Deutetrabenazine in the treatment of Huntington's disease.

Deutetrabenazine (DTBZ) is a US FDA-approved treatment for chorea in Huntington's disease. The substitution of deuterium for hydrogen at specific positions imparts a longer half-life on DTBZ, allowing for less-frequent daily dosing. As a reversible vesicular monoamine transporter Type 2 inhibitor, DTBZ depletes monoamines at presynaptic nerve terminals.

Vitamin D status and its determinants in healthy pregnant women living in Switzerland in the first trimester of pregnancy.

Objectives: Our study aimed at assessing the prevalence and determinants of vitamin D deficiency (25-hydroxy-vitamin D [25(OH)D] < 20 ng/mL) in pregnant women in the first trimester living in Switzerland.

Methods: From September 2014 through December 2015, 204 pregnant women were conveniently recruited during their first clinical appointment at the Clinic of Obstetrics of the University Hospital Zurich (between week 6 and 12 of pregnancy). Blood samples were collected and a questionnaire focusing on lifestyle and skin colour was completed face-to-face with the responsible physician.

Using prepared mixtures of ToxCast chemicals to evaluate non-targeted analysis (NTA) method performance.

Non-targeted analysis (NTA) methods are increasingly used to discover contaminants of emerging concern (CECs), but the extent to which these methods can support exposure and health studies remains to be determined. EPA's Non-Targeted Analysis Collaborative Trial (ENTACT) was launched in 2016 to address this need. As part of ENTACT, 1269 unique substances from EPA's ToxCast library were combined to make ten synthetic mixtures, with each mixture containing between 95 and 365 substances.

Indacaterol acetate/mometasone furoate provides sustained improvements in lung function compared with salmeterol xinafoate/fluticasone propionate in patients with moderate-to-very-severe COPD: results from a Phase II randomized, double-blind 12-week study.

Background And Purpose: Fixed-dose combinations of a long-acting beta agonist and an inhaled corticosteroid are more effective than the individual components in COPD. The primary study objective was to demonstrate that the combination indacaterol acetate/mometasone furoate (IND/MF [QMF149]) was non-inferior to the twice-daily combination salmeterol xinafoate/fluticasone propionate (Sal/Flu) in terms of trough FEV at week 12 (day 85). Secondary objectives were to compare the efficacy of IND/MF (QMF149) vs Sal/Flu with respect to other lung function parameters, COPD exacerbations, symptoms and dyspnea, health status/health-related quality of life, and rescue medication use.

A Hybrid RNN-HMM Approach for Weakly Supervised Temporal Action Segmentation.

Action recognition has become a rapidly developing research field within the last decade. But with the increasing demand for large scale data, the need of hand annotated data for the training becomes more and more impractical. One way to avoid frame-based human annotation is the use of action order information to learn the respective action classes.

A combined mindfulness-prolonged chewing intervention reduces body weight, food craving, and emotional eating.

Objective: Conventional weight-loss programs that induce a calorie deficit mostly fail in long-term weight reduction and disadvantageous eating styles often remain unchanged. Mindfulness interventions therefore redirect the focus away from the weight-loss goal and toward the process of eating itself. By eating more mindfully, at a slower pace, and with an enhanced focus on bodily sensations, participants might not only indirectly reduce their daily calorie intake but also eat less craving and stress driven.

Positive and negative cycles in Boolean networks.

We review and discuss some results about the influence of positive and negative feedback cycles in asynchronous Boolean networks. These results merge several ideas of Thomas: positive and negative feedback cycles have been largely emphasized by Thomas, through the so called Thomas' rules, and asynchronous Boolean networks have been introduced by Thomas as a model for the dynamics of gene networks, which is nowadays very popular.

EPA's non-targeted analysis collaborative trial (ENTACT): genesis, design, and initial findings.

In August 2015, the US Environmental Protection Agency (EPA) convened a workshop entitled "Advancing non-targeted analyses of xenobiotic chemicals in environmental and biological media." The purpose of the workshop was to bring together the foremost experts in non-targeted analysis (NTA) to discuss the state-of-the-science for generating, interpreting, and exchanging NTA measurement data. During the workshop, participants discussed potential designs for a collaborative project that would use EPA resources, including the ToxCast library of chemical substances, the DSSTox database, and the CompTox Chemicals Dashboard, to evaluate cutting-edge NTA methods.

Identification of potential genetic risk factors for bipolar disorder by whole-exome sequencing.

This study aims at assessing the burden of rare (minor allele frequency < 1%) predicted damaging variants in the whole exome of 92 bipolar I disorder (BD) patients and 1051 controls of French ancestry. Patients exhibiting an extreme phenotype (earlier onset and family history of mood disorder) were preferentially included to increase the power to detect an association. A collapsing strategy was used to test the overall burden of rare variants in cases versus controls at the gene level.

Using reflective practice in interprofessional education and practice: a realist review of its characteristics and effectiveness.

This article presents the results of a realist review of the use of reflective practice interventions aimed at improving interprofessional education and collaborative practice (IPECP). Reflective practice is recognized as one of the determining factors in health and social service professionals' skills development and maintenance, as well as in the establishment of good collaboration practices. In this respect, it is a key element of interprofessional education (IPE) and its relevance in this field is being asserted more and more strongly.

Recover your smile: Effects of a beauty care intervention on depressive symptoms, quality of life, and self-esteem in patients with early breast cancer.

Objective: Medical cancer treatment is often accompanied by appearance-related side effects such as hair loss, skin irritation, and paleness, which can subsequently lead to psychosocial distress. Initial evidence suggests that beauty care interventions may reduce distress and improve quality of life (QoL), body image, and self-esteem immediately.

Methods: We investigated the effects of a brief beauty care intervention on self-reported symptoms of depression, quality of life, body image, and self-esteem in 39 female primary breast cancer patients with appearance-related treatment side effects.

A Mechanistic Framework for Integrating Chemical Structure and High-Throughput Screening Results to Improve Toxicity Predictions.

Adverse Outcome Pathways (AOPs) establish a connection between a molecular initiating event (MIE) and an adverse outcome. Detailed understanding of the MIE provides the ideal data for determining chemical properties required to elicit the MIE. This study utilized high-throughput screening data from the ToxCast program, coupled with chemical structural information, to generate chemical clusters using three similarity methods pertaining to nine MIEs within an AOP network for hepatic steatosis.

Readability of advance directive documentation in Canada: a cross-sectional study.

Background: In the Canadian context, health literacy has been shown to depend on place of birth, education level, socioeconomic status, language spoken and geographic location. This study seeks to determine whether currently available advance directive documentation in Canada is written in accordance with the average reading level of the population and to assess whether recommendations for health literacy are currently being met.

Methods: A cross-sectional study design was used.

Potent suppression of HIV-1 cell attachment by Kudzu root extract.

There is a constant need to improve antiretrovirals against HIV since therapy is limited by cost, side effects and the emergence of drug resistance. Kudzu is a climbing vine from which the root extract (Pueraria lobata), rich in isoflavones and saponins, has long been used in traditional Chinese medicine for a variety of purposes, from weight loss to alcoholism prevention. Here we show that Kudzu root extract significantly inhibits HIV-1 entry into cell lines, primary human CD4T lymphocytes and macrophages, without cell-associated toxicity.

PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes.

How cytotoxic T lymphocytes (CTLs) sense T cell receptor (TCR) signaling in order to specialize an area of plasma membrane for granule secretion is not understood. Here, we demonstrate that immune synapse formation led to rapid localized changes in the phosphoinositide composition of the plasma membrane, both reducing phosphoinositide-4-phosphate (PI(4)P), PI(4,5)P2, and PI(3,4,5)P3 and increasing diacylglycerol (DAG) and PI(3,4)P2 within the first 2 min of synapse formation. These changes reduced negative charge across the synapse, triggering the release of electrostatically bound PIP5 kinases that are required to replenish PI(4,5)P2.

Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with susceptibility to inflammatory bowel disease.

Chronic inflammation in inflammatory bowel disease (IBD) results from a breakdown of intestinal immune homeostasis and compromise of the intestinal barrier. Genome-wide association studies have identified over 200 genetic loci associated with risk for IBD, but the functional mechanisms of most of these genetic variants remain unknown. Polymorphisms at the TNFSF15 locus, which encodes the TNF superfamily cytokine commonly known as TL1A, are associated with susceptibility to IBD in multiple ethnic groups.

Correcting the Mean-Variance Dependency for Differential Variability Testing Using Single-Cell RNA Sequencing Data.

Cell-to-cell transcriptional variability in otherwise homogeneous cell populations plays an important role in tissue function and development. Single-cell RNA sequencing can characterize this variability in a transcriptome-wide manner. However, technical variation and the confounding between variability and mean expression estimates hinder meaningful comparison of expression variability between cell populations.

An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro.

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo.

Loss of DBC1 (CCAR2) affects TNFα-induced lipolysis and gene expression in murine adipocytes.

STAT5A (signal transducer and activator of transcription 5A) is a transcription factor that plays a role in adipocyte development and function. In this study, we report DBC1 (deleted in breast cancer 1; also known as CCAR2) as a novel STAT5A-interacting protein. DBC1 has been primarily studied in tumor cells, but there is evidence that loss of this protein may promote metabolic health in mice.

[Upper-extremity venous thrombosis: A retrospective study about 160 cases].

Aim: To describe the clinical features and etiologies of upper limb venous thrombosis (ULVT).

Methods: All patients with a clinically suspected ULVT, were included retrospectively from January to December 2016. Diagnosis of ULVT was based on doppler-ultrasonography.

Somatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer's disease.

Introduction: A minority of patients with sporadic early-onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP, PSEN1, or PSEN2. We hypothesized that negatively screened patients may harbor somatic variants in these genes.

Methods: We applied an ultrasensitive approach based on single-molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic patients with AD (>80% exhibited an early onset, <66 years).

Erasure of striatal chondroitin sulfate proteoglycan-associated extracellular matrix rescues aging-dependent decline of motor learning.

Cognitive decline is a feature of aging. Accumulating evidence suggests that the brain extracellular matrix (ECM) is involved in the process of aging-dependent cognitive impairment and neurodegeneration by regulating synaptic neurotransmission and affecting neuroplasticity. Age-related changes in brain structure and cognition are not uniform across the whole brain.

Amendment of soil by biochars and activated carbons to reduce chlordecone bioavailability in piglets.

Chlordecone (Kepone or CLD) is a highly persistent pesticide formerly used in French West Indies. Nowadays high levels of this pesticide are still found in soils which represent a subsequent source of contamination for outdoor-reared animals. In that context, sequestering matrices like biochars or activated carbons (ACs) are believed to efficiently decrease the bioavailability of such compounds when added to contaminated soils.

T cell cytolytic capacity is independent of initial stimulation strength.

How cells respond to myriad stimuli with finite signaling machinery is central to immunology. In naive T cells, the inherent effect of ligand strength on activation pathways and endpoints has remained controversial, confounded by environmental fluctuations and intercellular variability within populations. Here we studied how ligand potency affected the activation of CD8 T cells in vitro, through the use of genome-wide RNA, multi-dimensional protein and functional measurements in single cells.