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Background: Proprotein convertase subtilisin/kexin type-9 (PCSK-9) is a serine protease with profound effects on plasma LDL-C, the major risk factor for cardiovascular diseases (CVDs). However, plasma PCSK-9 level and its association with the biomarkers of CVDs, diabetes, and associated complications have not yet been reported in the northeastern population of India. Methods: Of the total cohort (n = 233), we analyzed healthy controls (HC; n = 50), freshly diagnosed type-2-diabetes mellitus (T2DM-FD; n = 46), T2DM treated (T2DM-T; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemia (T2DM-DL; n = 45) subjects. Plasma PCSK-9 and other biological determinants associated with T2DM, CVD, and nephrotic dysfunction were assessed. Results: The level of plasma PCSK-9 in HC, T2DM-FD, T2DM-T, T2DM-N, and T2DM-DL groups was found to be 184.1 ± 13.83, 183.1 ± 24.4.3, 241.8 ± 75.42, 403.7 ± 85.94, and 641.3 ± 135.5 ng/mL, respectively, indicating its role in the severity of the here-mentioned complications. Moreover, plasma PCSK-9 levels further showed a significant correlation with the biomarkers of hyperglycemia, particularly HbA1c, as well as LDL-C in T2DM-FD, T2DM-N, and T2DM-DL subjects of the Indian population, while moderate association in T2DM-T subjects. Conclusions: Our first-of-its-kind clinical study aiming to quantify the circulatory PCSK-9 level in the Indian population concluded that elevated PCSK-9 was significantly associated with the severity of diabetes and associated complications. Moreover, such elevation in PCSK-9 might be attributed to the lipid- and glucose-lowering medication-induced SREBP-2-dependent mechanisms. Since our conclusion is based on a pilot study, further cohort studies in larger populations of India are required to get a generalization regarding the role of PCSK-9 in DM and associated complications. [ABSTRACT FROM AUTHOR]

Background Efficacy of Colistin the last line agent against infections due to multidrug-resistant (MDR) gram-negative pathogens, has been challenged when Liu et al. reported a plasmid-mediated gene, mcr-1 , in 2015. Thereby this plasmid-borne mcr has been reported in bacterial isolates worldwide taken from humans, animals, farms, foods, and the environment. The present work invesitigate the mcr gene among clinical isolates of Acinetobacter Baumannii at our tertiary referral hospital of India. Methods The study was conducted at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. MIC values for 100 consecutive non-duplicate MDR isolates of Acinetobacter were checked for Colistin. PCR amplification of mcr gene was performed followed by sequencing of the amplicons. Clinical features of patients infected with mcr positive isolates were unveiled. Clonal relatedness of these isolates was investigated by Pulsed-field gel electrophoresis (PFGE). The mcr-1 localization was checked by conjugation followed by PFGE southern hybridization. Results 20/100 (20%) isolates were colistin resistant with having MIC Values of more than 8≤ µg/mL. The 20 colistin resistances isolates were PCR positive for mcr-1 and had been assigned EMBL/GeneBank nucleotide accession numbers MH730099-MH730118. Oher antibiotic resistance gene like ESBL, NDM-1, VIM, and 16s rRNA methyl transferases like Arm A, rmtC, rmt F were also found in these isolates. Majority of these patients recovered from the infection (65%) after proper antibiotic therapy.The IS Apl1 transposable elements were not detected in these isolates. These isolates were found clonally unrelated when analyze by pulsed-field gel electrophoresis. The conjugation attempt to transfer mcr-1 to recipient's E. coli J53 failed, Southern hybridization showed that mcr-1 was found located on chromosome in multiple copies. Conclusion This is the first case of mcr-1 in a human clinical isolate in Acinetobacter Baumnnii from India. These findings highlight the vertical transferability of colistin resistance by mcr-1 gene in Acinetobacter Baumnnii with the association of known some unknown insertion sequence located on chromosome. Strategies required to contain their spread and evolution of such genes. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

New Delhi metallo-beta-lactamase (NDM)-mediated carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii is a major concern. We investigated the presence of NDM and its variants in P. aeruginosa and A. baumannii at a tertiary hospital in North India. A total of 236 isolates (130 P. aeruginosa and 106 A. baumannii) were included; 38 (29.23%) P. aeruginosa and 20 A. baumannii isolates (18.8%) were resistant to carbapenems and all of them were bla NDM positive. All 38 carbapenem-resistant P. aeruginosa harbored bla NDM-1, while 12 (60%) of 20 A. baumannii harbored bla NDM-2 . Pulsed-field gel electrophoresis showed that all 58 isolates were clonally unrelated. By Southern blot analysis, bla NDM-2 was located on chromosome. The bla NDM-2 -positive isolates were more frequently recovered from tracheal aspirate (67% vs.16%; p = 0.02) and intensive care unit (67% vs. 20%; p = 0.001) than bla NDM-1 . Among other carbapenemases, VIM was significantly associated with bla NDM-1 than bla NDM-2 (61% vs. 17%; p = 0.006). Mortality between bla NDM-1 - and bla NDM-2 -infected patients was comparable. When expressed in Escherichia coli, bla NDM-2 transformant conferred one doubling dilution higher MIC value for cefotaxime, piperacillin/tazobactam than bla NDM-1 . The study shows the emergence of bla NDM- mediated resistance among P. aeruginosa and A. baumannii and rapid evolution of bla NDM-2 in A. baumannii with its chromosomal localization.