Automatic-Scoring Actigraph Compares Favourably to a Manually-Scored Actigraph for Sleep Measurement in Healthy Adults.

Introduction  Actigraphy has been used widely in sleep research due to its non-invasive, cost-effective ability to monitor sleep. Traditionally, manually-scored actigraphy has been deemed the most appropriate in the research setting; however, technological advances have seen the emergence of automatic-scoring wearable devices and software. Methods  A total of 60-nights of sleep data from 20-healthy adult participants (10 male, 10 female, age: 26 ± 10 years) were collected while wearing two devices concomitantly. The objective was to compare an automatic-scoring device (Fatigue Science Readiband™ [AUTO]) and a manually-scored device (Micro Motionlogger® [MAN]) based on the Cole-Kripke method. Manual-scoring involved trained technicians scoring all 60-nights of sleep data. Sleep indices including total sleep time (TST), total time in bed (TIB), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO), wake episodes per night (WE), sleep onset time (SOT) and wake time (WT) were assessed between the two devices using mean differences, 95% levels of agreement, Pearson-correlation coefficients ( r ), and typical error of measurement (TEM) analysis. Results  There were no significant differences between devices for any of the measured sleep variables ( p  ≥0.05). All sleep indices resulted in very-strong correlations ( all r  ≥0.84) between devices. A mean difference between devices of <1 minutes for TST was associated with a TEM of 15.5 minute (95% CI =12.3 to 17.7 minutes). Conclusion  Given there were no significant differences between devices in the current study, automatic-scoring actigraphy devices may provide a more practical and cost-effective alternative to manually-scored actigraphy in healthy populations

Preterm birth and exercise capacity: what do we currently know?

ObjectivesThe long-term cardiopulmonary outcomes following preterm birth during the surfactant era remain unclear. Respiratory symptoms, particularly exertional symptoms, are common in preterm children. Therefore, cardiopulmonary exercise testing may provide insights into the pathophysiology driving exertional respiratory symptoms in those born preterm. This review aims to outline the current knowledge of cardiopulmonary exercise testing in the assessment of children born preterm in the surfactant era.DesignThis study is a narrative literature review.MethodsPublished manuscripts concerning the assessment of pulmonary outcomes using cardiopulmonary exercise testing in preterm children (aged &lt;18 years) were reviewed. Search terms related to preterm birth, bronchopulmonary dysplasia, and exercise were entered into electronic databases, including Medline, PubMed, and Google Scholar. Reference lists from included studies were scanned for additional manuscripts.ResultsPreterm children have disrupted lung development with significant structural and functional lung disease and increased respiratory symptoms. The association between these (resting) assessments of respiratory health and exercise capacity is unclear; however, expiratory flow limitation and an altered ventilatory response (rapid, shallow breathing) are seen during exercise. Due to the heterogeneity of participants, treatments, and exercise protocols, the effect of the aforementioned limitations on exercise capacity in children born preterm is conflicting and poorly understood.ConclusionRisk factors for reduced exercise capacity in those born preterm remain poorly understood; however, utilizing cardiopulmonary exercise testing to its full potential, the pathophysiology of exercise limitation in survivors of preterm birth will enhance our understanding of the role exercise may play. The role of exercise interventions in mitigating the risk of chronic disease and premature death following preterm birth has yet to be fully realized and should be a focus of future robust randomized controlled trials

Structural changes in the BH3 domain of SOUL protein upon interaction with the anti-apoptotic protein Bcl-xL

The SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition, and a sequence homologous with the BH3 (Bcl-2 homology 3) domains has recently been identified in the protein, thus making it a potential new member of the BH3-only protein family. In the present study, we provide NMR, SPR (surface plasmon resonance) and crystallographic evidence that a peptide spanning residues 147–172 in SOUL interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL, and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted β-barrel with eight anti-parallel strands and two α-helices. The BH3 domain extends across 15 residues at the end of the second helix and eight amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL

Cholesterol Pathways Affected by Small Molecules That Decrease Sterol Levels in Niemann-Pick Type C Mutant Cells

Niemann-Pick type C (NPC) disease is a genetically inherited multi-lipid storage disorder with impaired efflux of cholesterol from lysosomal storage organelles.The effect of screen-selected cholesterol lowering compounds on the major sterol pathways was studied in CT60 mutant CHO cells lacking NPC1 protein. Each of the selected chemicals decreases cholesterol in the lysosomal storage organelles of NPC1 mutant cells through one or more of the following mechanisms: increased cholesterol efflux from the cell, decreased uptake of low-density lipoproteins, and/or increased levels of cholesteryl esters. Several chemicals promote efflux of cholesterol to extracellular acceptors in both non-NPC and NPC1 mutant cells. The uptake of low-density lipoprotein-derived cholesterol is inhibited by some of the studied compounds.Results herein provide the information for prioritized further studies in identifying molecular targets of the chemicals. This approach proved successful in the identification of seven chemicals as novel inhibitors of lysosomal acid lipase (Rosenbaum et al, Biochim. Biophys. Acta. 2009, 1791:1155-1165)

Circular dichroism spectroscopic detection of ligand binding induced subdomain IB specific structural adjustment of human serum albumin

This work demonstrates for the first time that binding of various compounds within subdomain IB of human serum albumin (HSA) provokes characteristic changes in the near-UV circular dichroism (CD) spectrum of the protein. It can be inferred from the spectroscopic features of difference ellipticity signals and from CD displacement experiments that tyrosine residues located in subdomain IB are the source of the observed spectral alterations. It is proposed that inclusion of some ligand molecules (bile acids, dehydroepiandrosterone sulfate, steroidal terpenes, fatty acids, ibuprofen, and gemfibrozil) into the pocket of subdomain IB disrupts the Tyr138?Tyr161 interhelical π?π stacking interaction, which is reflected in the CD spectrum. This phenomenon can be utilized for the CD detection of subdomain IB specific binding of endo- as well as exogenous agents and to study the drug binding associated local conformational adaptation of the HSA molecule

Reporting on the Seminar - Risk interpretation and action (RIA): Decision making under conditions of uncertainty

The paper reports on the World Social Science (WSS) Fellows seminar on Risk Interpretation and Action (RIA), undertaken in New Zealand in December, 2013. This seminar was coordinated by the WSS Fellows program of the International Social Science Council (ISSC), the RIA working group of the Integrated Research on Disaster Risk (IRDR) program, the IRDR International Center of Excellence Taipei, the International START Secretariat and the Royal Society of New Zealand. Twenty-five early career researchers from around the world were selected to review the RIA framework under the theme of \u27decision-making under conditions of uncertainty\u27, and develop novel theoretical approaches to respond to and improve this framework. Six working groups emerged during the seminar: 1. the assessment of water-related risks in megacities; 2. rethinking risk communication; 3. the embodiment of uncertainty; 4. communication in resettlement and reconstruction phases; 5. the integration of indigenous knowledge in disaster risk reduction; and 6. multi-scale policy implementation for natural hazard risk reduction. This article documents the seminar and initial outcomes from the six groups organized; and concludes with the collective views of the participants on the RIA framework

The Genetic Basis of Hepatosplenic T-cell Lymphoma

Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets

Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

Purpose: To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods: Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg 21; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, doubleblind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75 % 1RM load) and muscle power adaptations (1 m s 21 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOK LEG) were measured to identify caffeine’s action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85 % 1RM) 6 repetitions bout of SQ (POST). Results: In the PM PLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AM PLA