Seasonal effect and long-term nutritional status following exit from a Community-Based Management of Severe Acute Malnutrition program in Bihar, India.

BACKGROUND/OBJECTIVES: Children aged 6 months to 5 years completing treatment for severe acute malnutrition (SAM) in a Médecins Sans Frontières Community Management of Acute Malnutrition (CMAM) program in Bihar, India, showed high cure rates; however, the program suffered default rates of 38%. This report describes the nutritional status of 1956 children followed up between 3 and 18 months after exiting the program. SUBJECTS/METHODS: All children aged 6-59 months discharged as cured with mid-upper arm circumference (MUAC) ⩾120 mm or who defaulted from the program with MUAC <115 mm were traced at 3, 6, 9, 12 and 18 months (±10 days) before three exit reference dates: first at the end of the food insecure period, second after the 2-month food security and third after the 4-month food security. RESULTS: Overall, 68.7% (n=692) of defaulters and 76.2% (n=1264) of children discharged as cured were traced. Combined rates of non-recovery in children who defaulted with MUAC <115 mm were 41%, 30.1%, 9.9%, 6.1% and 3.6% at 3, 6, 9, 12 and 18 months following exit, respectively. Combined rates of relapse among cured cases (MUAC ⩾120 mm) were 9.1%, 2.9%, 2.1%, 2.8% and 0% at 3, 6, 9, 12 and 18 months following discharge, respectively. Prevalence of undernutrition increased substantially for both groups traced during low food security periods. Odds of death were much higher for children defaulting with MUAC <110 mm when compared with children discharged as cured, who shared the same mortality risk as those defaulting with MUAC 110-<115 mm. CONCLUSIONS: Seasonal food security predicted short-term nutritional status after exit, with relapse rates and non-recovery from SAM much higher during food insecurity. Mortality outcomes suggest that a MUAC of 110 mm may be considered an appropriate admission point for SAM treatment programs in this context

Metabolomics analysis as a tool to measure cobalt neurotoxicity : an in vitro validation

In this study, cobalt neurotoxicity was investigated in human astrocytoma and neuroblastoma (SH-SY5Y) cells using proliferation assays coupled with LC–MS-based metabolomics and transcriptomics techniques. Cells were treated with a range of cobalt concentrations between 0 and 200 µM. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed cobalt cytotoxicity and decreased cell metabolism in a dose and time-dependent manner was observed by metabolomics analysis, in both cell lines. Metabolomic analysis also revealed several altered metabolites particularly those related to DNA deamination and methylation pathways. One of the increased metabolites was uracil which can be generated from DNA deamination or fragmentation of RNA. To investigate the origin of uracil, genomic DNA was isolated and analyzed by LC–MS. Interestingly, the source of uracil, which is uridine, increased significantly in the DNA of both cell lines. Additionally, the results of the qRT-PCR showed an increase in the expression of five genes Mlh1, Sirt2, MeCP2, UNG, and TDG in both cell lines. These genes are related to DNA strand breakage, hypoxia, methylation, and base excision repair. Overall, metabolomic analysis helped reveal the changes induced by cobalt in human neuronal-derived cell lines. These findings could unravel the effect of cobalt on the human brain

Association of interleukin-18 promoter polymorphism with comorbid conditions of cardiovascular disease

Objectives: Cardiovascular disease (CVD) is one of the most clinically relevant pathologies that remains the largest single contributor to global mortality. It is often associated with more than one comorbid condition, which obscures its clinical outcome. The current study aimed to evaluate the possible association of interleukin-18 (IL-18) promoter polymorphism with comorbid conditions of CVD. Methods: We used case-control comparison of specific genotypes of three clinically relevant IL-18 polymorphism hotspots, viz. −656 T/G (rs1946519), −607C/A (rs1946518), and −137 G/C (rs187238) with commonly associated comorbid conditions of CVD such as diabetes, hypertension, and dyslipidemia. For this study, whole blood of CVD patients and healthy control subjects were collected in a citrate coated/plain tube. The routine biochemical parameters were estimated in each sample, and DNA samples were extracted for PCR amplification for further sequencing of targeted amplicons using Sanger method. Results: The studied biochemical parameters showed a significant increase in CVD patients compared with control individuals. Fasting glucose and glycosylated hemoglobin (HBA1C) showed an increase from 4.82 to 8.6 (p < 0.05) and 4.33 to 8.2 (p < 0.05), respectively. The results showed a statistically significant association with CVD-diabetes and CVD-hypertension group with GG, GC, and CC genotype at IL-18 gene locus, rs187238. On the other hand, the CVD-dyslipidemia group showed a positive association with allele distribution at the same hotspot. In addition, the GG, GT, and TT genotype and G and T allele distribution at rs1946519 locus showed statistically significant association with CVD-diabetes, CVD-hypertension, and CVD-dyslipidemia p compared with control subjects. We also observed a statistically significant association of dyslipidemia with three genotypic combinations viz. (rs1946518 AA, rs1946519 GG, rs187238 GG); (rs1946518 AA, rs1946519 GT, rs187238 GG), and (rs1946518 AA, rs1946519 TT, rs187238 GG). Conclusions: Based on our study, we conclude that IL-18 loci, rs1946519 has a significant association with each studied comorbid condition and can be considered a prognostic marker of CVD and comorbidities. Our results are anticipated to be utilized to launch a significant pharmaco-genomic investigation that could identify patients with comorbidities who are more likely to develop CVD