Background: Stroke is the second most common cause of death and disability worldwide. It is a multi-factorial disease influenced by both environmental and genetic factors. Studies from the different ethnic regions of world have reported variable results on association of Apolioprotein E (APOE), Methylenetetrahydrofolate reductase (MTHFR), Endothelial Nitric Oxide Synthase (ENOS), Factor V Leiden (F5), Cytochrome P450 4F2 (CYP4F2), beta-fibrinogen and Phosphodiesterase 4D (PDE4D) gene in stroke. There has been substantial evidence from the European descent genetic studies showing that genetic risk of stroke varies as per specific subtypes of ischemic stroke. This study aims to test the hypothesis that above mentioned encoding gene polymorphisms are associated with stroke and to determine whether risk varies as per specific subtypes of stroke. Methods/Design: The study design would be case–control study. Six hundred cases with diagnosis of stroke and 600 age and sex matched controls will be recruited. Controls will be matched in 1:1 ratio. Baseline and demographic data will be collected in standardized data collection form. Four ml of blood will be collected in EDTA coated vial and will be used for DNA isolation. Genotyping will be done by using PCR-RFLP method. For the reconfirmation of RFLP results, PCR product of each genotype in triplet for all the selected polymorphism will be sent for DNA sequencing. Data will be analyzed using conditional logistic regression to determine odds ratio associated with the above genes. Discussion: This protocol will assess the association of above mentioned gene polymorphisms with ischemic stroke in North Indian Population. This study will also helpful to determine genetic component of stroke and whether variation in genetic risk as per different subtypes of stroke.

Background: To study the effect of timing of total enteral feeding on various nutritional parameters and neurological outcome in patients with severe traumatic brain injury (TBI). Methods: One hundred and fourteen patients, in the age group of 20-60 years, admitted within 24 h of TBI with Glasgow Coma Scale (GCS) 4-8 were enrolled for the study. Nineteen patients who had expired before the attainment of total enteral feeding were excluded from the analysis. Total enteral feeding was attained before 3 days, 4-7 days, and after 7 days in 12, 52, and 31 patients, respectively, depending on gastric tolerance. They were prospectively assessed for various markers of nutrition and outcome was assessed at 3 and 6 months. Results: Prospective assessment of 67 hospitalized patients at 3 weeks revealed significant differences in anthropometric measurements, total protein, albumin levels, clinical features of malnutrition, and mortality among the three groups. 80% of those fed before 3 days had favorable outcome at 3 months compared to 43% among those fed later. The odds ratio (OR) was 5.29 (95% CI 1.03-27.03) and P value was 0.04. The difference between those fed before 3 days and 4-7 days was not significant at 6 months even though patients fed before 7 days had still significantly higher favorable outcome compared to those fed after 7 days (OR 7.69, P = 0.002). Multivariate analysis for unfavorable outcome showed significance of P = 0.03 for feeding after 3 days and P = 0.01 for feeding after 7 days. Conclusions: In severe TBI, unfavorable outcome was significantly associated with attainment of total enteral feeding after 3 days and more so after 7 days following injury.

Analysis of serum brain-derived neurotrophic factor (BDNF) levels in Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and controls with BDNF gene polymorphism and cognitive function were investigated. The study recruited 63 AD patients, 15 aMCI and 63 age- and sex-matched healthy controls from All India Institute of Medical Sciences, New Delhi, India. Patients with AD (12268.3 ± 7099.9 pg BDNF/ml) and aMCI (10780 ± 4184.2 pg BDNF/ml) had higher serum levels than had the controls (9362.833 ± 5883.32 pg BDNF/ml). Significant difference in BDNF levels was not found between the three groups. No significant difference was obtained between BDNF genotype and allele distribution between AD patients, aMCI versus controls; genotypic frequency: Chi-square = 3.21; p-value = 0.20 and allelic frequency: Chi-square = 0.412, p-value = 0.521, df = 1 (AD vs controls); Chi-square = 1.63, p-value = 0.201, df = 1 (aMCI vs controls). In conclusion, val66met polymorphism and BDNF serum level between the three groups and genotype did not significantly affect the serum BDNF level or age, Mini-Mental State Examination score in AD and aMCI. Further studies are necessary to elucidate the kinetics and the potential role of serum BDNF as a marker of disease progression in AD patients.

Summary: Background: Rivastigmine is an acetylcholinesterase inhibitor; the genotype data seen alongside the phenotype data explain the mutation or the molecular genetics involved and also help to relate the phenotype of an individual with their genotype.Aim: To determine the clinical effectiveness of CYP2D6, CYP3A4, CYP2C9/19, and UGT polymorphism on the steady‐state plasma concentrations and therapeutic outcome of rivastigmine monotherapy and combination therapy in patients with Alzheimer's disease.Result: In this study, a significant allele frequency was observed for CYP2D6*3 polymorphism in patients under rivastigmine combination therapy (A>del = 0.50 [patients] and A>del = 0.20 [controls]), UGT2B7 (T = 0.17 [patients] and 0.33 [Controls], and UGT1A9*5 A = 0.58 [patients] and 0.26 [Controls]). The drug levels and P value of responders/nonresponders were found to be 0.17 ± 0.08/0.22 ± 0.16 and 0.574 for rivastigmine and 0.18 ± 0.11/0.66 ± 0.63 and 0.009 for rivastigmine in combination therapy and 1.40 ± 0.65/0.59 ± 0.84 and 0.05 for memantine in combination therapy.Conclusion: Poor metabolizer subjects of UGT2B7 polymorphism in patients under rivastigmine combination therapy have higher drug levels with a poor response to the drug treatments.