A Gene-Acculturation Study of Obesity Among US Hispanic/Latinos: The Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: In the United States, Hispanic/Latino adults face a high burden of obesity; yet, not all individuals are equally affected, partly due in part to this ethnic group's marked sociocultural diversity. We sought to analyze the modification of body mass index (BMI) genetic effects in Hispanic/Latino adults by their level of acculturation, a complex biosocial phenomenon that remains understudied. METHODS: Among 11,747 Hispanic/Latinos adults in the Hispanic Community Health Study/Study of Latinos aged 18 to 76 years from four urban communities (2008-2011), we a) tested our hypothesis that the effect of a genetic risk score (GRS) for increased BMI may be exacerbated by higher levels of acculturation and b) examined if GRS acculturation interactions varied by gender or Hispanic/Latino background group. All genetic modeling controlled for relatedness, age, gender, principal components of ancestry, center, and complex study design within a generalized estimated equation framework. RESULTS: We observed a GRS increase of 0.34 kg/m 2 per risk allele in weighted mean BMI. The estimated main effect of GRS on BMI varied both across acculturation level and across gender. The difference between high and low acculturation ranged from 0.03 to 0.23 kg/m 2 per risk allele, but varied across acculturation measure and gender. CONCLUSIONS: These results suggest the presence of effect modification by acculturation, with stronger effects on BMI among highly acculturated individuals and female immigrants. Future studies of obesity in the Hispanic/Latino community should account for sociocultural environments and consider their intersection with gender to better target obesity interventions.

Poor clinical guideline adherence and inappropriate testing for incident lower urinary tract symptoms associated with benign prostatic hyperplasia.

BACKGROUND: The American Urological Association makes recommendations for evaluation and testing for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) to help primary care providers and specialists identify LUTS/BPH and harmful related conditions including urinary retention and prostate or bladder cancer. Our understanding of provider adherence to these Guidelines is limited to single-site or nonrepresentative settings. METHODS: We analyzed two insurance claims databases: the Optum® de-identified Clinformatics® Data Mart database for privately insured males aged 40-64 years (N ≈ 1,650,900 annually) and the Medicare 5% Sample for males aged ≥65 years (N ≈ 546,000 annually). We calculated the annual prevalence of LUTS/BPH and comorbid bladder cancer and bladder stones from 2004 to 2013. We additionally examined LUTS/BPH incidence and adherence to testing guidelines in a cohort of men newly diagnosed with LUTS/BPH in 2009. RESULTS: While LUTS/BPH prevalence and incidence increased with increasing age, evaluation testing became less common. Urinalysis was the most common testing type but was performed in <60% of incident patients. Serum prostate-specific antigen (PSA) was the second most common test across age groups (range: 15-34%). Prevalence of comorbid bladder cancer (range: 0-4%), but not bladder stones (range: 1-2%), increased with increasing age. CONCLUSIONS: Although older men were at greater risk of LUTS/BPH than younger men, they were less likely to undergo testing at diagnosis. Recommended testing with urinalysis was poor despite higher prevalence of bladder cancer in older men and a standard recommendation for urinalysis since 1994. Providers should be more cognizant of AUA Guidelines when assessing LUTS/BPH patients.

Disparities in multiple sleep characteristics among non-Hispanic White and Hispanic/Latino adults by birthplace and language preference: cross-sectional results from the US National Health Interview Survey.

OBJECTIVE: To investigate whether sleep disparities vary by birthplace among non-Hispanic White (NHW) and Hispanic/Latino adults in the USA and to investigate language preference as an effect modifier. DESIGN: Cross-sectional. SETTING: USA. PARTICIPANTS: 254 699 men and women. METHODS: We used pooled 2004-2017 National Health Interview Survey data. Adjusting for sociodemographic and behavioural/clinical characteristics, survey-weighted Poisson regressions with robust variance estimated prevalence ratios (PRs) and 95% CIs of self-reported sleep characteristics (eg, sleep duration, trouble staying asleep) among (1) foreign-born NHW adults and Hispanic/Latino heritage groups versus US-born NHW adults and (2) Hispanic/Latino heritage groups versus foreign-born NHW adults. We further stratified by language preference in comparisons of Hispanic/Latino heritage groups with the US-born NHW group. RESULTS: Among 254 699 participants with a mean age±SE 47±0.9 years, 81% self-identified their race/ethnicity as NHW, 12% Mexican, 2% Puerto Rican, 1% Cuban, 1% Dominican and 3% Central/South American. Compared with US-born NHW adults, foreign-born NHW adults were more likely to report poor sleep quality (eg, PRtrouble staying asleep=1.27 (95% CI: 1.17 to 1.37)), and US-born Mexican adults were no more likely to report non-recommended sleep duration while foreign-born Mexican adults were less likely (eg, PR≤5-hours=0.52 (0.47 to 0.57)). Overall, Mexican adults had lower prevalence of poor sleep quality versus US-born NHW adults, and PRs were lowest for foreign-born Mexican adults. US-born Mexican adults were more likely than foreign-born NHW adults to report shorter sleep duration. Regardless of birthplace, Puerto Rican adults were more likely to report shorter sleep duration versus NHW adults. Generally, sleep duration and quality were better among Cuban and Dominican adults versus US-born NHW adults but were similar versus foreign-born NHW adults. Despite imprecision in certain estimates, Spanish language preference was generally associated with increasingly better sleep among Hispanic/Latino heritage groups compared with US-born NHW adults. CONCLUSION: Sleep disparities varied by birthplace, Hispanic/Latino heritage and language preference, and each characteristic should be considered in sleep disparities research.

Prevalence of Urinary Incontinence among a Nationally Representative Sample of Women, 2005-2016: Findings from the Urologic Diseases in America Project.

PURPOSE: Urinary incontinence is frequently underreported and underdiagnosed in the clinical setting. We analyzed 12 years of data from a large, nationally representative sample of women in the United States to assess the prevalence, severity, and daily impact of urinary incontinence and its subtypes at the population level. MATERIALS AND METHODS: We analyzed data from 15,003 women aged ≥20 years who participated in the 2005-2016 National Health and Nutrition Examination Survey. We estimated the prevalence of urinary incontinence in the prior year, overall and by subtype (stress, urgency or mixed). Among women with urinary incontinence, we additionally assessed symptom severity using the validated 4-level Incontinence Severity Index, as well as impact on daily activities. RESULTS: The 2005-2016 prevalence of any urinary incontinence was 53%; 16% of women had mixed urinary incontinence, 26% had stress only and 10% had urgency only. While urgency urinary incontinence and mixed urinary incontinence were highest among women aged ≥60 years, stress urinary incontinence was highest among women aged 40-59 years. NonHispanic Black women had higher prevalence of urgency urinary incontinence and lower prevalence of stress urinary incontinence compared to other racial/ethnic groups. Of women with urinary incontinence, 30% reported moderate or severe symptoms, which were more common among older than younger women. In addition, 24% of women with urinary incontinence reported that the condition affected their daily activities. CONCLUSIONS: Our study demonstrates a high prevalence of urinary incontinence among a nationally representative population of women in the United States, with many reporting that urinary incontinence affected their daily activities. Age and racial/ethnic trends varied by urinary incontinence subtype.

Longitudinal Associations of US Acculturation With Cognitive Performance, Cognitive Impairment, and Dementia.

US Latinos, a growing, aging population, are disproportionately burdened by cognitive decline and dementia. Identification of modifiable risk factors is needed for interventions aimed at reducing risk. Broad sociocultural context may illuminate complex etiology among culturally diverse Latinos. Among 1,418 older (≥60 years), low-socioeconomic position (SEP) Latinos (predominantly of Mexican descent) in Sacramento, California, we examined whether US acculturation was associated with cognitive performance, cognitive decline, and dementia/ cognitive impairment without dementia over a 10-year period and whether education modified the associations (Sacramento Area Latino Study on Aging, 1998-2008). Analyses used linear mixed models, competing-risk regression, and inverse probability of censoring weights for attrition. Participants with high US acculturation had better cognitive performance (0.21 fewer cognitive errors at grand-mean-centered age 70 years) than those with low acculturation after adjustment for sociodemographic factors, practice effects, and survey language. Results may have been driven by cultural language use rather than identity factors (e.g., ethnic identity, interactions). Rate of cognitive decline and risk of dementia/cognitive impairment without dementia did not differ by acculturation, regardless of education (ß = 0.00 (standard error, 0.00) and hazard ratio = 0.81 (95% confidence interval: 0.49, 1.35), respectively). High US acculturation was associated with better cognitive performance among these older, low-SEP Latinos. Acculturation may benefit cognition when SEP is low. Future studies should incorporate extended longitudinal assessments among more diverse groups.

Metabolic Syndrome and Cognitive Impairment among High Socioeconomic, Nondemented Older US Adults.

OBJECTIVES: Nondemented cognitive impairment (CI) presents opportunities for early interventions among individuals at risk for dementia. Identification of modifiable determinants is paramount to the development of effective clinical interventions. Metabolic syndrome (MetS) was theorized as a risk factor, but current research yields inconsistent findings. Few studies have examined the association between MetS and CI among US populations, and global results may be ungeneralizable. We investigated the MetS-CI association among high socioeconomic, nondemented older US adults, examining the roles of sociodemographic, clinical, behavioral, and genetic factors. DESIGN: Cross-sectional. SETTING: Cooper Clinic of Dallas, Texas: Cooper Center Longitudinal Study (2009-2017). PARTICIPANTS: A total of 5200 dementia-free older adult Cooper Clinic patients. MEASUREMENTS: CI was detected with a Montreal Cognitive Assessment (MoCA) score lower than 26. MetS was established based on National Cholesterol Education Program Adult Treatment Panel guidelines. Unadjusted and multivariable log-binomial regression were used to assess the MetS-CI association, with modification assessment by age, sex, education, cardiorespiratory fitness (CRF), and apolipoprotein-ε4 carrier status (APOE-ε4). RESULTS: MetS was not associated with CI when adjusting for age, sex, minority status, education, and marital status (prevalence ratio [PR] = 1.09; 95% confidence interval = .97-1.23) or when additionally adjusting for body mass index, CRF, alcohol consumption, current smoking status, and APOE-ε4 (PR = 1.07; 95% confidence interval = .80-1.45). The association was not modified by age, sex, CRF, or APOE-ε4 (P for interaction >.05). CONCLUSION: In contrast with some global and US studies, MetS and CI were not associated among our study population of nondemented older US adults. MetS may not be a suitable intervention target for poor cognitive outcomes among high socioeconomic older US adults, although separate MetS components may have different recommendations. Future studies should explore more diverse older US populations. If replicated, these findings would inform clinical efforts to reduce the burden of poor cognitive outcomes in the United States.

US acculturation and poor sleep among an intergenerational cohort of adult Latinos in Sacramento, California.

Acculturation may shape the disproportionate burden of poor sleep among Latinos in the United States. Existing studies are limited by unidimensional acculturation proxies that are incapable of capturing cultural complexities across generations. Understanding how acculturation relates to sleep may lead to the identification of modifiable intervention targets. We used multivariable regression and latent class methods to examine cross-sectional associations between a validated multidimensional scale of US acculturation and self-reported poor sleep measures. We analyzed an intergenerational cohort: first-generation (GEN1) older Latinos (Sacramento Area Latino Study on Aging; N = 1,716; median age: 69.5) and second-generation (GEN2) middle-aged offspring and relatives of GEN1 (Niños Lifestyle and Diabetes Study; N = 670; median age: 54.0) in Sacramento, California. GEN1 with high US acculturation, compared with high acculturation towards another origin/ancestral country, had less restless sleep (prevalence ratio [PR] [95% confidence interval (CI)]: 0.67 [0.54, 0.84]) and a higher likelihood of being in the best sleep class than the worst (OR [95% CI]: 1.62 [1.09, 2.40]), but among nonmanual occupations, high intergenerational US acculturation was associated with more general fatigue (PR [95% CI: 1.86 [1.11, 3.10]). GEN2 with high intergenerational US acculturation reported shorter sleep (PR [95% CI]: 2.86 [1.02, 7.99]). High US acculturation shaped sleep differentially by generation, socioeconomic context, and intergenerational acculturative status. High US acculturation was associated with better sleep among older, lower socioeconomic Latinos, but with shorter sleep duration among middle-aged, higher socioeconomic Latinos; results also differed by parental acculturation status. Upon replication, future studies should incorporate prospective and intergenerational designs to uncover sociobehavioral pathways by which acculturation may shape sleep to ultimately inform intervention efforts.

Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?

Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [ß = -0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (ß=0.09, SE = 0.06, P<0.12) (Pinteraction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (ß = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m2 (Pinteraction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.

Comparison of Breast Cancer Risk Predictive Models and Screening Strategies for Chinese Women.

BACKGROUND: Previous studies have shown that organized mammographic screening implementation in China may not be cost-effective. Our aim was to develop a valid predictive mathematical model for selecting high-risk groups eligible for mammography examinations (MAMs) and cost-effective strategies for breast cancer screening among Chinese women. METHODS: Between 2009 and 2012, 13,355 eligible women aged 30-65 years were enrolled from the community in Chengdu City. All subjects were administered a valid questionnaire and given MAMs. Using biopsies and 1-year follow up, we compared the accuracy indexes of three predictive models (back-propagation artificial neural network [BP-ANN], logistic regression [LR], and Gail) and four serial screening strategies (BP-ANN→MAM, LR→MAM, Gail→MAM, and MAM alone). We also evaluated the benefits of the four strategies by comparing their incidence-adjusted positive predictive value (PPV). All analyses were conducted with three age-based subgroups: 30-39, 40-49, and 50-65. RESULTS: The BP-ANN1, in conjunction with additional continuous risk factor variables, was the best predictive model, with the highest sensitivity (SEN, 76.99%) and specificity (SPE, 54.20%). The BP-ANN1→MAM strategy was best for the 40-49 age group, with the highest adjusted PPV (9.80%) and reasonable SEN (81.82%). CONCLUSION: We found that the BP-ANN model performed the best and was the most accurate for predicting high risk for breast cancer among Chinese women, and the BP-ANN→MAM screening strategy was most effective among the 40-49 age group. However, mammography alone may be a sufficient screening strategy for women aged 50-65.

Correlates of Physical Activity Differ by Sex and Country of Birth Among Mexican-Heritage Youth.

Barriers to physical activity (PA) may be experienced differently by sex and country of birth. We examine psychosocial correlates of PA in four groups based on sex (boy/girl) and country of birth [Mexico/United States (U.S.)]. 1154 Mexican heritage adolescents residing in Houston, Texas provided psychosocial data in 2008-09 and PA (number of days per week active for at least 60 min) in 2010-11 (N = 1001). Poisson regression models were fitted for each groups. Among boys, English language preference (p US-born  = 0.045, p Mexico-born  = 0.008) and higher subjective social status (p US-born  = 0.002, p Mexico-born  = 0.031) were associated with increased PA. Body image dissatisfaction was associated with decreased PA in Mexico-born girls (p = 0.007). Sensation-seeking tendencies were associated with increased PA among all groups; anxiety was associated with decreased PA among all but U.S.-born boys. Tailoring PA interventions to key sex-specific psychosocial correlates rather than country of birth may enhance efficacy of interventions to increase PA levels among Mexican heritage adolescents.

Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains.

BACKGROUND: Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimates associations between maternal vitamins B12, B6 (pyridoxal phosphate [PLP] and 4-pyridoxic acid [PA]), and homocysteine (Hcy) concentrations, offspring weight (birth weight and 3-year weight gain), and DNA methylation at four differentially methylated regions (DMRs) known to be involved in fetal growth and development (H19, MEG3, SGCE/PEG10, and PLAGL1). METHODS: Study participants (n = 496) with biomarker and birth weight data were enrolled as part of the Newborn Epigenetics STudy. Weight gain data were available for 273 offspring. Among 484 mother-infant pairs, DNA methylation at regulatory sequences of genomically imprinted genes was measured in umbilical cord blood DNA using bisulfite pyrosequencing. We used generalized linear models to estimate associations. RESULTS: Multivariate adjusted regression models revealed an inverse association between maternal Hcy concentration and male birth weight (ß = -210.40, standard error (SE) = 102.08, p = 0.04). The offspring of the mothers in the highest quartile of B12 experienced lower weight gain between birth and 3 years compared to the offspring of the mothers in the lowest (ß = -2203.03, SE = 722.49, p = 0.003). Conversely, maternal PLP was associated with higher weight gain in males; higher maternal PLP concentrations were also associated with offspring DNA methylation levels at the MEG3 DMR (p < 0.01). CONCLUSIONS: While maternal concentrations of B12, B6, and Hcy do not associate with birth weight overall, they may play an important role in 3-year weight gain. This is the first study to report an association between maternal PLP and methylation at the MEG3 DMR which may be an important epigenetic tag for maternal B vitamin adequacy.

Cross-Sectional Associations between Body Size, Circulating Sex-Steroid Hormones and IGF Components among Healthy Chinese Women.

The incidence of breast cancer has increased in Asian countries and rates of hormone receptor (HR) negative breast cancer exceed those of Western countries. Epidemiologic data suggest that the association between body size and BC risk may vary by HR status, and could differ geographically. While body size may influence BC risk by moderating the synthesis and metabolism of circulating sex-steroid hormones, insulin-like growth factor (IGF)-1 and related binding proteins, there is a dearth of literature among Asian women. We aimed to examine these specific associations in a sample of Chinese women. In Sichuan Province 143 women aged ≥40 years were recruited through outpatient services (2011-2012). Questionnaires, anthropometric measurements, and blood samples were utilized for data collection and linear regression was applied in data analyses. Among women <50 years we observed a non-monotonic positive association between body mass index (BMI) and 17ß-estradiol, and a reversed J-shaped association between BMI and IGF-1 (p ≤0.05). We observed similar associations between waist-to-hip ratio and these markers. Our finding of augmented IGF-1 among women with low body mass may have implications for understanding breast tumor heterogeneity in diverse populations and should be evaluated in larger prospective studies with cancer outcomes.

Associations between prenatal physical activity, birth weight, and DNA methylation at genomically imprinted domains in a multiethnic newborn cohort.

Birth weight is a commonly used indicator of the fetal environment and a predictor of future health outcomes. While the etiology of birth weight extremes is likely multifactorial, epidemiologic data suggest that prenatal physical activity (PA) may play an important role. The mechanisms underlying this association remain unresolved, although epigenetics has been proposed. This study aimed to estimate associations between prenatal PA, birth weight, and newborn DNA methylation levels at differentially methylated regions (DMRs) regulating 4 imprinted genes known to be important in fetal development. Study participants (N = 1281) were enrolled as part of the Newborn Epigenetics Study. Prenatal PA was ascertained using the Pregnancy Physical Activity Questionnaire, and birth weight data obtained from hospital records. Among 484 term mother-infant pairs, imprinted gene methylation levels were measured at DMRs using bisulfite pyrosequencing. Generalized linear and logistic regression models were used to estimate associations. After adjusting for preterm birth and race/ethnicity, we found that infants born to mothers in the highest quartile of total non-sedentary time had lower birth weight compared to infants of mothers in the lowest quartile (ß = -81.16, SE = 42.02, P = 0.05). These associations appeared strongest among male infants (ß = -125.40, SE = 58.10, P = 0.03). Methylation at the PLAGL1 DMR was related to total non-sedentary time (P < 0.05). Our findings confirm that prenatal PA is associated with reduced birth weight, and is the first study to support a role for imprinted gene plasticity in these associations. Larger studies are required.