Browsing by Author "Wang, Yi"
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Item Agreement between Clinical Screening Procedures for Neuropathy in the Feet(2012-05) Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, AlfredINTRODUCTION: The correlation between monofilament testing, symptom surveys, and electrodiagnostic studies for the diagnosis of axonal polyneuropathy has not been well studied. This investigation was done to assess the agreement between these procedures in a non-random sample of volunteers. METHODS: The procedures evaluated included electrodiagnostic tests of the sural nerve, monofilament testing of the great toe, a symptom survey, and a body diagram. Kappa coefficients and sensitivity and specificity, using nerve conduction as a "gold standard," were used to determine the agreement between various combinations of procedures. RESULTS: Poor agreement (kappa values -0.12-0.44) and sensitivity (sensitivity <30%) were found for all combinations of symptoms and monofilament results in comparison with sural peak latency and amplitude. CONCLUSIONS: Overall, the results demonstrated a low discriminatory power for the screening procedures for identifying persons with impaired sural nerve function. The results highlight the need for further development and evaluation of screening methods for distal neuropathy in population-based studies.Item Associations between air pollution indicators and prevalent and incident diabetes in an African American cohort, the Jackson Heart Study(Wolters Kluwer, 2021-04-22) Weaver, Anne M.; Bidulescu, Aurelian; Wellenius, Gregory A.; Hickson, DeMarc A.; Sims, Mario; Vaidyanathan, Ambarish; Wu, Wen-Chih; Correa, Adolfo; Wang, Yi; Environmental Health Science, School of Public HealthBackground: Diabetes is especially prevalent among African Americans. Prior studies suggest that long-term exposure to ambient air pollution may be associated with greater incidence of diabetes, but results remain heterogeneous. Few studies have included large numbers of African Americans. Methods: We assessed diabetes status and concentrations of 1- and 3-year fine particulate matter (PM2.5) and ozone (O3) among African American participants of the Jackson Heart Study at visits 1 (2000-2004, N = 5128) and 2 (2005-2008, N = 2839). We used mixed-effect modified Poisson regression to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of incidence of diabetes by visit 2 and prevalence ratios (PRs) of the association between air pollution exposure and prevalent diabetes at visits 1 and 2. We adjusted for potential confounding by patient characteristics, as well as inverse probability weights of diabetes at visit 2, accounting for clustering by census tract. Results: We observed associations between incident diabetes and interquartile range increase in 1-year O3 (RR 1.34, 95% CI = 1.11, 1.61) and 3-year O3 (RR 0.88, 95% CI = 0.76, 1.02). We observed associations between prevalent diabetes and 1-year PM2.5 (PR 1.08, 95% CI = 1.00, 1.17), 1-year O3 (PR 1.18, 95% CI = 1.10, 1.27), and 3-year O3 (PR 0.95, 95% CI = 0.90, 1.01) at visit 2. Conclusions: Our results provide some evidence of positive associations between indicators of long-term PM2.5 and O3 exposure and diabetes. This study is particularly relevant to African Americans, who have higher prevalence of diabetes but relatively few studies of environmental pollution risk factors.Item Day vs night: Does time of presentation matter in acute heart failure? A secondary analysis from the RELAX-AHF trial(Elsevier, 2017-05) Pang, Peter S.; Teerlink, John R.; Boer-Martins, Leandro; Gimpelewicz, Claudio; Davison, Beth A.; Wang, Yi; Voors, Adriaan A.; Severin, Thomas; Ponikowski, Piotr; Hua, Tsushung A.; Greenberg, Barry H.; Filippatos, Gerasimos; Felker, G. Michael; Cotter, Gad; Metra, Marco; Department of Emergency Medicine, IU School of MedicineBackground Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial. Methods This is a post hoc analysis of the RELAX AHF trial, which randomized 1,161 AHF patients to serelaxin vs placebo, both in addition to usual AHF therapy. Prespecified end points of the primary trial were used: dyspnea, 60-day heart failure/renal failure rehospitalization or cardiovascular (CV) death, and 180-day CV death. Both unadjusted and adjusted analyses for outcomes stratified by daytime vs nighttime presentation were performed. Results Of the 1,161 RELAX-AHF patients, 775 (66.8%) patients presented during daytime and 386 (33.2%) at nighttime. Baseline characteristics were largely similar, although daytime patients were more likely to be male, have greater baseline body weight, have higher New York Heart Association class, have history of atrial fibrillation, and have more peripheral edema compared with nighttime patients. No differences in dyspnea relief or 60-day outcomes were observed. However, daytime presentation was associated with greater risk for 180-day CV death after adjustment (hazard ratio 2.28, 95% CI 1.34-3.86; c statistic = 0.82, 95% CI 0.78-0.86). Conclusion In this secondary analysis of the RELAX-AHF trial, baseline characteristics suggest that daytime-presenting patients may have more gradual worsening of chronic HF. Patients with AHF who presented at night had less risk for 180-day CV death, but similar risk for 60-day CV death or rehospitalization and symptom improvement for patients who presented during the daytime.Item Effects of smoke-free air law on acute myocardial infarction hospitalization in Indianapolis and Marion County, Indiana(BMC Public Health, 2018-02-09) Weaver, Anne M.; Wang, Yi; Rupp, Katelin; Watson, Dennis P.Background A comprehensive smoke-free air law was enacted on June 1, 2012 in most of Marion County, Indiana, including all of the City of Indianapolis. We evaluated changes in acute myocardial infarction (AMI) admission rates in Indianapolis and Marion County before compared to after the law. Methods We collected AMI admissions from five Marion County hospitals between May 2007 and December 2014. We used Poisson regression to evaluate the overall effects of the law on monthly AMI hospitalizations, adjusting for month, seasonality, meteorology, air pollution, and hospital utilization. We tested the interactions between the law and AMI risk factors on monthly AMI admission rates to identify subpopulations for which the effects might be stronger. Results Monthly AMI admissions declined 20% (95% CI 14–25%) in Marion County and 25% (95% CI 20–29%) in Indianapolis after the law was implemented. We observed decreases among never (21%, 95% CI 13–29%), former (28%, 95% CI 21–34%), and current smokers (26%, 95% CI 11–38%); Medicaid beneficiaries (19%, 95% CI 9–29%) and non-beneficiaries (26%, 95% CI 20–31%). We observed decreases among those with a history of diabetes (Yes: 22%, 95% CI 14–29%; No: 25%, 95% CI 18–31%), congestive heart failure (Yes: 23%, 95% CI 16–30%; No: 24%, 95% CI 17–31%), and hypertension (Yes: 23%, 95% CI 17–28%: No: 26%, 95% CI 15–36%). Conclusions We observed decreases in AMI admissions comparable with previous studies. We identified subpopulations who benefitted from the law, such as former and current smokers, and those without comorbidities such as congestive heart failure and hypertension.Item Glutathione Enzyme and Selenoprotein Polymorphisms Associate with Mercury Biomarker Levels in Michigan Dental Professionals(2011-12) Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, NiladriMercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione S-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 microg/L) and hair mercury levels (0.49±0.63 microg/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).Item Hoosiers’ Health in a Changing Climate: A Report from the Indiana Climate Change Impacts Assessment(Purdue University, 2018-01-01) Filippelli, Gabriel; Widhalm, Melissa; Filley, Rose; Comer, Karen; Ejeta, Gebisa; Field, William; Freeman, Jennifer; Gibson, Joe; Jay, Stephen; Johnson, Daniel P.; Moreno-Madriñán, Max; Mattes, Richard; Ogashawara, Igor; Prather, Jeremy; Rosenthal, Frank; Smirat, Jeries; Wang, Yi; Wells, Ellen; Dukes, JeffreyItem In Vivo Dissection of Chamber-Selective Enhancers Reveals Estrogen-Related Receptor as a Regulator of Ventricular Cardiomyocyte Identity(Wolters Kluwer, 2023) Cao, Yangpo; Zhang, Xiaoran; Akerberg, Brynn N.; Yuan, Haiyun; Sakamoto, Tomoya; Xiao, Feng; VanDusen, Nathan J.; Zhou, Pingzhu; Sweat, Mason E.; Wang, Yi; Prondzynski, Maksymilian; Chen, Jian; Zhang, Yan; Wang, Peizhe; Kelly, Daniel P.; Pu, William T.; Pediatrics, School of MedicineBackground: Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined. Methods: We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-HiChIP on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes. Results: We identified 134 066 and 97 506 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs. Conclusions: We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.Item An investigation of modifying effects of metallothionein single-nucleotide polymorphisms on the association between mercury exposure and biomarker levels(2012-04) Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri; Franzblau, AlfredBACKGROUND: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. OBJECTIVE: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure-biomarker relationships. METHODS: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. RESULTS: The mean mercury levels in urine (1.06 µg/L) and hair (0.51 µg/g) were not significantly different from the U.S. general population (0.95 µg/L and 0.47 µg/g, respectively). The mean estimated daily MeHg intake was 0.084 µg/kg/day (range, 0-0.98 µg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 µg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) [corrected] AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. CONCLUSION: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general population.Item An Investigation of Modifying Effects of Single Nucleotide Polymorphisms in Metabolism-related Genes on the Relationship between Peripheral Nerve Function and Mercury Levels in Urine and Hair(2012-02) Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, AlfredMercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n=515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves was recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl-mercury exposure were also collected. Subjects included 244 dentists (47.4%) and 269 non-dentists (52.2%; mostly dental hygienists and dental assistants). The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the US general population (0.95 μg/L and 0.47 μg/g, respectively). In multivariate linear models predicting nerve function adjusting for covariates, only 3 out of a total of 504 models showed stable and statistically significant interaction of SNPs with mercury biomarkers. Overall, given the possibility of false positives, the results suggested little evidence of effect modification of the SNPs on the relationship between mercury biomarkers with peripheral nerve function at exposure levels that are relevant to the general US population.Item Long-term air pollution and blood pressure in an African-American cohort: the Jackson Heart Study(Elsevier, 2021) Weaver, Anne M.; Wang, Yi; Wellenius, Gregory A.; Bidulescu, Aurelian; Sims, Mario; Vaidyanathan, Ambarish; Hickson, DeMarc A.; Shimbo, Daichi; Abdalla, Marwah; Diaz, Keith M.; Seals, Samantha R.; Environmental Health Science, School of Public HealthIntroduction: African Americans are disproportionately affected by high blood pressure, which may be associated with exposure to air pollutants, such as fine particulate matter and ozone. Methods: Among African American Jackson Heart Study participants, this study examined associations between 1-year and 3-year mean fine particulate matter and ozone concentrations with prevalent and incident hypertension at Visits 1 (2000-2004, n=5,191) and 2 (2005-2008, n=4,105) using log binomial regression. Investigators examined associations with systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure using linear regression and hierarchical linear models, adjusting for sociodemographic, behavioral, and clinical characteristics. Analyses were conducted in 2017-2019. Results: No associations were observed between fine particulate matter or ozone concentration and prevalent or incident hypertension. In linear models, an IQR increase in 1-year ozone concentration was associated with 0.67 mmHg higher systolic blood pressure (95% CI=0.27, 1.06), 0.42 mmHg higher diastolic blood pressure (95% CI=0.20, 0.63), and 0.50 mmHg higher mean arterial pressure (95% CI=0.26, 0.74). In hierarchical models, fine particulate matter was inversely associated with systolic blood pressure (-0.72, 95% CI= -1.31, -0.13), diastolic blood pressure (-0.69, 95% CI= -1.02, -0.36), and mean arterial pressure (-0.71, 95% CI= -1.08, -0.33). Attenuated associations were observed with 1-year concentrations and at Visit 1. Conclusions: Positive associations were observed between ozone and systolic blood pressure, diastolic blood pressure, and mean arterial pressure, and inverse associations between fine particulate matter and systolic blood pressure, diastolic blood pressure, and mean arterial pressure in an African American population with high (56%) prevalence of hypertension. Effect sizes were small and may not be clinically relevant.