Molecular diversity of Mycobacterium tuberculosis isolates in Treatment-experienced Patients from Andhra Pradesh, India.

INTRODUCTION: To get a comprehensive idea about the transmission and epidemiology of TB globally and locally, the use of molecular typing methods has become imperative not only for understanding genetic diversity but also the population structure of Mycobacterium tuberculosis complex (MTBC). We aimed to investigate the drug resistance pattern and genetic diversity of MTBC among previously treated patients with sputum smear-positive pulmonary tuberculosis in a South Indian population. METHODOLOGY: 104 patients with sputum smear positivity and who had previously undergone treatment were selected. Drug susceptibility testing, Spoligotyping, MIRU-VNTR, and SNP typing were performed. RESULTS: Mono-resistance to isoniazid 16 (15.38%) was the highest among all drugs. Out of 104 isolates, 24 (23%) isolates were classified as MDR strains. The distributions of most common lineages were: EAI3-Ind-20 (19.23%), EAI5-13 (12.50%), Beijing-12 (11.54%), CAS1-Delhi- 9 (8.65%), and 7 (6.73%) each of T-H37rv, Unknown and Orphan types. MIRU-VNTR-based analysis revealed that there are two major groups: CAS1-Delhi and Beijing groups. Out of 104 isolates, 82 belonged to well-defined lineages and 6 clusters, and the remaining 22 were singletons. SNP analysis showed no mutations associated with five sets of genes in 33 strains. CONCLUSIONS: The occurrence of 11.54% Beijing strains in South India is an important finding. High frequency of Isoniazid mono resistance noticed. Spoligotyping along with MIRU-VNTR and SNP typing is the best approach to the identification of strain lineages. No mutation with Antigen85C gene represents, can be used for vaccine candidates.

Thrombophilic risk factors and ABO blood group profile for arteriovenous access failure in end stage kidney disease patients: a single-center experience.

INTRODUCTION: Thrombosis of fistula occurs most frequently in end-stage kidney disease (ESKD) patients receiving hemodialysis. However, the role of thrombophilia in arteriovenous fistula (AVF) failure has not been well established. Hence, this study was aimed at assessing the roles of hereditary and acquired thrombophilic factors in association with AVF failure among patients with ESKD undergoing hemodialysis. METHODS: A cross-sectional study was conducted on 100 ESKD patients, of whom 50 patients with well-functioning AVFs with no fistula failures earlier were enrolled as Group 1, and 50 patients who have had AVF failure were enrolled as Group 2. The hereditary factors as factor V Leiden, factor XIII, prothrombin, and methylene tetrahydrofolate reductase and the acquired factors as lipoprotein (a), fibrinogen, homocysteine, and anticardiolipin antibodies IgG and IgM were studied. RESULTS: Among the hereditary factors, no statistically significant difference was observed in relation to factor V Leiden and Prothrombin (p > 0.05). However, for factor XIII and methylene tetrahydrofolate reductase, a statistically significant difference was observed between patients with well-functioning AVFs and patients who have had AVF failure (p < 0.05). We found a statistically significant increase in all the acquired factors in patients who have had AVF failure in comparison with patients with well-functioning AVFs (p < 0.001). Association between ABO blood groups and thrombophilic factors showed significant association between factor V Leiden, anticardiolipin antibody IgG and IgM and ABO blood groups (p < 0.05), whereas none of the other thrombophilic factors showed significant association (p > 0.05). CONCLUSION: Thus, our study suggests significant role of acquired factors in causing AVF failure.

Comparison and correlation of binding mode of ATP in the kinase domains of Hexokinase family.

Hexokinases (HKs) are the enzymes that catalyses the ATP dependent phosphorylation of Hexose sugars to Hexose-6-Phosphate (Hex-6-P). There exist four different forms of HKs namely HK-I, HK-II, HK-III and HK-IV and all of them share a common ATP binding site core surrounded by more variable sequence that determine substrate affinities. Although they share a common binding site but they differ in their kinetic functions, hence the present study is aimed to analyze the binding mode of ATP. The analysis revealed that the four ATP binding domains are showing 13 identical, 7 similar and 6 dissimilar residues with similar structural conformation. Molecular docking of ATP into the kinase domains using Molecular Operating Environment (MOE) soft ware tool clearly showed the variation in the binding mode of ATP with variable docking scores. This probably explains the variable phosphorylation rates among hexokinases family.