Evidence-Based African First Aid Guidelines and Training Materials

Stijn Van de Velde and colleagues describe the African First Aid Materials project, which developed evidence-based guidelines on administering first aid in the African context as well as training materials to support the implementation of the guidelines

Perinatal Mortality in Eastern Uganda: A Community Based Prospective Cohort Study

To achieve a child mortality reduction according to millennium development goal 4, it is necessary to considerably reduce neonatal mortality. We report stillbirth and early neonatal mortality risks as well as determinants of perinatal mortality in Eastern Uganda.A community-based prospective cohort study was conducted between 2006 and 2008. A total of 835 pregnant women were followed up for pregnancy outcome and survival of their children until 7 days after delivery. Mother's residence, age, parity, bed net use and whether delivery took place at home were included in multivariable regression analyses to identify risk factors for perinatal death.The stillbirth risk was 19 per 1,000 pregnancies and the early neonatal death risk 22 per 1,000 live births. Overall, the perinatal mortality risk was 41 [95%CI: 27, 54] per 1,000 pregnancies. Of the deaths, 47% followed complicated deliveries and 24% preterm births. Perinatal mortality was 63/1,000 pregnancies among teenage mothers, 76/1,000 pregnancies among nulliparous women and 61/1,000 pregnancies among women delivering at home who, after controlling for potential confounders, had a 3.7 (95%CI: 1.8, 7.4) times higher perinatal mortality than women who gave birth in a health facility. This association was considerably stronger among nulliparous women [RR 8.0 (95%CI: 2.9, 21.6)] than among women with a previous live birth [RR 1.8 (95%CI: 0.7, 4.5)]. All perinatal deaths occurred among women who did not sleep under a mosquito net. Women living in urban slums had a higher risk of losing their babies than those in rural areas [RR: 2.7 (95%CI: 1.4, 5.3)].Our findings strengthen arguments for ensuring that pregnant women have access to and use adequate delivery facilities and bed nets

Endotoxaemia in Haemodialysis: A Novel Factor in Erythropoetin Resistance?

Background/Objectives Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients. Methodology/Principal Findings 50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500–20,000] u/wk and ERI of 13.7 [IQR 6.9–23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (r = 0.324, p = 0.03) with a trend towards association with hsCRP (r = 0.280, p = 0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (r = 0.295, p = 0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis. Conclusions This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin

Trait determinants of impulsive behavior: a comprehensive analysis of 188 rats

Impulsivity is a naturally occurring behavior that, when accentuated, can be found in a variety of neuropsychiatric disorders. The expression of trait impulsivity has been shown to change with a variety of factors, such as age and sex, but the existing literature does not reflect widespread consensus regarding the influence of modulating effects. We designed the present study to investigate, in a cohort of significant size (188 rats), the impact of four specific parameters, namely sex, age, strain and phase of estrous cycle, using the variable delay-to-signal (VDS) task. This cohort included (i) control animals from previous experiments; (ii) animals specifically raised for this study; and (iii) animals previously used for breeding purposes. Aging was associated with a general decrease in action impulsivity and an increase in delay tolerance. Females generally performed more impulsive actions than males but no differences were observed regarding delay intolerance. In terms of estrous cycle, no differences in impulsive behavior were observed and regarding strain, Wistar Han animals were, in general, more impulsive than Sprague-Dawley. In addition to further confirming, in a substantial study cohort, the decrease in impulsivity with age, we have demonstrated that both the strain and sex influences modulate different aspects of impulsive behavior manifestations.FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE) and the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement as well as national funds, through the Foundation for Science and Technology (FCT) [projects POCI-01–0145-FEDER-007038, NORTE-01-0145-FEDER-000013, NORTE-01-0145-FEDER-000023 and PTDC/NEU-SCC/5301/2014]. Researchers were supported by FCT [grant numbers SFRH/BD/52291/2013 to ME and PD/BD/114117/2015 to MRG via Inter-University Doctoral Programme in Ageing and Chronic Disease, PhDOC; PDE/BDE/113601/2015 to PSM via PhD Program in Health Sciences (Applied) and Phd-iHES; SFRH/BD/109111/2015 to AMC; SFRH/BD/51061/2010 to MMC; SFRH/SINTD/60126/2009 to AM; SFRH/BD/98675/2013 to BC; IF/00883/2013 to AJR; IF/00111/2013 to AJS; SFRH/BPD/80118/2011 to HLA]info:eu-repo/semantics/publishedVersio

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein–protein and protein–immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS