Household aggregation of Staphylococcus aureus by clonal complex and methicillin resistance profiles in Starr County, Texas.

Staphylococcus aureus is one of the most common causes of skin and soft tissue infections in health-care and community settings, but transmission of S. aureus in community-based populations is incompletely understood. S. aureus carriage phenotypes (persistent, intermittent, and non-carriers) were determined for households from Starr County, TX. Nasal swabs were collected from a cohort of 901 residents and screened for the presence of S. aureus. Isolated strains were spa-typed and assigned to clonal complexes. Of the 901 participants there were 134 pairs, 28 trios, 11 quartets, 3 quintets and 1 septet residing in the same household. There was a significant increase in "ever" carriers (persistent and intermittent carriers combined) in these households over that expected based on population frequencies (p = 0.029). There were 42 ever carrier pairs of individuals with 21 concordant for clonal complex type whereas only 4.7 were expected to be so (p = 6.9E-11). These results demonstrated clear aggregation of S. aureus carriage and concordance for strain types within households. As antibiotic-resistant S. aureus strains increase in community settings, it is important to better understand risk factors for colonization, mechanisms of transmission, clonal complexes present, and the role of household concordance/transmission.

Randomised clinical trial: faecal microbiota transplantation for recurrent Clostridum difficile infection - fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy.

BACKGROUND: Faecal microbiota transplantation (FMT) has become routine in managing recurrent C. difficile infection (CDI) refractory to antibiotics. AIM: To compare clinical response and improvements in colonic microbiota diversity in subjects with recurrent CDI using different donor product. METHODS: Seventy-two subjects with ≥3 bouts of CDI were randomised in a double-blind study to receive fresh, frozen or lyophilised FMT product via colonoscopy from 50 g of stool per treatment from eight healthy donors. Recipients provided stools pre- and 7, 14 and 30 days post-FMT for C. difficile toxin and, in a subset, microbiome composition by 16S rRNA gene profiling. RESULTS: Overall resolution of CDI was 87% during 2 months of follow-up after FMT. Stool samples before FMT had significantly decreased bacterial diversity with a high proportion of Proteobacteria compared to donors. Cure rates were highest for the group receiving fresh product seen in 25/25 (100%), lowest for the lyophilised product 16/23 (78%; P = 0.022 vs. fresh and 0.255 vs. frozen) and intermediate for frozen product 20/24 (P = 0.233 vs. fresh). Microbial diversity was reconstituted by day 7 in the subjects receiving fresh or frozen product. Improvement in diversity was seen by day 7 in those randomised to lyophilised material with reconstitution by 30 days. CONCLUSIONS: Comparative efficacy in faecal microbiota transplantation was observed in subjects receiving fresh or frozen faecal product from the same donors. The lyophilised product had a slightly lowered efficacy compared with fresh product, but it resembled other treatments in microbial restoration 1 month after faecal microbiota transplantation.

Host susceptibility to tuberculosis: insights from a longitudinal study of gene expression in diabetes.

Tuberculosis (TB) remains a major global disease, and diabetes, which is documented to increase susceptibility to TB threefold, is also becoming pandemic. This susceptibility has been attracting extensive research interest. The increased risk of TB in diabetes may serve as a unique model to understand host susceptibility to specific pathogens in humans. To examine this rationale, we investigated the expression of reported TB candidate genes in a longitudinal diabetes study. Two genes, HK2 and CD28, emerged as potential culprits in diabetes-increased TB susceptibility.

Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals.

AIMS/HYPOTHESIS: We conducted genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) analyses to identify and characterise risk loci for type 2 diabetes in Mexican-Americans from Starr County, TX, USA. METHOD: Using 1.8 million directly interrogated and imputed genotypes in 837 unrelated type 2 diabetes cases and 436 normoglycaemic controls, we conducted Armitage trend tests. To improve power in this population with high disease rates, we also performed ordinal regression including an intermediate class with impaired fasting glucose and/or glucose tolerance. These analyses were followed by meta-analysis with a study of 967 type 2 diabetes cases and 343 normoglycaemic controls from Mexico City, Mexico. RESULT: The top signals (unadjusted p value <1 × 10(-5)) included 49 single nucleotide polymorphisms (SNPs) in eight gene regions (PER3, PARD3B, EPHA4, TOMM7, PTPRD, HNT [also known as RREB1], LOC729993 and IL34) and six intergenic regions. Among these was a missense polymorphism (rs10462020; Gly639Val) in the clock gene PER3, a system recently implicated in diabetes. We also report a second signal (minimum p value 1.52 × 10(-6)) within PTPRD, independent of the previously implicated SNP, in a population of Han Chinese. Top meta-analysis signals included known regions HNF1A and KCNQ1. Annotation of top association signals in both studies revealed a marked excess of trans-acting eQTL in both adipose and muscle tissues. CONCLUSIONS/INTERPRETATION: In the largest study of type 2 diabetes in Mexican populations to date, we identified modest associations of novel and previously reported SNPs. In addition, in our top signals we report significant excess of SNPs that predict transcript levels in muscle and adipose tissues.

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.

AIMS/HYPOTHESIS: We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets. METHODS: We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances. RESULTS: In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70. CONCLUSIONS/INTERPRETATION: We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

Linkage analysis of plasma ApoE in three ethnic groups: multiple genes with context-dependent effects.

We performed variance component-based linkage analysis in four samples (two of non-Hispanic European-Americans from Rochester, MN; African-Americans from Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD > or = 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE epsilon2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD= 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter-individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism.

Physical activity does not mitigate G-protein-related genetic risk for obesity in individuals of African descent.

The G-protein beta3 subunit 825 TT genotype has been associated with obesity and hypertension. We examined the interaction between the G-protein TT genotype, physical activity and body mass index (BMI) in a cross-sectional study of African immigrants and African Americans. The genotype frequencies were 6.3% CC, 37.7% CT, and 56% TT. After adjusting for potential confounders, BMI was found to be significantly higher in the sedentary than in the physically active participants (p=0.045). There was no statistically significant effect for genotype (p=0.215) or the interaction between genotype and the level of physical activity (p=0.219). However, the individuals with the CC or CT genotype who were physically active had substantially lower BMIs (M+/-SE) (i.e., 25.74+/-2.02) than any of the other groups: sedentary CC + CT (30.58+/-1.03), sedentary TT (30.65+/-1.00) or active TT (29.43+/-1.65). Because of the low statistical power of this study, further research is needed to confirm these findings and to explore potential gene-environment/lifestyle interactions.

Prevalence and determinants of type 2 diabetes among Filipino-Americans in the Houston, Texas metropolitan statistical area.

OBJECTIVE: The few available studies suggest that Filipino-Americans have an increased risk for developing type 2 diabetes. The purpose of this study was to determine the prevalence of previously diagnosed type 2 diabetes and its major risk factors among Filipino-Americans. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted in the Houston, Texas, metropolitan statistical area between September 1998 and March 2000. The convenience sample included 831 Filipino-American participants aged 20-74 years. The major risk factors assessed were age, sex, family history of diabetes, socioeconomic status, obesity (BMI >30), physical inactivity, acculturation, region of birth and, in women, history of gestational diabetes and delivery of a baby weighing > 9 lb. RESULTS: Overall prevalence was estimated to be 16.1% (95% CI 13.5-18.7). Multivariate logistic regression analyses identified independent risk factors: increasing age from ages 35-44 years (odds ratio [OR] 5.6, 95% CI 1.5-20.5) to 65-74 years (34.2, 7.2-163.0); male sex (1.8, 1.1-32.1); family history of diabetes (4.7, 2.6-8.5); obesity (3.6, 1.4-9.0); region of birth, Mindanao (3.2, 1.3-7.7); and, among women, gestational diabetes (21.7, 6.7-69.7) and low income (5.3, 1.4-20.2). CONCLUSIONS: The study observed a high prevalence of type 2 diabetes and supports earlier studies suggesting that Filipinos are at higher risk for type 2 diabetes than the U.S. non-Hispanic white population.

Development of a life events/icon calendar questionnaire to ascertain occupational histories and other characteristics of migrant farmworkers.

BACKGROUND: Specialized methods are necessary to collect data from migrant farmworkers for epidemiologic research. METHODS: We developed a questionnaire that collected lifetime occupational histories and other lifestyle risk factors via a life events/icon calendar, and administered the questionnaire to a convenience sample of 162 migrant farmworkers in nine areas of the U.S. RESULTS: The average duration of the interviews was about 1 h 30 min, with an average of 45 min for the work history section. The occupational histories covered a median of 27.6 years per person for men and 20.8 years per person for women. The median number of years spent in farm jobs was 11.3 for men and 5.8 for women. The median number of farm jobs (crop/task combination) per person was 59 among men and 27 among women. Many farmworkers performed the same crop/task combinations at multiple times throughout their lives, yielding a median of 13 unique farm jobs and 8 unique crops among men and 7 jobs and 5 crops among women. CONCLUSIONS: The project demonstrated that it is feasible to collect detailed work histories and other risk factor data from farmworkers, documented the complexity of work histories encountered among farmworkers, and yielded recommendations for refining a questionnaire that will facilitate future epidemiologic research on farmworkers.

Ascertainment of pesticide exposures of migrant and seasonal farmworker children: findings from focus groups.

BACKGROUND: To design questionnaires for epidemiologic research among children of migrant farmworkers, researchers need to consider ways to best solicit information about pesticide exposures. METHODS: Bilingual facilitators conducted five focus groups with either migrant farmworker mothers or their children (age range 8-16 years) in southern Texas and northeastern Colorado. Guided questions were used to assess activities of migrant farmworker children and the ways to best elicit information about exposure to pesticides. RESULTS: Participants reported a large number of activities that may potentially expose children to pesticides through both direct and indirect routes. Prompting, indirect questions about chemical use, and use of local and trusted facilitators increased information elicited from focus group participants. CONCLUSIONS: These focus groups helped to provide information for developing questionnaire items related to pesticide exposure among migrant farmworker children, and highlighted the importance of using bilingual community interviewers and including children as respondents.

Tracing migrant farmworkers in Starr County, Texas.

BACKGROUND: In response to The National Cancer Institute (NCI) concerns about the ability to conduct studies among migrant farmworkers, this study evaluated the feasibility of identifying migrant farmworkers in their home state and tracing them over an extended period of time. METHODS: In 1995, a group of 196 persons who had classified themselves as "migrant farmworkers" in two earlier chronic disease studies was identified. The primary objective of the current study was to determine the proportion of these farmworkers who could be located in 1995-1996. RESULTS: Of these farmworkers, 163 were located and were living (83.2%), 15 had died (7.6%), and 18 (9.2%) were lost to follow-up. CONCLUSIONS: The excellent follow-up rate was due in part to the high participation rates among persons contacted for information, stability of the farmworkers' permanent homes, predictable timing of migration, and a longstanding health research program with established community contacts.

Evaluation of a culturally appropriate intervention to increase physical activity.

OBJECTIVE: To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women. METHODS: Participants were randomly assigned to a physical activity program or wait-list control. RESULTS: Treated participants were not more active than controls at 6 or 12 months. In addition, we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups. CONCLUSION: The intervention did not increase physical activity in this population. Differences in baseline activity and contamination of the control group may partially account for the outcome.

Calpains play a role in insulin secretion and action.

Studies of the genetic basis of type 2 diabetes suggest that variation in the calpain-10 gene affects susceptibility to this common disorder, raising the possibility that calpain-sensitive pathways may play a role in regulating insulin secretion and/or action. Calpains are ubiquitously expressed cysteine proteases that are thought to regulate a variety of normal cellular functions. Here, we report that short-term (4-h) exposure to the cell-permeable calpain inhibitors calpain inhibitor II and E-64-d increases the insulin secretory response to glucose in mouse pancreatic islets. This dose-dependent effect is observed at glucose concentrations above 8 mmol/l. This effect was also seen with other calpain inhibitors with different mechanisms of action but not with cathepsin inhibitors or other protease inhibitors. Enhancement of insulin secretion with short-term exposure to calpain inhibitors is not mediated by increased responses in intracellular Ca2+ or increased glucose metabolism in islets but by accelerated exocytosis of insulin granules. In muscle strips and adipocytes, exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose transport. Incorporation of glucose into glycogen in muscle also was reduced. These results are consistent with a role for calpains in the regulation of insulin secretion and insulin action.

Genetic bottlenecks, perceived racism, and hypertension risk among African Americans and first-generation African immigrants.

The complexity of factors influencing the development of hypertension (HTN) in African Americans has given rise to theories suggesting that genetic changes occurred due to selection pressures/genetic bottleneck effects (ie, constriction of existing genetic variability) over the course of the slave trade. Ninety-nine US-born and 86 African-born health professionals were compared in a cross-sectional survey examining genetic and psychosocial predictors of HTN. We examined the distributions of three genetic loci (G-protein, AGT-235, and ACE I/D) that have been associated with increased HTN risk. There were no significant differences between US-born African Americans and African-born immigrants in the studied genetic loci or biological variables (eg, plasma renin and angiotensin converting enzyme activity), except that the AGT-235 homozygous T genotype was somewhat more frequent among African-born participants than US-born African Americans. Only age, body mass index, and birthplace consistently demonstrated associations with HTN status. Thus, there was no evidence of a genetic bottleneck in the loci studied, ie, that US-born African Americans have different genotype distributions that increase their risk for HTN. In fact, some of the genotypic distributions evidenced lower frequencies of HTN-related alleles among US-born African Americans, providing evidence of European admixture. The consistent finding that birthplace (ie, US vs Africa) was associated with HTN, even though it was not always significant, suggests potential and unmeasured cultural, lifestyle, and environmental differences between African immigrants and US-born African Americans that are protective against HTN.

The Starr County Diabetes Education Study: development of the Spanish-language diabetes knowledge questionnaire.

OBJECTIVE: This study reports the psychometric properties of the 24-item version of the Diabetes Knowledge Questionnaire (DKQ). RESEARCH DESIGN AND METHODS: The original 60-item DKQ was administered to 502 adult Mexican-Americans with type 2 diabetes who are part of the Starr County Diabetes Education Study. The sample was composed of 252 participants and 250 support partners. The subjects were randomly assigned to the educational and social support intervention (n = 250) or to the wait-listed control group (n = 252). A shortened 24-item version of the DKQ was derived from the original instrument after data collection was completed. Reliability was assessed by means of Cronbach's coefficient alpha. To determine validity, differentiation between the experimental and control groups was conducted at baseline and after the educational portion of the intervention. RESULTS: The 24-item version of the DKQ (DKQ-24) attained a reliability coefficient of 0.78, indicating internal consistency, and showed sensitivity to the intervention, suggesting construct validation. CONCLUSIONS: The DKQ-24 is a reliable and valid measure of diabetes-related knowledge that is relatively easy to administer to either English or Spanish speakers.

Change in level of physical activity and risk of all-cause mortality or reinfarction: The Corpus Christi Heart Project.

BACKGROUND: The role of physical activity (PA) in reducing the risk of all-cause mortality or reinfarction after a first myocardial infarction (MI) remains unresolved, particularly for minority populations. The association between change in level of PA and risk of death or reinfarction was studied in 406 Mexican American and non-Hispanic white women and men who survived a first MI. METHODS AND RESULTS: MI patients were interviewed at baseline and annually thereafter about PA, medical history, and risk factors of coronary heart disease. Change in level of PA after the index MI was categorized as (1) sedentary, no change (referent group), (2) decreased activity, (3) increased activity, and (4) active, no change. Over a 7-year period, the relative risk (95% CI) of death was as follows: 0.21 (0.10 to 0.44) for the active, no change group; 0.11 (0.03 to 0.46) for the increased activity group; and 0.49 (0.26 to 0.90) for the decreased activity group. The relative risk of reinfarction was as follows: 0.40 (0.24 to 0.66) for the active, no change group; 0.22 (0.09 to 0.50) for the increased activity group; and 0.93 (0.59 to 1.42) for the decreased activity group. CONCLUSIONS: These findings are consistent with a beneficial role of PA for Mexican American and non-Hispanic white women and men who survive a first MI and have practical implications for the management of MI survivors.

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Sequence variation within the neuropeptide Y gene and obesity in Mexican Americans.

OBJECTIVE: Recently, we reported evidence for linkage between neuropeptide Y (NPY) and both obesity and several obesity-related quantitative measures in a sample of Mexican Americans from Starr County, Texas. The purpose of this study was to investigate putative variation within the coding and promoter regions of NPY. RESEARCH METHODS AND PROCEDURES: Five young, obese individuals (body mass index [BMI] 33 to 45 kg/m2, age 14 to 30 years); five adult, lean individuals (BMI 20 to 26 kg/m2, age 39 to 65 years); and five sibling pairs sharing no alleles that were identical by descent at a marker locus proximal to NPY were selected for fluorescence-based sequencing of approximately 1100 base pairs (bp) immediately 5' from the start site and all four exons of NPY. We identified a total of eight variant sites, including a 2-bp insertion/deletion (I/D) within a putative negative regulatory region (-880I/D) and a 17-bp deletion at the exon 1/intron 1 junction (69I/D). The -880I/D and 69I/D variants were typed in a separate random sample of Mexican Americans (N = 914) from Starr County, Texas. RESULTS: Analyses of variance resulted in a significant association between -880I/D and waist-to-hip ratio (p = 0.041) in the entire sample and between -880I/D and BMI (p = 0.031), abdominal circumference (p = 0.044), and waist-to-hip ratio (p = 0.041) in a non-obese subsample (BMI < 30 kg/m2, n = 594). The 69I/D variant was observed in only one pedigree and does not appear to segregate with obesity within this pedigree. DISCUSSION: This study reports newly identified common human sequence variation within the regulatory and coding sequence of NPY. Several variants were observed, and of those tested, the -880I/D promoter region variant may influence body fat patterning in non-obese individuals but does not appear to play a major role in the etiology of common forms of obesity in this population.

Gender and treatment differences in knowledge, health beliefs, and metabolic control in Mexican Americans with type 2 diabetes.

PURPOSE: The purpose of this project was to describe metabolic control, knowledge, and health beliefs of Mexican Americans with type 2 diabetes. METHODS: The study site was Starr County, Texas, a border community located on the Rio Grande River and bordering northern Mexico. Of the total sample of 360 persons, 252 agreed to participate in this intervention study and were randomized either to the treatment group or the control group that waited 1 year to begin the intervention. RESULTS: The majority of individuals were Spanish-speaking females with a mean age of 54 years and a mean diabetes duration of 8 years. For those treated with diet only, males exhibited higher fasting blood glucose levels than females. Gender effects were seen for cholesterol level, with females exhibiting higher levels than males. Males expressed stronger perceptions of control and social support for diet. Bivariate relationships were found between acculturation and diabetes knowledge. The health belief subscales of control and impact on job together explained 16% of the variance in HbA1c values. CONCLUSIONS: Males and females held differing beliefs about ability to control their diabetes and degree of social support for diet. The impact of gender differences on ability to integrate diabetes self-care and on effectiveness of diabetes programs has not been determined but should be considered in future research.