Medical Research Council

About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.

Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia.

Abstract: There has been considerable debate over whether asymptomatic neonatal hypoglycaemia results in neurological damage. In a detailed multicentre study of 661 preterm infants hypoglycaemia was found to be common. Moderate hypoglycaemia (plasma glucose concentration less than 2.6 mmol/l) occurred in 433 of the infants and in 104 was found on three to 30 separate days. There was considerable variation among the centres, implying differences in decisions to intervene. The number of days on which moderate hypoglycaemia occurred was strongly related to reduced mental and motor development scores at 18 months (corrected age), even after adjustment for a wide range of factors known to influence development. When hypoglycaemia was recorded on five or more separate days adjusted mental and motor developmental scores at 18 months (corrected age) were significantly reduced by 14 and 13 points respectively, and the incidence of neurodevelopmental impairment (cerebral palsy or developmental delay) was increased by a factor of 3.5 (95% confidence interval 1.3 to 9.4). These data suggest that, contrary to general belief, moderate hypoglycaemia may have serious neurodevelopmental consequences, and reappraisal of current management is urgently required.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity

Abstract: Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

A systematic review of reliability and objective criterion-related validity of physical activity questionnaires

Abstract: Physical inactivity is one of the four leading risk factors for global mortality. Accurate measurement of physical activity (PA) and in particular by physical activity questionnaires (PAQs) remains a challenge. The aim of this paper is to provide an updated systematic review of the reliability and validity characteristics of existing and more recently developed PAQs and to quantitatively compare the performance between existing and newly developed PAQs. A literature search of electronic databases was performed for studies assessing reliability and validity data of PAQs using an objective criterion measurement of PA between January 1997 and December 2011. Articles meeting the inclusion criteria were screened and data were extracted to provide a systematic overview of measurement properties. Due to differences in reported outcomes and criterion methods a quantitative meta-analysis was not possible. In total, 31 studies testing 34 newly developed PAQs, and 65 studies examining 96 existing PAQs were included. Very few PAQs showed good results on both reliability and validity. Median reliability correlation coefficients were 0.62–0.71 for existing, and 0.74–0.76 for new PAQs. Median validity coefficients ranged from 0.30–0.39 for existing, and from 0.25–0.41 for new PAQs. Although the majority of PAQs appear to have acceptable reliability, the validity is moderate at best. Newly developed PAQs do not appear to perform substantially better than existing PAQs in terms of reliability and validity. Future PAQ studies should include measures of absolute validity and the error structure of the instrument.

Fumonisins Disrupt Sphingolipid Metabolism, Folate Transport, and Neural Tube Development in Embryo Culture and In Vivo: A Potential Risk Factor for Human Neural Tube Defects among Populations Consuming Fumonisin-Contaminated Maize

Abstract: Fumonisins are a family of toxic and carcinogenic mycotoxins produced by Fusarium verticillioides (formerly Fusarium moniliforme), a common fungal contaminant of maize. Fumonisins inhibit ceramide synthase, causing accumulation of bioactive intermediates of sphingolipid metabolism (sphinganine and other sphingoid bases and derivatives) as well as depletion of complex sphingolipids, which interferes with the function of some membrane proteins, including the folate-binding protein (human folate receptor alpha). Fumonisin causes neural tube and craniofacial defects in mouse embryos in culture. Many of these effects are prevented by supplemental folic acid. Recent studies in LMBc mice found that fumonisin exposure in utero increases the frequency of developmental defects and administration of folate or a complex sphingolipid is preventive. High incidences of neural tube defects (NTD) occur in some regions of the world where substantial consumption of fumonisins has been documented or plausibly suggested (Guatemala, South Africa, and China); furthermore, a recent study of NTD in border counties of Texas found a significant association between NTD and consumption of tortillas during the first trimester. Hence, we propose that fumonisins are potential risk factors for NTD, craniofacial anomalies, and other birth defects arising from neural crest cells because of their apparent interference with folate utilization.