Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

Background: Following recruitment of a private sector company, an 8week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. Methods. For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. Discussion. The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace. © 2012 Brown et al.; licensee BioMed Central Ltd

P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.

Invasion of erythrocytes by Plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development. RH5 is a leading subunit vaccine candidate because anti-RH5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion. RH5 is secreted, complexes with other parasite proteins including CyRPA and RIPR, and contains a conserved N-terminal region (RH5Nt) of unknown function that is cleaved from the native protein. Here, we identify P113 as a merozoite surface protein that directly interacts with RH5Nt. Using recombinant proteins and a sensitive protein interaction assay, we establish the binding interdependencies of all the other known RH5 complex components and conclude that the RH5Nt-P113 interaction provides a releasable mechanism for anchoring RH5 to the merozoite surface. We exploit these findings to design a chemically synthesized peptide corresponding to RH5Nt, which could contribute to a cost-effective malaria vaccine

Incentivizing the Use of Quantified Self Devices: The Cases of Digital Occupational Health Programs and Data-Driven Health Insurance Plans

Initially designed for a use in private settings, smartwatches, activity trackers and other quantified self devices are receiving a growing attention from the organizational environment. Firms and health insurance companies, in particular, are developing digital occupational health programs and data-driven health insurance plans centered around these systems, in the hope of exploiting their potential to improve individual health management, but also to gather large quantities of data. As individual participation in such organizational programs is voluntary, organizations often rely on motivational incentives to prompt engagement. Yet, little is known about the mechanisms employed in organizational settings to incentivize the use of quantified self devices. We therefore seek, in this exploratory paper, to offer a first structured overview of this topic and identify the main motivational incentives in two emblematical cases: digital occupational health programs and data-driven health insurance plans. By doing so, we aim to specify the nature of this new dynamic around the use of quantified self devices and define some of the key lines for further investigation

Partial Order Optimum Likelihood (POOL): Maximum Likelihood Prediction of Protein Active Site Residues Using 3D Structure and Sequence Properties

A new monotonicity-constrained maximum likelihood approach, called Partial Order Optimum Likelihood (POOL), is presented and applied to the problem of functional site prediction in protein 3D structures, an important current challenge in genomics. The input consists of electrostatic and geometric properties derived from the 3D structure of the query protein alone. Sequence-based conservation information, where available, may also be incorporated. Electrostatics features from THEMATICS are combined with multidimensional isotonic regression to form maximum likelihood estimates of probabilities that specific residues belong to an active site. This allows likelihood ranking of all ionizable residues in a given protein based on THEMATICS features. The corresponding ROC curves and statistical significance tests demonstrate that this method outperforms prior THEMATICS-based methods, which in turn have been shown previously to outperform other 3D-structure-based methods for identifying active site residues. Then it is shown that the addition of one simple geometric property, the size rank of the cleft in which a given residue is contained, yields improved performance. Extension of the method to include predictions of non-ionizable residues is achieved through the introduction of environment variables. This extension results in even better performance than THEMATICS alone and constitutes to date the best functional site predictor based on 3D structure only, achieving nearly the same level of performance as methods that use both 3D structure and sequence alignment data. Finally, the method also easily incorporates such sequence alignment data, and when this information is included, the resulting method is shown to outperform the best current methods using any combination of sequence alignments and 3D structures. Included is an analysis demonstrating that when THEMATICS features, cleft size rank, and alignment-based conservation scores are used individually or in combination THEMATICS features represent the single most important component of such classifiers

The contribution of office work to sedentary behaviour associated risk

Background: Sedentary time has been found to be independently associated with poor health and mortality. Further, a greater proportion of the workforce is now employed in low activity occupations such as office work. To date, there is no research that specifically examines the contribution of sedentary work to overall sedentary exposure and thus risk. The purpose of the study was to determine the total exposure and exposure pattern for sedentary time, light activity and moderate/vigorous physical activity (MVPA) of office workers during work and non-work time.Methods: 50 office workers from Perth, Australia wore an Actical (Phillips, Respironics) accelerometer during waking hours for 7 days (in 2008–2009). Participants recorded wear time, waking hours, work hours and daily activities in an activity diary. Time in activity levels (as percentage of wear time) during work and non-work time were analysed using paired t-tests and Pearson’s correlations.Results: Sedentary time accounted for 81.8% of work hours (light activity 15.3% and MVPA 2.9%), which was significantly greater than sedentary time during non-work time (68.9% p 30 minutes) and significantly less brief duration (0–10 minutes) light intensity activity during work hours compared to non-work time (p < 0.001). Further, office workers had fewer breaks in sedentary time during work hours compared to non-work time (p < 0.001).Conclusions: Office work is characterised by sustained sedentary time and contributes significantly to overall sedentary exposure of office workers

Influence of antenatal physical exercise on haemodynamics in pregnant women: a flexible randomisation approach

Background: Normal pregnancy is associated with marked changes in haemodynamic function, however theinfluence and potential benefits of antenatal physical exercise at different stages of pregnancy and postpartumremain unclear. The aim of this study was therefore to characterise the influence of regular physical exercise onhaemodynamic variables at different stages of pregnancy and also in the postpartum period.Methods: Fifty healthy pregnant women were recruited and randomly assigned (2 × 2 × 2 design) to a land orwater-based exercise group or a control group. Exercising groups attended weekly classes from the 20th week ofpregnancy onwards. Haemodynamic assessments (heart rate, cardiac output, stroke volume, total peripheralresistance, systolic and diastolic blood pressure and end diastolic index) were performed using the Task Forcehaemodynamic monitor at 12–16, 26–28, 34–36 and 12 weeks following birth, during a protocol including posturalmanoeurvres (supine and standing) and light exercise.Results: In response to an acute bout of exercise in the postpartum period, stroke volume and end diastolic indexwere greater in the exercise group than the non-exercising control group (p = 0.041 and p = 0.028 respectively).Total peripheral resistance and diastolic blood pressure were also lower (p = 0.015 and p = 0.007, respectively) in theexercise group. Diastolic blood pressure was lower in the exercise group during the second trimester (p = 0.030).Conclusions: Antenatal exercise does not appear to substantially alter maternal physiology with advancinggestation, speculating that the already vast changes in maternal physiology mask the influences of antenatalexercise, however it does appear to result in an improvement in a woman’s haemodynamic function (enhancedventricular ejection performance and reduced blood pressure) following the end of pregnancy

Ensemble-Based Computational Approach Discriminates Functional Activity of p53 Cancer and Rescue Mutants

The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain (“cancer mutants”). Activity can be restored by second-site suppressor mutations (“rescue mutants”). This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD), without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC) metric was strongly correlated (r2 = 0.77) with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants were more flexible than wild-type protein, (ii) second-site rescue mutations decreased the flexibility of cancer mutants, and (iii) negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants