Impact of ministry of health interventions on private medicine retailer knowledge and practices on anti-malarial treatment in Kenya.

Small-scale interventions on training medicine retailers on malaria treatment improve over-the-counter medicine use, but there is little evidence on effectiveness when scaled up. This study evaluated the impact of Ministry of Health (MoH) training programs on the knowledge and practices of medicine retailers in three districts in Kenya. A cluster randomized trial was planned across 10 administrative divisions. Findings indicated that 30.7% (95% confidence interval [CI]: 23.3, 39.0) and 5.2% (95% CI: 2.1, 10.3) of program and control retailers, respectively, sold MoH amodiaquine with correct advice on use to surrogate clients (OR = 8.8; 95% CI: 2.9, 26.9; P < 0.001). Similarly, 61.8% (95% CI: 54.2, 69.1) and 6.3% (95% CI: 2.7, 12.1) of program and control retailers, respectively, reported correct knowledge on dosing with amodiaquine (OR = 29.8; 95% CI: 8.2, 108.8). Large-scale retailer training programs within the national malaria control framework led to significant improvements in retailers' practices across three districts

Fibroblasts as architects of cancer pathogenesis

AbstractStudies of epithelial cancers (i.e., carcinomas) traditionally focused on transformation of the epithelium (i.e., the cancer cells) and how aberrant signaling within the cancer cells modulates the surrounding tissue of origin. In more recent decades, the normal cells, blood vessels, molecules, and extracellular components that surround the tumor cells, collectively known as the “tumor microenvironment” or “stroma”, have received increasing attention and are now thought to be key regulators of tumor initiation and progression. Of particular relevance to the work reviewed herein are the fibroblasts, which make up the major cell type within the microenvironment of most carcinomas. Due to their inherent heterogeneity, plasticity, and function, it is perhaps not surprising that fibroblasts are ideal modulators of normal and cancerous epithelium; however, these aspects also present challenges if we are to interrupt their tumor-supportive functions. Here, we review the current body of knowledge and the many questions that still remain about the special entity known as the cancer-associated fibroblast. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease

Seasonality in the Surface Energy Balance of Tundra in the Lower Mackenzie River Basin

This study details seasonal characteristics in the annual surface energy balance of upland and lowland tundra during the 1998–99 water year (Y2). It contrasts the results with the 1997–98 water year (Y1) and relates the findings to the climatic normals for the lower Mackenzie River basin region. Both years were much warmer than the long-term average, with Y1 being both warmer and wetter than Y2. Six seasons are defined as early winter, midwinter, late winter, spring, summer, and fall. The most rapid changes in the surface energy balance occur in spring, fall, and late winter. Of these, spring is the most dynamic, and there is distinct asymmetry between rates of change in spring and those in fall. Rates of change of potential insolation (extraterrestrial solar radiation) in late winter, spring, and fall are within 10% of one another, being highest in late winter and smallest in spring. Rates of change in air temperature and ground temperature are twice as large in spring as in fall and late winter, when they are about the same. Rates of change in components of the energy balance in spring are twice and 4 times as large as in fall and late winter, respectively. The timing of snowpack ripening and snowmelt is the major agent determining the magnitude of asymmetry between fall and spring. This timing is a result of interaction between the solar cycle, air temperature, and snowpack longevity. Based on evidence from this study, potential surface responses to a 18C increase in air temperature are small to moderate in most seasons, but are large in spring when increases range from 7% to 10% of average surface energy fluxes

Second generation catalytic enantioselective nucleophilic desymmetrization at P(V): improved generality, efficiency and modularity

A broadly improved second generation catalytic two-phase strategy for the enantioselective synthesis of chiral at phosphorus (V) compounds is described. This protocol, consisting of a bifunctional iminophosphorane (BIMP) catalyzed nucleophilic desymmetrization of prochiral, bench stable P(V) precursors and subsequent enantiospecific substitution allows for divergent access to a wide range of C-, N-, O- and S- substituted P(V) containing compounds from a handful of enantioenriched precursors. A new ureidopeptide BIMP catalyst/thiaziolidinone leaving group combination allowed for a far wider substrate scope and increased reaction efficiency and practicality over previously established protocols. The resulting enantioenriched intermediates could then be transformed into an even greater range of distinct classes of P(V) compounds by displacement of the remaining leaving group as well as allowing for even further diversification downstream. Density functional theory (DFT) calculations were performed to pinpoint the origin of enantioselectivity for the BIMP-catalyzed desymmetrization, to rationalize how a superior catalyst/leaving group combination leads to increased generality in our second-generation catalytic system, as well as to shed light onto observed retention and inversion pathways when performing late-stage enantiospecific SN2@P reactions with Grignard reagents

Second generation catalytic enantioselective nucleophilic desymmetrization at P(V): improved generality, efficiency and modularity

A broadly improved second generation catalytic two-phase strategy for the enantioselective synthesis of chiral at phosphorus (V) compounds is described. This protocol, consisting of a bifunctional iminophosphorane (BIMP) catalyzed nucleophilic desymmetrization of prochiral, bench stable P(V) precursors and subsequent enantiospecific substitution allows for divergent access to a wide range of C-, N-, O- and S- substituted P(V) containing compounds from a handful of enantioenriched precursors. A new ureidopeptide BIMP catalyst/thiaziolidinone leaving group combination allowed for a far wider substrate scope and increased reaction efficiency and practicality over previously established protocols. The resulting enantioenriched intermediates could then be transformed into an even greater range of distinct classes of P(V) compounds by displacement of the remaining leaving group as well as allowing for even further diversification downstream. Density functional theory (DFT) calculations were performed to pinpoint the origin of enantioselectivity for the BIMP-catalyzed desymmetrization, to rationalize how a superior catalyst/leaving group combination leads to increased generality in our second-generation catalytic system, as well as to shed light onto observed retention and inversion pathways when performing late-stage enantiospecific SN2@P reactions with Grignard reagents