Non-communicable diseases in the Western Area District, Sierra Leone, before and during the Ebola outbreak.

Setting: Twenty-seven peripheral health units, five secondary hospitals and one tertiary hospital, Western Area District, Sierra Leone. Objectives: To describe reporting systems, monthly attendances and facility-based patterns of six non-communicable diseases (NCDs) in the pre-Ebola and Ebola virus disease outbreak periods. Design: A cross-sectional study using programme data. Results: Reporting was 89% complete on the six selected NCDs pre-Ebola and 86% during the Ebola outbreak (P < 0.01). Overall, marked declining trends in NCDs were reported during the Ebola period, with a monthly mean of 342 cases pre-Ebola and 164 during the Ebola outbreak. The monthly mean number of cases per disease in the pre-Ebola and Ebola outbreak periods was respectively 228 vs. 85 for hypertension, 43 vs. 27 for cardiovascular diseases, 36 vs. 18 for diabetes and 25 vs. 29 for peptic ulcer disease; this last condition increased during the outbreak. There were higher proportions of NCDs among females during the Ebola outbreak compared with the pre-Ebola period. Except for peptic ulcer disease, the number of patients with NCDs declined by 25% in peripheral health units, 91% in the secondary hospitals and 70% in the tertiary hospital between the pre-Ebola and the Ebola outbreak periods. Conclusion: Comprehensive reporting of NCDs was suboptimal, and declined during the Ebola epidemic. There were decreases in reported attendances for NCDs between the pre-Ebola and the Ebola outbreak periods, which were even more marked in the hospitals. This study has important policy implications

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans

This is the final version. Available on open access from Wiley via the DOI in this record. Background: Skeletal muscle atrophy manifests across numerous diseases; however, the extent of similarities/differences in causal mechanisms between atrophying conditions in unclear. Ageing and disuse represent two of the most prevalent and costly atrophic conditions, with resistance exercise training (RET) being the most effective lifestyle countermeasure. We employed gene-level and network-level meta-analyses to contrast transcriptomic signatures of disuse and RET, plus young and older RET to establish a consensus on the molecular features of, and therapeutic targets against, muscle atrophy in conditions of high socio-economic relevance. Methods: Integrated gene-level and network-level meta-analysis was performed on publicly available microarray data sets generated from young (18–35 years) m. vastus lateralis muscle subjected to disuse (unilateral limb immobilization or bed rest) lasting ≥7 days or RET lasting ≥3 weeks, and resistance-trained older (≥60 years) muscle. Results: Disuse and RET displayed predominantly separate transcriptional responses, and transcripts altered across conditions were mostly unidirectional. However, disuse and RET induced directly inverted expression profiles for mitochondrial function and translation regulation genes, with COX4I1, ENDOG, GOT2, MRPL12, and NDUFV2, the central hub components of altered mitochondrial networks, and ZMYND11, a hub gene of altered translation regulation. A substantial number of genes (n = 140) up-regulated post-RET in younger muscle were not similarly up-regulated in older muscle, with young muscle displaying a more pronounced extracellular matrix (ECM) and immune/inflammatory gene expression response. Both young and older muscle exhibited similar RET-induced ubiquitination/RNA processing gene signatures with associated PWP1, PSMB1, and RAF1 hub genes. Conclusions: Despite limited opposing gene profiles, transcriptional signatures of disuse are not simply the converse of RET. Thus, the mechanisms of unloading cannot be derived from studying muscle loading alone and provides a molecular basis for understanding why RET fails to target all transcriptional features of disuse. Loss of RET-induced ECM mechanotransduction and inflammatory profiles might also contribute to suboptimal ageing muscle adaptations to RET. Disuse and age-dependent molecular candidates further establish a framework for understanding and treating disuse/ageing atrophy.Medical Research Council (MRC)Biotechnology and Biological Sciences Research Council (BBSRC)National Institute for Health Research (NIHR

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

Cyclic Behavior of HPFRCC Coupling Beams with Bundled Diagonal Bars

Coupled shear walls are efficient in resisting lateral forces induced by winds and earthquakes. However, it is difficult to construct coupled shear walls particularly because current design codes require complex reinforcing details within coupling beams. The objective of this study was to develop simple reinforcement details for diagonally reinforced coupling beams; reducing transverse steel by use of high-performance fiber-reinforced cementitious composites (HPFRCCs) and bundling diagonal bars are explored. Four coupling beam specimens with length-to-depth aspect ratios of 2.0 or 3.5 were fabricated and tested under cyclic lateral displacements. The test results revealed that HPFRCC coupling beams with bundled diagonal bars and widely spaced transverse reinforcement (one-half the amount of reinforcement required by current seismic codes) exhibited excellent seismic performance compared with ordinary concrete coupling beams having code-required distributed diagonal reinforcement and transverse reinforcement

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Intra-week spatial-temporal patterns of crime

Since its original publication, routine activity theory has proven most instructive for understanding temporal patterns in crime. The most prominent of the temporal crime patterns investigated is seasonality: crime (most often assault) increases during the summer months and decreases once routine activities are less often outside. Despite the rather widespread literature on the seasonality of crime, there is very little research investigating temporal patterns of crime at shorter time intervals such as within the week or even within the day. This paper contributes to this literature through a spatial-temporal analysis of crime patterns for different days of the week. It is found that temporal patterns are present for different days of the week (more crime on weekends, as would be expected) and there is a spatial component to that temporal change. Specifically, aside from robbery and sexual assault at the micro-spatial unit of analysis (street segments) the spatial patterns of crime changed. With regard to the spatial pattern changes, we found that assaults and theft from vehicle had their spatial patterns change in predictable ways on Saturdays: assaults increased in the bar district and theft from vehicles increased in the downtown and recreational car park areas

“A good little tool to get to know yourself a bit better”: a qualitative study on users’ experiences of app-supported menstrual tracking in Europe

Background: Menstrual apps facilitate observation and analysis of menstrual cycles and associated factors through the collection and interpretation of data entered by users. As a subgroup of health-related apps, menstrual apps form part of one of the most dynamic and rapidly growing developments in biomedicine and health care. However, despite their popularity, qualitative research on how people engaging in period-tracking use and experience these apps remains scarce. Results: An inductive content analysis was performed and eight characteristics of app-supported menstrual tracking were identified: 1) tracking menstrual cycle dates and regularities, 2) preparing for upcoming periods, 3) getting to know menstrual cycles and bodies, 4) verifying menstrual experiences and sensations, 5) informing healthcare professionals, 6) tracking health, 7) contraception and seeking pregnancy, and 8) changes in tracking. Our study finds that period-tracking via apps has the potential to be an empowering practice as it helps users to be more aware of their menstrual cycles and health and to gain new knowledge. However, we also show that menstrual tracking can have negative consequences as it leads to distress in some cases, to privacy issues, and the work it requires can result in cessation. Finally, we present practical implications for healthcare providers and app developers. Conclusions: This qualitative study gives insight into users’ practices and experiences of app-supported menstrual tracking. The results provide information for researchers, health care providers and app designers about the implications of app-supported period-tracking and describe opportunities for patient-doctor interactions as well as for further development of menstrual apps.This research has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 675378

Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Successful antiretroviral treatment programs in rural sub-Saharan Africa may face different challenges than programs in urban areas. The objective of this study was to identify patient characteristics, barriers to care, and treatment responses of HIV-infected children seeking care in rural Zambia.</p> <p>Methods</p> <p>Cross-sectional analysis of HIV-infected children seeking care at Macha Hospital in rural southern Zambia. Information was collected from caretakers and medical records.</p> <p>Results</p> <p>192 HIV-infected children were enrolled from September 2007 through September 2008, 28% of whom were receiving antiretroviral therapy (ART) at enrollment. The median age was 3.3 years for children not receiving ART (IQR 1.8, 6.7) and 4.5 years for children receiving ART (IQR 2.7, 8.6). 91% travelled more than one hour to the clinic and 26% travelled more than 5 hours. Most participants (73%) reported difficulties accessing the clinic, including insufficient money (60%), lack of transportation (54%) and roads in poor condition (32%). The 54 children who were receiving ART at study enrollment had been on ART a median of 8.6 months (IQR: 2.7, 19.5). The median percentage of CD4⁺T cells was 12.4 (IQR: 9.2, 18.6) at the start of ART, and increased to 28.6 (IQR: 23.5, 36.1) at the initial study visit. However, the proportion of children who were underweight decreased only slightly, from 70% at initiation of ART to 61% at the initial study visit.</p> <p>Conclusion</p> <p>HIV-infected children in rural southern Zambia have long travel times to access care and may have poorer weight gain on ART than children in urban areas. Despite these barriers, these children had a substantial rise in CD4⁺T cell counts in the first year of ART although longer follow-up may indicate these gains are not sustained.</p