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Mara Z Vitolins,1 L Douglas Case,1 Stephen R Rapp,2 Mark O Lively,3 Edward G Shaw,4 Michelle J Naughton,5 Jeffrey Giguere,6 Glenn J Lesser7 1Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 5Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; 6Greenville Community Oncology Research Program of the Carolinas, Greenville, SC, USA; 7Department of Internal Medicine-Hematology and Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA Purpose: Women with breast cancer were randomized to receive coenzyme Q10 (CoQ10) plus Vitamin E or placebo in a clinical trial. The objective of this evaluation is to examine the association between participant self-reported adherence to the study supplements and changes in plasma biomarker levels.Patients and methods: Correlation coefficients quantified the association between changes in alpha-tocopherol and CoQ10 levels and the association between self-reported adherence and changes in biomarkers. Participants were categorized by self-reported adherence; Kruskal–Wallis tests compared changes in alpha-tocopherol and CoQ10 levels between self-reported adherence groups.Results: Women (N=155) provided baseline and post-treatment biomarkers; 147 completed at least one diary. While changes in alpha-tocopherol and CoQ10 levels were moderately correlated, correlations ranged from 0.40 to 0.48, association between self-reported adherence and plasma alpha-tocopherol or CoQ10 levels was weak; correlations ranged from 0.10 to 0.29 at weeks 8, 16, and 24. Some participants with high self-reported adherence actually had decreases in their biomarker levels.Conclusion: These findings support that self-reported adherence is likely to be overestimated. Biological and other measures of adherence that can better identify true adherence to study pills provided in clinical trials are greatly needed as they may assist in improving the interpretation of findings of future clinical trials. Keywords: adherence, self-report, blood biomarkers, clinical trial, CoQ10, alpha-tocopherol

SummaryThe Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.IntroductionThis study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.MethodsWHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).ResultsAmong women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.ConclusionThough based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

BACKGROUND- Simultaneous contribution of hundreds of electrocardiographic (ECG) biomarkers to prediction of long-term mortality in postmenopausal women with clinically normal resting ECGs is unknown. METHODS AND RESULTS- We analyzed ECGs and all-cause mortality in 33 144 women enrolled in the Women's Health Initiative trials who were without baseline cardiovascular disease or cancer and had normal ECGs by Minnesota and Novacode criteria. Four hundred and seventy-seven ECG biomarkers, encompassing global and individual ECG findings, were measured with computer algorithms. During a median follow-up of 8.1 years (range for survivors, 0.5 to 11.2 years), 1229 women died. For analyses, the cohort was randomly split into derivation (n=22 096; deaths, 819) and validation (n=11 048; deaths, 410) subsets. ECG biomarkers and demographic and clinical characteristics were simultaneously analyzed using both traditional Cox regression and random survival forest, a novel algorithmic machine-learning approach. Regression modeling failed to converge. Random survival forest variable selection yielded 20 variables that were independently predictive of long-term mortality, 14 of which were ECG biomarkers related to autonomic tone, atrial conduction, and ventricular depolarization and repolarization. CONCLUSIONS- We identified 14 ECG biomarkers from among hundreds that were associated with long-term prognosis using a novel random forest variable selection methodology. These biomarkers were related to autonomic tone, atrial conduction, ventricular depolarization, and ventricular repolarization. Quantitative ECG biomarkers have prognostic importance and may be markers of subclinical disease in apparently healthy postmenopausal women. [ABSTRACT FROM AUTHOR]

Objective: Although the Diabetes Prevention Program (DPP) and the Finnish Diabetes Prevention Study (FDPS) demonstrated that weight loss from lifestyle change reduces type 2 diabetes incidence in patients with prediabetes, the translation into community settings has been difficult. The objective of this study is to report the first-year results of a community-based translation of the DPP lifestyle weight loss (LWL) intervention on fasting glucose, insulin resistance, and adiposity.Research Design and Methods: We randomly assigned 301 overweight and obese volunteers (BMI 25-40 kg/m(2)) with fasting blood glucose values between 95 and 125 mg/dL to a group-based translation of the DPP LWL intervention administered through a diabetes education program (DEP) and delivered by community health workers (CHWs) or to an enhanced usual-care condition. CHWs were volunteers with well-controlled type 2 diabetes. A total of 42.5% of participants were male, mean age was 57.9 years, 26% were of a race/ethnicity other than white, and 80% reported having an education beyond high school. The primary outcome is mean fasting glucose over 12 months of follow-up, adjusting for baseline glucose.Results: Compared with usual-care participants, LWL intervention participants experienced significantly greater decreases in blood glucose (-4.3 vs. -0.4 mg/dL; P<0.001), insulin (-6.5 vs. -2.7 μU/mL; P<0.001), homeostasis model assessment of insulin resistance (-1.9 vs. -0.8; P<0.001), weight (-7.1 vs. -1.4 kg; P<0.001), BMI (-2.1 vs. -0.3 kg/m2; P<0.001), and waist circumference (-5.9 vs. -0.8 cm; P<0.001).Conclusions: This translation of the DPP intervention conducted in community settings, administered through a DEP, and delivered by CHWs holds great promise for the prevention of diabetes by significantly decreasing glucose, insulin, and adiposity. [ABSTRACT FROM AUTHOR]

Objective: To compare the validity of a modified Block food-frequency questionnaire (FFQ), a picture-sort administration of the FFQ (PSFFQ) and a meal pattern-based questionnaire (MPQ) in a multi-ethnic population of low socio-economic status (SES).Design: Participants completed six 24-hour dietary recalls (24HR) over six months; the FFQ, PSFFQ and MPQ were completed in random order in the subsequent month. Instruments were interviewer-administered. The PSFFQ and MPQ were developed in formative research concerning difficulties for older adults in responding to standard food-frequency instruments.Setting: Rural North Carolina, USA. Subjects One hundred and twenty-two African American, Native American and white adults aged > or = 65 years, with approximately one-third in each ethnic group. Inclusion criteria included education < or = 12 years and income < or = 150% of national poverty level or Medicaid recipient.Results: Comparing median intakes from the average of the 24HR with the three diet assessment instruments, the MPQ tended to overestimate intakes compared with the FFQ and PSFFQ. Correlations among nutrients obtained by the 24HR and the other three instruments were generally statistically significant and positive. Across nutrients, the PSFFQ was most highly correlated with the 24HR for women, while the FFQ was most highly correlated with the 24HR for men.Conclusions: Dietary assessments using 24HR and FFQ were similar to results reported elsewhere, although correlations between 24HR and FFQ were somewhat lower. Interviewer-administered dietary assessments should be used with caution to evaluate dietary intake among older adults with low SES. Gender differences and the lower correlations should be investigated more thoroughly to assist in choosing dietary assessment instruments for this population. [ABSTRACT FROM AUTHOR]

Little research has considered older adults? health beliefs related to the use of complementary and alternative medicine (CAM). Based on a conceptual model of health selfmanagement, this analysis delineates health beliefs and behaviors related to CAM use among community-dwelling rural elders. In-depth interviews were conducted with 145 female and male African Americans, Native Americans, and Whites aged 70 and older residing in two rural, central North Carolina counties. CAM therapies are widely used but are largely limited to folk and home remedies and vitamin and mineral supplements. These rural elders integrate CAM use with conventional health care, and they are concerned that remedies they use not interfere with prescribed conventional treatment. They justify CAM use in terms of advice from their physician or nurse or from published sources. Most rural elders state that their knowledge of CAM therapies is limited. [ABSTRACT FROM AUTHOR]

The Multidimensional Health Locus of Control (MHLC) is a commonly used measure of health management orientation. Three general domains have been identified from MHLC: chance, internal, and powerful others. These domains have been used to identify degree of adherence to health behaviors such as weight loss, hypertension and diabetes control, and physical activity. However, there have not been many studies of the degree of adherence to health-promoting behaviors among older adults. This study examined MHLC among 76 older white, African American, and Native American adults in two rural communities. A wide variety of MHLC typologies were observed in this population. Associations of demographic and health characteristics with MHLC were found which may be useful for researchers and health care professionals in understanding these health management orientations for older rural adults. [ABSTRACT FROM AUTHOR]

Little research has investigated Complementary and Alternative Medicine (CAM) use prevalence and its determinants among older adults. We examined ethnic and gender variation in CAM use among rural older adults who reside in two North Carolina counties. Home and folk remedies, and vitamin and mineral supplements, were used by most participants. Men and women did not differ. African and Native American elders used home and folk remedies more than European Americans; European and Native Americans used vitamin and mineral supplements more than African Americans. Health care providers should be aware that their patients use CAM and may need counseling to minimize CAM-drug interactions. [ABSTRACT FROM AUTHOR]

Older adults residing in rural communities are at risk for low dietary quality because of a variety of social, physical and environmental circumstances. Minority elders are at additional risk because of poorer health status and lower socioeconomic status. This study evaluated the food group intake of 130 older (>70 years) African American (34%), European American (36%), and Native American (30%) residents of two rural communities in central North Carolina. An interviewer-administered food frequency questionnaire was used to measure dietary intake. Food items were classified into food groups similar to the United States Department of Agriculture (USDA) Food Guide Pyramid and the National Cancer Institutes 5 A Day for Better Health program. None of the survey participants met minimum intake recommendations and most over-consumed fats, oils, sweets and snacks. African Americans and Native Americans consumed fewer servings of meats,fruits and vegetables, and fats, oils, sweets and snacks than European Americans. African American men consumed the fewest servings of fruits and vegetables of all gender/ethnic groups. Consumption of fats, oils and sweets was greatest among those 85 years and older and was more common among denture users. National strategies to educate the public about the importance of consuming a varied diet based on the recommendations presented in national nutrition education campaigns may not be reaching older adults in rural communities, particularly minority group members. [ABSTRACT FROM AUTHOR]

Objective: To describe the prevalence and correlates of selected health behaviors among rural older adults. Methods: Data were collected from 114 elders (>70 years) of 3 ethnic groups (whites, African Americans, and Native Americans) in two rural North Carolina communities. Self-reported health behaviors included diet, tobacco/alcohol use, exercise/weight maintenance, accident avoidance, and health care use. Results: High rates were reported for most behaviors and varied according to ethnicity, gender, age, health conditions, and self-rated health. Poor agreement was found for actual intake of dietary fiber and fat and self-reported adherence to recommendations for those nutrients. Conclusion: These data add to the limited information on health behaviors of rural elders, including ethnic minorities, and indicate that these behaviors may be difficult to implement. [ABSTRACT FROM AUTHOR]

Background: Vitamin and mineral supplement products are widely consumed by older adults. This study describes supplement product use in a multiethnic rural population, relates supplement usage to dietary nutrient intake, and determines predictors of supplement usage.Methods: Data are from a population-based sample of 130 community-dwelling adults aged 70 years and older in two rural North Carolina counties. The sample was 34% African American, 36% European American, and 30% Native American. Interviewer-administered semiquantitative food frequency questionnaires were used to obtain data on usual diet and supplement use. In-home interviews allowed verification of supplement composition. Intakes from diet and supplement products were examined for vitamins A, E, B6, C, folate, iron, zinc, and calcium.Results: Of those who participated in the study, 47% reported using one or more supplement products. African Americans were significantly less likely to take supplements than Native Americans or European Americans. Based on dietary intakes, 65% of the participants were deficient (<2/3 recommended dietary allowance [RDA]) for at least one nutrient. The use of supplement products for the eight nutrients investigated was not related to dietary nutrient deficiency. For all nutrients investigated, except iron and calcium, a greater proportion of those without dietary deficiency took a supplement product than those with deficiency. Using logistic regression, ethnicity (European American and Native American), and gender (women) were significant predictors of supplement use.Conclusions: These findings suggest that although both dietary deficiencies of vitamins and minerals and supplement use are relatively high in this population, there is no association between supplement use and deficient dietary intakes for the eight nutrients examined. Health care providers should be aware that nutritional counseling and guidance on appropriate supplement usage is needed in this population. [ABSTRACT FROM AUTHOR]

This paper draws upon qualitative research conducted among older adults in the rural, southern United States in which they articulated their beliefs and experiences with nutrition and foods, and lay models of the connection of diet with chronic disease. Salt emerged as a focus of contention. The goals of the paper are to (1) present the culturally constructed meaning of salt, (2) contrast the cultural meaning with biomedical views, and (3) discuss how these findings can be applied to health education and better doctor--patient communication. Data were collected in two rural communities characterized by high rates of poverty and a high proportion of minority residents. A total of 116 African American, Native American and white adults aged 60 years and older participated in 55 in-depth interviews or seven focus groups. A systematic analysis of text showed that salt was a highly contested component of food. While valued for its role in traditional foods and cuisine, it also held negative connotations because of biomedical links to chronic diseases prevalent in the population. We suggest that attempts to control salt intake are made difficult by the changes in taste perceptions that accompany aging. Respondents' articulation of salt's role in health and disease shows cross-over among different chronic diseases and a lay interpretation of blood as the medium through which salt affects disease. These older adults' narratives demonstrate their attempts to reconcile the important role of traditional foods in their identity as Southerners with their attempts to meet medical recommendations for healthy eating. [ABSTRACT FROM AUTHOR]

Background: Higher diet quality scores are associated with a lower risk for many chronic diseases and all-cause mortality; however, it is unclear if diet quality is associated with aging biology., Objective: This study aimed to examine the association between diet quality and a measure of biological aging known as epigenetic aging., Design: A cross-sectional data analysis was used to examine the association between three diet quality scores based on self-reported food frequency questionnaire data and five measures of epigenetic aging based on DNA methylation (DNAm) data from peripheral blood., Participants/setting: This study included 4,500 postmenopausal women recruited from multiple sites across the United States (1993-98), aged 50 to 79 years, with food frequency questionnaire and DNAm data available from the Women's Health Initiative baseline visit., Main Outcome Measures: Five established epigenetic aging measures were generated from HumanMethylation450 Beadchip DNAm data, including AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno, AgeAccelGrim, and DunedinPACE., Statistical Analyses Performed: Linear mixed models were used to test for associations between three diet quality scores (Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores) and epigenetic aging measures, adjusted for age, race and ethnicity, education, tobacco smoking, physical activity, Women's Health Initiative substudy from which DNAm data were obtained, and DNAm-based estimates of leukocyte proportions., Results: Healthy Eating Index, Dietary Approaches to Stop Hypertension, and alternate Mediterranean diet scores were all inversely associated with AgeAccelPheno, AgeAccelGrim, and DunedinPACE (P < 0.05), with the largest effects with DunedinPACE. A one standard deviation increment in diet quality scores was associated with a decrement (β ± SE) in DunedinPACE z score of -0.097 ± 0.014 (P = 9.70 x 10 -13 ) for Healthy Eating Index, -0.107 ± 0.014 (P = 1.53 x 10 -14 ) for Dietary Approaches to Stop Hypertension, and -0.068 ± 0.013 (P = 2.31 x 10 -07 ) for the alternate Mediterranean diet., Conclusions: In postmenopausal women, diet quality scores were inversely associated with DNAm-based measures of biological aging, particularly DunedinPACE., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to assess how parent stress and COVID-19 impact on the family are associated with parental pressure to eat during the COVID-19 pandemic. Parents of healthy preschool-aged children completed measures including pressure to eat (Child Feeding Questionnaire), parent perception of their stress (Perceived Stress Scale), household food insecurity (Hunger Vital Sign) and effects of COVID-19 on families (COVID-19 Exposure and Family Impact). Children (N = 228) were racially, ethnically, and socioeconomically diverse (34 % Black, 15 % Hispanic, and 29 % with household income <$20,000). Bivariate analyses showed that parent stress at Year 1 (β 0.02; 95 % CI 0.006, 0.04) was significantly associated with pressure to eat at Year 1 and that COVID-19 impact at Year 1 (β 0.02; 95 % CI 0.001, 0.03) was also significantly associated with pressure to eat. Multivariable linear regression analyses showed that parent stress at Year 1 was significantly associated with pressure to eat at Year 1 (β 0.39; 95 % CI 0.16, 0.61) while COVID-19 impact was not significantly associated with pressure to eat at Year 1. This study, consisting of racially and socioeconomically diverse children, found that while parent stress was significantly associated with increased parental utilization of pressure to eat feeding practice, COVID-19 impact was not significantly associated with pressure to eat in adjusted analyses. This suggests that overall perceived stress by parents could be an important factor in parent pressuring feeding practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Frequent premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) have been associated with cardiovascular disease and mortality. Their prevalence, especially in ambulatory populations, is understudied and limited by few female participants and the use of short-duration (24- to 48-hour) monitoring., Objective: The objective of this study was to report the prevalence of frequent PVCs and NSVT in a community-based population of women likely to undergo electrocardiogram (ECG) screening by sequential patch monitoring., Methods: Participants from the Women's Health Initiative Strong and Healthy (WHISH) trial with no history of atrial fibrillation (AF) but 5-year predicted risk of incident AF ≥5% by CHARGE-AF score were randomly selected to undergo screening with 7-day ECG patch monitors at baseline, 6 months, and 12 months. Recordings were reviewed for PVCs and NSVT (>5 beats); data were analyzed with multivariate regression models., Results: There were 1067 participants who underwent ECG screening at baseline, 866 at 6 months, and 777 at 12 months. Frequent PVCs were found on at least 1 patch from 4.3% of participants, and 1 or more episodes of NSVT were found in 12 (1.1%) women. PVC frequency directly correlated with CHARGE-AF score and NSVT on any patch. Detection of frequent PVCs increased with sequential monitoring., Conclusion: In postmenopausal women at high risk for AF, frequent PVCs were relatively common (4.3%) and correlated with higher CHARGE-AF score. As strategies for AF screening continue to evolve, particularly in those individuals at high risk of AF, the prevalence of incidental ventricular arrhythmias is an important benchmark to guide clinical decision-making., Competing Interests: Disclosures Dr Perez is a consultant for Apple Inc, Boston Scientific, Janssen, Bristol Myers Squibb, and Thryv Inc and has ownership interest in QALY, Inc. Dr Wheeler had prior consulting income from BioTelemetry. Dr Froelicher has stock interest in Cardiac Insight (electrocardiographic patch company employed in this study) and is contracted by Cardiac Insight to develop patch interpretation software. The remaining authors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Controlling feeding practices, such as pressure to eat, are associated with a child's disinhibited eating and extremes in bodyweight. We aimed to explore which factors are associated with parent dyads' pressuring feeding practices, including how mothers and fathers perceive the sharing of household tasks such as mealtime and child feeding responsibilities. In this cross-sectional study, parent dyads (mother and father) of healthy preschool-aged children completed an identical questionnaire consisting of measures of picky eating (food fussiness subscale of Child Eating Behavior Questionnaire), parental concern for undereating, and pressure to eat (Child Feeding Questionnaire). We used separate multivariable linear regression models for mothers and fathers to assess correlates associated with pressure to eat subscale score, including slowness of eating and enjoyment of food, child BMI z-score and race/ethnicity, and household income. Separate unadjusted linear regression models for mothers and fathers were used to report the association of pressure to eat with household responsibilities. Parents (N = 88) had similar mean picky eating, concern for undereating, and pressure to eat scores; more fathers had high pressure to eat scores (36% vs 27%). Higher pressure to eat was significantly associated with lower income, non-Hispanic Black or Black race/ethnicity, slow eating, and lower enjoyment of food. Pressure was not associated with household responsibilities. While there were similar maternal and paternal perceptions of child eating behaviors, more fathers reported pressuring their child to eat. Identifying differences in parental feeding practices may assist in intervention development to improve feeding practices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Patel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Female cancer survivors have a higher chance of experiencing infertility than females without a history of cancer diagnosis. This risk remains high despite advances in fertility treatments. There is a need to augment fertility treatments with cost-effective methods such as nutritional guidance to improve fertility chances. The aim of this review article is to connect the current literature on cancer survivorship nutrition and fertility nutrition, focusing on the importance of integrating nutritional guidance into fertility counseling, assessment, and treatment for female cancer survivors. Consuming a healthful diet comprising whole grains, soy, fruits, vegetables, seafood, and unsaturated fats has improved both female fertility and cancer survivorship. Similarly, maintaining a healthy body weight also improves female fertility and cancer survivorship. Therefore, dietary interventions to support female cancer survivors with fertility challenges are of immense importance. The period of follow-up fertility counseling and assessment after cancer treatment may provide a unique opportunity for implementing nutritional guidance for female cancer survivors. Dietary interventions are a promising strategy to improve pregnancy chances and overall quality of life among female cancer survivors; thus, researchers should investigate perceptions regarding fertility, barriers, and challenges to changing nutrition-related behaviors, and preferences for nutritional guidance to support fertility treatments in this population., (© 2024 The Author(s).)

Interacting with nature may promote mental and physical health. There are multiple ways to interact with nature: indirectly, incidentally, and intentionally. How these types of interactions with nature may be associated with mental and physical health status and health behaviors is unclear. The purpose of this narrative review is to (1) describe the relationship between interactions with nature (indirect, incidental, and intentional) and mental and physical health outcomes and behaviors, (2) identify gaps in the literature, and (3) provide recommendations for future research. Considerable evidence suggests that interacting with nature, indirectly and intentionally, is associated with improvements in mental health and physical exhibitions of mental status. Furthermore, intentionally interacting with nature is associated with engagement in physical activity and gardening is associated with fruit and vegetable consumption. Research suggests that incidentally interacting with nature may be associated with positive mental health status. More research is needed to understand the relationships between incidental interactions with nature and physical health status and behaviors; as well as among all types of interactions with nature and physical health disorders, sleep, and dietary behaviors.

Background and Objectives: Little is known about the role of radon in the epidemiology of stroke among women. We therefore examined the association between home radon exposure and risk of stroke among middle-aged and older women in the United States., Methods: We conducted a prospective cohort study of postmenopausal women aged 50-79 years at baseline (1993-1998) in the Women's Health Initiative. We measured exposures as 2-day, indoor, lowest living-level average radon concentrations in picocuries per liter (pCi/L) as estimated in 1993 by the US Geological Survey and reviewed by the Association of American State Geologists under the Indoor Radon Abatement Act. We used Cox proportional hazards models to estimate risk of incident, neurologist-adjudicated stroke during follow-up through 2020 as a hazard ratio and 95% CI, adjusting for study design and participant demographic, social, behavioral, and clinical characteristics., Results: Among 158,910 women without stroke at baseline (mean age 63.2 years; 83% white), 6,979 incident strokes were identified over follow-up (mean 13.4 years). Incidence rates were 333, 343, and 349 strokes per 100,000 woman-years at radon concentrations of <2, 2-4, and >4 pCi/L, respectively. Compared with women living at concentrations <2 pCi/L, those at 2-4 and >4 pCi/L had higher covariate-adjusted risks of incident stroke: hazard ratio (95% CI) 1.06 (0.99-1.13) and 1.14 (1.05-1.22). Using nonlinear spline functions to model radon, stroke risk was significantly elevated at concentrations ranging from 2 to 4 pCi/L ( p = 0.0004), that is, below the United States Environmental Protection Agency Radon Action Level for mitigation (4 pCi/L). Associations were slightly stronger for ischemic (especially cardioembolic, small vessel occlusive, and large artery atherosclerotic) than hemorrhagic stroke, but otherwise robust in sensitivity analyses., Discussion: Radon exposure is associated with moderately increased stroke risk among middle-aged and older women in the United States, suggesting that promulgation of a lower Radon Action Level may help reduce the domestic impact of cerebrovascular disease on public health.

Background: Lifestyle Africa is an adapted version of the Diabetes Prevention Program designed for delivery by community health workers to socioeconomically disadvantaged populations in low- and middle-income countries (LMICs). Results from the Lifestyle Africa trial conducted in an under-resourced community in South Africa indicated that the programme had a significant effect on reducing haemoglobin A1c (HbA1c)., Objective: To estimate the cost of implementation and the cost-effectiveness (in cost per point reduction in HbA1c) of the Lifestyle Africa programme to inform decision-makers of the resources required and the value of this intervention., Methods: Interviews were held with project administrators to identify the activities and resources required to implement the intervention. A direct-measure micro-costing approach was used to determine the number of units and unit cost for each resource. The incremental cost per one point improvement in HbA1c was calculated., Results: The intervention equated to 71 United States dollars (USD) in implementation costs per participant and a 0.26 improvement in HbA1c per participant., Conclusions: Lifestyle Africa reduced HbA1c for relatively little cost and holds promise for addressing chronic disease in LMIC. Decision-makers should consider the comparative clinical effectiveness and cost-effectiveness of this intervention when making resource allocation decisions., Trial Registration: Trial registration is at ClinicalTrials.gov (NCT03342274).

Subclinical liver impairment due to fibrosis could influence the development and detectability of prostate cancer. To investigate the association between liver fibrosis and prostate cancer incidence and mortality, we included 5,284 men (mean age: 57.6 years, 20.1% Black) without cancer or liver disease at Visit 2 in the Atherosclerosis Risk in Communities study. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index, fibrosis 4 index (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). Over 25 years, 215 Black and 511 White men were diagnosed with prostate cancer, and 26 Black and 51 White men died from the disease. We estimated HRs for total and fatal prostate cancer using Cox regression. FIB-4 [quintile 5 vs. 1: HR = 0.47, 95% confidence interval (CI): 0.29-0.77, Ptrend = 0.004] and NFS (HR = 0.56, 95% CI: 0.33-0.97, Ptrend = 0.03) were inversely associated with prostate cancer risk in Black men. Compared with no abnormal score, men with ≥1 abnormal score had a lower prostate cancer risk if they were Black (HR = 0.46, 95% CI: 0.24-0.89), but not White (HR = 1.04, 95% CI: 0.69-1.58). Liver fibrosis scores did not appear to be associated with fatal prostate cancer in Black or White men. Among men without a clinical diagnosis of liver disease, higher liver fibrosis scores were associated with lower incidence of prostate cancer in Black men, but not in White men, and not with fatal prostate cancer in either race. Further research is needed to understand the influence of subclinical liver disease on prostate cancer development versus detectability and the racial differences observed., Prevention Relevance: Investigating the link between liver fibrosis and prostate cancer risk and mortality, our study reveals the potential influence of liver health on prostate cancer development and on detection using PSA test, urging further research to understand the differential findings by race and to optimize prevention and intervention strategies., (©2023 American Association for Cancer Research.)

Adequate dietary quality is necessary for children's appropriate development and may be influenced by family factors. This study with 24 healthy 3-5-year-old children assessed the associations of parental stress and household food insecurity (HFI) with a child's dietary quality. Parents completed three 24 h dietary recalls, and the Healthy Eating Index was calculated to assess dietary quality. Parents also completed a questionnaire, including The Perceived Stress Scale (assessing overall parental stress) and the Hunger Vital Sign screen (assessing HFI). Children's height/weight were measured, and BMIz was calculated. Separate multivariable linear regression models assessed the association of dietary quality components with HFI and parental stress, adjusting for household income, child sex, and child BMI z-score. In bivariate analyses, children with HFI consumed more added sugars, and parental stress was associated with the child's greens/beans intake. In multivariable analysis, HFI was associated with lower total protein scores and higher added sugar intake, while parental stress was associated with lower greens/beans intake. Higher household income was associated with higher total vegetable and sodium intake, and children with a higher BMIz had a lower total protein intake. Parental stress and HFI can impact a child's dietary quality; providers should counsel families on strategies to improve diet quality.

Background: Household food insecurity (HFI) is associated with poor general and mental health. Prior studies assessed parent and child mental health separately and did not assess other social risks., Objective: To assess the relationship between HFI and both parental and child mental health., Methods: Parents of 3-5-year-old children completed validated measures of food insecurity and mental health. Separate linear regression models were used for unadjusted analysis for each mental health outcome (parent depression, anxiety, and stress, and child mental health). Multivariable analysis was performed using hierarchical regression to adjust for relevant covariates., Results: Children (n = 335) were racially and socioeconomically diverse. HFI was reported in 10% of participants. HFI was associated with worse parent depression and stress in unadjusted analyses; however, after adjusting for covariates, the associations became insignificant. HFI was significantly associated with worse child mental health in unadjusted and multivariable analysis (aβ 2.24, 95% CI 0.59-3.88) compared to those without HFI., Conclusion: HFI was not associated with parental mental health outcomes when other social risks were included in the analyses; however, HFI was significantly associated with worse childhood mental health in all analyses. Pediatric providers should screen for and develop interventions to target both HFI and mental health., Impact: Household food insecurity was associated with worse parent depression and stress in unadjusted analyses; however, after adjusting for other social risks, the associations became insignificant. Household food insecurity was significantly associated with worse child mental health, even after adjusting for demographics, other social risks, and parent mental health. Social risks are differentially associated with parent and child mental health. Understanding the complexities of family stressors can help better support parents and children struggling with mental health problems and social risks., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Ovarian dysfunction increases risk for chronic diseases of aging including cardiovascular disease, depression, cognitive impairment, as well as bone and muscle loss which promote frailty. Psychosocial stress can disrupt ovarian function, and recent observations suggest that consumption of a Western Diet may also. Determination of causal relationships among diet, psychosocial stress, and ovarian physiology is difficult in humans. Long-tailed (a.k.a. cynomolgus) macaques (Macaca fascicularis) are an excellent translational model for the study of diet and psychosocial effects on ovarian physiology and aging-related processes. They have 28-day menstrual cycles with hormonal fluctuations like those of women, and similar physiologic responses to alterations and/or cessation of cyclicity. We examined ovarian function in 38 middle-aged socially housed females fed either a Western or Mediterranean diet for 31 months (≈ a 9-year period for humans). During the last year, we examined cycle length and peak progesterone per cycle using blood sampling (3/week) and vaginal swabbing for menses (6/week). Repeated measures analysis revealed a circannual pattern consistent with increased menstrual cycle disturbance during the late Summer and early Fall (F(11,348)= 4.05 p < 0.001). In addition, both Western diet (F(1,34)= 3.99; p = 0.05) and the stress of low social status (F(1,34)= 3.99; p = 0.04) reduced mean progesterone levels. Thus, on average, subordinates in the Western group had the lowest average progesterone levels (10.02 ng/pl). Compared to Western diets, Mediterranean diets exhibited protective effects via menstrual cycle regularity. For dominant monkeys, consuming Mediterranean diets resulted in significantly greater likelihood of having regular menstrual cycles. Mediterranean diets also protected individuals from shorter than normal menstrual cycles. The relationships between diet and menstrual regularity were partially mediated by both adrenal reactivity and social isolation. This study demonstrates the additive negative effects of poor diet and psychosocial stress on ovarian physiology in mid-life and lays the groundwork for future investigations to uncover their impact on metabolic signatures of accelerated aging. The results also suggest that - compared to Western-style diets - a Mediterranean diet may exert a protective influence against ovarian dysfunction and its pathologic sequelae., Competing Interests: Declaration of Competing Interest The authors have no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk., (© 2023. The Author(s).)

Introduction: Polyunsaturated fatty acids (PUFA) and highly unsaturated fatty acid (HUFA) synthetic products and their signaling metabolites play vital roles in immunity, inflammation, and brain development/function. Frequency differences of variants within the fatty acid desaturase ( FADS ) gene cluster affect levels of HUFAs, their biologically active products, and numerous physiological phenotypes. Fundamental questions remain regarding the impact of this genetic variation on the health of Hispanic/Latino populations., Methods: Data and biospecimens (plasma, red blood cells, buffy coat-derived DNA) from 135 participants (83.7% female) were used to assess the relationship(s) between dietary PUFA levels, a FADS haplotype tagging SNP, rs174537, and the capacity of Hispanic/Latino populations to generate HUFAs in plasma and RBC as well as its potential impact on anthropomorphic phenotypes., Results: The dietary habits of the cohort showed that participant diets contained a high ratio (9.3 ± 0.2, mean ± SEM) of linoleic acid ( n -6) to alpha-linolenic acid ( n -3) and also contained extremely low levels of n -3 HUFAs (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA), both features of the Modern Western Diet. Compared to African and European American cohorts, the frequency of the TT rs174537 genotype was highly enriched (53% of subjects) in this Hispanic/Latino cohort and was strongly associated with lower circulating HUFA levels. For example, plasma levels of arachidonic acid (ARA: 20:4, n -6) and EPA (20:5, n -3) were 37% and 23%, respectively, lower in the TT versus the GG genotype. HUFA biosynthetic efficiency, as determined by metabolic product to precursor ratios, was highly dependent ( p  < 0.0001) on the rs174537 genotype (GG > GT > TT) for both circulating n -6 and n -3 HUFAs. In contrast, the RBC Omega-3 Index (EPA + DHA) was extremely low (2.89 ± 1.65, mean ± sd) in this population and independent of rs174537 genotype. Importantly, the rs174537 genotype was also related to female height with TT genotype participants being 4.5 cm shorter ( p  = 0.0001) than the GG + GT participants., Discussion: Taken together, this study illustrates that dietary PUFA + HUFA ×  FADS gene- interactions place a large proportion (>50%) of Hispanic/Latino populations at high risk of a deficiency in both circulating and cellular levels of n -3 HUFAs., Competing Interests: FC is a co-founder of a start-up company TyrianOmega, which focuses on the production of omega-3 PUFAs by cyanobacteria, largely for animal feeds and aquaculture. He is also the co-founder of Resonance Pharma, which focuses on determining clinical level of and inhibitors that block secreted phospholipase A2 isoforms. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sergeant, Keith, Seeds, Legins, Young, Vitolins and Chilton.)

Introduction: Young women diagnosed with cancer are at an increased risk for infertility compared to women without a cancer diagnosis. Consuming a healthful diet comprised of whole grains, fruits, vegetables, and unsaturated fats has been found to improve both fertility and cancer survivorship. Given this reason, dietary interventions tailored to support female cancer survivors with fertility challenges are of immense importance. Therefore, the aim of this study was to explore barriers and facilitators to healthful nutrition among female cancer survivors with fertility challenges, to inform the development of dietary interventions for this population., Methods: Using a formative research design, interview, survey, and dietary intake data were collected from 20 female cancer survivors of reproductive age. Participant-check focus group discussions were conducted to validate findings. All interviews were recorded and transcribed verbatim. Transcripts were coded and analyzed using a thematic analysis approach. Quantitative data were analyzed using means, standard deviations, ranges, frequencies, and percentages., Results: The average age of respondents was 31.47 ± 3.5 years and the average BMI was 24.78 ± 4.1 kg/m 2 . All participants were college educated, 45% identified as White, 50% as Black, and 10% as Hispanic or Latinx. Cancer diagnoses included breast, thyroid, ovarian, leukemia, and gastrointestinal cancers. The following themes were identified: (1) Lack of nutrition-related resources and detailed guidance, (2) Work-life balance, (3) Perceived rigidity of dietary guidance, (4) Treatment-related fatigue, (5) Having trust in healthcare providers, (6) Higher motivation to change nutrition behavior, and (7) Recognizing the additional benefits of nutrition., Conclusion: These findings indicate a sought-after yet unmet need for post-cancer treatment fertility nutrition recommendations. Interventions should be tailored to women's needs and focus on improving their self-efficacy to make healthful dietary choices.

Objective: Parents' concerns about their child's feeding may lead parents to pressure their child to eat, which may lead to a greater risk for obesity. We aimed to assess if parental concerns for picky eating and undereating are associated with pressure to eat and increased child BMI z-score (BMIz)., Methods: We performed a cross-sectional study of 328 parents of healthy preschoolers assessing parent concerns about picky eating (Child Eating Behavior Questionnaire) and child undereating ("Are you concerned …doesn't eat enough?"), parent pressure to eat (Child Feeding Questionnaire), and covariates. Dyads' heights and weights were measured. Structural equation modeling (SEM) was performed to examine the relationships between parental concerns, pressure to eat, and child BMIz. Measurement models were tested and refined, and the structural model was tested. Model fit was determined using multiple goodness-of-fit indices., Results: Dyads were racially and socioeconomically diverse. The SEM model demonstrated good goodness-of-fit. Children who were perceived as not eating enough had significantly higher picky eating scores (β 0.756; p < 0.001). Parents had higher pressure to eat scores if children were more picky (β 0.148; p = 0.02) or were perceived as not eating enough (β 0.654; p < 0.001). Parental pressure to eat was not associated with the child's BMIz., Conclusions: In a cohort of diverse preschoolers, parent concerns about eating were associated with increased pressure to eat, but pressure to eat was not associated with BMIz. Identifying these relationships is important to develop effective interventions to improve feeding practices in young children., Competing Interests: Conflicts of interests The authors have no competing interests to disclose., (Copyright © 2022 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short-term well-controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel-arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free-living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [-0.024 L, 0.058 L], P =0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high-sensitivity C-reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low-density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low-density lipoprotein concentrations, and total cholesterol:high-density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free-living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

Background: Low- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of "Lifestyle Africa," an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care., Methods and Findings: Participants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body mass index (BMI) ≥ 25 kg/m2 who were members of existing social support groups or "clubs" receiving health services from local nongovernmental organizations (NGOs) were enrolled in a cluster randomized controlled trial that compared Lifestyle Africa (the intervention condition) to usual care (the control condition). The Lifestyle Africa intervention consisted of 17 video-based group sessions delivered by trained community health workers (CHWs). Clusters were randomized using a numbered list of the CHWs and their assigned clubs based on a computer-based random allocation scheme. CHWs, participants, and research team members could not be blinded to condition. Percentage weight loss (primary outcome), hemoglobin A1c (HbA1c), blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol were assessed 7 to 9 months after enrollment. An individual-level intention-to-treat analysis was conducted adjusting for clustering within clubs and baseline values. Trial registration is at ClinicalTrials.gov (NCT03342274). Between February 2018 and May 2019, 782 individuals were screened, and 494 were enrolled. Participants were predominantly retired (57% were receiving a pension) and female (89%) with a mean age of 68 years. Participants from 28 clusters were allocated to Lifestyle Africa (15, n = 240) or usual care (13, n = 254). Fidelity assessments indicated that the intervention was generally delivered as intended. The modal number of sessions held across all clubs was 17, and the mean attendance of participants across all sessions was 61%. Outcome assessment was completed by 215 (90%) intervention and 223 (88%) control participants. Intent-to-treat analyses utilizing multilevel modeling included all randomized participants. Mean weight change (primary outcome) was -0.61% (95% confidence interval (CI) = -1.22, -0.01) in Lifestyle Africa and -0.44% (95% CI = -1.06, 0.18) in control with no significant difference (group difference = -0.17%; 95% CI = -1.04, 0.71; p = 0.71). However, HbA1c was significantly lower at follow-up in Lifestyle Africa compared to the usual care group (mean difference = -0.24, 95% CI = -0.39, -0.09, p = 0.001). None of the other secondary outcomes differed at follow-up: systolic blood pressure (group difference = -1.36; 95% CI = -6.92, 4.21; p = 0.63), diastolic blood pressure (group difference = -0.39; 95% CI = -3.25, 2.30; p = 0.78), LDL (group difference = -0.07; 95% CI = -0.19, 0.05; p = 0.26), triglycerides (group difference = -0.02; 95% CI = -0.20, 0.16; p = 0.80). There were no unanticipated problems and serious adverse events were rare, unrelated to the intervention, and similar across groups (11 in Lifestyle Africa versus 13 in usual care). Limitations of the study include the lack of a rigorous dietary intake measure and the high representation of older women., Conclusions: In this study, we found that Lifestyle Africa was feasible for CHWs to deliver and, although it had no effect on the primary outcome of weight loss or secondary outcomes of blood pressure or triglycerides, it had an apparent small significant effect on HbA1c. The study demonstrates the potential feasibility of CHWs to deliver a program without expert involvement by utilizing video-based sessions. The intervention may hold promise for addressing cardiovascular disease (CVD) and diabetes at scale in LMICs., Trial Registration: ClinicalTrials.gov NCT03342274., Competing Interests: The authors have declared that no competing interests exist.

Background Food insecurity (FI) has been associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk; however, the pathways by which FI leads to worse cardiovascular health are unknown. We tested the hypothesis that FI is associated with ASCVD risk through nutritional/anthropometric (eg, worse diet quality and increased weight), psychological/mental health (eg, increased depressive symptoms and risk of substance abuse), and access to care pathways. Methods and Results We conducted a cross-sectional study of adults (aged 40-79 years) using the 2007 to 2016 National Health and Nutrition Examination Survey. Our primary exposure was household FI, and our outcome was 10-year ASCVD risk categorized as low (<5%), borderline (≥5% -<7.5%), intermediate (≥7.5%-<20%), and high risk (≥20%). We used structural equation modeling to evaluate the pathways and multiple mediation analysis to determine direct and indirect effects. Of the 12 429 participants, 2231 (18.0%) reported living in a food-insecure household; 5326 (42.9%) had a low ASCVD risk score, 1402 (11.3%) borderline, 3606 (29.0%) intermediate, and 2095 (16.9%) had a high-risk score. In structural models, we found significant path coefficients between FI and the nutrition/anthropometric (β, 0.130; SE, 0.027; P <0.001), psychological/mental health (β, 0.612; SE, 0.043; P <0.001), and access to care (β, 0.110; SE, 0.036; P =0.002) pathways. We did not find a significant direct effect of FI on ASCVD risk, and the nutrition, psychological, and access to care pathways accounted for 31.6%, 43.9%, and 15.8% of the association, respectively. Conclusions We found that the association between FI and ASCVD risk category was mediated through the nutrition/anthropometric, psychological/mental health, and access to care pathways. Interventions that address all 3 pathways may be needed to mitigate the negative impact of FI on cardiovascular disease.

Background The plant-based Dietary Portfolio combines established cholesterol-lowering foods (plant protein, nuts, viscous fiber, and phytosterols), plus monounsaturated fat, and has been shown to improve low-density lipoprotein cholesterol and other cardiovascular disease (CVD) risk factors. No studies have evaluated the relation of the Dietary Portfolio with incident CVD events. Methods and Results We followed 123 330 postmenopausal women initially free of CVD in the Women's Health Initiative from 1993 through 2017. We used Cox proportional-hazard models to estimate adjusted hazard ratios (HRs) and 95% CI of the association of adherence to a Portfolio Diet score with CVD outcomes. Primary outcomes were total CVD, coronary heart disease, and stroke. Secondary outcomes were heart failure and atrial fibrillation. Over a mean follow-up of 15.3 years, 13 365 total CVD, 5640 coronary heart disease, 4440 strokes, 1907 heart failure, and 929 atrial fibrillation events occurred. After multiple adjustments, adherence to the Portfolio Diet score was associated with lower risk of total CVD (HR, 0.89; 95% CI, 0.83-0.94), coronary heart disease (HR, 0.86; 95% CI, 0.78-0.95), and heart failure (HR, 0.83; 95% CI, 0.71-0.99), comparing the highest to lowest quartile of adherence. There was no association with stroke (HR, 0.97; 95% CI, 0.87-1.08) or atrial fibrillation (HR, 1.10; 95% CI, 0.87-1.38). These results remained statistically significant after several sensitivity analyses. Conclusions In this prospective cohort of postmenopausal women in the United States, higher adherence to the Portfolio Diet was associated with a reduction in incident cardiovascular and coronary events, as well as heart failure. These findings warrant further investigation in other populations.

Background: Triple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women's Health Initiative., Methods: Five hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status., Results: Of the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components., Conclusions: Postmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death., (© 2020 American Cancer Society.)

Introduction: Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer's disease (AD), have been reported, but causal relationships are difficult to determine in human studies., Methods: We used structural magnetic resonance imaging in a well-validated non-human primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean vs Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and 20 individual regions of interest (ROIs)., Results: Western diet resulted in greater cortical thicknesses, total brain volumes, and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants., Discussion: The observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathology, whereas the Mediterranean diet may protect the brain., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Objectives: To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs)., Methods: Data were included from 70,750 NHW and NHB postmenopausal women from the Women's Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline., Results: In both crude and adjusted models, NHBs were more likely to experience ≥10% weight gain than NHWs within the same category of baseline weight status. Moreover, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain in both crude and adjusted models. Age-stratified results were consistent with overall findings. In all age categories, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain. Based on the results of adjusted models, the joint influence of NHB race/ethnicity and weight status on risk of postmenopausal weight gain was both sub-additive and sub-multiplicative., Conclusion: NHBs are more likely to experience postmenopausal weight gain than NHWs, and the disparity in risk is most pronounced among those who are normal weight at baseline. To address the disparity in postmenopausal obesity, future studies should focus on identifying and modifying factors that promote weight gain among normal weight NHBs., Competing Interests: CEB is employed by the RAND Corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Persistent psychological stress increases the risk of many chronic diseases of aging. Little progress has been made to effectively reduce stress responses or mitigate stress effects suggesting a need for better understanding of factors that influence stress responses. Limited evidence suggests that diet may be a factor in modifying the effects of stress. However, long-term studies of diet effects on stress reactive systems are not available, and controlled randomized clinical trials are difficult and costly. Here we report the outcomes of a controlled, randomized preclinical trial of the effects of long-term consumption (31 months, ~ equivalent to 9 human years) of Western versus Mediterranean - like diets on behavioral and physiological responses to acute (brief social separation) and chronic (social subordination) psychosocial stress in 38 adult, socially-housed, female cynomolgus macaques. Compared to animals fed a Western diet, those fed the Mediterranean diet exhibited enhanced stress resilience as indicated by lower sympathetic activity, brisker and more overt heart rate responses to acute stress, more rapid recovery, and lower cortisol responses to acute psychological stress and adrenocorticotropin (ACTH) challenge. Furthermore, age-related increases in sympathetic activity and cortisol responses to stress were delayed by the Mediterranean diet. Population level diet modification in humans has been shown to be feasible. Our findings suggest that population-wide adoption of a Mediterranean-like diet pattern may provide a cost-effective intervention on psychological stress and promote healthy aging with the potential for widespread efficacy., Competing Interests: None., (© 2020 Published by Elsevier Inc.)

Background: Insulin resistance is associated with higher all-cause and cancer-specific mortality in postmenopausal women. However, to the authors' knowledge, information regarding insulin resistance and breast cancer mortality risk is limited. Therefore, the authors examined associations between insulin resistance and breast cancer incidence and mortality in a subsample of Women's Health Initiative participants., Methods: A total of 22,837 postmenopausal women with fasting baseline glucose and insulin levels were followed for incident breast cancer and breast cancer mortality. Breast cancers were verified by medical record review and serial National Death Index linkage-enhanced mortality findings. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) with 95% confidence intervals (95% CIs) for quartile comparisons. Outcomes included breast cancer incidence, deaths from breast cancer, and deaths after breast cancer (breast cancer followed by death from any cause)., Results: During a median of 19.8 years of follow-up of 1328 breast cancer cases, there were 512 deaths reported, 151 of which were from breast cancer. Breast cancer incidence was higher in women in the highest HOMA-IR quartile (HR, 1.34; 95% CI, 1.12-1.61 [P for trend = .003]). Although HOMA-IR was not found to be associated with risk of death from breast cancer (HR, 1.04; 95% CI, 0.60-1.79), women in the highest versus those in the lowest HOMA-IR quartile were at a higher risk of death after breast cancer (HR, 1.78; 95% CI, 1.32-2.39 [P for trend <.001])., Conclusions: Higher levels of insulin resistance in postmenopausal women are associated with higher breast cancer incidence and higher all-cause mortality after breast cancer., (© 2020 American Cancer Society.)

Background: Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer., Materials and Methods: In a cohort of 56,997 Women's Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer., Results: Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23)., Conclusion: These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors., Implications for Practice: Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population., (© AlphaMed Press 2020.)

Purpose: It has been hypothesized that selenium (Se) can prevent cancer, and that Se deficiency may be associated with an increased risk of breast cancer. However, findings from epidemiological studies have been inconsistent. The objective of this study was to assess the association between Se intake and risk of breast cancer in the Women's Health Initiative (WHI)., Methods: This study included 145,033 postmenopausal women 50-79 years who completed baseline questionnaires between October 1993 and December 1998, which addressed dietary and supplemental Se intake and breast cancer risk factors. The association between baseline Se intake and incident breast cancer was examined in Cox proportional hazards analysis., Results: During a mean follow-up of 15.5 years, 9487 cases of invasive breast cancer were identified. Total Se (highest versus lowest quartile: HR 1.00, 95% CI 0.92-1.09, P trend  = 0.66), dietary Se (highest versus lowest quartile: HR 0.99, 95% CI 0.89-1.08, P trend  = 0.61), and supplemental Se (yes versus no: HR 0.99, 95% CI 0.95-1.03) were not associated with breast cancer incidence., Conclusions: This study indicates that Se intake is not associated with incident breast cancer among postmenopausal women in the United States. Further studies are needed to confirm our findings by using biomarkers such as toenail Se to reduce the potential for misclassification of Se status.