Educational status and religion influence uptake of voluntary HIV counseling and testing by Ghanaian antenatal clinic attendees.

A cross-sectional survey of 150 gravidae, randomly sampled from three antenatal clinics in Tema was conducted to investigate factors influencing their acceptance of routine “opt-out” counseling and testing. Descriptive analysis was done for participants’ demographic characteristics, as well as knowledge of vertical transmission and its implications for mother and child. Other measures of interest were rate and potential determinants of acceptance. Associations between respondents’ socio-demographic variables and acceptance behaviour were determined using odds ratios, with p-values and 95% confidence intervals. P-values were obtained from Fisher’s exact tests and significance levels set at a p-value of 0.05. Participants’ mean age was 29.7years±1.31 (95% CI 24.15-35.25). Of 150 participants, 76.7% (115/150) were married, 9.3% (14/150) had received no formal education, 25.3% (38/150) were unemployed and 78.7% (118/150) were Christians. Most (96%; 144/150) respondents knew about the disease and 89% (128/144) of this proportion identified vertical transmission as a means for its spread. Within the latter, 69% (87/128) knew of preventive interventions against vertical transmission. Acceptance rate of counseling and testing was approximately 93% (140/150). Main reasons cited for acceptance were to safeguard mother’s own health (92.1%, 129/140) and to prevent transmission to baby (87.1%, 122/140). Respondents identified fear (80%, 8/10) and stigmatization (70%, 7/10) as perceived barriers to acceptance. Age (OR=2.78; 95% CI=0.62-12.42; p=0.16), parity (OR=1.98; 95%CI=0.39-10.14; p=0.41) and marital status (OR=2.04; 95%CI=0.46-9.02; p=0.34) did not influence acceptance behaviour. Educated women were about 1.5 times [(132/136)/(9/14); OR=24.44; 95%CI=5.02-118.99; p=0.001)] more likely than their uneducated counterparts to accept counseling and testing services, while Christian women were 1.2 times [(115/118)/(26/32]); OR=13.27; 95%CI=2.53- 69.51; p=0.001)] more likely to do so than Muslims. Counseling and testing services were highly acceptable among our sample irrespective of age, parity and marital status. Educational status and religion were potential determinants of acceptance. Keywords: HIV, voluntary counseling and testing (VCT), prevention of mother-to-child transmission (PMTCT), Ghana

Self-Organization of Muscle Cell Structure and Function

The organization of muscle is the product of functional adaptation over several length scales spanning from the sarcomere to the muscle bundle. One possible strategy for solving this multiscale coupling problem is to physically constrain the muscle cells in microenvironments that potentiate the organization of their intracellular space. We hypothesized that boundary conditions in the extracellular space potentiate the organization of cytoskeletal scaffolds for directed sarcomeregenesis. We developed a quantitative model of how the cytoskeleton of neonatal rat ventricular myocytes organizes with respect to geometric cues in the extracellular matrix. Numerical results and in vitro assays to control myocyte shape indicated that distinct cytoskeletal architectures arise from two temporally-ordered, organizational processes: the interaction between actin fibers, premyofibrils and focal adhesions, as well as cooperative alignment and parallel bundling of nascent myofibrils. Our results suggest that a hierarchy of mechanisms regulate the self-organization of the contractile cytoskeleton and that a positive feedback loop is responsible for initiating the break in symmetry, potentiated by extracellular boundary conditions, is required to polarize the contractile cytoskeleton

Structural Basis for Substrate Specificity in Human Monomeric Carbonyl Reductases

Carbonyl reduction constitutes a phase I reaction for many xenobiotics and is carried out in mammals mainly by members of two protein families, namely aldo-keto reductases and short-chain dehydrogenases/reductases. In addition to their capacity to reduce xenobiotics, several of the enzymes act on endogenous compounds such as steroids or eicosanoids. One of the major carbonyl reducing enzymes found in humans is carbonyl reductase 1 (CBR1) with a very broad substrate spectrum. A paralog, carbonyl reductase 3 (CBR3) has about 70% sequence identity and has not been sufficiently characterized to date. Screening of a focused xenobiotic compound library revealed that CBR3 has narrower substrate specificity and acts on several orthoquinones, as well as isatin or the anticancer drug oracin. To further investigate structure-activity relationships between these enzymes we crystallized CBR3, performed substrate docking, site-directed mutagenesis and compared its kinetic features to CBR1. Despite high sequence similarities, the active sites differ in shape and surface properties. The data reveal that the differences in substrate specificity are largely due to a short segment of a substrate binding loop comprising critical residues Trp229/Pro230, Ala235/Asp236 as well as part of the active site formed by Met141/Gln142 in CBR1 and CBR3, respectively. The data suggest a minor role in xenobiotic metabolism for CBR3. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Effects of Genetic Variation in Protease Activated Receptor 4 after an Acute Coronary Syndrome: Analysis from the TRACER trial

© 2018 Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (Sept 2018) in accordance with the publisher’s archiving policyVariation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02–0.92] P = 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is ~65%.This work was supported by the National Institutes of Health [grant number HL102482]; the University of Utah Division of Hematology and Hematologic Malignancies; and the Cardeza Foundation for Hematologic Research

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome