Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates ... more Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates in the U.S., creating an urgent need for novel early detection tools. A candidate biomarker for use in early detection is the soluble MHC class I-related chain A (s-MICA) ligand, which pancreatic tumors shed to escape immune detection. The objective of this study was to define the association between s-MICA levels and pancreatic cancer, in a population-based case-control study. S-MICA was measured in 163 pancreatic cancer cases and 542 controls. Unconditional logistic regression was used to calculate odds ratio (OR) for pancreatic cancer, and 95% confidence intervals (CI). There was a positive association between increasing s-MICA levels and pancreatic cancer: compared to the lowest tertile, the ORs for pancreatic cancer were 1.25 (95% CI: 0.75 - 2.07) and 2.10 (95% CI: 1.29 -3.42) in the second and highest tertiles, respectively (p-trend=0.02). Our study supports previous work demonstra...
Previous studies have shown that plasma mtDNA can be separated into two fractions; a supernatant ... more Previous studies have shown that plasma mtDNA can be separated into two fractions; a supernatant form that is cell-free and a pelleted form that is thought to be platelet associated. These fractions of plasma mtDNA should be measured in studies evaluating the role of plasma mtDNA as biomarkers for early detection or susceptibility to various cancers. Though one case-control study has shown lower plasma mitochondrial DNA (mtDNA) copy number to be associated with increased breast cancer risk this study did not evaluate the two fractions of plasma mtDNA. Hence, the role of plasma mtDNA in determining breast cancer risk was investigated further. We conducted a case-control study of 29 breast cancer cases and 28 cancer free controls to evaluate the association between (a) plasma mtDNA copy number and (b) peripheral blood leucocyte mtDNA copy number and breast cancer risk. Plasma obtained from the breast cancer cases and controls was centrifuged further at 18,000 g for 10 minutes to separ...
Submission of vaginal samples collected at home could remove barriers that women face in getting ... more Submission of vaginal samples collected at home could remove barriers that women face in getting screened for cervical cancer. From December 2013 to January 2014, women aged 21-30 years were recruited online to participate in either (1) self-collected testing for human papillomavirus (HPV) infection and an online survey, or (2) an online survey regarding their perceptions of self-collected testing for HPV infection. Demographics, risk factors, testing perceptions, and satisfaction with self-collected testing were assessed with online questionnaires. Women who performed self-collection were sent a home sampling kit by US mail, which was returned via US mail for HPV testing. A total of 197 women were enrolled, with 130 completing the online survey and 67 participating in both the survey and self-collection. Of the 67 women who were sent kits, 62 (92.5 %) were returned for testing. Sixty kits contained a sample sufficient for testing. The overall prevalence of HPV infection was 17.8 %,...
Background: Graft-versus-host disease (GvHD) continues to be a major cause of transplant related ... more Background: Graft-versus-host disease (GvHD) continues to be a major cause of transplant related mortality, morbidity and decreased quality of life post allogeneic hematopoietic cell transplant (HCT). Despite extensive use of histocompatibility antigen (HLA) matching between patients and donors and a variety of prophylactic regimens, the rates of GvHD have not declined substantially over the last decade. Recent studies have shown mitochondrial reactive oxygen species (ROS) plays an important role in T lymphocyte activation and initiation of the inflammatory response and represents a novel biological pathway that influences GvHD risk. We hypothesized that lower mitochondrial DNA (mtDNA) copy number that increases ROS related oxidative damage will be associated with acute and chronic GvHD. Methods: In a cohort of 201 patients who underwent allogeneic HCT for treatment of hematologic malignancies at the University of Minnesota between 2009 and 2012, we evaluated the association between...
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Jan 6, 2018
The association between residence and allergy has been well studied in children living on a farm;... more The association between residence and allergy has been well studied in children living on a farm; however, studies of this association in late adulthood are lacking. This study examined the association between residence and allergy in 25,393 women aged 55-69 years in the large prospective Iowa Women's Health Study (IWHS). IWHS questionnaires collected information on socio-demographic and anthropometric characteristics, medical history, lifestyle behaviors, dietary intake, residence and allergy. Residence reported at baseline (1986) was categorized into 5 groups based on living on a farm, rural, or urban areas and population size. Allergy was determined from four self-reported questions about physician-diagnosed asthma, hay fever, skin allergy, and other allergy. Logistic regression was used to determine significant risk factors for allergy and prevalence odds ratios (OR) and 95% confidence intervals (CI) for allergy associated with residence. Compared to large city of >10,000...
We conducted a nested case control study of 178 incident breast cancer cases and 356 controls in ... more We conducted a nested case control study of 178 incident breast cancer cases and 356 controls in the Atherosclerosis Risk in Communities study. We evaluated the association between breast cancer and Val432Leu polymorphism in the CYP1B1 gene and the tetranucleotide repeats in intron 4 of the CYP19 gene. After adjustment for height, age at menopause, age at menarche, BMI, HRT, and alcohol intake, carriers of the Val/Leu or Val/Val genotype had a 1.45 fold (95% CI 0.85-2.47) greater odds of breast cancer than Leu/Leu carriers. There was no association of the breast cancer with any individual CYP19 allele. Compared to individuals homozygous with the 167 allele, odds ratios were close to 1.0 for the 167 heterozygous genotype and for the remaining tetranucleotide repeats combined. Our data shows no association between breast cancer and the Leu432Val polymorphism of the CYP1B1 gene or the tetranucleotide repeats of the CYP19 gene.
Supplemental Table 9 shows the associations between pre-selected SNPs and mean of Visit 2 and Vis... more Supplemental Table 9 shows the associations between pre-selected SNPs and mean of Visit 2 and Visit 3 sMICA and sMICB levels (continuous variables).
Due to evolving population demographics, altered exposures, and new technology, new cohorts need ... more Due to evolving population demographics, altered exposures, and new technology, new cohorts need to be initiated. Here we report our efforts from a pilot cohort study of the 10,000 Families Study (10KFS). The goal of the pilot is to establish the infrastructure, protocols, and standard operating procedures for a larger study that would provide the data to further our understanding of the determinants of health across the life course and intergenerational transmission of environmental, genetic, and epigenetic risk factors. We have focused on cancer, as this is the leading cause of death in Minnesota. Data collection methods include online questionnaires and attendance at a health fair for various physical and biologic measurements. For this family-based study, a family is eligible if at least one member of two, preferably three, generations enrolls, and each member is willing, or willing for their child(ren), to provide DNA from blood or saliva. To facilitate eventual scale-up of the...
Background: Life course socioeconomic and demographic factors including educational attainment, r... more Background: Life course socioeconomic and demographic factors including educational attainment, race and ethnicity, and childhood (SES) are very powerful predictors of large inequalities in aging, morbidity, and mortality. Immune aging, including accumulation of late-differentiated, senescent-like lymphocytes and lower level of naive lymphocytes, may play a role in the development of the age-related health inequalities. However, there has been little research investigating association between socioeconomic status and immune aging, particularly age-related changes in lymphocyte percentages. Methods: This study used nationally representative data from more than 9000 US adults from the Health and Retirement Study to investigate associations between educational attainment, race and ethnicity, and childhood SES and lymphocyte percentages. Results: Respondents with lower educational attainment, Hispanic adults, and those who had a parent with less than high school education had lymphocyte...
Introduction: Mean corpuscular volume (MCV) of red blood cells (RBCs) is a heritable index common... more Introduction: Mean corpuscular volume (MCV) of red blood cells (RBCs) is a heritable index commonly used in clinical workup of anemia. Macrocytosis, or high MCV, is associated with cardiovascular events in chronic kidney disease patients and all-cause mortality. Genome-wide association studies (GWAS) of MCV have been conducted primarily in European and Asian populations; few have included populations of African or American ancestry. The Multiethnic Genotyping Array (MEGA) was designed to improve variant discovery and fine-mapping in US minorities by better capturing population-specific genetic variation. To identify novel MCV loci and examine evidence of generalization of previously reported MCV loci to populations with African and Amerindian genetic admixture, we conducted a GWAS of African American and Hispanic/Latino Population Architecture using Genomics and Epidemiology (PAGE II) participants on the MEGA array. Methods: We employed Illumina MEGA genotype data to evaluate the as...
Introduction: The relationship between gut microbiome and human obesity is not fully elucidated. ... more Introduction: The relationship between gut microbiome and human obesity is not fully elucidated. Most evidence is from animal models or small case-control studies. Data in population-based cohort are limited. Hypothesis: We hypothesized that some specific bacterial taxonomy are associated with host obesity, some of them may also associated with obesity-related cardiometabolic traits. Methods: This study included 2759 participants from the HCHS/SOL. Fecal samples were analyzed by shotgun metagenomics sequencing, with the SHOGUN pipeline for bacterial taxonomic identification. Multivariate linear regression models were used to examine associations of bacterial genera with multiple obesity and cardiometabolic traits. Results: Of 87 predominant genera (average relative abundance >0.01%), 43 were significantly associated with BMI after multiple testing correction ( Fig 1 ). These included some known obesity-associated taxa (e.g., Acidaminococcus , Dorea etc.) , some taxa with controve...
Background: Associations of insulin resistance and glycemia with liver enzymes have not been well... more Background: Associations of insulin resistance and glycemia with liver enzymes have not been well studied in a young, heterogeneous Hispanic/Latino population. We aimed to assess these associations, and to examine the role of endothelial dysfunction as a potential mediator. Methods: We examined 1,275 participants aged 8-16 years from the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth) (2012-14). We examined the distribution of liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST], and gamma-glutamyl transpeptidase [GGT]), the pediatric nonalcoholic fatty liver disease (NAFLD) fibrosis index (PNFI), glycemic markers (fasting glucose and hemoglobin A1c [HbA1c]), and insulin resistance (HOMA-IR) by age, sex, and body mass index (BMI). We assessed the adjusted cross-sectional associations of insulin resistance and hyperglycemia (as continuous variables) with elevated liver enzymes and PNFI (as binary variables) using Poisson regression to o...
Background The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other... more Background The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other respiratory-related diseases. Helicobacter pylori and hepatitis A virus (HAV) are common fecal–oral infections. Our study aimed to examine associations of seropositivity to these agents with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods A total of 12,471 HCHS/SOL participants with baseline data on self-reported physician-diagnosed asthma, and antibodies anti-H. pylori and anti-HAV were included in this cross-sectional analysis. Multivariable logistic regression models were used to estimate the odds ratios and 95% confidence intervals for the overall associations of seropositivity to each agent with asthma. Analyses were also stratified by Hispanic/Latino background. Effect modification by smoking status and nativity were tested. An analysis restricted to individuals with spirometry-defined chronic obstructive pulmonary disease (COPD) was also conside...
Background: CT-derived muscle density (MD) reflects the degree of adiposity in muscle (i.e., myos... more Background: CT-derived muscle density (MD) reflects the degree of adiposity in muscle (i.e., myosteatosis) with lower MD indicating greater adiposity. Previous research indicates lower MD is associated with increased risk of type 2 diabetes (T2D). However, few studies have compared the association of simultaneously measured MD by anatomic location. The relationship between myosteatosis and cardiometabolic health may differ by body site and influence which location(s) is most useful for risk assessment. We investigated potential differential relationships between T2D and MD of the locomotor muscles of the abdomen (psoas), thigh, and calf among 539 African Caribbean men from Tobago. Methods: Men were aged 50-91 years (mean 64.4 years, mean BMI 27.5 kg/m 2 ). Calf MD was measured at 66% of calf length using peripheral quantitative CT; calf MD was defined as the ratio of muscle mass to cross-sectional muscle area. Psoas MD was measured in the abdomen (between L3/L4) and thigh MD was mea...
Pharmacogenomics (PGx) studies how a person’s genes affect the response to medications and is qui... more Pharmacogenomics (PGx) studies how a person’s genes affect the response to medications and is quickly becoming a significant part of precision medicine. The clinical application of PGx principles has consistently been cited as a major opportunity for improving therapeutic outcomes. Several recent studies have demonstrated that most individuals (> 90%) harbor PGx variants that would be clinically actionable if prescribed a medication relevant to that gene. In multiple well-conducted studies, the results of PGx testing have been shown to guide therapy choice and dosing modifications which improve treatment efficacy and reduce the incidence of adverse drug reactions (ADRs). Although the value of PGx testing is evident, its successful implementation in a clinical setting presents a number of challenges to molecular diagnostic laboratories, healthcare systems, providers and patients. Different molecular methods can be applied to identify PGx variants and the design of the assay is the...
Non‐alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident dia... more Non‐alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD.
Background: Antibody tests are critical in elucidating the epidemiology of the rapidly evolving C... more Background: Antibody tests are critical in elucidating the epidemiology of the rapidly evolving Coronavirus Disease 2019 (COVID-19) global pandemic and in developing effective infection control measures. To avoid the significant risks posed by the use of tests with poor performance characteristics and associated supply chain disruptions, we developed an in-house SARS-CoV-2 total antibody test. The performance of our robustly validated test was compared with that of three commercial antibody tests, and our test was used to determine the seroprevalence of COVID-19 among healthcare workers and outpatients in Minnesota. Methods: To evaluate the clinical performance of our SARS-CoV-2 total antibody assay, 63 plasma and serum samples were analyzed from 34 SARS-CoV-2 PCR positive patients 4 - 35 days after symptom onset. Positive samples were analyzed for IgG titers in a follow up assay. Samples were analyzed from PCR negative (n=30) and presumed true negative pre-pandemic (n=207) patients. Among samples collected from patients >14 days after symptom onset, the assay had 100% diagnostic sensitivity (95% CI: 85·7 - 100·0%), 100% diagnostic specificity (95%CI: 98·5 - 100·0%), 100% positive predictive value (95% CI: 86·2 - 100·0%), and 100% negative predictive value (95%CI: 98·6 - 100·0%). The analytical specificity was 99·8% (95% CI: 98·92 - 99·97%), indicating minimal cross-reactivity. A screening study was conducted to ascertain the seroprevalence of COVID-19 among healthcare workers and outpatients in Minnesota. Findings: Serum collected from 1,282 healthcare workers (1,000 females, 280 males, 2 gender unreported; median age 41 years [range 18 - 73]) and 2,379 outpatients (1,460 females, 916 males, 3 gender unreported; median age 49 years [range 2 months - 93 years]) between April 13 and May 21, 2020 was analyzed using our SARS-CoV-2 total antibody assay. The COVID-19 seroprevalence was 2·96% (95% CI: 2·04 - 3·89%) among healthcare workers and 4·46% (95% CI: 3·63 - 5·28%) among outpatients from 35 clinics who had a previous COVID-19 exposure or symptoms. Interpretation: Rigorously validated serology tests with robust clinical and analytical performance, such as our in-house SARS-CoV-2 total antibody test, are of critical importance when conducting epidemiological studies to inform public health decisions during the COVID-19 pandemic. Funding: University of Minnesota Department of Laboratory Medicine and Pathology Declaration of Interests: The authors do not declare any competing interests. Ethics Approval Statement: The University of Minnesota Institutional Review Board (IRB) determined that this study was not considered human research.
Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates ... more Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates in the U.S., creating an urgent need for novel early detection tools. A candidate biomarker for use in early detection is the soluble MHC class I-related chain A (s-MICA) ligand, which pancreatic tumors shed to escape immune detection. The objective of this study was to define the association between s-MICA levels and pancreatic cancer, in a population-based case-control study. S-MICA was measured in 163 pancreatic cancer cases and 542 controls. Unconditional logistic regression was used to calculate odds ratio (OR) for pancreatic cancer, and 95% confidence intervals (CI). There was a positive association between increasing s-MICA levels and pancreatic cancer: compared to the lowest tertile, the ORs for pancreatic cancer were 1.25 (95% CI: 0.75 - 2.07) and 2.10 (95% CI: 1.29 -3.42) in the second and highest tertiles, respectively (p-trend=0.02). Our study supports previous work demonstra...
Previous studies have shown that plasma mtDNA can be separated into two fractions; a supernatant ... more Previous studies have shown that plasma mtDNA can be separated into two fractions; a supernatant form that is cell-free and a pelleted form that is thought to be platelet associated. These fractions of plasma mtDNA should be measured in studies evaluating the role of plasma mtDNA as biomarkers for early detection or susceptibility to various cancers. Though one case-control study has shown lower plasma mitochondrial DNA (mtDNA) copy number to be associated with increased breast cancer risk this study did not evaluate the two fractions of plasma mtDNA. Hence, the role of plasma mtDNA in determining breast cancer risk was investigated further. We conducted a case-control study of 29 breast cancer cases and 28 cancer free controls to evaluate the association between (a) plasma mtDNA copy number and (b) peripheral blood leucocyte mtDNA copy number and breast cancer risk. Plasma obtained from the breast cancer cases and controls was centrifuged further at 18,000 g for 10 minutes to separ...
Submission of vaginal samples collected at home could remove barriers that women face in getting ... more Submission of vaginal samples collected at home could remove barriers that women face in getting screened for cervical cancer. From December 2013 to January 2014, women aged 21-30 years were recruited online to participate in either (1) self-collected testing for human papillomavirus (HPV) infection and an online survey, or (2) an online survey regarding their perceptions of self-collected testing for HPV infection. Demographics, risk factors, testing perceptions, and satisfaction with self-collected testing were assessed with online questionnaires. Women who performed self-collection were sent a home sampling kit by US mail, which was returned via US mail for HPV testing. A total of 197 women were enrolled, with 130 completing the online survey and 67 participating in both the survey and self-collection. Of the 67 women who were sent kits, 62 (92.5 %) were returned for testing. Sixty kits contained a sample sufficient for testing. The overall prevalence of HPV infection was 17.8 %,...
Background: Graft-versus-host disease (GvHD) continues to be a major cause of transplant related ... more Background: Graft-versus-host disease (GvHD) continues to be a major cause of transplant related mortality, morbidity and decreased quality of life post allogeneic hematopoietic cell transplant (HCT). Despite extensive use of histocompatibility antigen (HLA) matching between patients and donors and a variety of prophylactic regimens, the rates of GvHD have not declined substantially over the last decade. Recent studies have shown mitochondrial reactive oxygen species (ROS) plays an important role in T lymphocyte activation and initiation of the inflammatory response and represents a novel biological pathway that influences GvHD risk. We hypothesized that lower mitochondrial DNA (mtDNA) copy number that increases ROS related oxidative damage will be associated with acute and chronic GvHD. Methods: In a cohort of 201 patients who underwent allogeneic HCT for treatment of hematologic malignancies at the University of Minnesota between 2009 and 2012, we evaluated the association between...
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Jan 6, 2018
The association between residence and allergy has been well studied in children living on a farm;... more The association between residence and allergy has been well studied in children living on a farm; however, studies of this association in late adulthood are lacking. This study examined the association between residence and allergy in 25,393 women aged 55-69 years in the large prospective Iowa Women's Health Study (IWHS). IWHS questionnaires collected information on socio-demographic and anthropometric characteristics, medical history, lifestyle behaviors, dietary intake, residence and allergy. Residence reported at baseline (1986) was categorized into 5 groups based on living on a farm, rural, or urban areas and population size. Allergy was determined from four self-reported questions about physician-diagnosed asthma, hay fever, skin allergy, and other allergy. Logistic regression was used to determine significant risk factors for allergy and prevalence odds ratios (OR) and 95% confidence intervals (CI) for allergy associated with residence. Compared to large city of >10,000...
We conducted a nested case control study of 178 incident breast cancer cases and 356 controls in ... more We conducted a nested case control study of 178 incident breast cancer cases and 356 controls in the Atherosclerosis Risk in Communities study. We evaluated the association between breast cancer and Val432Leu polymorphism in the CYP1B1 gene and the tetranucleotide repeats in intron 4 of the CYP19 gene. After adjustment for height, age at menopause, age at menarche, BMI, HRT, and alcohol intake, carriers of the Val/Leu or Val/Val genotype had a 1.45 fold (95% CI 0.85-2.47) greater odds of breast cancer than Leu/Leu carriers. There was no association of the breast cancer with any individual CYP19 allele. Compared to individuals homozygous with the 167 allele, odds ratios were close to 1.0 for the 167 heterozygous genotype and for the remaining tetranucleotide repeats combined. Our data shows no association between breast cancer and the Leu432Val polymorphism of the CYP1B1 gene or the tetranucleotide repeats of the CYP19 gene.
Supplemental Table 9 shows the associations between pre-selected SNPs and mean of Visit 2 and Vis... more Supplemental Table 9 shows the associations between pre-selected SNPs and mean of Visit 2 and Visit 3 sMICA and sMICB levels (continuous variables).
Due to evolving population demographics, altered exposures, and new technology, new cohorts need ... more Due to evolving population demographics, altered exposures, and new technology, new cohorts need to be initiated. Here we report our efforts from a pilot cohort study of the 10,000 Families Study (10KFS). The goal of the pilot is to establish the infrastructure, protocols, and standard operating procedures for a larger study that would provide the data to further our understanding of the determinants of health across the life course and intergenerational transmission of environmental, genetic, and epigenetic risk factors. We have focused on cancer, as this is the leading cause of death in Minnesota. Data collection methods include online questionnaires and attendance at a health fair for various physical and biologic measurements. For this family-based study, a family is eligible if at least one member of two, preferably three, generations enrolls, and each member is willing, or willing for their child(ren), to provide DNA from blood or saliva. To facilitate eventual scale-up of the...
Background: Life course socioeconomic and demographic factors including educational attainment, r... more Background: Life course socioeconomic and demographic factors including educational attainment, race and ethnicity, and childhood (SES) are very powerful predictors of large inequalities in aging, morbidity, and mortality. Immune aging, including accumulation of late-differentiated, senescent-like lymphocytes and lower level of naive lymphocytes, may play a role in the development of the age-related health inequalities. However, there has been little research investigating association between socioeconomic status and immune aging, particularly age-related changes in lymphocyte percentages. Methods: This study used nationally representative data from more than 9000 US adults from the Health and Retirement Study to investigate associations between educational attainment, race and ethnicity, and childhood SES and lymphocyte percentages. Results: Respondents with lower educational attainment, Hispanic adults, and those who had a parent with less than high school education had lymphocyte...
Introduction: Mean corpuscular volume (MCV) of red blood cells (RBCs) is a heritable index common... more Introduction: Mean corpuscular volume (MCV) of red blood cells (RBCs) is a heritable index commonly used in clinical workup of anemia. Macrocytosis, or high MCV, is associated with cardiovascular events in chronic kidney disease patients and all-cause mortality. Genome-wide association studies (GWAS) of MCV have been conducted primarily in European and Asian populations; few have included populations of African or American ancestry. The Multiethnic Genotyping Array (MEGA) was designed to improve variant discovery and fine-mapping in US minorities by better capturing population-specific genetic variation. To identify novel MCV loci and examine evidence of generalization of previously reported MCV loci to populations with African and Amerindian genetic admixture, we conducted a GWAS of African American and Hispanic/Latino Population Architecture using Genomics and Epidemiology (PAGE II) participants on the MEGA array. Methods: We employed Illumina MEGA genotype data to evaluate the as...
Introduction: The relationship between gut microbiome and human obesity is not fully elucidated. ... more Introduction: The relationship between gut microbiome and human obesity is not fully elucidated. Most evidence is from animal models or small case-control studies. Data in population-based cohort are limited. Hypothesis: We hypothesized that some specific bacterial taxonomy are associated with host obesity, some of them may also associated with obesity-related cardiometabolic traits. Methods: This study included 2759 participants from the HCHS/SOL. Fecal samples were analyzed by shotgun metagenomics sequencing, with the SHOGUN pipeline for bacterial taxonomic identification. Multivariate linear regression models were used to examine associations of bacterial genera with multiple obesity and cardiometabolic traits. Results: Of 87 predominant genera (average relative abundance >0.01%), 43 were significantly associated with BMI after multiple testing correction ( Fig 1 ). These included some known obesity-associated taxa (e.g., Acidaminococcus , Dorea etc.) , some taxa with controve...
Background: Associations of insulin resistance and glycemia with liver enzymes have not been well... more Background: Associations of insulin resistance and glycemia with liver enzymes have not been well studied in a young, heterogeneous Hispanic/Latino population. We aimed to assess these associations, and to examine the role of endothelial dysfunction as a potential mediator. Methods: We examined 1,275 participants aged 8-16 years from the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth) (2012-14). We examined the distribution of liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST], and gamma-glutamyl transpeptidase [GGT]), the pediatric nonalcoholic fatty liver disease (NAFLD) fibrosis index (PNFI), glycemic markers (fasting glucose and hemoglobin A1c [HbA1c]), and insulin resistance (HOMA-IR) by age, sex, and body mass index (BMI). We assessed the adjusted cross-sectional associations of insulin resistance and hyperglycemia (as continuous variables) with elevated liver enzymes and PNFI (as binary variables) using Poisson regression to o...
Background The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other... more Background The hygiene hypothesis posits that microbial exposure reduces risk of asthma and other respiratory-related diseases. Helicobacter pylori and hepatitis A virus (HAV) are common fecal–oral infections. Our study aimed to examine associations of seropositivity to these agents with asthma in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods A total of 12,471 HCHS/SOL participants with baseline data on self-reported physician-diagnosed asthma, and antibodies anti-H. pylori and anti-HAV were included in this cross-sectional analysis. Multivariable logistic regression models were used to estimate the odds ratios and 95% confidence intervals for the overall associations of seropositivity to each agent with asthma. Analyses were also stratified by Hispanic/Latino background. Effect modification by smoking status and nativity were tested. An analysis restricted to individuals with spirometry-defined chronic obstructive pulmonary disease (COPD) was also conside...
Background: CT-derived muscle density (MD) reflects the degree of adiposity in muscle (i.e., myos... more Background: CT-derived muscle density (MD) reflects the degree of adiposity in muscle (i.e., myosteatosis) with lower MD indicating greater adiposity. Previous research indicates lower MD is associated with increased risk of type 2 diabetes (T2D). However, few studies have compared the association of simultaneously measured MD by anatomic location. The relationship between myosteatosis and cardiometabolic health may differ by body site and influence which location(s) is most useful for risk assessment. We investigated potential differential relationships between T2D and MD of the locomotor muscles of the abdomen (psoas), thigh, and calf among 539 African Caribbean men from Tobago. Methods: Men were aged 50-91 years (mean 64.4 years, mean BMI 27.5 kg/m 2 ). Calf MD was measured at 66% of calf length using peripheral quantitative CT; calf MD was defined as the ratio of muscle mass to cross-sectional muscle area. Psoas MD was measured in the abdomen (between L3/L4) and thigh MD was mea...
Pharmacogenomics (PGx) studies how a person’s genes affect the response to medications and is qui... more Pharmacogenomics (PGx) studies how a person’s genes affect the response to medications and is quickly becoming a significant part of precision medicine. The clinical application of PGx principles has consistently been cited as a major opportunity for improving therapeutic outcomes. Several recent studies have demonstrated that most individuals (> 90%) harbor PGx variants that would be clinically actionable if prescribed a medication relevant to that gene. In multiple well-conducted studies, the results of PGx testing have been shown to guide therapy choice and dosing modifications which improve treatment efficacy and reduce the incidence of adverse drug reactions (ADRs). Although the value of PGx testing is evident, its successful implementation in a clinical setting presents a number of challenges to molecular diagnostic laboratories, healthcare systems, providers and patients. Different molecular methods can be applied to identify PGx variants and the design of the assay is the...
Non‐alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident dia... more Non‐alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident diabetes. But such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD.
Background: Antibody tests are critical in elucidating the epidemiology of the rapidly evolving C... more Background: Antibody tests are critical in elucidating the epidemiology of the rapidly evolving Coronavirus Disease 2019 (COVID-19) global pandemic and in developing effective infection control measures. To avoid the significant risks posed by the use of tests with poor performance characteristics and associated supply chain disruptions, we developed an in-house SARS-CoV-2 total antibody test. The performance of our robustly validated test was compared with that of three commercial antibody tests, and our test was used to determine the seroprevalence of COVID-19 among healthcare workers and outpatients in Minnesota. Methods: To evaluate the clinical performance of our SARS-CoV-2 total antibody assay, 63 plasma and serum samples were analyzed from 34 SARS-CoV-2 PCR positive patients 4 - 35 days after symptom onset. Positive samples were analyzed for IgG titers in a follow up assay. Samples were analyzed from PCR negative (n=30) and presumed true negative pre-pandemic (n=207) patients. Among samples collected from patients >14 days after symptom onset, the assay had 100% diagnostic sensitivity (95% CI: 85·7 - 100·0%), 100% diagnostic specificity (95%CI: 98·5 - 100·0%), 100% positive predictive value (95% CI: 86·2 - 100·0%), and 100% negative predictive value (95%CI: 98·6 - 100·0%). The analytical specificity was 99·8% (95% CI: 98·92 - 99·97%), indicating minimal cross-reactivity. A screening study was conducted to ascertain the seroprevalence of COVID-19 among healthcare workers and outpatients in Minnesota. Findings: Serum collected from 1,282 healthcare workers (1,000 females, 280 males, 2 gender unreported; median age 41 years [range 18 - 73]) and 2,379 outpatients (1,460 females, 916 males, 3 gender unreported; median age 49 years [range 2 months - 93 years]) between April 13 and May 21, 2020 was analyzed using our SARS-CoV-2 total antibody assay. The COVID-19 seroprevalence was 2·96% (95% CI: 2·04 - 3·89%) among healthcare workers and 4·46% (95% CI: 3·63 - 5·28%) among outpatients from 35 clinics who had a previous COVID-19 exposure or symptoms. Interpretation: Rigorously validated serology tests with robust clinical and analytical performance, such as our in-house SARS-CoV-2 total antibody test, are of critical importance when conducting epidemiological studies to inform public health decisions during the COVID-19 pandemic. Funding: University of Minnesota Department of Laboratory Medicine and Pathology Declaration of Interests: The authors do not declare any competing interests. Ethics Approval Statement: The University of Minnesota Institutional Review Board (IRB) determined that this study was not considered human research.
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Papers by Bharat Thyagarajan