Bangladesh arsenic mitigation programs: lessons from the past

Ensuring access to safe drinking water by 2015 is a global commitment by the Millennium Development Goals (MDGs). In Bangladesh, significant achievements in providing safe water were made earlier by nationwide tubewell-installation programme. This achievement was overshadowed in 1993 by the presence of arsenic in underground water. A total of 6 million tubewells have been tested for arsenic since then, the results of which warranted immediate mitigation. Mitigation measures included tubewell testing and replacing; usage of deeper wells; surface water preservation and treatment; use of sanitary dug wells, river sand and pond sand filters; rainwater collection and storage; household-scale and large-scale arsenic filtrations; and rural pipeline water supply installation. Shallow tubewell installation was discouraged. Efforts have been made to increase people's awareness. This paper describes the lessons learned about mitigation efforts by the authors from experience of arsenic-related work. In spite of national mitigation plans and efforts, a few challenges still persist: inadequate coordination between stakeholders, differences in inter-sectoral attitudes, inadequate research to identify region-specific, suitable safe water options, poor quality of works by various implementing agencies, and inadequate dissemination of the knowledge and experiences to the people by those organizations. Issues such as long-time adaptation using ground water, poor surface water quality including bad smell and turbidity, and refusal to using neighbor's water have delayed mitigation measures so far. Region-specific mitigation water supply policy led by the health sector could be adopted with multisectoral involvement and responsibility. Large-scale piped water supply could be arranged through Public Private Partnerships (PPP) in new national approach

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Keep off the grass?:Cannabis, cognition and addiction

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.This work was supported by grants from the US National Institutes of Health to L.H.P. (AA020404, AA006420, AA022249 and AA017447) and by grants from the UK Medical Research Council to H.V.C. and C.J.A.M. (G0800268; MR/K015524/1)

Association of the Fc gamma receptor IIA-R/R131 genotype with myasthenia gravis in Dutch patients

Myasthenia gravis (MG) susceptibility is partially determined by allelic heterogeneity of immune-modulatory genes. IgG receptors (FcgammaR) link the humoral and cellular branches of the immune system, and regulate immune responses and inflammation. Three FcgammaR subclasses (FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb) exhibit functional polymorphisms, which affect efficiency of FcgammaR-mediated functions. FcgammaRIIa genotypes, but not FcgammaRIIIa and FcgammaRIIIb genotypes, were differentially distributed among 107 MG patients as compared to 239 healthy controls (Pmuch less than0.01), with a relative increase of the FcgammaRIIa-R/R131 genotype (Odds ratio 2.4, 95% confidence interval 1.4-3.9). These data suggest that the FcgammaRIIa-R/R131 genotype is a marker for susceptibility to MG. (C) 2003 Elsevier B.V. All rights reserved