Aluminum phosphide (ALP), a widely used insecticide and rodenticide, is also infamous for the mortality and morbidity it causes in ALP-poisoned individuals. The toxicity of metal phosphides is due to phosphine liberated when ingested phosphides come into contact with gut fluids. ALP poisoning is lethal, having a mortality rate in excess of 70%. Circulatory failure and severe hypotension are common features of ALP poisoning and frequent cause of death. Severe poisoning also has the potential to induce multi-organ failure. The exact site or mechanism of its action has not been proved in humans. Rather than targeting a single organ to cause gross damage, ALP seems to work at the cellular level, resulting in widespread damage leading to multiorgan dysfunction (MOD) and death. There has been proof in vitro that phosphine inhibits cytochrome c oxidase. However, it is unlikely that this interaction is the primary cause of its toxicity. Mitochondria could be the possible site of maximum damage in ALP poisoning, resulting in low ATP production followed by metabolic shutdown and MOD; also, owing to impairment in electron flow, there could be free radical generation and damage, again producing MOD. Evidence of reactive oxygen species-induced toxicity owing to ALP has been observed in insects and rats. A similar mechanism could also play a role in humans and contribute to the missing link in the pathogenesis of ALP toxicity. There is no specific antidote for ALP poisoning and supportive measures are all that are currently available.
India is experiencing an alarming rise in the burden of non-communicable diseases, but data on the incidence of chronic kidney disease (CKD) are sparse. Using the Center for Cardiometabolic Risk Reduction in South Asia surveillance study (a population-based survey of Delhi and Chennai, India) we estimated overall, and age-, sex-, city-, and diabetes-specific prevalence of CKD, and defined the distribution of the study population by the Kidney Disease Improving Global Outcomes (KDIGO) classification scheme. The likelihood of cardiovascular events in participants with and without CKD was estimated by the Framingham and Interheart Modifiable Risk Scores. Of 12,271 participants, 80% had complete data on serum creatinine and albuminuria. The prevalence of CKD and albuminuria, age standardized to the World Bank 2010 world population, were 8.7% (95% confidence interval: 7.9 to 9.4%) and 7.1% (6.4 to 7.7%) respectively. Nearly 80% of patients with CKD had an abnormally high hemoglobin A1c (5.7 and above). Based on KDIGO guidelines, 6.0, 1.0, and 0.5% of study participants are at moderate, high, or very high risk for experiencing CKD-associated adverse outcomes. The cardiovascular risk scores placed a greater proportion of patients with CKD in the high-risk categories for experiencing cardiovascular events, when compared with participants without CKD. Thus one in 12 persons living in two of India’s largest cities have evidence of CKD, with features that put them at high risk for adverse outcomes.
With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the ‘IndiGen’ program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as ‘IndiGenomes’ http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.
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