Biology subjects

Tiwari, H. K.

Publications and source records attributed to Tiwari, H. K..

6 recordsLinked to original sources

bioRxiv2021

Mitochondrial Haplogroup Association with Fasting Glucose Response in African Americans Treated with a Thiazide Diuretic

Hypertensive African Americans have ~50% response rate to thiazide diuretic treatment. This contributes to a high prevalence of uncontrolled high blood pressure. Here, we examine the role the mitochondrial genome has on thiazide diuretic treatment response in hypertensive African Americans enrolled in a clinical trial. Participants from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT, n= 4279) were genotyped using the Illumina Infinium Multi-Ethnic Beadchip. Haplotype groups were called using HaploGrep. We used linear regression analysis to examine the association between mitochondrial haplogroups (L, M, and N) and change in blood pressure and change in fasting glucose over 6 months and two years, respectively. The analysis revealed a null association between mitochondrial haplogroups M and N vs. L for each of the outcomes. In subgroup analysis, the L subclades L1, L2, and L3/L4 (vs. L0) were each inversely associated with fasting glucose response (p < 0.05). This discovery analysis suggests the mitochondrial genome has a small effect on fasting glucose but not blood pressure response to thiazide diuretic treatment in African Americans.

pharmacology and toxicology↗

bioRxiv2021

Leveraging a founder population to identify novel rare-population genetic determinants of lipidome

Identifying the genetic determinants of inter-individual variation in lipid species (lipidome) may provide deeper understanding and new insight into the mechanistic effect of complex lipidomic pathways in CVD risk and progression beyond simple traditional lipids. Previous studies have been largely population based and thus only powered to discover associations with common genetic variants. Founder populations represent a powerful resource to accelerate discovery of novel biology associated with rare population alleles that have risen to higher frequency due to genetic drift. We performed a GWAS of 355 lipid species in 650 individuals from the Old Order Amish founder population including 127 lipid species not previously tested. We report for the first time the lipid species associated with two rare-population but Amish-enriched lipid variants: APOB_rs5742904 and APOC3_rs76353203. We also identified novel associations for 3 rare-population Amish-enriched loci with several sphingolipids and with proposed potential functional/causal variant in each locus including GLPTD2_rs536055318, CERS5_rs771033566, and AKNA_rs531892793. We replicated 7 previously known common loci including novel associations with two sterols: androstenediol with UGT locus on chromosome 2 and estriol with SLC22A8/A24 locus on chromosome 11. Our results show the power of founder populations to discover novel biology due to genetic drift that can increase the frequency of an allele from only few copies in large sample cohorts such as the UK Biobank to dozens of copies in sample size as small as 650.

genetics↗

bioRxiv2018

Physicochemical and microbiological profile of the potable water of Eastern Himalayan State Sikkim: An Indication of Severe Fecal Contamination and Immediate Health Risk

Increasing population, rapid urbanization and climate change have immensely affected the freshwater sources around the world. The continuous decline in the number of natural potable water sources raises serious concern about the overall health of the human population. Developing countries are the most affected in this regard due to lack of proper hygienic maintenance protocols. Sikkim an Eastern Himalayan state with mountains as predominant topological features, harbors several natural spring water (SW). These spring waters are the primary source of potable water for the population in the four districts of the state viz. East (E), West (W), South (S) and North (N). Several incidences of water-borne diseases and the relative lack of scientific evaluation reports on the water quality of the area have educed this study. Lack of any standard filtration and purification practice among the population is one of the prime factors for the outspread of different waterborne pathogen in the state. The people of the state mostly use boiling as a dominant method of water purification, while only a small percentage of people in the West district were found to use modern standard purification system (W = 30%). The rainy season was found to be the major contributor of different diseases (E = 86%; W=100%; S=100%; N=80%) and statistical analysis of the fecal coliforms of the different season also indicated a significant difference at p < 0.05. There was no statistical significance among the physicochemical parameter of the SW but surprisingly the water from the four districts was recorded with traces of highly toxic heavy metals like mercury/WHO limit (0.001-0.007mg/l/0.001) as well as lead/WHO limit (0.001-0.007mg/l/0.05) and selenium/WHO limit (0.526-0.644 mg/l/0.01) which was above the WHO permissible limit. Piper analysis showed that water was dominated by cation sodium ion (Na+) and bicarbonate (HCO3-) anion and the water can be categorized as Mg-HCO3- type. Pairwise Pearson correlation showed a significant correlation between Electrical conductivity and TDS (r = 0.998/1.00) as well as alkalinity and turbidity (0.993/1.00). The microbial confirmatory test showed severity in fecal contamination with high counts of Total Coliform (TC), Escherichia coli (EC) and Enterococcus (EN). Highest TC was recorded from W (37.26/ml) and lowest in N (22.13/ ml) in spring water. Highest contamination of Escherichia coli and Enterococcus was found in E (EC = 8.7/ml; EN = 2.08/ml) followed by S (EC = 8.4/ml and EN = 2.05/ml). It was found that community reservoir (CR) tank was more contaminated than SP, which indicates the negligence in maintenance and fecal contamination during transportation to the reservoir. Though household water was least contaminated compared to CR and SP, but it fails in WHO standard criteria for drinking water. These results indicate an immediate health risk of the resident of the state and which needs to be taken care of sooner as possible by protecting the important potable sources with required policies and regulations.

microbiology↗

bioRxiv2018

Emergence of Multidrug-Resistant Uropathogens harboring ESBL, Carbapenem, Aminoglycosides and AmpC resistant genes from Northern India

Extended-spectrum {beta}-lactamase (ESBL) producing bacteria acts as a serious threat, and its co-existence with other antibiotic resistant gene makes the clinical scenario worse nowadays. Therefore in this study, we investigated the occurrence of ESBL genes coexisting with carbapenem, AmpC and aminoglycoside resistance gene in uropathogens. Out of 1516 urine samples, 454 showed significant bacteriuria with a prevalence rate of 29.94 %. Escherichia coli (n=340) were found to be the most predominant uropathogen followed by Klebsiella pneumoniae (n=92), Pseudomonas aeruginosa (n=10) and Proteus mirabilis (n=9). Among the total uropathogens, sixty-three ESBL-producers were identified which included blaCTX-M-15 (n=32), followed by blaCTX-M-15 + blaOXA-2 (n=15), blaCTX-M-15 + blaOXA-2 + blaTEM (n=6), blaOXA-2 (n=5), bla OXA-2 + bla SHV-76 (n=1), bla TEM+SHV-76 (n= 1) and bla TEM (n=1). All ESBL genes were found on plasmid incompatibility types: HI1, I1, FIA+FIB, FIA and Y and were horizontally transferable. Among 63 ESBL-producers, 59 isolates harboured carbapenem-resistant genes which included blaNDM-5 (n=48), blaNDM-5 + blaOXA-48 (n=5), blaNDM-5 + blaIMP (n=5) and blaNDM-5 + blaIMP + blaVIM (n=1). The ESBL producing uropathogens also harbored 16S rRNA methylase genes which included rmtB (n=9), rmtA (n=4), rmtC (n=1) and ArmA (n=1) followed by AmpC genes which includes CIT (n=8) and DHA-1 (n=1) genes. Imipenem and gentamicin were found to be more effective. We speculating, this is the first report showing the prevalence of multidrug-resistant uropathogens in this area demanding regular surveillance for such resistance mechanisms which will be useful for health personnel to treat ESBL infection and its co-existence with another antibiotic resistance gene.

microbiology↗

bioRxiv2018

First report on Bacterial Diversity of Potable Spring water of Indian Himalayan Region

Water quality of a region directly corroborates with the health index of people. People in the Himalayan hills mainly depend upon the spring water for potability. To determine the microbial ecology of the spring waters of Sikkim, the variable region of 16S rRNA has been sequenced using Illumina MiSeq. Phylum wise annotation showed the East and North district are mostly dominated by Proteobacteria (41% and 35.80%), whereas West and South district is dominated by Planctomycetes (38.46%) and Verrucomicrobia (33%). The consistent dominance phyla in the all the four districts were Bacteriodetes (34-24%) which was highest dominancy in North district and lowest in wets district. Genus wise distribution showed the abundance of Brevifolis, Flavobacterium, Verrucomicrobia subdivision3, Emticica, Cytophaga, Prosthecobacter, Planctomycetes, Varivorax, Arcicella, Isosphera, Sedimunibacterium etc. The East district showed highest dominancy of genus Emticicia whereas Planctomycetes in the West district. The North district was mainly dominated by genus Arcicella and Brevifollis in the South district. North on the antonymous showed totally different sets of microbial diversity. North district showed an abundance of Arcicella, Planctomycetes, Schlerensia and Azohydromonas. The heat map produced by Bray Curtis distance method produced three clusters which showed the close relationship between West and East district microbiome that further related to South district. The sample of North district formed out group that showed different community structure from other three districts. The principle component analysis was showed that the east and South district samples are closely related and distantly correlated to the west Sikkim, but the North district showed completely different microbial community. The canonical correspondence analysis showed correlation between bacterial diversity and hydrochemistry and it was found that the bacterial diversity was influenced by the concentration of different metallic ions like sodium, calcium, barium and iron. This is a first report from the Eastern Himalayan region of India and it largely enhances our knowledge about the microbial structure of potable spring water of Eastern Himalayan. This study is useful for Government of India as well as the state government to adopt the different strategic treatment procedures to improve the quality of water that is supplied to the community resides in the Himalayan regions and solely dependent on this untreated spring water.

microbiology↗

bioRxiv2018

Prevalence of Antibiotic Resistance in Commensal Escherichia Coli among the Children in Rural Hill Communities of North East India

Commensal bacteria are the representative of the reservoir of antibiotic resistance genes present in a community. Merely a few community-based studies on the prevalence of antibiotic resistance in commensal bacteria have been conducted so far in Southeast Asia and other parts of India. Northeastern India is still untapped regarding the surveillance of antibiotic-resistant genes and prevalence in commensal bacteria. In the present work, the prevalence of antibiotic resistance in commensal Escherichia coli was investigated along with the associated demographic factors in pre-school and school going children in rural areas of Sikkim. A total of 550 fecal E. coli isolates were obtained from children of the age 1-14 years living in different villages at various altitudes of Sikkim from July 2015 to June 2017. Standard antibiotic susceptibility testing of these isolates was performed. A structured questionnaire was designed to study the factors associated with carriage of antibiotic resistance in commensal E. coli isolates among children. Descriptive statistics analysis and a logistic regression model were used to identify the effect of external factors on antibiotic resistance pattern. High prevalence of resistance was found against commonly used antibiotics ampicillin (92%), ceftazidime (90%), cefoxitin (88%), streptomycin (40%) and tetracycline (36%) among the samples examined in our present study. No resistance to chloramphenicol was recorded. Fifty-two percent of the isolates were resistant to the combination of penicillin and quinolone group of antibiotics. Children living in nuclear families showed higher incidence of resistance to ampicillin (63.15%, OR 0.18,95% CI:0.11 - 0.28, p<0.01) while children of mothers having education up to school level displayed higher incidence of ceftazidime (59.27% OR 0.75, 95% CI:0.55 - 1.02, p<0.02). Our study demonstrates a high prevalence of antibiotic-resistant commensal E. coli against the commonly used antibiotics among children in the study area. A close association between different demographic factors and the pattern of carriage of antibiotic-resistant isolates was observed suggesting a concern over misuse of antibiotics and warrants a future threat of emerging multidrug resistant isolates.

microbiology↗