High-dose corticosteroids in severe acute asthma.

Twenty-six patients admitted to hospital for treatment of severe exacerbations of asthma unresponsive to bronchodilators were assigned to high-, medium-, or low-dose corticosteroid treatment regimens. The rates of recovery were assessed by changes in pulse rate, peak expiratory flow rate, and spirometric measurements and were not related to the dose of corticosteroids given. Very high systemic doses of corticosteroids do not offer significant advantages in treating severe exacerbations of asthma.     

N-Alkyl-N-arylmethylpiperidin-4-amines: novel dual inhibitors of serotonin and norepinephrine reuptake

A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake.     

Discrepant Prevalence and Incidence of Leishmania Infection between Two Neighboring Villages in Central Mali Based on Leishmanin Skin Test Surveys

Apart from a single report, the last publication of cutaneous leishmaniasis (CL) in Mali dates back more than 20 years. The absence of information on the current status of CL in Mali led us to conduct a cohort study in Kemena and Sougoula, two villages in Central Mali from which cases of CL have been recently diagnosed by Mali''s reference dermatology center in Bamako. In May 2006, we determined the baseline prevalence of Leishmania infection in the two villages using the leishmanin skin test (LST). LST-negative individuals were then re-tested over two consecutive years to estimate the annual incidence of Leishmania infection. The prevalence of Leishmania infection was significantly higher in Kemena than in Sougoula (45.4% vs. 19.9%; OR: 3.36, CI: 2.66–4.18). The annual incidence of Leishmania infection was also significantly higher in Kemena (18.5% and 17% for 2007 and 2008, respectively) than in Sougoula (5.7% for both years). These data demonstrate that the risk of Leishmania infection was stable in both villages and confirm the initial observation of a significantly higher risk of infection in Kemena (OR: 3.78; CI: 2.45–6.18 in 2007; and OR: 3.36; CI: 1.95–5.8 in 2008; P<0.005). The absence of spatial clustering of LST-positive individuals in both villages indicated that transmission may be occurring anywhere within the villages. Although Kemena and Sougoula are only 5 km apart and share epidemiologic characteristics such as stable transmission and random distribution of LST-positive individuals, they differ markedly in the prevalence and annual incidence of Leishmania infection. Here we establish ongoing transmission of Leishmania in Kemena and Sougoula, Central Mali, and are currently investigating the underlying factors that may be responsible for the discrepant infection rates we observed between them.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00344084","term_id":"NCT00344084"}}NCT00344084     

Use of magnetically purified Plasmodium falciparum parasites improves the accuracy of erythrocyte invasion assays

Merozoite invasion of erythrocytes is a crucial step for the asexual cycle of Plasmodium falciparum. Multiple invasion pathways, which involve different ligand-receptor interactions, have been identified in P. falciparum by examining the entry of purified parasite into erythrocytes with different surface receptors, either mutant or under different enzyme treatments. The most critical step for a successful invasion assay is the isolation of erythrocytes infected with viable schizonts. Here, we applied a magnetic column to purify the schizonts for the erythrocyte invasion assay. Comparing to Percoll-sorbitol purification method, this modified approach showed great improvement on reproducibility and reliability of invasion assay, particularly for short-term, culture-adapted parasite isolates. The magnetic purification method is an excellent alternative for parasite isolates that do not tolerate or with unknown sensitivity to Percoll-sorbitol exposure.     

Evolving origin-of-transfer sequences on staphylococcal conjugative and mobilizable plasmids—who’s mimicking whom?

In Staphylococcus aureus, most multiresistance plasmids lack conjugation or mobilization genes for horizontal transfer. However, most are mobilizable due to carriage of origin-of-transfer (oriT) sequences mimicking those of conjugative plasmids related to pWBG749. pWBG749-family plasmids have diverged to carry five distinct oriT subtypes and non-conjugative plasmids have been identified that contain mimics of each. The relaxasome accessory factor SmpO, encoded by each conjugative plasmid, determines specificity for its cognate oriT. Here we characterized the binding of SmpO proteins to each oriT. SmpO proteins predominantly formed tetramers in solution and bound 5′-GNNNNC-3′ sites within each oriT. Four of the five SmpO proteins specifically bound their cognate oriT. An F7K substitution in pWBG749 SmpO switched oriT-binding specificity in vitro. In vivo, the F7K substitution reduced but did not abolish self-transfer of pWBG749. Notably, the substitution broadened the oriT subtypes that were mobilized. Thus, this substitution represents a potential evolutionary intermediate with promiscuous DNA-binding specificity that could facilitate a switch between oriT specificities. Phylogenetic analysis suggests pWBG749-family plasmids have switched oriT specificity more than once during evolution. We hypothesize the convergent evolution of oriT specificity in distinct branches of the pWBG749-family phylogeny reflects indirect selection pressure to mobilize plasmids carrying non-cognate oriT-mimics.     

Quantifying the robustness of first arrival dates as a measure of avian migratory phenology

As the climate changes, many long‐term studies have shown that the timing of bird migration is shifting, increasing the need for reliable measures of migratory phenology. Ideally, daily counts of birds at a site are used to calculate the mean arrival date (MAD) but, as this approach is not always possible and is very labour‐intensive, simpler metrics such as first arrival date (FAD) have commonly been used. Here, we examine the relationship between FAD and MAD in 28 summer migrant bird species over a 42‐year period (1970–2011) at Portland Bird Observatory, UK. Although significant correlations between FAD and MAD were detected, relationships were weak, particularly in long‐distance migrants. We suggest that FAD, although a simple and straightforward measure, is not particularly robust as a proxy for overall migratory phenology at a population level.     

Benzothienyloxy phenylpropanamines, novel dual inhibitors of serotonin and norepinephrine reuptake

A series of benzothienyloxy propylamines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake.