Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease.

Infection of subcutaneous tissue with Mycobacterium ulcerans can lead to chronic skin ulceration known as Buruli ulcer. The pathogenesis of this neglected tropical disease is dependent on a lipid-like toxin, mycolactone, which diffuses through tissue away from the infecting organisms. Since its identification in 1999, this molecule has been intensely studied to elucidate its cytotoxic and immunosuppressive properties. Two recent major advances identifying the underlying molecular targets for mycolactone have been described. First, it can target scaffolding proteins (such as Wiskott Aldrich Syndrome Protein), which control actin dynamics in adherent cells and therefore lead to detachment and cell death by anoikis. Second, it prevents the co-translational translocation (and therefore production) of many proteins that pass through the endoplasmic reticulum for secretion or placement in cell membranes. These pleiotropic effects underpin the range of cell-specific functional defects in immune and other cells that contact mycolactone during infection. The dose and duration of mycolactone exposure for these different cells explains tissue necrosis and the paucity of immune cells in the ulcers. This review discusses recent advances in the field, revisits older findings in this context and highlights current developments in structure-function studies as well as methodology that make mycolactone a promising diagnostic biomarker

STAR-loc: Dataset for STereo And Range-based localization

This document contains a detailed description of the STAR-loc dataset. For a quick starting guide please refer to the associated Github repository (https://github.com/utiasASRL/starloc). The dataset consists of stereo camera data (rectified/raw images and inertial measurement unit measurements) and ultra-wideband (UWB) data (range measurements) collected on a sensor rig in a Vicon motion capture arena. The UWB anchors and visual landmarks (Apriltags) are of known position, so the dataset can be used for both localization and Simultaneous Localization and Mapping (SLAM).Comment: 15 pages, 15 figure

Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort

<p>Abstract</p> <p>Background</p> <p>Irritable bowel syndrome (IBS) is a common disorder that affects 10–15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26).</p> <p>Methods</p> <p>Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay.</p> <p>Results</p> <p>Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio.</p> <p>Conclusion</p> <p>These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.</p

SHIV-162P3 Infection of Rhesus Macaques Given Maraviroc Gel Vaginally Does Not Involve Resistant Viruses

Maraviroc (MVC) gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0) but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294±0.027%; limited entropy changes were noted across the envelope (gp160). No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14–21, the time of first detectable viremia, nor selected at later time points, days 42–70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC50] 1.87 nM) and virus isolated from the three MVC-treated macaques (MVC IC50 1.18 nM, 1.69 nM, and 1.53 nM, respectively). Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants

Body composition and morphological assessment of nutritional status in adults : a review of anthropometric variables

This document is the Accepted Manuscript version of the following article: A. M. Madden, and S. Smith, ‘Body composition and morphological assessment of nutritional status in adults: a review of anthropometric variables’, Journal of Human Nutrition and Dietetics, vol. 29 (1): 7-25, February 2016, DOI: https://doi.org/10.1111/jhn.12278 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Evaluation of body composition is an important part of assessing nutritional status and provides prognostically useful data and opportunity to monitor the effects of nutrition-related disease progression and nutritional intervention. The aim of this narrative review is to critically evaluate body composition methodology in adults, focusing on anthropometric variables. The variables considered include height, weight, body mass index and alternative indices, trunk measurements (waist and hip circumferences and sagittal abdominal diameter) and limb measurements (mid-upper arm and calf circumferences) and skinfold thickness. The importance of adhering to a defined measurement protocol, checking measurement error and the need to interpret measurements using appropriate population-specific cut-off values to identify health risks were identified. Selecting the optimum method of assessing body composition using anthropometry depends on the purpose, i.e. evaluating obesity or undernutrition, and requires practitioners to have a good understanding of both practical and theoretical limitations and to wisely interpret the results.Peer reviewe

Development of Functional and Molecular Correlates of Vaccine-Induced Protection for a Model Intracellular Pathogen, F. tularensis LVS

In contrast with common human infections for which vaccine efficacy can be evaluated directly in field studies, alternative strategies are needed to evaluate efficacy for slowly developing or sporadic diseases like tularemia. For diseases such as these caused by intracellular bacteria, serological measures of antibodies are generally not predictive. Here, we used vaccines varying in efficacy to explore development of clinically useful correlates of protection for intracellular bacteria, using Francisella tularensis as an experimental model. F. tularensis is an intracellular bacterium classified as Category A bioterrorism agent which causes tularemia. The primary vaccine candidate in the U.S., called Live Vaccine Strain (LVS), has been the subject of ongoing clinical studies; however, safety and efficacy are not well established, and LVS is not licensed by the U.S. FDA. Using a mouse model, we compared the in vivo efficacy of a panel of qualitatively different Francisella vaccine candidates, the in vitro functional activity of immune lymphocytes derived from vaccinated mice, and relative gene expression in immune lymphocytes. Integrated analyses showed that the hierarchy of protection in vivo engendered by qualitatively different vaccines was reflected by the degree of lymphocytes' in vitro activity in controlling the intramacrophage growth of Francisella. Thus, this assay may be a functional correlate. Further, the strength of protection was significantly related to the degree of up-regulation of expression of a panel of genes in cells recovered from the assay. These included IFN-γ, IL-6, IL-12Rβ2, T-bet, SOCS-1, and IL-18bp. Taken together, the results indicate that an in vitro assay that detects control of bacterial growth, and/or a selected panel of mediators, may ultimately be developed to predict the outcome of vaccine efficacy and to complement clinical trials. The overall approach may be applicable to intracellular pathogens in general

Precocious Natural Mummification in a Temperate Climate (Western Cape, South Africa)

The general process and pattern of decomposition is well-documented and understood. However, specific environmental conditions may alter this pattern and prematurely terminate the decay process. An example of this is natural mummification – a preservative process characterized by desiccation, brittleness and shrinkage of the skin and body tissues. It is important to understand how, when, and where such variations may occur, and for this reason environmentally-specific studies of decay are required. The aim of the present study was the establish baseline data on soft-tissue decomposition in two terrestrial habitats in the Western Cape. A total of 16 pig carcasses serving as analogues for humans were deployed in these habitats during two successive winters and summers between 2014 and 2016. The rate and pattern of decomposition were assessed via measurement of weight loss over time and scoring the decomposition process using Megyesi et al. (2005) Total Body Score system and study-specific criteria for mummification. Carcasses typically followed the expected pattern of decay with a few exceptions, most notably instances of rapid natural mummification. Natural mummification, as defined by Megyesi et al. (2005), was observed to occur as early as 17 days postmortem, with five carcasses mummifying in less than one month. The timing of natural mummification varies widely, from a few days to several years, averaging around three months in temperate regions. Natural mummification occurring in less than one month is termed precocious mummification and is rarely observed in temperate regions. With only three reports globally, this study’s findings are globally significant, highlighting the importance of regionally-specific decomposition studies. Two local forensic cases wherein precocious mummification has been observed are also presented and, considered together with the study’s results, a possible mechanism driving this process is proposed

A systematic review of the psychometric properties of self-report research utilization measures used in healthcare

<p>Abstract</p> <p>Background</p> <p>In healthcare, a gap exists between what is known from research and what is practiced. Understanding this gap depends upon our ability to robustly measure research utilization.</p> <p>Objectives</p> <p>The objectives of this systematic review were: to identify self-report measures of research utilization used in healthcare, and to assess the psychometric properties (acceptability, reliability, and validity) of these measures.</p> <p>Methods</p> <p>We conducted a systematic review of literature reporting use or development of self-report research utilization measures. Our search included: multiple databases, ancestry searches, and a hand search. Acceptability was assessed by examining time to complete the measure and missing data rates. Our approach to reliability and validity assessment followed that outlined in the <it>Standards for Educational and Psychological Testing</it>.</p> <p>Results</p> <p>Of 42,770 titles screened, 97 original studies (108 articles) were included in this review. The 97 studies reported on the use or development of 60 unique self-report research utilization measures. Seven of the measures were assessed in more than one study. Study samples consisted of healthcare providers (92 studies) and healthcare decision makers (5 studies). No studies reported data on acceptability of the measures. Reliability was reported in 32 (33%) of the studies, representing 13 of the 60 measures. Internal consistency (Cronbach's Alpha) reliability was reported in 31 studies; values exceeded 0.70 in 29 studies. Test-retest reliability was reported in 3 studies with Pearson's <it>r </it>coefficients > 0.80. No validity information was reported for 12 of the 60 measures. The remaining 48 measures were classified into a three-level validity hierarchy according to the number of validity sources reported in 50% or more of the studies using the measure. Level one measures (n = 6) reported evidence from any three (out of four possible) <it>Standards </it>validity sources (which, in the case of single item measures, was all applicable validity sources). Level two measures (n = 16) had evidence from any two validity sources, and level three measures (n = 26) from only one validity source.</p> <p>Conclusions</p> <p>This review reveals significant underdevelopment in the measurement of research utilization. Substantial methodological advances with respect to construct clarity, use of research utilization and related theory, use of measurement theory, and psychometric assessment are required. Also needed are improved reporting practices and the adoption of a more contemporary view of validity (<it>i.e.</it>, the <it>Standards</it>) in future research utilization measurement studies.</p