Improving treatment adherence among tuberculosis patients through evening DOTS in Chennai, India.

Background Fixed days and timings of service are challenges in the care of patients with tuberculosis (TB). We assessed whether provision of evening DOTS (directly observed treatment, short course) improves treatment outcomes in a city with a working population. Methods We enrolled new adult patients with TB from seven tuberculous units (TUs) in this prospective cohort study. Participants were offered the option of DOTS during the day (8 a.m. to 3:30 p.m.) or evening (4 p.m. to 8 p.m.) and assigned accordingly. Results Of 127 patients enrolled between April and July 2017, 19 (15%) opted for evening DOTS. The number varied between the seven TUs (p=0.002). On an average, antitubercular therapy (ATT) was taken at 9:41 a.m. in the routine and 5:14 p.m. in the evening DOTS centres. Patients who were employed, left residence and returned back at 9:05 a.m. and 6:40 p.m., respectively. Around 96% (104/108) opted for day-time DOTS due to closeness of the centre to their residence. Around 74% (14/19) chose evening DOTS because of time convenience. Around 15% of patients on routine DOTS (16) had unfavourable treatment outcomes. All had favourable outcomes in the evening DOTS. Men were less likely and those withut alcohol disorders were more likely to have treatment success. Conclusion Provision of time convenient services might improve adherence and treatment outcome.

Insights from the clustering of microarray data associated with the heart disease.

Heart failure (HF) is the major of cause of mortality and morbidity in the developed world. Gene expression profiles of animal model of heart failure have been used in number of studies to understand human cardiac disease. In this study, statistical methods of analysing microarray data on cardiac tissues from dogs with pacing induced HF were used to identify differentially expressed genes between normal and two abnormal tissues. The unsupervised techniques principal component analysis (PCA) and cluster analysis were explored to distinguish between three different groups of 12 arrays and to separate the genes which are up regulated in different conditions among 23912 genes in heart failure canines' microarray data. It was found that out of 23912 genes, 1802 genes were differentially expressed in the three groups at 5% level of significance and 496 genes were differentially expressed at 1% level of significance using one way analysis of variance (ANOVA). The genes clustered using PCA and clustering analysis were explored in the paper to understand HF and a small number of differentially expressed genes related to HF were identified.

Computational structural analysis of proteins of Mycobacterium tuberculosis and a resource for identifying off-targets.

Advancement in technology has helped to solve structures of several proteins including M. tuberculosis (MTB) proteins. Identifying similarity between protein structures could not only yield valuable clues to their function, but can also be employed for motif finding, protein docking and off-target identification. The current study has undertaken analysis of structures of all MTB gene products with available structures was analyzed. Majority of the MTB proteins belonged to the α/ß class. 23 different protein folds are used in the MTB protein structures. Of these, the TIM barrel fold was found to be highly conserved even at very low sequence identity. We identified 21 paralogs and 27 analogs of MTB based on domains and EC classification. Our analysis revealed that many of the current drug targets share structural similarity with other proteins within the MTB genome, which could probably be off-targets. Results of this analysis have been made available in the Mycobacterium tuberculosis Structural Database (http://bmi.icmr.org.in/mtbsd/MtbSD.php/search.php) which is a useful resource for current and novel drug targets of MTB.

Factors influencing plasma nevirapine levels: a study in HIV-infected children on generic antiretroviral treatment in India.

BACKGROUND: Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression. OBJECTIVES: To study the influence of age, drug dose and formulation type, nutritional status and CYP2B6 516G>T polymorphism on blood concentrations of nevirapine in children treated with generic antiretroviral drugs. METHODS: A multicentre study was conducted at four sites in India. HIV-infected children receiving generic nevirapine-based fixed-dose combinations were recruited. Trough and 2 h nevirapine plasma concentrations were determined by HPLC. Characterization of the CYP2B6 gene polymorphism was performed using direct sequencing. Clinical and nutritional status was recorded. Groups were compared using the Mann-Whitney U-test and multivariable logistic regression analysis was performed to identify factors contributing to low drug levels. RESULTS: Ninety-four children of median age 78 months were studied; 60% were undernourished or stunted. Stunted children had a significantly lower 2 h nevirapine concentration compared with non-stunted children (P < 0.05); there were no significant differences in trough concentrations between different nutritional groups. Nevirapine levels were significantly higher in children with TT compared with GG and GT CYP2B6 genotypes (P < 0.01). Children ≤ 3 years had a 3.2 (95% confidence interval 1.07-9.45) times higher risk of having sub-therapeutic nevirapine concentrations. CONCLUSIONS: Nevirapine blood concentrations are affected by many factors, most notably age ≤ 3 years; a combination of young age, stunting and CYP2B6 GG or GT genotype could potentially result in sub-therapeutic nevirapine concentrations. Dosing recommendations for children should be reviewed in the light of these findings.

Synonymous codon usage analysis of thirty two mycobacteriophage genomes.

Synonymous codon usage of protein coding genes of thirty two completely sequenced mycobacteriophage genomes was studied using multivariate statistical analysis. One of the major factors influencing codon usage is identified to be compositional bias. Codons ending with either C or G are preferred in highly expressed genes among which C ending codons are highly preferred over G ending codons. A strong negative correlation between effective number of codons (Nc) and GC3s content was also observed, showing that the codon usage was effected by gene nucleotide composition. Translational selection is also identified to play a role in shaping the codon usage operative at the level of translational accuracy. High level of heterogeneity is seen among and between the genomes. Length of genes is also identified to influence the codon usage in 11 out of 32 phage genomes. Mycobacteriophage Cooper is identified to be the highly biased genome with better translation efficiency comparing well with the host specific tRNA genes.