. The formation of double strands containing up to four free base porphyrins is enabled without compromising duplex stability. UV/vis, fluorescence, and CD spectroscopy demonstrate the formation of porphyrins H-aggregates inside the DNA double helix and provide evidence for the existence of strong excitonic coupling between interstrand stacked porphyrins. H-aggregation results in considerable fluorescence quenching. Most intense CD effects are observed in stacks containing four porphyrins. The findings demonstrate the value of DNA for the controlled formation of molecularly defined porphyrin aggregates. | 25,186,936 | [
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Induction of apoptosis in colon cancer cells treated with isorhamnetin glycosides from Opuntia ficus-indica pads. | (OFI) contains health-promoting compounds like flavonoids, being the isorhamnetin glycosides the most abundant. We evaluated the effect of OFI extracts with different isorhamnetin glycosides against two different human colon cancer cells (HT-29 and Caco2). The extracts were obtained by alkaline hydrolysis with NaOH at 40 °C during 15, 30 or 60 min. Tri and diglycosides were the most abundant isorhamnetin glycosides, therefore these compounds were isolated to compare their cytotoxic effect with the obtained from the extracts. The OFI extracts and purified isorhamnetin glycosides were more cytotoxic against HT-29 cells than Caco2 cells. OFI-30 exhibited the lowest IC50 value against HT-29 (4.9 ± 0.5 μg/mL) and against Caco2 (8.2 ± 0.3 μg/mL). Isorhamnetin diglycosides IG5 and IG6 were more cytotoxic than pure isorhamnetin aglycone or triglycosides when they were tested in HT-29 cells. Bioluminescent analysis revealed increased activity of caspase 3/7 in OFI extracts-treated cells, particularly for the extract with the highest concentration of isorhamnetin triglycosides. Flow cytometry analysis confirmed that OFI extract and isorhamnetin glycosides induced a higher percentage of apoptosis in HT-29 than in Caco2, while isorhamnetin was more apoptotic in Caco2. This research demonstrated that glycosilation affected antiproliferative effect of pure isorhamnetin glycosides or when they are mixed with other phytochemicals in an extract obtained from OFI. | 25,186,940 | [
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The genomic landscape of pediatric Ewing sarcoma. | Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date, with only EWS-ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS-ETS fusions in this disease. We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS-ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma. | 25,186,949 | [
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Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran. | Borna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells of humans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability. This first report from the Middle East aimed to determine BDV infection prevalence in Iranian acute psychiatric disorder patients and healthy controls through circulating immune complexes (CIC), antibodies (Ab) and antigen (pAg) in blood plasma using a standardized triple enzyme immune assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood donors, and 131 healthy controls) were assayed and data analyzed quantitatively and qualitatively. CICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5% controls; 33.3% blood donors). In psychiatric patients CIC prevalence was higher than in controls (40.4%) and significantly correlating with bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR = 1.65). CIC values were significantly elevated in bipolar (p = 0.001) and major depressive disorder (p = 0.029) patients as compared to controls, and in females compared to males (p = 0.031). This study supports a similarly high prevalence of subclinical human BDV infections in Iran as reported for central Europe, and provides again an indication for the correlation of BDV infection and mood disorders. Further studies should address the morbidity risk for healthy carriers and those with elevated CIC levels, along with gender disparities. | 25,186,971 | [
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Use of facebook as a tool for knowledge dissemination in dermatology. | The presence of dermatology-related platforms in social media has been acknowledged; however, the level of engagement of the public with these platforms has not been evaluated. To use the Engagement Rate to assess the level of engagement of the public with Facebook pages devoted to dermatology. A search on Facebook identified Facebook pages for dermatology academic journals, professional societies, and patient-centered groups with the highest number of Facebook likes. Then the Yearly Page Engagement Rate was calculated for each Facebook page. The robust average of the Yearly Page Engagement Rate was 0.673 for academic journals, 0.313 for professional societies, and 1.563 for patient-centered groups. Patient-centered groups engaged with their fans most effectively. Engagement is a key determinant of a fan's exposure to the contents of the page and hence a gauge of whether the fans who "liked" the page continue to remain engaged or not. | 25,186,996 | [
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0.2705612,
0.05606419,
0.100859,
0.02075473,
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0.2393027,
0.2888967,
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0.2909965,
0.3236054,
-0.358810... |
Successful treatment of calciphylaxis with intravenous sodium thiosulfate in a nonuremic patient: case report and review of therapy side effects. | AbstractBackground:Calciphylaxis is a life-threatening condition traditionally observed in patients with end-stage renal disease. Cases of nonuremic calciphylaxis have also been reported, but data on this rare condition are mainly empirical. To present a case of severe nonuremic calciphylaxis treated with intravenous sodium thiosulfate (IV STS) and to assess the implications of this treatment. Case report and review of the literature. A nonuremic patient diagnosed with distal calciphylaxis was started on IV STS after a 12-month nonresponse to conventional therapy. On week 12, the patient requested palliative care, given her many side effects (transient severe nausea and significant electrolyte imbalance). Pain subsided after 14 weeks, and complete wound healing was observed after 6 months. Based on this case report, IV STS can improve refractory calciphylaxis in nonuremic patients. However, literature on the subject remains scarce. Careful monitoring for adverse transient side effects is advised. | 25,186,999 | [
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0.1232933,
0.04145706,
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0.1844604,
-0.25471... |
Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial. | ANTHEM-HF evaluated a novel autonomic regulation therapy (ART) via either left or right vagus nerve stimulation (VNS) in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Sixty subjects (New York Heart Association [NYHA] functional class II-III, left ventricular ejection fraction (LVEF) ≤ 40%, left ventricular end-diastolic diameter ≥ 50 mm to < 80 mm) receiving optimal pharmacologic therapy were randomized at 10 sites. VNS systems were randomly implanted on the left (n = 31) or right (n = 29) side. All patients were successfully implanted and 59 were titrated over 10 weeks to a well tolerated stimulation intensity. One patient died 3 days after an embolic stroke that occurred during implantation. Common device-related adverse events after VNS titration were transient mild dysphonia, cough, and oropharyngeal pain, which were similar for left- and right-side VNS. After 6 months of ART, the adjusted left-right differences in LVEF, left ventricular end-systolic volume (LVESV), and left ventricular end-systolic diameter (LVESD) were 0.2% (95% CI -4.4 to 4.7), 3.7 mL (95% CI -7.0 to 14.4), and 1.3 mm (95% CI -0.9 to 3.6), respectively. In the combined population, absolute LVEF improved by 4.5% (95% CI 2.4-6.6), LVESV improved by -4.1 mL (95% CI -9.0 to 0.8), and LVESD improved by -1.7 mm (95% CI -2.8 to -0.7). Heart rate variability improved by 17 ms (95% CI 6.5-28) with minimal left-right difference. Six-minute walk distance improved an average of 56 m (95% CI 37-75); however, improvement was greater for right-side ART (77 m [95% CI 49-105]). NYHA functional class improved in 77% of patients (baseline to 6 months). Chronic open-loop ART via left- or right-side VNS is feasible and well tolerated in HFrEF patients. Safety and efficacy measures are encouraging and warrant further study. | 25,187,002 | [
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0.2611654,
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0.01923293,
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0.005716395,
... |
A first look at the Oxford Nanopore MinION sequencer. | Oxford Nanopore's third-generation single-molecule sequencing platform promises to decrease costs for reagents and instrumentation. After a 2-year hiatus following the initial announcement, the first devices have been released as part of an early access program. We explore the performance of this platform by resequencing the lambda phage genome, and amplicons from a snake venom gland transcriptome. Although the handheld MinION sequencer can generate more than 150 megabases of raw data in one run, at most a quarter of the resulting reads map to the reference, with less than average 10% identity. Much of the sequence consists of insertion/deletion errors, or is seemingly without similarity to the template. Using the lambda phage data as an example, although the reads are long, averaging 5 kb, at best 890 ± 1932 bases per mapped read could be matched to the reference without soft clipping. In the course of a 36 h run on the MinION, it was possible to resequence the 48 kb lambda phage reference at 16× coverage. Currently, substantially larger projects would not be feasible using the MinION. Without increases in accuracy, which would be required for applications such as genome scaffolding and phasing, the current utility of the MinION appears limited. Library preparation requires access to a molecular laboratory, and is of similar complexity and cost to that of other next-generation sequencing platforms. The MinION is an exciting step in a new direction for single-molecule sequencing, though it will require dramatic decreases in error rates before it lives up to its promise. | 25,187,008 | [
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0.3247104,
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0.2259895,
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0.3595676,
0.01676176,
-0.2073895,
-0.... |
Perspectives of vulnerable U.S Hispanics with rheumatoid arthritis on depression: awareness, barriers to disclosure, and treatment options. | Despite the high prevalence of depression among vulnerable Hispanics with rheumatoid arthritis (RA), many do not disclose it or seek treatment. This study explored patient perceptions of depression, its association with their primary disease, barriers to disclosure, reasons for low utilization of mental health care resources, and culturally acceptable intervention approaches. Semistructured interviews were conducted with 46 participants with RA. Depression was evaluated using Patient Health Questionnaire 9 (PHQ-9). Thirty-three percent of participants were moderately depressed at the time of the interview, based on PHQ-9 score ≥10; 12 of 46 patients (26%) stated they were depressed regardless of PHQ-9 score. Depression was perceived as a long-term, severe problem leading to suicide. It was associated with weakness and character flaws, contributing to stigma and reduced likelihood of disclosure. Antidepressants were not acceptable; self-reliance and interventions incorporating interpersonal connections were preferred. Systems-related barriers to disclosure included lack of verbal screening, language barriers, limited clinic visit time, and lack of continuity of care, restricting trust with providers. Rectifying misconceptions, as well as providing education regarding the association between RA and depression, the continuum of symptoms, and the range of experiences incurred are needed to facilitate earlier recognition and reduce stigma. Use, duration, and goals of antidepressant therapy should be clarified. Providers should strive to establish trust and conduct in-person depression screening to facilitate disclosure. Interventions with an interpersonal component, such as support groups or patient navigators, were preferred. Themes emphasizing coping strategies, stress reduction, positive thinking, self-efficacy, and resiliency are likely to be most acceptable. | 25,187,020 | [
-0.04330029,
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0.1241551,
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0.1926107,
0.2378052,
0.1398643,
0.1468796,
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0.07309167,
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0.2378171,
0.06481165,
0.07784123,
-0.07986281,
-0.1115743,
0.0240443,
... |
Real-time PCR carried out on DNA extracted from serum or blood sample is not a good method for surveillance of bovine brucellosis. | Bovine brucellosis is endemic in many parts of the world including India. The disease diagnosis and surveillance are usually carried out by serological tests, which however have drawbacks. This study was undertaken to evaluate the potential of real-time PCR (RT-PCR) targeting bcsp31 gene for surveillance of bovine brucellosis. A total of 461 samples, which included 408 stored serum and 53 prospective blood samples, were used. It was found that 33 (7.15 %) samples were positive by RT-PCR, whereas 149 (32.32 %) and 132 (28.63 %) were positive by Rose Bengal plate test (RBPT) or standard agglutination test (STAT), respectively. The results of this study suggest that RT-PCR targeting bcsp31 gene carried out on DNA extracted from serum or blood may not be a suitable method for surveillance of brucellosis in bovines. | 25,187,027 | [
0.07041068,
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0.0456426,
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0.3572789,
0.4270003,
0.2794383,
0.1954025,
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0.1316027,
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0.003764995,
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0.05561262,
-0.04483366,
... |
Clone mapper: an online suite of tools for RNAi experiments in Caenorhabditis elegans. | RNA interference (RNAi), mediated by the introduction of a specific double-stranded RNA, is a powerful method to investigate gene function. It is widely used in the Caenorhabditis elegans research community. An expanding number of laboratories conduct genome-wide RNAi screens, using standard libraries of bacterial clones each designed to produce a specific double-stranded RNA. Proper interpretation of results from RNAi experiments requires a series of analytical steps, from the verification of the identity of bacterial clones, to the identification of the clones' potential targets. Despite the popularity of the technique, no user-friendly set of tools allowing these steps to be carried out accurately, automatically, and at a large scale, is currently available. We report here the design and production of Clone Mapper, an online suite of tools specifically adapted to the analysis pipeline typical for RNAi experiments with C. elegans. We show that Clone Mapper overcomes the limitations of existing techniques and provide examples illustrating its potential for the identification of biologically relevant genes. The Clone Mapper tools are freely available via http://www.ciml.univ-mrs.fr/EWBANK_jonathan/software.html. | 25,187,039 | [
0.06499947,
0.05764367,
0.553385,
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0.07390803,
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0.1128252,
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0.2420403,
0.03375721,
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0.3379592,
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-0.1363005,
-0.06... |
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