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Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value

Background: Aspirin, nonaspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) and acetaminophen all have biologic effects that might reduce the risk of ovarian cancer. However, epidemiologic data on this question are mixed.Methods: A population-based, case-control study in western Pennsylvania, eastern Ohio, and western New York State included 902 women with incident epithelial ovarian cancer who were diagnosed between February 2003 and November 2008 as well as 1802 matched controls. Regular use (at least 2 tablets per week for 6 months or more) of aspirin, NA-NSAIDs, and acetaminophen before the reference date (9 months before interview date) was assessed by in-person interview. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Results: The OR for aspirin use was 0.81 (95% CI = 0.63-1.03). Decreased risks were found among women who used aspirin continuously (0.71 [0.54-0.94]) or at a low-standardized daily dose (0.72 [0.53-0.97]), who used aspirin for the prevention of cardiovascular disease (0.72 [0.57-0.97]), who used aspirin more recently, or who used selective cyclooxygenase-2 inhibitors (0.60 [0.39-0.94]). No associations were observed among women using nonselective NA-NSAIDs or acetaminophen.Conclusions: Risk reductions of ovarian cancer were observed with use of aspirin or selective cyclooxygenase-2 inhibitors. However, the results should be interpreted with caution due to the inherent study limitations and biases. [ABSTRACT FROM AUTHOR]

Objective: Throughout the world, the proportion of the male population aged 65 years and older is increasing. Yet, we have limited information regarding diet quality and predictors of diet quality in this segment of the population. The objectives of the current analyses are to describe the diet quality of a cohort of men >65 years of age, and identify lifestyle factors associated with poor diet quality.Methods: We present a cross-sectional analysis of the diet quality of 5928 men, aged 65-100 years, who are participants in the Osteoporotic Fractures in Men (MrOS) cohort study. Dietary intake was determined using a modified Block 98 food-frequency questionnaire. Diet quality was calculated using the previously validated Diet Quality Index-Revised (DQI-R). Univariate and multivariate modelling was used to estimate the variance in diet quality predicted by a number of sociodemographic factors, including age, race/ethnicity, body mass index (BMI), marital status, education, smoking status, physical activity, self-perceived health and nutritional supplement use.Results: Overall, we found that in this geographically diverse group of older men, diet quality was low, with a mean modified DQI-R for the entire study population of 62.5 (standard deviation 13.1) out of an ideal of 100. Further, younger age, very low total calorie intake (< or = 1187 kcal day- 1), higher BMI, residence in a North or Southeast community, being of African-American or Hispanic race, being less educated, not using dietary supplements and smoking were each significant independent predictors of a poorer diet.Conclusion: These data may prove useful in both understanding the dietary intake of older US men as it relates to published dietary guidelines, and for targeting future dietary intervention programmes. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether hypertension rates were positively related to socioeconomic status (SES) in males in urban northern Nigerian civil servants in order to confirm this relationship previously observed in a southern Nigerian civil servant population which differed in tribal origin, religious practices and diet. Methods: Civil servants were recruited from the Sokoto State ministries, Sokoto, Nigeria. Professionals and administrators were designated as higher SES, and clerks and laborers as lower SES. In addition to blood pressure, the height and weight of individuals, as well as their urinary sodium- and potassium-creatinine, were also measured. Results: The age-adjusted occurrence of hypertension (systolic pressure >/= 140 mmHg or diastolic pressure >/= 90 mmHg or current use of hypertension medication) was similar in male higher (n = 155) and lower (n = 255) SES groups aged 25-54, 19.3% and 19.8%, respectively. However, the age-adjusted rate of definite hypertension (systolic pressure >/= 160 mmHg or diastolic pressure >/= 95 mmHg or current use of hypertension medication) was considerably higher in the higher SES than in the lower SES men, 11.2% versus 3.6%. Age-adjusted body mass index (BMI, kg/m2) was higher among the higher than in the lower SES group, 21.4 versus 20.4. Over-night sodium excretion did not differ. Among female civil servants (n = 73) aged 20-44, there were few of higher SES (n = 19) precluding SES-specific analyses. Total and definite hypertension rates among women were 17.2% and 55%, respectively. Mean BMI was 22.2. In logistic regression, definite hypertensive status was related to age group, BMI tertile, sodium excretion and SES in men and to sodium excretion in women. Conclusion: Even in this very lean population, the higher risk for hypertension in males of higher SES was confirmed. This was explained, in part, by higher BMI. [ABSTRACT FROM AUTHOR]

Objective: We sought to describe national trends for inpatient procedures for pelvic organ prolapse from 1979-2006.Study Design: The National Hospital Discharge Survey was analyzed for patient and hospital demographics, as were International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedures codes from 1979-2006. Age-adjusted rates (AARs) per 1000 women were calculated using the 1990 US Census data.Results: There was a significantly decreasing trend in the AARs for inpatient prolapse procedures, from 2.93-1.52 per 1000 women from 1979-2006. AARs for hysterectomy decreased from 8.39-4.55 per 1000 women from 1979-2006. Over the study period, AARs remained at about the 1979 level among the women>or=52 years old (2.73-2.86; P=.075). In women<52 years old, AARs declined to less than one-third of the 1979 rate (3.03-0.84; P<.001).Conclusion: AARs for inpatient procedures for prolapse in the United States remained stable for women aged>or=52 years from 1979-2006; rates declined by two-thirds for women aged<52 years. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine age-adjusted rates (AARs) of lower urinary tract injury and incidence in selected inpatient gynecologic and obstetric procedures.Study Design: We utilized the National Hospital Discharge Survey, 1979-2006. AARs of nonobstetric bladder and ureteral injuries and incidence of lower urinary tract injury for various hysterectomy types and deliveries were calculated for women>18 years old.Results: Overall AARs of ureteral injury decreased from 0.06-0.03 per 1000 women (1979-2006). AARs of inpatient gynecologic procedures decreased from 24.9-11.8 per 1000 women (1979-2006). By hysterectomy type, bladder injury was highest in laparoscopic-assisted vaginal hysterectomy (VH) (13.8 per 1000) and VH (13.1 per 1000). Ureteral injury recognized during hysterectomy was most common with radical hysterectomy (7.7 per 1000) and least common with laparoscopic-assisted VH (0 per 1000).Conclusion: Ureteral injuries at time of inpatient surgical procedures have decreased from 1979-2006. This corresponds with a sharp decrease in inpatient gynecologic procedures. [ABSTRACT FROM AUTHOR]

Background: Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg), lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women.Methods: We utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004.Results: Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0-3.2, p = 0.07). There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4-1.8, p = 0.68).Conclusion: Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women. [ABSTRACT FROM AUTHOR]

Background: A limited body of evidence, mostly based on self-report, is available regarding physical activity levels among American-Indian adults.Purpose: This study aims to examine physical activity levels objectively using pedometers among a large cohort of American-Indian adult participants in the Strong Heart Family Study (SHFS).Methods: Physical activity levels in 2604 American-Indian adults, aged 18-91 years, from 13 American-Indian communities were assessed using Accusplit AE120 pedometers over a period of 7 days during 2001-2003. Anthropometric measurements were also assessed. All data analyses were conducted in 2008. Age-adjusted Pearson correlations were used to examine the relationship between average steps per day and age and anthropometric variables. Subjects were placed in age and BMI categories (according to National Heart, Lung, and Blood Institute cut points) to examine trends in physical activity with increasing age and BMI.Results: Daily pedometer steps ranged from 1001 to 38,755. Mean step counts by age group for men were 5384 (aged 18-29 years); 5120 (aged 30-39 years); 5040 (aged 40-49 years); 4561(aged 50-59 years); 4321 (aged 60-69 years); and 3768 (aged >or=70 years) and for women, 5038 (aged 18-29 years); 5112 (aged 30-39 years); 5054 (aged 40-49 years); 4582 (aged 50-59 years); 3653 (aged 60-69 years); and 3770 (aged >or=70 years). A significant linear trend in physical activity was noted with increasing age (p=0.002 for men, p<0.0001 for women) and with increasing BMI (p=0.05 for men, p=0.04 for women).Conclusions: Objectively measured data suggest that inactivity is a problem among American-Indian adults and that a majority of American-Indian adults in the SHFS may not be meeting the minimum physical activity public health recommendations. Efforts to increase physical activity levels in this population are warranted. [ABSTRACT FROM AUTHOR]

Background: Both high and low maternal prepregnancy body mass index can lead to suboptimal fetal growth and risk of pregnancy complications. In developed countries, nearly half of all women of childbearing age are either overweight or obese, and most data linking maternal body mass index and adverse pregnancy complications are limited to these populations., Objective: This study aimed to prospectively evaluate the relationships between prepregnancy body mass index and adverse pregnancy outcomes using the Longitudinal Indian Family hEalth (LIFE) study., Study Design: We modeled the relationships between prepregnancy body mass index and adverse pregnancy outcomes such as low birthweight, preterm birth, cesarean delivery, intrauterine growth restriction, miscarriage, and fetal death among 675 women aged 15 to 35 years with singleton pregnancies in the Longitudinal Indian Family hEalth study, a population-based prospective pregnancy cohort study conducted in Telangana, India. Prepregnancy body mass index was calculated as weight in kilograms divided by height in meters squared and was classified into 4 categories using the World Health Organization recommendations for Asian adults. Prepregnancy body mass index was assessed at a mean of 12.3 months before pregnancy. Odds ratios and 95% confidence intervals of adverse pregnancy outcomes were modeled and adjusted for confounders., Results: Obese women had a 3-fold increased risk of cesarean delivery (odds ratio, 3.13; 95% confidence interval, 1.56-6.29) compared with normal-weight women. Those who were overweight also had a marginally increased risk of cesarean delivery, albeit not statistically significant (odds ratio, 1.17; 95% confidence interval, 0.61-2.24). Underweight women had a modestly increased risk of low birthweight, compared with normal-weight women (odds ratio, 1.12; 95% confidence interval, 0.71-1.77), although results were not significant. Conversely, obese (odds ratio, 0.71; 95% confidence interval, 0.28-1.77) and overweight (odds ratio, 0.61; 95% confidence interval, 0.24-1.51) women had a marginally decreased risk of low birthweight., Conclusion: Our data suggest that women with elevated prepregnancy body mass index may have a higher risk of adverse pregnancy outcomes, especially cesarean delivery. Although this study has limited generalizability, our findings are generalizable to rural to periurban regions of India. Further studies exploring the translatability of these findings to other populations are needed. In addition, targeted prepregnancy intervention studies and programs that include counseling on optimization of preconception health and lifestyle modification for improvement of subsequent pregnancy outcomes among overweight and obese women are needed., (© 2022 The Authors.)

Background: Consanguineous marriage (CM) has been linked to spontaneous abortion (SAB), although studies have largely been cross-sectional and likely underestimated early loss. We aimed to determine the relationships between CM and SAB in a prospective pregnancy cohort study in Telangana State, India., Methods: Data from 661 participants aged 15-35 years in the Longitudinal Indian Family hEalth (LIFE) study actively followed for pregnancy and pregnancy loss were analyzed. SAB was classified as early (< 8) or late (8-22) weeks gestation. We used logistic regression to model the relationships between CM, defined by first-cousin marriage, and SAB, adjusted for maternal age., Results: Women in CM were at a modestly increased risk of any (OR adj 1.15, 95% CI 0.69, 1.91) and early (OR adj 2.03, 95% CI 0.85, 4.83) SAB compared to women in non-CM, although results were not statistically significant. There was no relationship between CM and late SAB., Conclusion: Among couples in southern India, there was a modest increase in early but not late SAB among CMs which may be explained by the expected influence of chromosomal abnormalities and lethal homozygous recessive disease on early loss. Pre- and Peri-marital Health Counseling that addresses this risk may be warranted., Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-021-01498-7., Competing Interests: Conflicts of interestThe investigators have no conflicts of interest., (© Federation of Obstetric & Gynecological Societies of India 2021.)

Common variants in the hepatic lipase (LIPC) gene have been shown to be associated with plasma lipid levels; however, the distribution and functional features of rare and regulatory LIPC variants contributing to the extreme lipid phenotypes are not well known. This study was aimed to catalogue LIPC variants by resequencing the entire LIPC gene in 95 non-Hispanic Whites (NHWs) and 95 African blacks (ABs) with extreme HDL-C levels followed by in silico functional analyses. A total of 412 variants, including 43 novel variants were identified; 56 were unique to NHWs and 234 were unique to ABs. Seventy-eight variants in NHWs and 89 variants in ABs were present either in high HDL-C group or low HDL-C group. Two non-synonymous variants (p.S289F, p.T405M), found in NHWs with high HDL-C group were predicted to have damaging effect on LIPC protein by SIFT, MT2 and PP2. We also found several non-coding variants that possibly reside in the circRNA and lncRNA binding sites and may have regulatory potential, as identified in rSNPbase and RegulomeDB databases. Our results shed light on the regulatory nature of rare and non-coding LIPC variants as well as suggest their important contributions in affecting the extreme HDL-C phenotypes., Competing Interests: The authors have declared that no competing interests exist.

Background: Caesarean section delivery is increasing worldwide and in India, yet little is known about the effect on infants. We examined the association between caesarean delivery and adverse infant outcomes in an Indian national survey, accounting for factors related to the mode of delivery., Methods: Inverse probability weighted logistic regression analysis of the 2015-2016 India National Family Health Survey obtained adjusted ORs (aORs) and 95% CIs. Infant outcomes were maternal report of recent concomitant diarrhoea and acute respiratory infection (ARI) in infants age ≤6 mo and neonatal death., Results: Of the 189 143 reported most recent singleton births, 15.4% were delivered by caesarean, 860 (3.2%) of all infants age ≤6 mo had concomitant diarrhoea and ARI and 3480 (1.8%) neonatal deaths were reported. In adjusted analysis, caesarean delivery was not associated with concomitant diarrhoea and ARI (aOR 0.96 [95% CI 0.71 to 1.32]) but was associated with neonatal death (aOR 1.19 [95% CI 1.02 to 1.39])., Conclusions: Using nationally representative cross-sectional data for India, caesarean section delivery was found to be associated with neonatal death after accounting for factors associated with the mode of delivery. Prospective exploration of the relationship between caesarean delivery and adverse infant outcomes is warranted., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

We sought to identify factors associated with mode of delivery in a peri-urban Indian population with a high cesarean section rate. Poisson regression with robust error variance was applied to model factors associated with cesarean compared to vaginal delivery in a prospective, preconception pregnancy cohort study in Telangana State, India. Adjusted relative risks and 95% confidence intervals from multivariable models are presented. Among 1164 singleton births between 2010 and 2015, 46% were delivered by cesarean. In multiparous women ( n = 674), prior cesarean delivery (4.2, 3.2-5.6), prior twin delivery (1.4, 1.1-1.9), diagnosis of hypertension (1.4, 1.0-2.0), or preeclampsia (3.5, 2.1-5.7) in a prior pregnancy independently increased the risk of cesarean. Prepregnancy overweight/obesity (1.4, 1.0-1.9), a composite of prenatal complications (1.3, 1.0-1.7), a composite of labor complications (1.5, 1.0-2.3), nonreassuring fetal heart rate (2.3, 1.3-4.1), and breech position (2.6, 1.4-5.0) also increased the cesarean risk. Among nulliparous women ( n = 233), cephalo-pelvic disproportion (1.9, 1.2-3.0), a composite of labor complications (2.9, 1.8-4.9), and breech position (3.4, 1.9-6.2) increased the risk of cesarean. The high rate of cesarean delivery in this peri-urban Indian population is attributed to history of pregnancy complications, history of prior cesarean, prepregnancy body mass index, and medical indications at delivery., Competing Interests: The authors declare they have no conflicts of interest., (© 2019 Atlantis Press International B.V.)

The apolipoprotein E-C1-C4-C2 gene cluster at 19q13.32 encodes four amphipathic apolipoproteins. The influence of APOE common polymorphisms on plasma lipid/lipoprotein profile, especially on LDL-related traits, is well recognized; however, little is known about the role of other genes/variants in this gene cluster. In this study, we evaluated the role of common and uncommon/rare genetic variation in this gene region on inter-individual variation in plasma lipoprotein levels in non-Hispanic Whites (NHWs) and African blacks (ABs). In the variant discovery step, the APOE, APOC1, APOC4, APOC2 genes were sequenced along with their flanking and hepatic control regions (HCR1 and HCR2) in 190 subjects with extreme HDL-C/TG levels. The next step involved the genotyping of 623 NHWs and 788 ABs for the identified uncommon/rare variants and common tagSNPs along with additional relevant SNPs selected from public resources, followed by association analyses with lipid traits. A total of 230 sequence variants, including 15 indels were identified, of which 65 were novel. A total of 70 QC-passed variants in NHWs and 108 QC-passed variants in ABs were included in the final association analyses. Single-site association analysis of SNPs with MAF>1% revealed 20 variants in NHWs and 24 variants in ABs showing evidence of association with at least one lipid trait, including several variants exhibiting independent associations from the established APOE polymorphism even after multiple-testing correction. Overall, our study has confirmed known associations and also identified novel associations in this genomic region with various lipid traits. Our data also support the contribution of both common and uncommon/rare variation in this gene region in affecting plasma lipid profile in the general population., Competing Interests: The authors have declared that no competing interests exist.

Objective: African ancestry individuals are at high risk for hypertensive cardiovascular disease (CVD) and could benefit from early detection of arterial stiffening. We tested the association between the 2017 ACC/AHA hypertension categorizations, which include new blood pressure (BP) cutoffs and a definition for elevated BP, and arterial stiffness in 772 Afro-Caribbean men aged 50+ years (mean 64 years)., Methods: Arterial stiffness was assessed by brachial-ankle pulse-wave velocity (PWV) using a waveform analyzer. Hypertension groups were based on the 2017 ACC/AHA guidelines and by pharmacologic control status. Multiple linear/logistic regression was used to determine the association of PWV with BP and hypertension., Results: Mean (SD) PWV was 1609 (298) cm/s and was independently correlated with age, SBP, pulse, diabetes, height, and alcohol intake (all P < 0.02). After adjusting for these, in men aged at least 65 years, those with stage 1 or uncontrolled stage 2 hypertension had significantly greater PWV than all other groups (all P < 0.05). Men with controlled hypertension had similar PWV to those with elevated BP (P = 0.7); however, this was significantly greater than men with normal BP (all P < 0.05). Patterns were similar, but with smaller effect sizes, in men aged less than 65 years (all P < 0.05 except controlled hypertension versus elevated or normal BP were not significant)., Conclusion: In these high-risk Afro-Caribbeans: stage 1 hypertension is associated with increased PWV, which supports the new guidelines; and, pharmacologic control appears to partially protect men from increased PWV. Longitudinal studies are needed to determine optimal PWV and timing of antihypertensive treatment for preventing future CVD.

Background: Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry., Methods: Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models., Results: Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87)., Conclusions: Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. In vitro studies suggest that a Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m 2 ). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT [which reflects the intramuscular adiposity content (mg/cm 3 )]. Serum DKK1 was positively correlated with BMI ( r = 0.20; P = 0.01), waist circumference ( r = 0.15; P = 0.046), DXA total-body adiposity ( r = 0.24; P = 0.003), and DXA trunk adiposity ( r = 0.21; P = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density ( r = -0.25; P = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.

Background: Prospective studies examining the potential association of vitamin D with age-related muscle loss have shown inconsistent results., Objective: To examine the association between baseline serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and prospective change in lean mass with aging in African ancestry population. We also determined if associations were modulated by age and diabetes mellitus (DM)., Design: Prospective observational cohort study., Setting: Data were collected from a random sub-sample of 574 men, participants of the Tobago Bone Health Study (TBHS)., Participants: 574 Afro-Caribbean men, aged 43+ years (mean age: 59.1 ± 10.5), who were randomly selected as the participants in both the baseline and the follow-up visits., Measurements: Baseline fasting serum 25(OH)D was measured using liquid chromatography mass spectrometry (LC-MS/MS), and and 1,25(OH)2D was measured using radioimmunosassay (RIA). Changes in dual-energy X-ray absorptiometry (DXA)-measured appendicular lean mass (ALM), and total body lean mass (TBLM) were measured over an average of 6.0 ± 0.5 years. The associations of 25(OH)D and 1,25(OH)2D with ALM and TBLM were assessed by multiple linear regression model after adjusting for potential confounders., Results: When stratifying all men into two groups by age, greater baseline 25(OH)D and 1,25(OH)2D levels were associated with smaller losses of ALM and TBLM in older (age 60+ years) but not in younger (age 43 - 59 years) men. When stratifying by DM status, the associations of 25(OH)D and 1,25(OH)2D with declines in ALM and TBLM were statistically significant only in prediabetic, but not among normal glycemic or diabetic men., Conclusion: Higher endogenous vitamin D concentrations are associated with less lean mass loss with aging among older and prediabetic Afro-Caribbean men independent of potential confounders. Our findings raise a possibility that maintaining high serum vitamin D level might be important for musculoskeletal health in elderly and prediabetic African ancestry men., Competing Interests: None

Background: Previous studies have found a relationship between cesarean section delivery and adverse outcomes in the offspring, partially attributing these findings to differential development of immunity in infants delivered by cesarean compared to vaginal delivery. The purpose of this study is to determine whether cesarean section delivery is associated with higher reports of adverse short-term infant health outcomes in a peri-urban Indian population., Methods: Data from a prospective pregnancy cohort study in a peri-urban region of Telangana State, India, were analyzed to assess the association between mode of delivery, cesarean section or vaginal, and maternal report of recent infant diarrhea and/or respiratory symptoms at a 6 month follow-up visit. Inverse probability weights were applied to log-binomial regression models to account for maternal pre-pregnancy, prenatal, and labor and delivery factors., Results: Of the 851 singleton infants delivered between 2010 and 2015, 46.7% were delivered by cesarean. Cesarean delivery was not associated with an increased report of infants having one or more of the outcomes (diarrhea, respiratory infection, or difficulty breathing) at 6 months (adjusted risk ratio 0.89, 95% confidence interval 0.76-1.03), nor was it associated with infants having a more severe outcome of comorbid diarrhea and respiratory infection (adjusted risk ratio 1.08, 95% confidence interval 0.58-2.04)., Conclusion: Unlike findings in Western populations, in this peri-urban Indian population, cesarean delivery was not associated with higher reports of short-term adverse gastrointestinal or respiratory infant outcomes after accounting for pre-delivery maternal factors. Future research in this cohort could elucidate whether mode of delivery is associated with other adverse outcomes later in childhood.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men., Methods: Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height., Results: All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC., Conclusions: Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared., Methods: HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls)., Results: Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response., Conclusions: We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Increased ectopic adipose tissue infiltration in skeletal muscle is associated with insulin resistance and diabetes mellitus. We evaluated whether change in skeletal muscle adiposity predicts subsequent development of hypertension in men of African ancestry, a population sample understudied in previous studies. In the Tobago Health Study, a prospective longitudinal study among men of African ancestry (age range 40-91 years), calf intermuscular adipose tissue, and skeletal muscle attenuation were measured with computed tomography. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg, or receiving antihypertensive medications. Logistic regression was performed with adjustment for age, insulin resistance, baseline and 6-year change in body mass index, baseline and 6-year change in waist circumference, and other potential confounding factors. Among 746 normotensive men at baseline, 321 (43%) developed hypertension during the mean 6.2 years of follow-up. Decreased skeletal muscle attenuation was associated with newly developed hypertension after adjustment for baseline and 6-year change of body mass index (odds ratio [95% confidence interval] per SD, 1.3 [1.0-1.6]) or baseline and 6-year change of waist circumference (odds ratio [95% confidence interval] per SD, 1.3 [1.0-1.6]). No association was observed between increased intermuscular adipose tissue and hypertension. Our novel findings show that decreased muscle attenuation is associated with newly developed hypertension among men of African ancestry, independent of general and central adiposity and insulin resistance. Further studies are needed to adjust for inflammation, visceral and other ectopic adipose tissue depots, and to confirm our findings in other population samples., (© 2017 American Heart Association, Inc.)

Black men are known to have a higher risk for prostate cancer (PC). Carotenoids and retinol, linked to PC, have not been compared in different black populations at risk. We examined serum carotenoid and retinol levels between PC-free African-Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and African-American (AA) men with elevated serum prostate-specific antigen (PSA) levels (≥4 ng/ml). AC men who participated in the 2003 lycopene clinical trial and AA men who participated in the 2001-2006 National Health and Nutrition Examination Survey were compared. Serum specimens were analysed for carotenoid (β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to examine the association between serum carotenoid and retinol levels and black ethnicity, overall and among men with elevated serum PSA. There were sixty-nine AC men and sixty-five AA men, aged 41-79 years, included. AC men were associated with lower serum lycopene and retinol levels, and higher serum α- and β-carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for age, BMI, ever smoked cigarettes, education and hypertension (P≤0·03). Among men with elevated PSA, serum retinol was no longer statistically significant with ethnicity (P=0·06). Possible differences may be attributed to dietary intake, genetics and/or factors that influence bioavailability of these micronutrients. Prospective studies are warranted that investigate whether these differences in micronutrients between AC Tobagonian and AA men influence PC risk.

Aim: Falls are an important contributor to loss of function, morbidity, and mortality in elders. Little is known about falls in Indian populations. The objective of this cross-sectional report was to identify the prevalence and correlates of falls in a cohort of 562 rural southern Indian men and women., Methods: Risk factors included demographics, anthropometrics, self-reported health, medical history, physical function, vision, depression, and lifestyle. Odds ratios were calculated using logistic regression., Results: 71 (13%) subjects reported at least 1 fall in the past year. Prevalence was higher among women (17%) than men (8%), P = 0.003. Sex and age showed significant interaction ( P = 0.04) whereby falls prevalence increased with age among women but decreased among men. Correlates of falls among men included a history of osteoarthritis (OA) (odds ratio (OR): 6.91; 95% CI: 1.4-33.1), depression (OR:9.6; 3.1-30.1), and greater height (OR per 1 standard deviation increase: 2.33; 1.1-5.1). Among women, poor physical performance (OR: 3.33; 1.13-9.86) and history of cardiovascular disease (CVD) (OR: 2.42; 1.01-5.80) were independently associated with falls., Implications: Prevalence of falls in elderly South Indians was lower than published reports from western countries and likely reflects low exposure to fall risks. Patterns with age differed in men and women and may reflect sex differences in the accuracy of age recall. Presence of comorbidities specifically OA, CVD, and depression was independent correlate of falling.

Objectives: To compare the cytokine profile between human herpesvirus 8 seropositive and seronegative men with and without prostate cancer., Methods: The study sample was obtained from the Tobago Prostate Survey, an ongoing study of prostate cancer in the Caribbean island of Tobago. Participants in the study were recruited mostly by public service announcement and by word of mouth. For analyses of circulating levels of pro-inflammatory cytokines, participants with biopsy-confirmed prostate cancer (n = 79) were compared with control participants (n = 87)., Results: Cytokine analyses showed a T helper 2 response with suppressed T helper 1 response in prostate cancer patients, as evidenced by significantly increased levels of interleukin-13 and reduced levels of interleukin-12p70. Herpesvirus 8 seropositive men showed significantly increased levels of interleukin-13 and interleukin-10. At logistic regression analyses, interleukin-12p70 predicted prostate cancer in 94.4% of human herpesvirus 8 seropositive men., Conclusions: These findings show that prostate cancer elicits an antitumor, T helper 2 response with a suppressed T helper 1 response. Human herpesvirus 8 infection results in a similar immune response supporting the hypothesis that in Tobago, human herpesvirus 8 establishes a chronic infection that can contribute to an immune response favoring the formation and survival of prostate cancer., (© 2016 The Japanese Urological Association.)

Aim: The Mobility and Independent Living in Elders Study (MILES) was established in 2012 to estimate the prevalence, incidence, and risk factors for disability and age-related disease in rural older Indians. Here we describe the main goals of MILES, the essential elements of its design and examinations, and the initial findings from the baseline visit., Methods: A random sample of 562 men and women aged ≥60 years was enrolled from the Medchal region in Telangana State. Baseline examination consisted of two separate clinical visits, and included measurements of blood pressure, anthropometry, physical function, peripheral artery disease, cognitive function, bone and muscle quality, knee osteoarthritis, carotid intima-media thickness, and blood biomarkers. A comprehensive interview was carried out for demographics, disability and disease history. Annual follow-up visits are ongoing to collect information on incident disability and disease., Results: The median age of participants was 66 years (range 60-92 years); median body mass index 21.7 kg/m 2 , median gait speed 0.67 m/s and 55% self-reported their health status as fair or poor., Conclusions: These findings suggest a more frail population in the MILES cohort compared with older adults in USA cohorts. MILES will provide estimates of burden of disease, and disability and risk factors in older adults. Findings will be used to identify potential interventions to prevent disability in this rural Indian population. Geriatr Gerontol Int 2017; 17: 31-40., (© 2015 Japan Geriatrics Society.)

Background: fat infiltration within and around skeletal muscle (i.e. myosteatosis) increases with ageing, is greater in African versus European ancestry men and is associated with poor health. Myosteatosis studies of mortality are lacking, particularly among African ancestry populations., Methods: in the Tobago Health study, a prospective longitudinal study, we evaluated the association of all-cause mortality with quantitative computed tomography (QCT) measured lower leg myosteatosis (intermuscular fat (IM fat) and muscle density) in 1,652 African ancestry men using Cox proportional hazards models. Date of death was abstracted from death certificates and/or proxy., Results: one hundred and twelve deaths occurred during follow-up (mean 5.9 years). In all men (age range 40-91 years), higher all-cause mortality was associated with greater IM fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and lower muscle density (HR (95% CI) per SD lower: 1.37 (1.08-1.75)) in fully adjusted models. Similar mortality hazard rates were seen in the subset of elderly men (aged ≥65 years) with greater IM fat (1.40 (1.11-1.78) or lower muscle density (1.66 (1.24-2.21)) in fully adjusted models., Conclusions: our study identified a novel, independent association between myosteatosis and all-cause mortality in African ancestry men. Further studies are needed to establish whether this association is independent of other ectopic fat depots and to identify possible biological mechanisms underlying this relationship., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The Caribbean island of Tobago, which is 97% African ancestry, has one of the highest rates of prostate cancer in the world. We have previously reported that human herpesvirus 8 (HHV-8) infection is significantly associated with prostate cancer in Tobago. In this study, we extend those results testing the hypothesis that HHV-8 seropositive Tobagonian men have a chronic HHV-8 infection in their prostates that is associated with increased inflammation., Methods: Prostate sections were screened by immunohistochemistry for the expression of HHV-8 proteins K8.1 and LANA-1 and for presence of B cells (CD20) and macrophages (CD68)., Results: HHV-8 antigen expression representing lytic and latent infections was seen in 73.9% of prostates from HHV-8 seropositive subjects. Latent infections were seen predominantly in glandular epithelia whereas lytic gene expression was seen mainly in macrophages in prostate stroma. Macrophage infiltrates were significantly increased in sections expressing HHV-8 proteins., Conclusion: HHV-8 establishes a chronic latent infection in the prostate, which is associated with an increased macrophage infiltrate., (© 2016 Wiley Periodicals, Inc.)