Age-disparity, sexual connectedness and HIV infection in disadvantaged communities around Cape Town, South Africa: a study protocol

The original publication is available at http://www.biomedcentral.com/1471-2458/11/616Abstract: Background Crucial connections between sexual network structure and the distribution of HIV remain inadequately understood, especially in regard to the role of concurrency and age disparity in relationships, and how these network characteristics correlate with each other and other risk factors. Social desirability bias and inaccurate recall are obstacles to obtaining valid, detailed information about sexual behaviour and relationship histories. Therefore, this study aims to use novel research methods in order to determine whether HIV status is associated with age-disparity and sexual connectedness as well as establish the primary behavioural and socio-demographic predictors of the egocentric and community sexual network structures. Method/Design We will conduct a cross-sectional survey that uses a questionnaire exploring one-year sexual histories, with a focus on timing and age disparity of relationships, as well as other risk factors such as unprotected intercourse and the use of alcohol and recreational drugs. The questionnaire will be administered in a safe and confidential mobile interview space, using audio computer-assisted self-interview (ACASI) technology on touch screen computers. The ACASI features a choice of languages and visual feedback of temporal information. The survey will be administered in three peri-urban disadvantaged communities in the greater Cape Town area with a high burden of HIV. The study communities participated in a previous TB/HIV study, from which HIV test results will be anonymously linked to the survey dataset. Statistical analyses of the data will include descriptive statistics, linear mixed-effects models for the inter- and intra-subject variability in the age difference between sexual partners, survival analysis for correlated event times to model concurrency patterns, and logistic regression for association of HIV status with age disparity and sexual connectedness. Discussion This study design is intended to facilitate more accurate recall of sensitive sexual history data and has the potential to provide substantial insights into the relationship between key sexual network attributes and additional risk factors for HIV infection. This will help to inform the design of context-specific HIV prevention programmes.Publishers' versio

Diverse Profiles of Anxiety Related Disorders in Fragile X, Cornelia de Lange and Rubinstein–Taybi Syndromes

Anxiety disorders are heightened in specific genetic syndromes in comparison to intellectual disability of heterogeneous aetiology. In this study, we described and contrasted anxiety symptomatology in fragile X (FXS), Cornelia de Lange (CdLS) and Rubinstein–Taybi syndromes (RTS), and compared the symptomatology to normative data for typically-developing children and children diagnosed with an anxiety disorder. Scores did not differ between children diagnosed with an anxiety disorder and (a) participants with FXS on social phobia, panic/agoraphobia, physical injury fears, and obsessive–compulsive subscales (b) participants with CdLS on separation anxiety, generalized anxiety, panic/agoraphobia, physical injury fears and obsessive–compulsive subscales, and (c) participants with RTS on panic/agoraphobia and obsessive–compulsive subscales. The results highlight divergent profiles of anxiety symptomatology between these groups

Mavoglurant in Fragile X Syndrome:Results of two open-label, extension trials in adults and adolescents

Fragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual and developmental disabilities. Mavoglurant, a selective metabotropic glutamate receptor subtype-5 antagonist, has shown positive neuronal and behavioral effects in preclinical studies, but failed to demonstrate any behavioral benefits in two 12-week, randomized, placebo-controlled, double-blind, phase IIb studies in adults and adolescents with FXS. Here we report the long-term safety (primary endpoint) and efficacy (secondary endpoint) results of the open-label extensions. Adolescent (n = 119, aged 12-19 years) and adult (n = 148, aged 18-45 years) participants received up to 100 mg bid mavoglurant for up to 34 months. Both extension studies were terminated prematurely due to lack of proven efficacy in the core studies. Mavoglurant was well tolerated with no new safety signal. Five percent of adults and 16.9 percent of adolescents discontinued treatment due to adverse events. Gradual and consistent behavioral improvements as measured by the ABC-C <sub>FX</sub> scale were observed, which were numerically superior to those seen in the placebo arm of the core studies. These two extension studies confirm the long-term safety of mavoglurant in FXS, but further investigations are required to determine whether and under which conditions the significant preclinical results obtained with mGluR5 inhibition can translate to humans

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10-8).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee

The relationship between objectively measured attributes of the built environment and selected cardiovascular risk factors in a South African urban setting

BACKGROUND: Evidence concerning the relationship between objectively-measured attributes of the built environment with cardio-metabolic risk in populations from lower- and middle-income countries is lacking. In this paper, we describe the association between the objectively-measured built environment with body mass index, blood pressure and physical activity in adult South Africans. METHODS: This cross-sectional study included 341 adults aged ≥35 years drawn from the Cape Town arm of the Prospective Urban Rural Epidemiology (PURE) cohort study. All Cape Town PURE participants were invited to take part in the study. Actigraph GT3X accelerometer and Geographic Information Systems were used to measure physical activity and built environment attributes (community center, shopping center and taxi rank). RESULTS: In age and sex adjusted models (reference 500 m), access to community centers (1000 m) was positively related to body mass index [beta 4.70 (95%CI: 2.06 to 7.34)] and diastolic blood pressure [4.97 (0.00 to 9.95)]. Distance from a community center (1600 m) was positively related to diastolic blood pressure [6.58 (1.57 to 11.58)] and inversely with moderate-to-vigorous physical activity [− 69.30 (− 134.92 to − 3.70)]. Distance to a shopping center (1600 m) was positively related to body mass index [4.78 (1.11 to 8.45)] and shopping center (1000 m) was positively related to systolic blood pressure respectively [76.99 (0.03 to 83.95)]. CONCLUSION: Distance to community and shopping centers were significantly associated with BMI, systolic, diastolic blood pressure and moderate-to-vigorous physical activity. Future research should include multiple aspects of built environment variables in order to provide for a broader understanding of their effect on cardiovascular risk profile of African populations