Novel diabetes gene discovery through comprehensive characterization and integrative analysis of longitudinal gene expression changes.

Type 2 diabetes is a complex, systemic disease affected by both genetic and environmental factors. Previous research has identified genetic variants associated with type 2 diabetes risk; however, gene regulatory changes underlying progression to metabolic dysfunction are still largely unknown. We investigated RNA expression changes that occur during diabetes progression using a two-stage approach. In our discovery stage, we compared changes in gene expression using two longitudinally collected blood samples from subjects whose fasting blood glucose transitioned to a level consistent with type 2 diabetes diagnosis between the time points against those who did not with a novel analytical network approach. Our network methodology identified 17 networks, one of which was significantly associated with transition status. This 822-gene network harbors many genes novel to the type 2 diabetes literature but is also significantly enriched for genes previously associated with type 2 diabetes. In the validation stage, we queried associations of genetically determined expression with diabetes-related traits in a large biobank with linked electronic health records. We observed a significant enrichment of genes in our identified network whose genetically determined expression is associated with type 2 diabetes and other metabolic traits and validated 31 genes that are not near previously reported type 2 diabetes loci. Finally, we provide additional functional support, which suggests that the genes in this network are regulated by enhancers that operate in human pancreatic islet cells. We present an innovative and systematic approach that identified and validated key gene expression changes associated with type 2 diabetes transition status and demonstrated their translational relevance in a large clinical resource.

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.

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

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.

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.

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.

High Prevalence of Hepatic Fibrosis, Measured by Elastography, in a Population-Based Study of Mexican Americans.

BACKGROUND & AIMS: Hepatic fibrosis is a primary risk factor for cirrhosis and hepatocellular carcinoma, which affect a disproportionate number of Hispanics in the United States. We aimed to determine the prevalence of significant fibrosis, measured by point shear-wave elastography (pSWE), and determine characteristics of hepatic fibrosis and simple steatosis in a population-based study of Mexican American Hispanics in south Texas. METHODS: Liver stiffness was measured by pSWE, performed by 2 separate operators, for 406 participants in the Cameron County Hispanic Cohort from 2015 through 2017. Significant fibrosis (F2-F4) was defined as median stiffness > 1.34 m/s. Steatosis was determined by ultrasound. All participants underwent a clinical examination that included a comprehensive laboratory analysis and standardized interview about their medical and social history. We calculated weighted prevalence of fibrosis and determined clinical and demographic associations with significant fibrosis (with or without steatosis) and simple steatosis with no/minimal fibrosis using multinomial logistic regression. RESULTS: Fifty-nine participants were excluded due to unreliable pSWE findings or inconclusive ultrasound results, for a final analysis of 347 participants. The prevalence of significant fibrosis was 13.8%; most of these participants (37/42, 88.1%) had no evidence of viral hepatitis or heavy drinking. Levels of liver enzymes were associated with fibrosis and simple steatosis. Indicators of metabolic health (insulin resistance, triglycerides, and cholesterol) were significantly associated with simple steatosis. Fibrosis, but not simple steatosis, was significantly associated with of antibodies against HCV in plasma (odds ratio, 18.9; P = .0138) and non-significantly associated with reduced platelet count (odds ratio, 0.8 per 50x103/µL; 95% CI, 0.5-1.1). Multivariable analyses, as well as sensitivity analyses removing F4 fibrosis and viral or alcoholic etiologies, confirmed our results. CONCLUSION: We estimated the prevalence of fibrosis in a large population of Mexican American Hispanics using pSWE measurements. We found Mexican American Hispanics to have a higher prevalence of fibrosis compared to European and Asian populations, primarily attributable to metabolic disease.

PspA facilitates evasion of pneumococci from bactericidal activity of neutrophil extracellular traps (NETs).

Pneumococcal strains are variably resistant to killing by neutrophil extracellular traps (NETs). We hypothesize that this variability in resistance is due to heterogeneity in pneumococcal surface protein A (PspA), a structurally diverse virulence factor of Streptococcus pneumoniae. Pneumococcal strains showed variability in induction of NETs and in susceptibility to killing by NETs. The variability in susceptibility to NETs-mediated killing of pneumococcal strains is attributed to PspA, as strains lacking the surface expression of PspA were significantly more sensitive to NETs-mediated killing compared to the wild-type strains. Using pspA switch mutants we were further able to demonstrate that NETs induction and killing by NETs is a function of PspA as mutants with switch PspA demonstrated donor phenotype. Antibody to PspA alone showed an increase in induction of NETs, and NETs thus generated were able to trap and kill pneumococci. Pneumococci opsonized with antibody to PspA showed increase adherence to NETs but a decrease susceptibility to killing by NETs. In conclusion we demonstrate a novel role for pneumococcal PspA in resisting NETs mediated killing and allowing the bacteria to escape containment by blocking binding of pneumococci to NETs.

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.

The combined effect of physical activity and sedentary behavior on subclinical atherosclerosis: a cross-sectional study among Mexican Americans.

BACKGROUND: Physical activity and sedentary behavior are considered independent risk factors for chronic disease. However, we do not fully understand their interrelation with key health outcomes such as subclinical atherosclerosis. This study examines the combined effects of sedentary behavior and physical activity on carotid intima-media thickness (cIMT) and presence of carotid plaque in a Mexican American population on the Texas-Mexico border. METHODS: This cross-sectional study was conducted using retrospective data from a sample (n = 612) of participants from the Cameron County Hispanic Cohort. Carotid ultrasound was used to measure cIMT and presence of carotid plaque. Self-reported questionnaires were used to assess leisure time physical activity and sedentary behavior (TV/movie sitting and total sitting). A series of multivariable regression models were used to assess study aims. An interaction term between physical activity and sedentary behavior was included in models for each respective outcome. Models were controlled for demographic and health-related variables. RESULTS: There were no significant associations found between physical activity, sedentary behavior and mean cIMT, or cIMT thickness ≥ 75th percentile for age and gender. However, there was a significant interaction between physical activity and TV/movie sitting with presence of carotid plaque. Participants who reported moderate levels of physical activity had significantly lower odds for presence of plaque compared to participants with no activity when TV/movie sitting time was ≤3 h per day. However, there was no significant difference in odds for presence of plaque between physical activity groups when TV/movie sitting exceeded 3 h/day. These results were consistent with models examining total sitting time. CONCLUSIONS: Our results indicate that for Mexican Americans, there is a combined effect of sedentary behavior and physical activity on presence of carotid plaque. Participating in moderate physical activity is optimal for having lower levels of carotid plaque in addition to avoiding excessive levels of TV/movie sitting (≥3 h/day) and/or total sitting (≥8.5 h/day).

The Precarious Health of Young Mexican American Men in South Texas, Cameron County Hispanic Cohort, 2004-2015.

INTRODUCTION: Hispanic men have higher rates of illness and death from various chronic conditions than do non-Hispanic men. We aimed to characterize the health of Mexican American men living on the US-Mexico border in South Texas and elucidate indications of chronic disease in young men. METHODS: We sampled all male participants from the Cameron County Hispanic Cohort, an ongoing population-based cohort of Mexican Americans in Brownsville, Texas. We calculated descriptive statistics and stratified the sample into 3 age groups to estimate the prevalence of sociodemographic, behavioral, and clinical factors by age group and evaluated differences between age groups. RESULTS: Obesity prevalence was approximately 50% across all age groups (P = .83). Diabetes prevalence was high overall (26.8%), and 16.9% (95% confidence interval [CI], 10.1%-23.8%) of men younger than 35 had diabetes. More than 70% of these young men had elevated liver enzymes, and mean values of aspartate aminotransferase were significantly higher in younger men (45.0 u/L; 95% CI, 39.5-50.6 u/L) than in both older age groups. Less than 20% of young men had any form of health insurance. Current smoking was higher in young men than in men in the other groups, and the rate was higher than the national prevalence of current smoking among Hispanic men. CONCLUSIONS: We suggest a need for obesity and diabetes prevention programs and smoking cessation programs for men in this region. Opportunities exist to expand current intervention programs and tailor them to better reach this vulnerable population of young Hispanic men. Elevated liver enzymes in men younger than 35 suggest a substantial burden of liver abnormalities, a finding that warrants further study.

Demographic, psychosocial, and genetic risk associated with smokeless tobacco use among Mexican heritage youth.

BACKGROUND: Despite well-established negative health consequences of smokeless tobacco use (STU), the number and variety of alternative non-combustible tobacco products on the market have increased tremendously over the last 10 years, as has the market share of these products relative to cigarettes. While STU among non-Hispanic white youth has decreased over the last 10 years, the prevalence has remained constant among Hispanic youth. Here we examine demographic, psychosocial, and genetic risk associated with STU among Mexican heritage youth. METHODS: Participants (50.5 % girls) reported on psychosocial risk factors in 2008-09 (n = 1,087, mean age = 14.3 years), and smokeless tobacco use in 2010-11 (mean age = 16.7 years). Participants provided a saliva sample that was genotyped for genes in the dopamine, serotonin and opioid pathways. RESULTS: Overall 62 (5.7 %) participants reported lifetime STU. We identified five single nucleotide polymorphisms that increased the risk for lifetime use. Specifically, rs2023902 on SERGEF (OR = 1.93; 95 % CI: 1.05-3.53), rs16941667 on ALDH2 (OR = 3.14; 95 % CI: 1.65-5.94), and rs17721739 on TPH1 (OR = 1.71; 95 % CI: 1.00-2.91) in the dopamine pathway, rs514912 on TRH-DE (OR = 1.84; 95 % CI: 1.25-2.71) in the serotonin pathway, and rs42451417 on the serotonin transporter gene, SLC6A4 (OR = 3.53; 95 % CI: 1.56-7.97). After controlling for genetic risk, being male (OR = 1.86; 95 % CI: 1.02-3.41), obesity status (OR = 2.22; 95 % CI: 1.21-4.09), and both higher levels of anxiety (OR = 1.04; 95 % CI: 1.01-1.08) and social disinhibition (OR = 1.26; 95 % CI: 1.07-1.48) were associated with increased use. High subjective social status (OR = 0.78; 95 % CI: 0.64-0.93) was protective against use, while higher parental education (OR = 2.01; 95 % CI: 1.03-3.93) was associated with increased use. CONCLUSIONS: These data suggest that use of genetic risk, along with psychosocial, demographic, and behavioral risk factors may increase our ability to identify youth at increased risk for STU, which in turn may improve our ability to effectively target prevention messages to Mexican heritage youth.

Community-based assessment of surgical symptoms in a low-income urban population.

BACKGROUND: The global burden of surgical disease has not been well quantified, but is potentially immense. Given the enormity of the problem and the relative paucity of data, definition and monitoring of surgical burden of disease is an essential step in confronting the problem. This study aimed to estimate the prevalence of non-acute surgical disease symptoms in a low-income population. METHODS: The survey was conducted as part of the Indus Hospital Community Cohort in Karachi, Pakistan. A systematic random sampling design was used to enroll 667 households from March to August 2011. An unvalidated questionnaire intending to measure prevalence of surgical symptoms was administered to 780 participants. RESULTS: 761 participants completed the screening questionnaire, with 346 (45%) reporting one or more symptoms requiring surgical assessment (excluding those screened positive for symptoms of osteoarthritis), of which only 8.4% followed up on scheduled appointments at the referral hospital. A total of 126 past surgical procedures were recorded in 120 participants. CONCLUSION: There is a high prevalence of symptoms suggestive of surgical diseases in our urban catchment population with relatively convenient access to health facilities including a tertiary care hospital providing free of cost care. The perceived severity of symptoms, and a complex interaction of other factors, may play an important role in understanding health seeking behavior in our population. Developing a context-specific validated tool to correctly identify surgical symptoms disease in the community with appropriate referral for early management is essential to identify and therefore reduce the burden of surgical diseases within the community. This must happen hand in hand with further studies to understand the barriers to seeking timely health care.

Non-communicable diseases and preventive health behaviors: a comparison of Hispanics nationally and those living along the US-Mexico border.

BACKGROUND: Non-communicable diseases (NCDs) are rising among US Hispanics, but few studies have examined the preventive health behaviors for these NCDs among Hispanics. This study compared the preventive health behaviors of smoke-free living, physical activity, fruit and vegetable consumption, and avoidance of heavy alcohol use in Hispanics in the United States and Hispanics living along the US-Mexico border. METHODS: Two weighted data sets with information on Hispanic populations were analyzed: 1) the national Behavioral Risk Factor Surveillance Survey (n = 29,942) from 2009; and 2) the Cameron County Hispanic Cohort (n = 1,439) recruited from the US-Mexico border between 2008-2011. To compare the preventive health behaviors of the samples, within a generalized estimating equation framework, weighted univariate and multivariate logistic regression analyses were conducted controlling for age, educational attainment, employment, language, and insurance status. Statistical tests were two-sided with a significance level set at 0.05. RESULTS: Both samples reported low engagement in preventive behaviors. However, Hispanic males and females from the US-Mexico border were significantly less likely than the national sample to meet physical activity and fruit and vegetable consumption guidelines. Also, Hispanic males from the US-Mexico border were more likely to engage in heavy alcohol use. CONCLUSION: The lack of preventive health behaviors among Hispanics living along the US-Mexico border presents a dire prospect for NCD control in the region. Multipronged approaches to address multiple behaviors should be considered.

The association of depression and anxiety with glycemic control among Mexican Americans with diabetes living near the U.S.-Mexico border.

BACKGROUND: The prevalence of diabetes is alarmingly high among Mexican American adults residing near the U.S.-Mexico border. Depression is also common among Mexican Americans with diabetes, and may have a negative influence on diabetes management. Thus, the purpose of the current study was to evaluate the associations of depression and anxiety with the behavioral management of diabetes and glycemic control among Mexican American adults living near the border. METHODS: The characteristics of Mexican Americans with diabetes living in Brownsville, TX (N = 492) were compared by depression/anxiety status. Linear regression models were conducted to evaluate the associations of depression and anxiety with BMI, waist circumference, physical activity, fasting glucose, and glycated hemoglobin (HbA1c). RESULTS: Participants with clinically significant depression and/or anxiety were of greater age, predominantly female, less educated, more likely to have been diagnosed with diabetes, and more likely to be taking diabetes medications than those without depression or anxiety. In addition, anxious participants were more likely than those without anxiety to have been born in Mexico and to prefer study assessments in Spanish rather than English. Greater depression and anxiety were associated with poorer behavioral management of diabetes (i.e., greater BMI and waist circumference; engaging in less physical activity) and poorer glycemic control (i.e., higher fasting glucose, HbA1c). CONCLUSIONS: Overall, depression and anxiety appear to be linked with poorer behavioral management of diabetes and glycemic control. Findings highlight the need for comprehensive interventions along the border which target depression and anxiety in conjunction with diabetes management.

Anxiety, depression and smoking status among adults of Mexican heritage on the Texas-Mexico Border.

The goal of the current analysis is to examine relationships between smoking status and anxiety and depression among adults of Mexican heritage to inform the development of culturally relevant smoking cessations efforts. Mexican heritage residents (N=1,791) of the city of Brownsville, TX, aged 18 years or older, enrolled in the Cameron County Hispanic Cohort, were selected through two stage cluster sampling of randomly selected census tracts from the first and third quartile of SES using Census 2000. Among current smokers, anxiety and depression scores were highest among women who had not completed high school (p<0.05). Former smoking women, but not men, with at least a high school education and former smoking women born in the United States reported higher levels of anxiety and depression than never smoking women. Negative affective states may represent a greater barrier to smoking cessation among women than men.

A Laplacian regularized graph neural network for predictive modeling of multiple chronic conditions.

BACKGROUND AND GOALS: One of the biggest difficulties facing healthcare systems today is the prevalence of multiple chronic diseases (MCC). Mortality and the development of new chronic illnesses are more likely in those with MCC. Pre-existing diseases and risk factors specific to the patient have an impact on the complex stochastic process that guides the evolution of MCC. This study's goal is to use a brand-new Graph Neural Network (GNN) model to examine the connections between specific chronic illnesses, patient-level risk factors, and pre-existing conditions. METHODS: We propose a graph neural network model to analyze the relationship between five chronic conditions (diabetes, obesity, cognitive impairment, hyperlipidemia, and hypertension). The proposed model adds a graph Laplacian regularization term to the loss function, which aims to improve the parameter learning process and accuracy of the GNN based on the graph structure. For validation, we used historical data from the Cameron County Hispanic Cohort (CCHC). RESULTS: Evaluating the Laplacian regularized GNN on data from 600 patients, we expanded our analysis from two chronic conditions to five chronic conditions. The proposed model consistently surpassed a baseline GNN model, achieving an average accuracy of ≥89% across all combinations. In contrast, the performance of the standard model declined more markedly with the addition of more chronic conditions. The Laplacian regularization provided consistent predictions for adjacent nodes, beneficial in cases with shared attributes among nodes. CONCLUSIONS: The incorporation of Laplacian regularization in our GNN model is essential, resulting in enhanced node categorization and better predictive performance by harnessing the graph structure. This study underscores the significance of considering graph structure when designing neural networks for graph data. Future research might further explore and refine this regularization method for various tasks using graph-structured data.

Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes.

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of Inoviridae was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate Escherichia phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of Lactococcus phages r1t and BK5-T, and enrichment of the globally prevalent Crassvirales phages, including members of genus cluster IX (Burzaovirus coli, Burzaovirus faecalis) and VI (Kahnovirus oralis). The Lactococcus phages showed strong correlations and co-occurrence with Lactococcus lactis, while the Crassvirales phages, B. coli, B. faecalis, and UAG-readthrough crAss clade correlated and co-occurred with Prevotella copri. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.IMPORTANCEPhages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of Inoviridae, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of Escherichia coli-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of Lactococcus lactis-infecting phages, and enrichment of Crassvirales phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.