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Coronary artery disease (CAD) is a major health concern and the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Glutathione peroxidase-1 (GPx-1) and NAD(P)H: quinone oxidoreductase (NQO1) are known for its broad range of detoxification. The role of functional variants of these genes in the development of various disorders is proven. Hereby, we investigated the possible role of these variants in the development of CAD in T2DM patients of South Indian population. In this case-control study, a total of 539 patients (T2DM = 241; T2DM-CAD = 298) and 285 controls were included. The C198T GPx-1 and C609T NQO1 single-nucleotide polymorphisms were analyzed by PCR-RFLP. Further, these genotypes were correlated with blood lipid profile. Regression analysis showed that GPx1-C/T genotype is associated with a 1.35-fold increase (95% CI = 1.000-1.824; P = 0.048) and GPx1-T/T genotype is associated with a 1.76-fold increase (95% CI = 1.011 to 3.066; P = 0.046) to the T2DM development. Increased odds ratio showed that NQO1-T/T genotype had a higher occurrence of CAD in diabetic patients with CAD (95% CI = 1.003-2.674, P = 0.049) than T2DM patients without CAD. The level of triglycerides alone showed significant increase for GPx-1-C/T and -T/T genotypes in Tukey's Post hoc analysis (177.1 ± 19.2 vs. 184 ± 23.5; P = 0.039 and 177.1 ± 19.2 vs. 190 ± 22.4; P = 0.006) among the patients with T2DM-CAD. Our work concludes that GPx-1 variants might contribute to the development of diabetes and both GPx-1 and NQO1 variants confirm the association of CAD in people with T2DM of South Indian population.

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Tuberculosis (TB) remains a major global threat and diagnosis of active TB ((ATB) both extra-pulmonary (EPTB), pulmonary (PTB)) and latent TB (LTBI) infection remains challenging, particularly in high-burden countries which still rely heavily on conventional methods. Although molecular diagnostic methods are available, e.g., Cepheid GeneXpert, they are not universally available in all high TB burden countries. There is intense focus on immune biomarkers for use in TB diagnosis, which could provide alternative low-cost, rapid diagnostic solutions. In our previous gene expression studies, we identified peripheral blood leukocyte (PBL) mRNA biomarkers in a non-human primate TB aerosol-challenge model. Here, we describe a study to further validate select mRNA biomarkers from this prior study in new cohorts of patients and controls, as a prerequisite for further development. Whole blood mRNA was purified from ATB patients recruited in the UK and India, LTBI and two groups of controls from the UK (i) a low TB incidence region (CNTRLA) and (ii) individuals variably-domiciled in the UK and Asia ((CNTRLB), the latter TB high incidence regions). Seventy-two mRNA biomarker gene targets were analyzed by qPCR using the Roche Lightcycler 480 qPCR platform and data analyzed using GeneSpring™ 14.9 bioinformatics software. Differential expression of fifty-three biomarkers was confirmed between MTB infected, LTBI groups and controls, seventeen of which were significant using analysis of variance (ANOVA): CALCOCO2, CD52, GBP1, GBP2, GBP5, HLA-B, IFIT3, IFITM3, IRF1, LOC400759 (GBP1P1), NCF1C, PF4V1, SAMD9L, S100A11, TAF10, TAPBP, and TRIM25. These were analyzed using receiver operating characteristic (ROC) curve analysis. Single biomarkers and biomarker combinations were further assessed using simple arithmetic algorithms. Minimal combination biomarker panels were delineated for primary diagnosis of ATB (both PTB and EPTB), LTBI and identifying LTBI individuals at high risk of progression which showed good performance characteristics. These were assessed for suitability for progression against the standards for new TB diagnostic tests delineated in the published World Health Organization (WHO) technology product profiles (TPPs).

PURPOSE:Detection of carbapenemases among Gram-negative bacteria (GNB) is important for both clinicians and infection control practitioners. The Clinical and Laboratory Standards Institute recommends Carba NP (CNP) as confirmatory test for carbapenemase production. The reagents required for CNP test are costly and hence the test cannot be performed on a routine basis. The present study evaluates modifications of CNP test for rapid detection of carbapenemases among GNB.MATERIALS AND METHODS:The GNB were screened for carbapenemase production using CNP, CarbAcineto NP (CANP), and modified CNP (mCNP) test. A multiplex polymerase chain reaction (PCR) was performed on all the carbapenem-resistant bacteria for carbapenemase genes. The results of three phenotypic tests were compared with PCR.RESULTS:A total of 765 gram negative bacteria were screened for carbapenem resistance. Carbapenem resistance was found in 144 GNB. The metallo-β-lactamases were most common carbapenemases followed by OXA-48-like enzymes. The CANP test was most sensitive (80.6%) for carbapenemases detection. The mCNP test was 62.1% sensitive for detection of carbapenemases. The mCNP, CNP, and CANP tests were equally sensitive (95%) for detection of NDM enzymes among Enterobacteriaceae. The mCNP test had poor sensitivity for detection of OXA-48-like enzymes.CONCLUSION:The mCNP test was rapid, cost-effective, and easily adoptable on routine basis. The early detection of carbapenemases using mCNP test will help in preventing the spread of multidrug-resistant organisms in the hospital settings.

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