PfHRP2 and PfLDH antigen detection for monitoring the efficacy of artemisinin-based combination therapy (ACT) in the treatment of uncomplicated falciparum malaria

<p>Abstract</p> <p>Background</p> <p>An assessment of the accuracy of two malaria rapid diagnostic tests (RDT) for the detection of <it>Plasmodium falciparum </it>histidine-rich protein 2 (<it>Pf</it>HRP2) or <it>Pf </it>lactate dehydrogenase (<it>Pf</it>LDH) was undertaken in children aged between six and 59 months included in an anti-malarial efficacy study in Benin.</p> <p>Methods</p> <p>In Allada (Benin), 205 children aged 6-59 months with falciparum malaria received either artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL), or sulphadoxine-pyrimethamine (SP). Children included in the study were simultaneously followed by both RDT and high-quality microscopy for up to 42 days.</p> <p>Results</p> <p>At the time of inclusion, <it>Pf</it>HRP2-based tests were positive in 203 children (99%) and <it>Pf</it>LDH-based tests were positive in 204 (99.5%). During follow-up, independent of the treatment received, only 17.3% (28/162) of children effectively cured were negative with the <it>Pf</it>HRP2 RDT at day 3, with a gradual increase in specificity until day 42. The specificity of antigen detection with the <it>Pf</it>LDH test was 87% (141/162) on day 3, and between 92% and 100% on days 7 to 42. A statistical difference was observed between the persistence of <it>Pf</it>HRP2 and <it>Pf</it>LDH antigenaemia during follow-up in children treated with artemisinin-based combination therapy (ACT) but not with SP.</p> <p>Conclusion</p> <p>Although both RDTs are as sensitive as microscopy in detecting true malaria cases, the <it>Pf</it>HRP2 RDT had very low specificity during follow-up until day 28. On the other hand, the <it>Pf</it>LDH test could be used to detect failures and, therefore, to assess anti-malarial efficacy.</p

Acidic Extracellular pH Promotes Activation of Integrin αvβ3

Acidic extracellular pH is characteristic of the cell microenvironment in several important physiological and pathological contexts. Although it is well established that acidic extracellular pH can have profound effects on processes such as cell adhesion and migration, the underlying molecular mechanisms are largely unknown. Integrin receptors physically connect cells to the extracellular matrix, and are thus likely to modulate cell responses to extracellular conditions. Here, we examine the role of acidic extracellular pH in regulating activation of integrin [alpha]v[beta]3. Through computational molecular dynamics simulations, we find that acidic extracellular pH promotes opening of the [alpha]v[beta]3 headpiece, indicating that acidic pH can thereby facilitate integrin activation. This prediction is consistent with our flow cytometry and atomic force microscope-mediated force spectroscopy assays of integrin [alpha]v[beta]3 on live cells, which both demonstrate that acidic pH promotes activation at the intact cell surface. Finally, quantification of cell morphology and migration measurements shows that acidic extracellular pH affects cell behavior in a manner that is consistent with increased integrin activation. Taken together, these computational and experimental results suggest a new and complementary mechanism of integrin activation regulation, with associated implications for cell adhesion and migration in regions of altered pH that are relevant to wound healing and cancer.National Institute of Biomedical Imaging and Bioengineering (U.S.) (Award Number T32EB006348)Massachusetts Institute of Technology (Collamore-Rogers Fellowship)National Institutes of Health (U.S.) (NIH Cell Migration Consortium Grant U54-GM069668)National Science Foundation (U.S.) (CAREER Award)Singapore-MIT Alliance for Research and Technology (BioSystem and Micromechanics (BioSyM) Interdisciplinary Research Group

Rapid testing versus karyotyping in Down's syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities

In all, 80% of antenatal karyotypes are generated by Down's syndrome screening programmes (DSSP). After a positive screening, women are offered prenatal foetus karyotyping, the gold standard. Reliable molecular methods for rapid aneuploidy diagnosis (RAD: fluorescence in situ hybridization (FISH) and quantitative fluorescence PCR (QF-PCR)) can detect common aneuploidies, and are faster and less expensive than karyotyping

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Developmental pattern of androgen-regulated proteins in seminal vesicles from the mouse.

International audienceProteins from secretions or homogenates of mice seminal vesicles were analysed by polyacrylamide gel electrophoresis. In homogenates about 15 bands were differentially induced with molecular weights (MW's) of 12, 13, 14, 15, 15.5, 71, 120 and 140 kD, or repressed molecular weights of 12.5, 14.3, 28, 30, 53, 73, 90-105 kD). The effects of castration were reversed by testosterone and dihydrotestosterone but not by oestradiol, progesterone or corticosterone. When the androgen-dependence of proteins was investigated using radioactive methionine the protein spectra showed that about 12 bands with molecular weights of 13, 13.7, 14, 15, 15.5, 16, 20.5, 24, 37, 38.5, 56, 68, 96 and 180 kD were differentially induced or repressed by androgens. Of the induced proteins, those with low molecular weight (12-15.5 kD) were accumulated in significant amounts between 20 days and 30 days, coincident with the pubertal increase of androgens in the seminal vesicles. Those induced proteins with high molecular weight (71, 120 and 140 kD) appeared between 40 days and 60 days. The androgen-repressed proteins were strongly evident in immature males, but disappeared after day 40

Lack of expression of the mRNA encoding a major protein of the mouse vas deferens after neonatal exposure to oestrogens

International audienc