Protection against fibrosis by a bacterial consortium in metabolic dysfunction-associated steatohepatitis and the role of amino acid metabolism.

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against liver fibrosis. Six of the eight inoculated bacteria were detected in mouse stool and liver. Intrahepatic presence of bacteria was further confirmed by bacterial culture of mouse liver tissue. Changes in liver histological parameters, gut functional profiles, and amino acid profiles were additionally assessed. Comparison between fibrosis-associated human metagenome and bacteria-induced metagenome changes in mice identified microbial functions likely to mediate the protective effect against liver fibrosis. Amino acid profiling confirmed an increase in cysteine synthase activity, associated with reduced fibrosis. Other microbiota-induced changes in amino acids associated with reduced fibrosis included increased gut asparaginase activity and decreased hepatic tryptophan-to-kynurenine conversion. This human-to-mouse study identified bacterial species and their effects on amino acid metabolism as innovative strategies to protect against liver fibrosis in MASH.

The association of cancer-preventive lifestyle with colonoscopy screening use in border Hispanic adults along the Texas-Mexico border.

PURPOSE: The relationship between engaging in two domains of cancer-preventive behaviors, lifestyle behaviors and colonoscopy screening, is unknown in Hispanic adults. Accordingly, the study examined the association between lifestyle and colonoscopy screening in Hispanic adults along the Texas-Mexico border, where there is suboptimal colorectal cancer prevention. METHODS: Lifestyle behavior adherence and compliance with colonoscopy screening schedules were assessed using 2013-2023 data from the Cameron County Hispanic Cohorta population-based sample of Hispanic adults living along the Texas-Mexico border. The 2018 World Cancer Research Fund scoring system characterized healthy lifestyle engagement. Multivariable logistic regression quantified the association between lifestyle behaviors and colonoscopy screening. RESULTS: Among 914 Hispanic adults, there was a mean adherence score of 2.5 out of 7 for recommended behaviors. Only 33.0% (95% CI 25.64-41.39%) were up-to-date with colonoscopy. Complete adherence to fruit and vegetable (AOR [adjusted odds ratio] 5.2, 95% CI 1.68-16.30; p = 0.004), fiber (AOR 2.2, 95% CI 1.06-4.37; p = 0.04), and ultra-processed foods (AOR 2.8, 95% CI 1.30-6.21; p = 0.01) consumption recommendations were associated with up-to-date colonoscopy screening. Having insurance versus being uninsured (AOR 10.8, 95% CI 3.83-30.62; p < 0.001) and having local medical care versus in Mexico (AOR 7.0, 95% CI 2.26-21.43; p < 0.001) were associated with up-to-date colonoscopy. CONCLUSIONS: Adherence to dietary lifestyle recommendations was associated with being up-to-date with colonoscopy screenings. Those with poor dietary behavior are at risk for low-colonoscopy use. Improving lifestyle behaviors may complement colonoscopy promotion interventions. Healthcare accessibility influences up-to-date colonoscopy prevalence. Our findings can inform cancer prevention strategies for the Hispanic population.

A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing in parallel with an obesity pandemic, calling for novel strategies for prevention and treatment. We defined a circulating proteome of human MASLD across ≈7000 proteins in ≈5000 individuals from diverse, at-risk populations across the metabolic health spectrum, demonstrating reproducible diagnostic performance and specifying both known and novel metabolic pathways relevant to MASLD (central carbon and amino acid metabolism, hepatocyte regeneration, inflammation, fibrosis, insulin sensitivity). A parsimonious proteomic signature of MASLD was associated with a protection from MASLD and its related multi-system metabolic consequences in >26000 free-living individuals, with an additive effect to polygenic risk. The MASLD proteome was encoded by genes that demonstrated transcriptional enrichment in liver, with spatial transcriptional activity in areas of steatosis in human liver biopsy and dynamicity for select targets in human liver across stages of steatosis. We replicated several top relations from proteomics and spatial tissue transcriptomics in a humanized "liver-on-a-chip" model of MASLD, highlighting the power of a full translational approach to discovery in MASLD. Collectively, these results underscore utility of blood-based proteomics as a dynamic "liquid biopsy" of human liver relevant to clinical biomarker and mechanistic applications.

A high burden of diabetes and ankle brachial index abnormalities exists in Mexican Americans in South Texas.

Ethnic differences exist in the United States in the interrelated problems of diabetes (DM), peripheral arterial disease (PAD), and leg amputations. The purpose of this study was to determine the prevalence and risk factor associations for subclinical PAD in a population sample of Mexican Americans using the ankle brachial (ABI) index. The ABI-High (higher of the two ankle pressures/highest brachial pressure) and ABI-Low (lower of the two ankle pressures/highest brachial pressure) were calculated to define PAD. Toe brachial index (TBI) was also calculated. 746 participants were included with an age of 53.4 ± 0.9 years, 28.3 % had diabetes mellitus (DM), 12.6 % were smokers, and 51.2 % had hypertension (HTN). Using ABI-High ≤ 0.9, the prevalence of PAD was 2.7 %. This rose to 12.7 % when an ABI-Low ≤ 0.9 was used; 4.0 % of the population had an ABI-High > 1.4. The prevalence of TBI < 0.7 was 3.9 %. DM was a significant risk factor for ABI-High ≤ 0.9 and ABI-High > 1.4, and TBI < 0.7. Increased age, HTN, smoking was associated with ABI-High ≤ 0.9, while being male was associated with ABI-High > 1.4. Increased age, smoking, and lower education were all associated with abnormal TBI. Despite relatively younger mean age than other studied Hispanic cohorts, the present population has a high burden of ABI abnormalities. DM was a consistent risk factor for PAD. These abnormalities indicate an important underlying substrate of vascular and metabolic disease that may predispose this population to the development of symptomatic PAD and incident amputations.

A Comprehensive Program to Improve Treatment of Precancerous Cervical Lesions in the Rio Grande Valley of Texas.

OBJECTIVE: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment. DESIGN: Retrospective cohort study. INTERVENTION: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO. MAIN OUTCOME MEASURES: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation. RESULTS: A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation. CONCLUSIONS: Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings.

Addressing cervical cancer disparities in Texas: Expansion of a community-based prevention initiative for medically underserved populations.

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled with biweekly telementoring conferences using Project ECHO® (Extension for Community Healthcare Outcomes). This program was implemented in 2015 and expanded to other MUAs in Texas in 2019. From March 2019 to August 2022, 75,842 individuals were educated about cervical cancer screening and HPV vaccination. A total of 44,781 women underwent screening for cervical cancer, and 2,216 underwent colposcopy and 264 underwent LEEP. High-grade cervical dysplasia was diagnosed in 658 individuals and invasive cervical cancer in 33 individuals. We trained 22 providers to perform colposcopy and/or LEEP. In addition, 78 Project ECHO telementoring sessions were held with an average of 42 attendees per session, with 72 individual patient cases discussed. Our comprehensive community-based prevention initiative for medically underserved populations has led to a significant number of individuals undergoing cervical cancer screening in MUAs, as well as improved access to colposcopy and LEEP services.

Challenges and strategies for recruitment of minorities to clinical research and trials.

Minority populations are largely absent from clinical research trials. The neglect of these populations has become increasingly apparent, with escalating cancer burdens and chronic disease. The challenges to recruitment of minorities in the United States are multiple including trust or lack thereof. Keys to successful recruitment are responding to community issues, its history, beliefs, and its social and economic pressures. The strategy we have used in many low-income, sometimes remote, communities is to recruit staff from the same community and train them in the required basic research methods. They are the first line of communication. After our arrival in the Texas Rio Grande Valley in 2001, we applied these principles learned over years of global research, to studies of chronic diseases. Beginning in 2004, we recruited and trained a team of local women who enrolled in a cohort of over five thousand Mexican Americans from randomly selected households. This cohort is being followed, and the team has remained, acquiring not only advanced skills (ultrasound, FibroScan, retinal photos, measures of cognition, etc.) but capacity to derive key health information. Currently, we are participating in multiple funded studies, including an NIH clinical trial, liver disease, obesity, and diabetes using multiomics aimed at developing precision medicine approaches to chronic disease prevention and treatment.

Sex-specific associations between adipokine profiles and carotid-intima media thickness in the Cameron County Hispanic Cohort (CCHC).

BACKGROUND: Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures. METHODS: Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT. RESULTS: In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [ß(SE) = 0.060 (0.016), p = 2.52 × 10-4], and female-specific associations were between cIMT and adiponectin [ß(SE) = 0.010 (0.005), p = 0.043] and ARI [ß(SE) = - 0.011 (0.005), p = 0.036]. When stratified by metabolic health status, the male-specific positive association between LAR and cIMT was more evident among the metabolically healthy group [ß(SE) = 0.127 (0.015), p = 4.70 × 10-10] (p for interaction by metabolic health < 0.1). However, the female-specific associations between adiponectin and cIMT and ARI and cIMT were observed only among the metabolically elevated risk group [ß(SE) = 0.014 (0.005), p = 0.012 for adiponectin; ß(SE) = - 0.015 (0.006), p = 0.013 for ARI; p for interaction by metabolic health < 0.1]. CONCLUSION: Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.

Prevalence and factors associated with liver fibrosis among first-degree relatives of Mexican Americans with hepatocellular carcinoma.

BACKGROUND AND AIMS: Whether hepatocellular carcinoma (HCC) increases the familial risk for hepatic fibrosis has not been thoroughly explored, particularly in Mexican Americans who are disproportionately affected by obesity and metabolic syndrome. We evaluated the risk of significant hepatic fibrosis in first-degree relatives of Mexican American adults with HCC. METHODS: We performed a cross-sectional analysis of a prospective cohort of Mexican American probands with HCC and first-degree relatives enrolled in the Hispanic Liver Cancer Cohort study. We evaluated the prevalence of hepatic fibrosis in first-degree relatives, defined by liver stiffness measurement (LSM) >= 7.0 kPa with transient elastography (TE). Secondary outcomes included the prevalence of definite hepatic steatosis, defined by controlled attenuation parameter >=288 dB/m. RESULTS: We identified 70 probands diagnosed with HCC; 47% were female and the mean age was 62 years (±13 years). Among 112 first-degree relatives with a mean age of 43 years (±14 years), 19 (17%) had significant fibrosis and 47 (42%) had definite hepatic steatosis, respectively. The prevalence of significant fibrosis was 20% in first-degree relatives 40 years of age or older. Regression analysis revealed that diabetes (OR 3.2, 95% CI: 1.1-9.2, p = 0.03) and aspartate aminotransferase >=30 units/L (OR 4.0, 95% CI: 1.4-11.7, p = 0.01) were predictors of significant fibrosis in first-degree relatives. CONCLUSIONS: Using a well-phenotyped familial cohort, we found that the prevalence of significant fibrosis and definite hepatic steatosis are high in first-degree relatives of Mexican Americans with HCC, particularly those with diabetes, suggesting that this population may benefit from screening for liver disease.

Genetic variants associated with circulating liver injury markers in Mexican Americans, a population at risk for non-alcoholic fatty liver disease.

Objective: Mexican Americans are disproportionally affected by non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma. Noninvasive means to identify those in this population at high risk for these diseases are urgently needed. Approach: The Cameron County Hispanic Cohort (CCHC) is a population-based cohort with high rates of obesity (51%), type 2 diabetes (28%) and NAFLD (49%). In a subgroup of 564 CCHC subjects, we evaluated 339 genetic variants previously reported to be associated with liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in United Kingdom and Japanese cohorts. Results: Association was confirmed for 86 variants. Among them, 27 had higher effect allele frequency in the CCHC than in the United Kingdom and Japanese cohorts, and 16 had stronger associations with AST and ALT than rs738409 (PNPLA3). These included rs17710008 (MYCT1), rs2519093 (ABO), rs1801690 (APOH), rs10409243 (S1PR2), rs1800759 (LOC100507053) and rs2491441 (RGL1), which were also associated with steatosis and/or liver fibrosis measured by vibration-controlled transient elastography. Main contributors to advanced fibrosis risk were rs11240351 (CNTN2), rs1800759 (LOC100507053), rs738409 (PNPLA3) and rs1801690 (APOH), with advanced fibrosis detected in 37.5% of subjects with 3 of these 4 variants [AOR = 11.6 (95% CI) = 3.8-35.3]. AST- and ALT-associated variants implicated distinct pathways (ethanol and galactose degradation versus antigen presentation and B cell development). Finally, 8 variants, including rs62292950 (DNAJC13), were associated with gut microbiome changes. Conclusion: These genotype-phenotype findings may have utility in risk modeling and disease prevention in this high-risk population.

Gut microbiome features associated with liver fibrosis in Hispanics, a population at high risk for fatty liver disease.

BACKGROUND AND AIMS: Hispanics are disproportionately affected by NAFLD, liver fibrosis, cirrhosis, and HCC. Preventive strategies and noninvasive means to identify those in this population at high risk for liver fibrosis, are urgently needed. We aimed to characterize the gut microbiome signatures and related biological functions associated with liver fibrosis in Hispanics and identify environmental and genetic factors affecting them. APPROACH AND RESULTS: Subjects of the population-based Cameron County Hispanic Cohort (CCHC; n = 217) were screened by vibration-controlled transient elastography (FibroScan). Among them, 144 (66.7%) had steatosis and 28 (13.0%) had liver fibrosis. The gut microbiome of subjects with liver fibrosis was enriched with immunogenic commensals (e.g., Prevotella copri, Holdemanella, Clostridiaceae 1) and depleted of Bacteroides caccae, Parabacteroides distasonis, Enterobacter, and Marinifilaceae. The liver fibrosis-associated metagenome was characterized by changes in the urea cycle, L-citrulline biosynthesis and creatinine degradation pathways, and altered synthesis of B vitamins and lipoic acid. These metagenomic changes strongly correlated with the depletion of Parabacteroides distasonis and enrichment of Prevotella and Holdemanella. Liver fibrosis was also associated with depletion of bacterial pathways related to L-fucose biosynthesis. Alcohol consumption, even moderate, was associated with high Prevotella abundance. The single-nucleotide polymorphisms rs3769502 and rs7573751 in the NCK adaptor protein 2 (NCK2) gene positively associated with high Prevotella abundance. CONCLUSION: Hispanics with liver fibrosis display microbiome profiles and associated functional changes that may promote oxidative stress and a proinflammatory environment. These microbiome signatures, together with NCK2 polymorphisms, may have utility in risk modeling and disease prevention in this high-risk population.

Resistin levels decrease as insulin resistance increases in a Mexican-American cohort.

AIMS: Links between resistin, insulin resistance (IR), and resistin-stimulated cytokine signaling remain unknown in Mexican-Americans. A Mexican-American cohort was examined to determine (1) relationships between circulating resistin and IR, (2) resistin's associations with cytokines and demographic and anthropometric variables, and (3) similar measurements with other adipokines. METHODS: For cross sectional analyses, 953 adults (367 males and 586 females) in the Cameron County Hispanic Cohort (CCHC) were stratified into three groups: normal glucose tolerance, prediabetes, and diabetes mellitus. Differences in resistin and other adipokine levels were examined using linear regression via unadjusted model (Model 1), model adjusted for cytokines (Model 2), and model further adjusted for demographic and anthropometric variables (Model 3). RESULTS: HOMA-IR increased with worsening glucose tolerance (p < 0.0001). In all models, resistin significantly decreased as glucose tolerance deteriorated. Model 3 resistin was positively associated with IL-1ß (p = 0.0252) and IL-8 (p < 0.0001), inversely associated with TNF-α (p = 0.0352), but nonsignificantly associated with IL-6 (p = 0.8671). Model 3 leptin was significantly lower in diabetes mellitus compared to other groups (p < 0.005) and positively associated with female sex (p < 0.0001), age (p = 0.024), and BMI (p < 0.0001), without significant cytokine associations. Adiponectin displayed no significant associations with glucose tolerance, but was significantly associated with sex, BMI, and lipids (Model 3). CONCLUSIONS: Resistin unexpectedly decreased as IR increased while supporting evidence of a resistin-stimulated cytokine pathway in this Mexican-American cohort. Leptin fell with elevated IR after adjusting for cytokines, demographic and anthropometric variables. Adiponectin nonsignificantly decreased as IR increased while showing significant associations with sex, BMI, and lipids.

Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics.

Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.

Circulating Fatty Acids Associated with Advanced Liver Fibrosis and Hepatocellular Carcinoma in South Texas Hispanics.

BACKGROUND: Hispanics in South Texas have high rates of hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Liver fibrosis severity is the strongest predictive factor of NAFLD progression to HCC. We examined the association between free fatty acids (FA) and advanced liver fibrosis or HCC in this population. METHODS: We quantified 45 FAs in plasma of 116 subjects of the Cameron County Hispanic Cohort, 15 Hispanics with HCC, and 56 first/second-degree relatives of Hispanics with HCC. Liver fibrosis was assessed by FibroScan. RESULTS: Advanced liver fibrosis was significantly associated with low expression of very long chain (VLC) saturated FAs (SFA), odd chain SFAs, and VLC n-3 polyunsaturated FAs [PUFA; AOR; 95% confidence interval (CI), 10.4 (3.7-29.6); P < 0.001; 5.7 (2.2-15.2); P < 0.001; and 3.7 (1.5-9.3); P = 0.005]. VLC n3-PUFAs significantly improved the performance of the noninvasive markers for advanced fibrosis - APRI, FIB-4, and NFS. Plasma concentrations of VLC SFAs and VLC n-3 PUFAs were further reduced in patients with HCC. Low concentrations of these FAs were also observed in relatives of patients with HCC and in subjects with the PNPLA3 rs738409 homozygous genotype. CONCLUSIONS: Low plasma concentrations of VLC n-3 PUFAs and VLC SFAs were strongly associated with advanced liver fibrosis and HCC in this population. Genetic factors were associated with low concentrations of these FAs as well. IMPACT: These results have implications in identifying those at risk for liver fibrosis progression to HCC and in screening this population for advanced fibrosis. They also prompt the evaluation of VLC n-3 PUFA or VLC SFA supplementation to prevent cirrhosis and HCC.

An evaluation of lipid profile and pro-inflammatory cytokines as determinants of cardiovascular disease in those with diabetes: a study on a Mexican American cohort.

Sedentary life styles coupled with high-calorie diets and unhealthy social habits such as smoking, have put an ever-increasing number of people at risk of cardiovascular disorders (CVD), worldwide. A concomitant increase in the prevalence of type 2-diabetes (hyperglycemia), a risk factor for CVD, has further contributed towards escalating CVD-related mortalities. The increase in number of cases of type 2-diabetes underscores the importance of early diagnosis of cardiovascular disease in those with diabetes. In this work, we have evaluated the sensitivity and specificity of dyslipidemia and proinflammatory cytokines to be used as biomarkers for predicting the risk of CVD in those with diabetes. We hypothesize that interplay between dyslipidemia and diabetes-induced low-grade inflammation in those with type 2-diabetes increases the risk of CVD. A total of 215 participants were randomly recruited from the Cameron County Hispanic Cohort (CCHC). Of these, 99% were Mexican Americans living on Texas-Mexico border. Levels of cytokines, adipokines and lipid profile were measured. Cardiovascular disease (CVD) for this study was defined as prior diagnosis of heart attack, angina and stroke, while diabetes was defined by fasting blood glucose (FBG) of > 100 mg/dL and HbA1c of > 6.5, in accordance with American Diabetes Association (ADA) guidelines. Depending on type and distribution of data, various statistical tests were performed. Our results demonstrated higher rates of heart attack (14% vs 11.8%) and stroke (19.8% vs 10%) in those with diabetes as compared to non-diabetes. The odds of having a heart attack were eight times higher in the presence of elevated triglycerides and pro-inflammatory markers (TNFα and IL6) as compared to presence of pro-inflammatory markers only. The odds for heart attack among those with diabetes, increased by 20 fold in presence of high levels of triglycerides, TNFα, and IL6 when coupled with low levels of high-density lipid cholesterol (HDL-C). Lastly, our analysis showed that poorly controlled diabetes, characterized by HbA1c values of > 6.5 increases the odds of stroke by more than three fold. The study quantifies the role of lipid profile and pro-inflammatory markers in combination with standard risk factors towards predicting the risk of CVD in those with type 2-diabetes. The findings from the study can be directly translated for use in early diagnosis of heart disease and guiding interventions leading to a reduction in CVD-associated mortality in those with type 2-diabetes.

Dynamic Functional Continuous Time Bayesian Networks for Prediction and Monitoring of the Impact of Patients' Modifiable Lifestyle Behaviors on the Emergence of Multiple Chronic Conditions.

More than a quarter of all Americans are estimated to have multiple chronic conditions (MCC). It is known that shared modifiable lifestyle behaviors account for many common MCC. What is not precisely known is the dynamic effect of changes in lifestyle behaviors on the trajectories of MCC emergence. This paper proposes dynamic functional continuous time Bayesian networks to effectively formulate the dynamic effect of patients' modifiable lifestyle behaviors and their interaction with non-modifiable demographics and preexisting conditions on the emergence of MCC. The proposed method considers the parameters of the conditional dependencies of MCC as a nonlinear state-space model and develops an extended Kalman filter to capture the dynamics of the modifiable risk factors on the MCC evolution. It also develops a tensor-based control chart based on the integration of multilinear principal component analysis and multivariate exponentially weighted moving average chart to monitor the effect of changes in the modifiable risk factors on the risk of new MCC. We validate the proposed method based on a combination of simulation and a real dataset of 385 patients from the Cameron County Hispanic Cohort. The dataset examines the emergence of 5 chronic conditions (Diabetes, Obesity, Cognitive Impairment, Hyperlipidemia, Hypertension) based on 4 modifiable lifestyle behaviors representing (Diet, Exercise, Smoking Habits, Drinking Habits) and 3 non-modifiable demographic risk factors (Age, Gender, Education). For the simulated study, the proposed algorithm shows a run-length of 4 samples (4 months) to identify behavioral changes with significant impacts on the risk of new MCC. For the real data study, the proposed algorithm shows a run-length of one sample (one year) to identify behavioral changes with significant impacts on the risk of new MCC. The results demonstrate the sensitivity of the proposed methodology for dynamic prediction and monitoring of the risk of MCC emergence in individual patients.

Elevated Glycated Hemoglobin Is Associated With Liver Fibrosis, as Assessed by Elastography, in a Population-Based Study of Mexican Americans.

Diabetes is associated with liver disease and risk of hepatocellular carcinoma. In this study, we evaluated the association between liver fibrosis measured by transient elastography and four glucose metabolism measures in the Cameron County Hispanic Cohort, a population-based, randomly selected cohort of Mexican American Hispanics with high rates of diabetes and liver cancer. We measured liver fibrosis (a risk factor for hepatocellular carcinoma) in 774 well-characterized cohort participants using transient elastography. We evaluated the association of liver fibrosis with glycated hemoglobin (HbA1c), fasting blood glucose, insulin, and insulin resistance using multivariable linear regression models. In multivariable models, log-transformed HbA1c had the strongest association with liver fibrosis (ß = 0.37, 95% confidence interval [CI] 0.04-0.69, P = 0.038), after controlling for waist circumference, aspartate aminotransferase, alanine aminotransferase, liver fat, and other known confounders. The association was statistically significant among women (ß = 0.33, 95% CI 0.10-0.56, P = 0.009) and similar but nonsignificant among men (ß = 0.41, 95% CI -0.17 to 0.98, P = 0.593). Waist circumference, platelet count, aspartate transaminase, and liver steatosis were each associated with liver stiffness. Conclusions: Elevated HbA1c is associated with liver fibrosis, a key risk factor for HCC, particularly among women. Our results indicate that Mexican Americans with uncontrolled HbA1c may benefit from routine screening by liver elastography to identify individuals at risk of liver disease progression.

Bile Acid Changes Associated With Liver Fibrosis and Steatosis in the Mexican-American Population of South Texas.

Biomarkers to predict risk of liver fibrosis in subjects with nonalcoholic fatty liver disease, a common risk factor for hepatocellular carcinoma, would allow for early preventive interventions. We sought to characterize bile acid profiles associated with liver fibrosis in subjects from the community-based Cameron County Hispanic Cohort, a population in South Texas with high rates of nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma. Plasma bile acid levels were measured in 390 subjects. These subjects were screened with liver elastography, detecting significant liver fibrosis in 58 subjects and steatosis in 186 subjects. Unsupervised clustering of the bile acid profiles revealed five clusters that differed by liver fibrosis, liver steatosis, liver injury, age and gender, identifying these parameters as major determinants of circulating bile acid changes. Total bile acid levels were significantly higher in subjects with fibrosis, with chenodeoxycholic acid displaying the greatest increase among individual bile acids. The primary conjugated bile acids, glycocholic and glycochenodeoxycholic acids, displayed the strongest association with fibrosis by logistic regression. High lithocholic acid levels were strongly associated with advanced fibrosis. In contrast, deoxycholic acid and total unconjugated secondary bile acids were positively associated with steatosis, whereas relative glycoursodeoxycholic acid abundance was negatively associated. Milk and yogurt intake notably contributed to fibrosis-associated bile acid changes. In addition, multiple families within the Firmicutes phylum, Prevotellaceae, and Bacteroides species in stool significantly correlated with fibrosis-associated and steatosis-associated bile acid parameters, suggesting that the gut microbiome contributes to bile acid changes in the context of liver disease. Conclusion: Circulating bile acid levels were markedly but differently changed in liver fibrosis and steatosis in a high-risk Mexican-American population.

Low-cost, high-resolution imaging for detecting cervical precancer in medically-underserved areas of Texas.

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. RESULTS: 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). CONCLUSIONS: HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.

Fruit and Vegetable Intake is Inversely Associated with Cancer Risk in Mexican-Americans.

Objective: There is inconsistent evidence and limited data in the Hispanic population concerning fruit and vegetable intake and cancer risk. This study explored the effect of fruit and vegetable intake on cancer risk in Mexican-Americans. Methods: Participants in this cross-sectional study were drawn from the Cameron County Hispanic Cohort. Consumption of fruits and vegetables were assessed using a validated questionnaire. Cancer was self-reported by the participants based on being told by a health care provider that they had cancer. Results: Among 2,381 participants with available dietary data, 82 reported a diagnosis of cancer. Participants who met recommendations of five or more servings of fruit and vegetable per day had a significantly 86% lower risk for reported cancer compared with those who did not meet recommendations, after adjusting for other covariates. Every portion increment of total fruit and vegetable intake was significantly associated with the reduced cancer risk by 11% with the adjustment of other covariates. Conclusions: Fruit and vegetable intake was inversely associated with cancer risk in Mexican-Americans. Improving the consumption of fruit and vegetable might be an effective area for further research as part of a strategy for cancer prevention and control among Mexican-Americans independent of other factors.