Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission\ud in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead\ud role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a\ud predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate\ud all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major\ud mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1

Initial results of secukinumab drug survival in patients with psoriasis: A multicentre daily practice cohort study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan–Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice

Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells

Hematopoietic stem cells (HSCs) in adult marrow are believed to be derived from fetal liver precursors. To study cell kinetics involved in long-term hematopoiesis, we studied single-sorted candidate HSCs from fetal liver that were cultured in the presence of a mixture of stimulatory cytokines. After 8–10 d, the number of cells in primary cultures varied from <100 to >10,000 cells. Single cells in slow growing colonies were recloned upon reaching a 100–200 cell stage. Strikingly, the number of cells in subclones varied widely again. These results are indicative of asymmetric divisions in primitive hematopoietic cells in which proliferative potential and cell cycle properties are unevenly distributed among daughter cells. The continuous generation of functional heterogeneity among the clonal progeny of HSCs is in support of intrinsic control of stem cell fate and provides a model for the long-term maintenance of hematopoiesis in vitro and in vivo

The caribbean coastal marine productivity program (CARICOMP)

CARICOMP is a regional scientific program to study land-sea interaction processes in the Caribbean coastal zone. It has been collecting data since 1992, when a Data Management Centre was established at the University of the West Indies in Jamaica. Initially it focuses on documenting the structure and productivity of major coastal communities (mangrove forests, seagrass meadows and coral reefs) at relatively undisturbed sites in diverse physical settings. Second, by regular recording of physical and biological parameters, it monitors for change, seeking to distinguish natural from anthropogenic disturbance. Third, it constitutes a regional network of observers, able to collaborate on studies of region-wide events. Examples are presented of the diverse data sets collected by the Program.Fil: Alcolado, Pedro M.. Instituto de Oceanología; CubaFil: Alleng, Gerard. No especifíca;Fil: Bonair, Kurt. No especifíca;Fil: Bone, David. Universidad Simón Bolívar; VenezuelaFil: Buchan, Kenneth. No especifíca;Fil: Bush, Phillippe G.. Protection and Conservation Unit; Islas CaimánFil: De Meyer, Kalli. No especifíca;Fil: Garcia, Jorge R.. Universidad de Puerto Rico; Puerto RicoFil: Garzón Ferreira, Jaime. Instituto de Investigaciones Marinas y Costeras; ColombiaFil: Gayle, Peter M. H.. Discovery Bay Marine Laboratory; JamaicaFil: Gerace, Donald T.. Bahamian Field Station; BahamasFil: Geraldes, Francisco X.. Universidad Autonoma de Santo Domingo.; República DominicanaFil: Dahlgren, Eric Jordán. Universidad Nacional Autónoma de México; MéxicoFil: Kjferve, Björn. University of South Carolina; Estados UnidosFil: Klein, Eduardo. Universidad Simón Bolívar; VenezuelaFil: Koltes, Karen. Smithsonian Institution; Estados UnidosFil: Laydoo, Richard S.. No especifíca;Fil: Linton, Dulcie M.. University of the West Indies ; JamaicaFil: Ogden, John C.. Florida Institute of Oceanography; Estados UnidosFil: Oxenford, Hazel A.. McGill University; BarbadosFil: Parker, Christoph. McGill University; BarbadosFil: Penchaszadeh, Pablo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Pors, Leon P. P. J.. Universidad Simón Bolívar; VenezuelaFil: Ramírez Ramírez, Javier. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Física; MéxicoFil: Ruiz Rentería, Francisco. Universidad Nacional Autónoma de México; MéxicoFil: Ryan, Joseph D.. Centro de Investigación y Documentación de la Costa Atlántica; NicaraguaFil: Smith, Struan R.. Bermuda Biological Station for Research; BermudasFil: Tschirky, John. Latin American and Caribbean Division; Estados UnidosFil: Varela, Ramon. Estación de Investigaciones Marinas de Margarita; VenezuelaFil: Walker, Susan. No especifíca;Fil: Weil, Ernesto. Universidad de Puerto Rico; Puerto RicoFil: Wiebe, William J.. University of Georgia; Estados UnidosFil: Woodley, Jeremy D.. University of the West Indies; JamaicaFil: Zieman, Joseph C.. University of Virginia; Estados Unido

A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer

<p>Abstract</p> <p>Background</p> <p>NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC.</p> <p>Methods</p> <p>An in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance.</p> <p>Results</p> <p>GC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells.</p> <p>Conclusions</p> <p>NET1 plays an important role in GC cell migration and invasion, key aspects of GC progression. Furthermore, the gene expression profile further elucidates the molecular mechanisms underpinning NET1-mediated aggressive GC cell behaviour.</p

Initial Results of Secukinumab Drug Survival in Patients with Psoriasis:A Multicentre Daily Practice Cohort Study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials (RCTs). However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least 1 episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practic

Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older. Methods Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health. Findings Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week. Interpretation Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.Peer reviewe