HIVToolbox, an Integrated Web Application for Investigating HIV

Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid and convenient than current approaches using isolated repositories. Several new hypotheses for integrase were created as an example, and we experimentally confirmed a predicted CK2 phosphorylation site. Weblink: [http://hivtoolbox.bio-toolkit.com

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Cashew Nut Production in Tanzania: Constraints and Progress through Integrated Crop Management.

Cashew (Anacardium occidentale L.) is the fourth most valuable Tanzanian export crop after coffee, cotton and tea. Following a steady increase in production from the middle of this century, there was a dramatic decline from 145,000 t in 1973 to 16,500 t in 1986. This was caused by a complex of socio-economic (low producer prices, inefficient marketing, villagisation) and biological factors (cashew powdery mildew disease, low tree yields, overcrowding of trees). Recently, higher cashew prices and liberalised marketing have created favourable conditions that have encouraged farmers to tackle several of the biological constraints on production. As a result, cashew production has risen steadily from 16,500 t in 1986 to 70,320 t in 1994

Alcohol Use Trajectories and Problem Drinking Over the Course of Adolescence: A Study of North American Indigenous Youth and Their Caretakers

This study investigated the links between alcohol use trajectories and problem drinking (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition abuse/dependence) using five waves of data from 727 North American Indigenous adolescents between 10 and 17 years from eight reservations sharing a common language and culture. Growth mixture models linking fundamental causes, social stressors, support, and psychosocial pathways to problem drinking via alcohol use trajectories over the early life course were estimated. Results indicated that 20 percent of the adolescents began drinking at 11 to 12 years of age and that another 20 percent began drinking shortly thereafter. These early drinkers were at greatly elevated risk for problem drinking, as were those who began drinking at age 13. The etiological analysis revealed that stressors (e.g., perceived discrimination) directly and indirectly influenced early and problem alcohol use by decreasing positive school attitudes while increasing feelings of anger and perceived delinquent friendships. Girls were found to be at risk independently of these other factors

Where should patients with or at risk of delirium be treated in an acute care system? Comparing the rates of delirium in patients receiving usual care versus alternative care : a systematic review and meta‐analysis

Background: Delirium is an acute condition that occurs in hospitalised patients and leads to poor patient outcomes that can last long term. Therefore, the importance of prevention is undeniable and adopting new models of care for at risk patients should be prioritised. Objectives: This systematic review and meta‐analysis will assess the effectiveness of different interventions designed to prevent or manage delirium in acutely unwell hospitalised patients. Methods: MEDLINE, EMBASE, PsychINFO, OpenGrey, Web of Science and reference lists of journals were searched. Eligible studies reported on incidence or duration of delirium, used a validated delirium diagnostic tool, and compared an intervention to either a control or another intervention group. Meta‐analyses were conducted, and GRADE pro software was used to assess the certainty of evidence. This review is registered on PROSPERO. Results: A total of 59 studies were included and 33 were eligible for meta‐analysis. Delirium incidence was most significantly reduced by non‐pharmacological multicomponent interventions compared to usual care, with pooled risk ratios of 0.57 (95% CI: 0.44 to 0.73, ten randomised controlled trials) and 0.47 (95% CI: 0.35 to 0.64, six observational studies). Single component interventions did not significantly reduce delirium incidence compared to usual care in seven randomised trials (risk ratio= 0.92, 95% CI: 0.81 to 1.04). The most effective single component intervention in reducing delirium incidence, was a hospital‐at‐home intervention (risk ratio = 0.29, 95% CI: 0.09 to 0.87). Conclusions: Non‐pharmacological multicomponent interventions are effective in preventing delirium, however the same cannot be said for other interventions due to uncertain results. There is some evidence that providing multicomponent interventions in patients’ homes is more effective than a hospital setting. Therefore, researching the benefits of hospital‐at‐home interventions in delirium prevention is recommended