Clues for Early Diagnosis of MEN2B Syndrome Before Medullary Thyroid Carcinoma.

Early onset medullary thyroid carcinoma, later pheochromocytomas, and nonspecific extra-endocrine features (hypermobility and persistent constipation) are part of the clinical phenotype of Multiple Endocrine Neoplasia type 2B (MEN2B). A de novo pathogenic M918T variant in the rearranged during transfection proto-oncogene is usually identified. Affected children are often seen by multiple clinicians over a long period before consideration of a diagnosis of MEN2B, with metastatic medullary thyroid carcinoma often the precipitator. We describe the clinical presentation and course of 5 children ultimately diagnosed with MEN2B in New South Wales and the Australian Capital Territory, Australia between 1989 and 2021. All cases had intestinal ganglioneuromatosis that could have prompted an earlier diagnosis. Population wide newborn genomic screening for rare diseases is on the horizon. We propose that MEN2B genomic screening should be included in newborn screening programs and that careful exclusion of intestinal ganglioneuromatosis would allow earlier identification leading to improved clinical outcomes.

Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

Acylcarnitines are associated with lower depressive symptomatology in a mainland puerto rican cohort.

INTRODUCTION: Recent studies have implicated acetyl-L-carnitine as well as other acylcarnitines in depression. To our knowledge, no untargeted metabolomics studies have been conducted among US mainland Puerto Ricans. OBJECTIVES: We conducted untargeted metabolomic profiling on plasma from 736 participants of the Boston Puerto Rican Health Study. METHODS: Using Weighted Gene Co-expression Network Analysis, we identified metabolite modules associated with depressive symptomatology, assessed via the Center for Epidemiologic Studies Depression scale. We identified metabolites contributing to these modules and assessed the relationship between these metabolites and depressive symptomatology. RESULTS: 621 annotated metabolites clustered into eight metabolite modules, of which one, the acylcarnitine module, was significantly inversely associated with depressive symptomatology (ß = - 27.7 (95% CI (- 54.5-0.8); p = 0.043). Several metabolite hub features in the acylcarnitine module were significantly associated with depressive symptomatology, after correction for multiple comparisons. CONCLUSIONS: In this untargeted plasma metabolomics study among mainland Puerto Rican older adults, acylcarnitines, as a metabolite module were inversely associated with depressive symptomatology.

Magnesium and Cognitive Health in Adults: A Systematic Review and Meta-Analysis.

Magnesium (Mg) plays a key role in neurological functioning and manifestations. However, the evidence from randomized controlled trials (RCTs) and cohorts on Mg and cognitive health among adults has not been systematically reviewed. We aimed to examine the associations of various Mg forms (supplements, dietary intake, and biomarkers) with cognitive outcomes by summarizing evidence from RCTs and cohorts. PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for relevant peer-reviewed articles published up to May 3, 2024. Three random-effects models were performed, when appropriate, to evaluate the relationship between Mg and cognitive outcomes: 1) linear meta-regression, 2) nonlinear (quadratic) meta-regression, and 3) meta-analysis using Mg variables categorized based on pre-existing recommendations. Three RCTs and 12 cohort studies were included in this systematic review. Evidence from the limited number of RCTs was insufficient to draw conclusions on the effects of Mg supplements. Cohort studies showed inconsistent dose-response relationships between dietary Mg and cognitive disorders, with high heterogeneity across populations. However, consistent U-shape associations of serum Mg with all-cause dementia and cognitive impairment were found in cohorts, suggesting an optimal serum Mg concentration of ∼0.85 mmol/L. This nonlinear association was detected in meta-regression (Pquadratic = 0.003) and in meta-analysis based on the reference interval of serum Mg (0.75-0.95 mmol/L) [<0.75 compared with 0.85 mmol/L: pooled hazard ratio (HR) = 1.43; 95% confidence interval (CI) = 1.05, 1.93; >0.95 compared with 0.85 mmol/L: pooled HR = 1.30; 95% CI = 1.03, 1.64]. More evidence from RCTs and cohorts is warranted. Future cohort studies should evaluate various Mg biomarkers and collect repeated measurements of Mg intake over time, considering different sources (diet or supplements) and factors affecting absorption (for example, calcium-to-Mg intake ratio). This systematic review was preregistered in PROSPERO (CRD42023423663).

Disproportionately higher cardiovascular disease risk and incidence with high fructose corn syrup sweetened beverage intake among black young adults-the CARDIA study.

BACKGROUND: The black/white heart disease mortality disparity began increasing in the early 1980's, coincident with the switch from sucrose to high-fructose-corn-syrup/(HFCS) in the US food supply. There has been more fructose in HFCS than generally-recognized-as-safe/GRAS, which has contributed to unprecedented excess-free-fructose/(unpaired-fructose) in foods/beverages. Average- per-capita excess-free-fructose, from HFCS, began exceeding dosages/(5-10 g) that trigger fructose-malabsorption in the early 1980's. Fructose malabsorption contributes to gut-dysbiosis and gut-in-situ-fructosylation of dietary peptides/incretins/(GLP-1/GIP) which forms atherosclerotic advanced-glycation-end-products. Both dysregulate gut endocrine function and are risk factors for cardiovascular disease/(CVD). Limited research shows that African Americans have higher fructose malabsorption prevalence than others. CVD risk begins early in life. METHODS: Coronary-Artery-Risk-Development-in-Adults/(CARDIA) study data beginning in 1985-86 with 2186 Black and 2277 White participants, aged 18-30 y, were used to test the hypothesis that HFCS sweetened beverage intake increases CVD risk/incidence, more among Black than White young adults, and at lower intakes; while orange juice-a low excess-free-fructose juice with comparable total sugars and total fructose, but a 1:1 fructose-to-glucose-ratio, i.e., low excess-free-fructose, does not. Cox proportional hazards models were used to calculate hazard ratios. RESULTS: HFCS sweetened beverage intake was associated with higher CVD risk (HR = 1.7) than smoking (HR = 1.6). CVD risk was higher at lower HFCS sweetened beverage intake among Black than White participants. Intake, as low as 3 times/wk, was associated with twice the CVD risk vs. less frequent/never, among Black participants only (HR 2.1, 95% CI 1.2-3.7; P = 0.013). Probability of an ordered relationship approached significance. Among Black participants, CVD incidence jumped 62% from 59.8/1000, among ≤ 2-times/wk, to 96.9/1000 among 3-6 times/wk consumers. Among White participants, CVD incidence increased from 37.6/1000, among ≤ 1.5-times/wk, to 41.1/1000, among 2 times/wk-once/d - a 9% increase. Hypertension was highest among Black daily HFCS sweetened beverage consumers. CONCLUSION: The ubiquitous presence of HFCS over-the-past-40 years, at higher fructose-to-glucose ratios than generally-recognized-as-safe, may have contributed to CVD racial disparities, due to higher fructose-malabsorption prevalence among Black individuals, unpaired/excess-free-fructose induced gut dysbiosis and gut fructosylation of dietary peptides/incretins (GLP-1/GIP). These disturbances contribute to atherosclerotic plaque; promote incretin insufficiency/dysregulation/altered satiety/dysglycemia; decrease protective microbiota metabolites; and increase hypertension, CVD morbidity and mortality.

Agreement Between the National Cancer Institute's diet history questionnaire II and III in a preconception cohort.

Food frequency questionnaires require updating over time, due to population changes in diet, posing analytical challenges in consistently measuring diet in prospective studies. We compared reliability and agreement between nutrients in two versions of the National Cancer Institute's web-based Diet History Questionnaire (DHQ, III vs. II) in an ongoing North American preconception study. We invited 51 consecutively-enrolled U.S. female participants aged 21-45 years to complete both DHQ versions within a 2-week period, in a randomized order. We compared 30 nutrients from both DHQ versions and calculated within-person reliability using intraclass correlation coefficients (ICCs). Bland-Altman plots and 95% limits of agreement (LOA) were generated to assess nutrient agreement between DHQ versions. We observed highest reliability in percent energy from carbohydrates and cholesterol (ICCs: 0.88; 95% CI: 0.80-0.93) and lowest for percent energy from protein and vitamin D (ICCs: 0.56; 95% CI: 0.34-0.72). At the group level, all nutrients had most observations within the LOA. Bland-Altman plots showed assessment differences between DHQs for protein, fat, monounsaturated fat, and vitamin D. The remaining nutrients showed good agreement and good-to-moderate reliability. Some nutrients may require adjustment and calibration analysis before using them interchangeably across DHQ versions.

Adherence to Mediterranean, Dietary Approaches to Stop Hypertension and Healthy Eating Indices are associated with lower risk of disability among Puerto Rican adults from the longitudinal Boston Puerto Rican Health Study.

BACKGROUND: Emerging evidence suggests that poor dietary quality is an important risk factor for disability. However, few studies have compared adherence to dietary patterns with disability and none among Puerto Rican adults. OBJECTIVES: This study was designed to examine relationships between 3 dietary patterns-including Dietary Approaches to Stop Hypertension (DASH), Mediterranean dietary score (MeDS), and Healthy Eating Index (HEI)-2010-and ∼6-y incidence of activities of daily living (ADL) and instrumental activities of daily living (IADL) disability and to assess potential mediation by handgrip strength. METHODS: Data are from the Boston Puerto Rican Health Study, a longitudinal cohort of Puerto Rican adults aged 45-75 y (N = 1502). Adherence to dietary pattern variables were derived from food frequency questionnaire (FFQ) data averaged at baseline and ∼2 y. Handgrip strength was assessed at baseline. Cox proportional hazards models were used to assess longitudinal associations between DASH, MeDS, and HEI-2010 and incident ∼6-y ADL (and subscales) and IADL disability. Mediation by handgrip strength was also tested. RESULTS: Participants with higher adherence DASH had lower risk of ADL, ADL mobility, and ADL manual dexterity disabilities (hazards ratio [HR]: 0.96; 95% confidence interval [CI]: 0.91, 0.98; HR: 0.96; 95% CI: 0.92, 0.99; and HR: 0.95; 95% CI: 0.92, 0.98, respectively). Higher adherence to MeDS was associated with lower risk of ADL and ADL mobility disabilities (HR: 0.89; 95% CI: 0.81, 0.98; HR: 0.90; 95% CI: 0.82, 1.00), and higher adherence to HEI with lower risk of ADL manual dexterity (HR: 0.98; 95% CI: 0.97, 0.99) in fully adjusted models. Only DASH tended to be associated with IADL (HR: 0.97; 95% CI: 0.94, 1.00). Baseline handgrip strength was a mediator between HEI and ADL manual dexterity (23.7% of the indirect effect was explained through handgrip strength). CONCLUSIONS: Higher adherence to a healthy diet pattern may decrease risk of disability and may be an important prevention strategy for ADL and IADL disability associated with aging.

Healthy Lifestyle and the Likelihood of Becoming a Centenarian.

Importance: Previous studies have reported that lifestyle factors were associated with life expectancy and/or mortality, but most of them studied the middle-aged or older age groups (aged ≥60 years), and few focused on people aged 80 years or older. Objectives: To examine healthy lifestyle and the likelihood of becoming centenarians among people aged 80 years or older in China. Design, Settings, and Participants: Using data from the Chinese Longitudinal Healthy Longevity Survey, a nationally representative and one of the largest prospective cohorts targeting people aged 80 years or older established in 1998, a community-based, prospective nested case-control study was performed. Data were analyzed from December 1, 2022, to April 15, 2024. Exposures: A healthy lifestyle score for 100 (HLS-100, ranging from 0 to 6), including smoking, exercise, and dietary diversity, was constructed, with higher scores indicating potentially better health outcomes. Main Outcomes and Measures: The primary outcome was survivorship to becoming a centenarian by 2018 (the end of follow-up). Information on sociodemographic characteristics, lifestyle factors, and other covariates was collected. Results: The sample comprised 5222 individuals (61.7% women, mean [SD] age, 94.3 [3.3] years), including 1454 identified centenarians and 3768 controls (died before becoming centenarians) matched by age, sex, and year of entry. During a median follow-up of 5 (IQR, 3-7) years, 373 of 1486 individuals among the lowest HLS-100 (0-2) group and 276 of 851 individuals among the highest HLS-100 (5-6) group became centenarians. The adjusted odds ratio (AOR) comparing the highest vs the lowest HLS-100 groups was 1.61 (95% CI, 1.32-1.96; P < .001 for trend). An association was noted when we further treated centenarians with relatively healthy status as the outcome, as evaluated by self-reported chronic conditions, physical and cognitive function, and mental wellness (AOR, 1.54; 95% CI, 1.05-2.26). Similar results were observed in other sensitivity analyses. Conclusions and Relevance: In this case-control study of Chinese older adults, adhering to a healthy lifestyle appears to be important even at late ages, suggesting that constructing strategic plans to improve lifestyle behaviors among all older adults may play a key role in promoting healthy aging and longevity.

Longitudinal associations between biopsychosocial stress indicators and sleep in older Puerto Rican adults.

OBJECTIVES: To examine the association of biopsychosocial stress indicators (perceived stress, perceived discrimination, stressful life events, and allostatic load) with sleep outcomes (sleep duration and insomnia symptoms) and to examine sex and age interactions for associations between stress and sleep in older Puerto Rican adults. METHODS: Secondary analyses were performed with 830 participants (72% female) from wave 2 (2006-2011) of the Boston Puerto Rican Health Study (BPRHS), a prospective population-based cohort study (45-75years at baseline) and Boston Puerto Rican Osteoporosis Study (BPROS) (2007-2012), an ancillary study of the BPRHS. Recruitment occurred in randomly selected census blocks using door-to-door and community-based activities. In-home data collection visits included a baseline assessment and follow-up interviews. Questionnaires assessed perceived stress, discrimination, stressful life events, and sleep. Allostatic load indicators were measured objectively. Regression models controlled for sociodemographic, behavioral, and health factors, with interaction analyses, followed by sex- and sex-by-age-stratified analyses. RESULTS: In the prior 2years, participants with chronic stress had 50% greater odds of reporting nonoptimal sleep duration (<7 or >9 hours). Life events trajectories were significantly related to insomnia symptoms. Men ≥65years who experienced chronic stress had greater insomnia symptoms than women, or than men with low stress or acute stress. CONCLUSIONS: Stressful life events may affect sleep duration and insomnia symptoms among older Puerto Rican adults, particularly men 65 years and older who experienced chronic stress. Given the differences in sleep patterns experienced by older adults and their relationships with health outcomes, identifying methods to support sleep health among those with chronic stress is important.

From ownership to custodianship of tumor biopsy tissue in genomic testing: a mixed methods study of patient views.

Tumor mutation profiling (MP) is often conducted on tissue from biopsies conducted for clinical purposes (diagnostic tissue). We aimed to explore the views of patients with cancer on who should own tumor biopsy tissue, pay for its storage, and decide on its future use; and determine their attitudes to and predictors of undergoing additional biopsies if required for research purposes. In this mixed methods, cross-sectional study, patients with advanced solid cancers enrolled in the Molecular Screening and Therapeutics Program (n = 397) completed a questionnaire prior to undergoing MP (n = 356/397). A subset (n = 23) also completed a qualitative interview. Fifty percent of participants believed they and/or relatives should own and control access to diagnostic tissue. Most (65.5%) believed the government should pay for tissue preparation. Qualitative themes included (1) custodianship of diagnostic tissue, (2) changing value of tissue across time and between cultures, (3) equity regarding payment, and (4) cost-benefit considerations in deciding on additional biopsies. Policy and regulation should consider patient perspectives. Extension of publicly funded health care to include tissue retrieval for clinical trials should be considered.

Association Between Dietary Intake of Phosphorus and Measures of Obesity in the Jackson Heart Study.

BACKGROUND: The relation between phosphorus (P) intake and obesity is equivocal, with hypotheses in both directions. OBJECTIVES: We investigated the relationship between P intake, assessed from a current database, and calculated bioavailable P intake and obesity among African-American adults. METHODS: We examined associations between original and bioavailable P (total, added, and natural) and BMI and waist circumference (WC) in a cross-sectional study of 5306 African-American adults (21-84 y) from the Jackson Heart Study. A total of 3300 participants had complete interviews, valid dietary data, and normal kidney function. Diet was assessed by food frequency questionnaire. A novel algorithm was used to estimate P bioavailability. BMI or WC was regressed on each P variable, adjusting for total energy intake and potential confounders. RESULTS: After adjusting for covariates, original P (total and added) and bioavailable P (total and added) intakes (expressed/100 mg) were associated with BMI (ß: 0.11, 0.67, 0.31, and 0.71, respectively; all P < 0.0001). Neither original nor bioavailable natural P was significantly associated (ß: -0.03 and 0.09, respectively; both P > 0.05). When added and natural P were included in the same model, added P (original and bioavailable) intakes remained strongly associated with BMI (0.70 and 0.73, respectively; both P < 0.0001). Similar results were seen for WC. Intake of original added P tended to be more strongly associated with BMI, in females (ß: 0.72; P < 0.0001) than in males (ß: 0.56; P = 0.003) (P-interaction = 0.06). CONCLUSIONS: We found that greater intake of added, not natural, which may be a proxy for intake of processed foods was associated with higher BMI and WC. These were somewhat stronger when bioavailability was considered and for women than for men. Further investigation is needed to fully understand the mechanisms driving these associations.

Work-Related Cognitive Behavioral Therapy for racially and economically diverse unemployed persons with social anxiety: A randomized clinical trial.

Individuals with Social Anxiety Disorder (SAD) are at risk for employment problems. This multi-site trial examined the efficacy of Work-Related Cognitive Behavioral Therapy provided alongside vocational services as usual (WCBT+VSAU), a group-based treatment designed to improve mental health and employment outcomes for individuals with SAD. Vocational service-seeking participants with SAD (N = 250) were randomized to either WCBT+VSAU or VSAU-alone. Hypotheses were that participants randomized to WCBT+VSAU would report less social anxiety, less depression, and more hours worked than participants randomized to VSAU-alone. WCBT+VSAU participants had significantly greater improvements on the Liebowitz Social Anxiety Scale (LSAS; d=-.25, CI=-0.49 to -0.02, p = .03) at post-assessment compared to VSAU-alone. The conditions did not differ on any variable at later time points or on secondary outcomes. Unexpectedly, participants randomized to VSAU-alone experienced LSAS improvements, similar to WCBT+VASU at later timepoints. Baseline psychological flexibility (beta=-.098 [-0.19-0.008]) and depression (beta=-0.18 [-0.34-0.009]) moderated change in social anxiety. Participants with lower psychological flexibility and higher depression responded more strongly to WCBT+VSAU than VSAU-alone over the duration of the study, suggesting that WCBT+VSAU may particularly benefit those with greater psychopathology. Results indicate that vocational centers are promising settings for treating SAD and employment-focused refinements are likely needed to improve work outcomes.

Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts.

BACKGROUND: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). METHODS: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. RESULTS: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). LIMITATIONS: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. CONCLUSIONS: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

Rapid implementation of blood pressure self-monitoring in pregnancy at a UK NHS Trust during the COVID-19 pandemic: a quality improvement evaluation.

BACKGROUND: This service evaluation describes the rapid implementation of self-monitoring of blood pressure (SMBP) into maternity care at a tertiary referral centre during the COVID-19 pandemic. It summarises findings, identifies knowledge gaps and provides recommendations for further research and practice. INTERVENTION: Pregnant and postpartum women monitored their blood pressure (BP) at home, with instructions on actions to take if their BP exceeded pre-determined thresholds. Some also conducted proteinuria self-testing. DATA COLLECTION AND ANALYSIS: Maternity records, app data and staff feedback were used in interim evaluations to assess process effectiveness and guide adjustments, employing a Plan-Do-Study-Act and root cause analysis approach. RESULTS: Between March 2020 and August 2021, a total of 605 women agreed to self-monitor their BP, including 10 women with limited English. 491 registered for telemonitoring (81.2%). 21 (3.5%) took part in urine self-testing. Engagement was high and increased over time with no safety issues. Biggest concerns related to monitor supply and postnatal monitoring. In December 2020, SMBP was integrated into the standard maternity care pathway. CONCLUSIONS: This project demonstrated successful integration of SMBP into maternity care. Early stakeholder engagement and clear guidance were crucial and community midwifery support essential. Supplying BP monitors throughout pregnancy and post partum could improve the service and fully digitised maternity records would aid data collection. More research is needed on SMBP in the postnatal period and among non-English speakers. These findings support efforts to implement app-supported self-monitoring and guide future research.

Predictors of Health-Related Quality of Life Among Women Participating in an Appointment-Based Cardiac Rehabilitation Program.

BACKGROUND: An alternative patient-centered appointment-based cardiac rehabilitation (CR) program has led to significant improvements in health outcomes for patients with cardiovascular disease. However, less is known about the effects of this approach on health-related quality of life (HRQoL), particularly for women. OBJECTIVE: We examined the effects of a patient-centered appointment-based CR program on HRQoL by sex and examined predictors of HRQoL improvements specifically for women. METHODS: Data were used from an urban single-center CR program at Yale New Haven Health (2012-2017). We collected information on patient demographics, socioeconomic status, and clinical characteristics. The Outcome Short-Form General Health Survey (SF-36) was used to measure HRQoL. We evaluated sex differences in SF-36 scores using t tests and used a multivariate linear regression model to examine predictors of improvements in HRQoL (total SF-36 score) for women. RESULTS: A total of 1530 patients with cardiovascular disease (23.7% women, 4.8% Black; mean age, 64 ± 10.8 years) were enrolled in the CR program. Women were more likely to be older, Black, and separated, divorced, or widowed. Although women had lower total SF-36 scores on CR entry, there was no statistically significant difference in CR adherence or total SF-36 score improvements between sexes. Women who were employed and those with chronic obstructive pulmonary disease were more likely to have improvements in total SF-36 scores. CONCLUSION: Both men and women participating in an appointment-based CR program achieved significant improvements in HRQoL. This approach could be a viable alternative to conventional CR to optimize secondary outcomes for patients.

Metabolites and Cognitive Decline in a Puerto Rican Cohort.

Background: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer's disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans. Objective: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population. Methods: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory. Results: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory. Conclusions: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline.

Association of Gut Microbiota-Related Metabolites and Type 2 Diabetes in Two Puerto Rican Cohorts.

(1) Aims: Gut microbiota metabolites may play integral roles in human metabolism and disease progression. However, evidence for associations between metabolites and cardiometabolic risk factors is sparse, especially in high-risk Hispanic populations. We aimed to evaluate the cross-sectional and longitudinal relationships between gut microbiota related metabolites and measures of glycemia, dyslipidemia, adiposity, and incident type 2 diabetes in two Hispanic observational cohorts. (2) Methods: We included data from 670 participants of the Boston Puerto Rican Health Study (BPRHS) and 999 participants of the San Juan Overweight Adult Longitudinal Study (SOALS). Questionnaires and clinical examinations were conducted over 3 years of follow-up for SOALS and 6 years of follow-up for BPRHS. Plasma metabolites, including L-carnitine, betaine, choline, and trimethylamine N-oxide (TMAO), were measured at baseline in both studies. We used multivariable linear models to evaluate the associations between metabolites and cardiometabolic risk factors and multivariable logistic and Poisson regressions to assess associations with prevalent and incident type 2 diabetes, adjusted for potential confounding factors. Cohort-specific analyses were combined using a fixed-effects meta-analysis. (3) Results: Higher plasma betaine was prospectively associated with lower fasting glucose [-0.97 mg/dL (95% CI: -1.59, -0.34), p = 0.002], lower HbA1c [-0.02% (95% CI: -0.04, -0.01), p = 0.01], lower HOMA-IR [-0.14 (95% CI: -0.23, -0.05), p = 0.003], and lower fasting insulin [-0.27 mcU/mL (95% CI: -0.51, -0.03), p = 0.02]. Betaine was also associated with a 22% lower incidence of type 2 diabetes (IRR: 0.78, 95% CI: 0.65, 0.95). L-carnitine was associated with lower fasting glucose [-0.68 mg/dL (95% CI: -1.29, -0.07), p = 0.03] and lower HbA1c at follow-up [-0.03% (95% CI: -0.05, -0.01), p < 0.001], while TMAO was associated with higher fasting glucose [0.83 mg/dL (95% CI: 0.22, 1.44), p = 0.01] and higher triglycerides [3.52 mg/dL (95% CI: 1.83, 5.20), p < 0.0001]. Neither choline nor TMAO were associated with incident type 2 diabetes. (4) Conclusions: Higher plasma betaine showed consistent associations with a lower risk of glycemia, insulinemia, and type 2 diabetes. However, TMAO, a metabolite of betaine, was associated with higher glucose and lipid concentrations. These observations demonstrate the importance of gut microbiota metabolites for human cardiometabolic health.

Associations among diabetes medication use, serum magnesium, and insulin resistance in a cohort of older Puerto Rican adults.

BACKGROUND: Hypomagnesemia is commonly observed in individuals with diabetes, but how diabetes medications alter magnesium (Mg) status remains unclear. OBJECTIVES: We aimed to examine the association between diabetes medication and hypomagnesemia and evaluate whether serum Mg mediates the association between diabetes medication and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in a prospective cohort. METHODS: Adults from the Boston Puerto Rican Health Study were included (n = 1106). Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for cross-sectional association between diabetes medication and hypomagnesemia (serum Mg <0.75 mmol/L). Longitudinal mediation analysis was performed to evaluate the direct and indirect (via serum Mg) associations between diabetes medication and 4-y HOMA-IR in 341 participants with baseline hemoglobin A1c (HbA1c) of ≥6.5%. RESULTS: Mean age at baseline was 59.0 ± 7.6 y, with 28.0% male and 45.8% with hypomagnesemia. Use of metformin [OR (95% CI) = 3.72 (2.53, 5.48)], sulfonylureas [OR (95% CI) = 1.68 (1.00, 2.83)], and glitazones [OR (95% CI) = 2.09 (1.10, 3.95)], but not insulin, was associated with higher odds of hypomagnesemia. Use of multiple diabetes medications and longer duration of use were associated with higher odds of hypomagnesemia. Serum Mg partially mediated the association between metformin and HOMA-IR [indirect association: ß (95% CI) = 1.11 (0.15, 2.07)], which weakened the direct association [ß (95% CI) = -5.16 (-9.02, -1.30)] by 22% [total association: ß (95% CI) = -4.05 (-7.59, -0.51)]. Similarly, serum Mg mediated 17% of the association between sulfonylureas and elevated HOMA-IR. However, the mediation by serum Mg was weak for insulin and glitazones. CONCLUSIONS: Diabetes medication, especially metformin, was associated with elevated odds of hypomagnesemia, which may weaken the association between metformin and lowering of HOMA-IR. The causal inference needs to be confirmed in further studies.

Perspective: Beyond the Mediterranean Diet-Exploring Latin American, Asian, and African Heritage Diets as Cultural Models of Healthy Eating.

The Mediterranean diet is a well-studied cultural model of healthy eating, yet research on healthy models from other cultures and cuisines has been limited. This perspective article summarizes the components of traditional Latin American, Asian, and African heritage diets, their association with diet quality and markers of health, and implications for nutrition programs and policy. Though these diets differ in specific foods and flavors, we present a common thread that emphasizes healthful plant foods and that is consistent with high dietary quality and low rates of major causes of disability and deaths. In this perspective, we propose that nutrition interventions that incorporate these cultural models of healthy eating show promise, though further research is needed to determine health outcomes and best practices for implementation.

Multidisciplinary approach combining food metabolomics and epidemiology identifies meglutol as an important bioactive metabolite in tempe, an Indonesian fermented food.

This study introduces a multidisciplinary approach to investigate bioactive food metabolites often overlooked due to their low concentrations. We integrated an in-house food metabolite library (n = 494), a human metabolite library (n = 891) from epidemiological studies, and metabolite pharmacological databases to screen for food metabolites with potential bioactivity. We identified six potential metabolites, including meglutol (3-hydroxy-3-methylglutarate), an understudied low-density lipoprotein (LDL)-lowering compound. We further focused on meglutol as a case study to showcase the range of characterizations achievable with this approach. Green pea tempe was identified to contain the highest meglutol concentration (21.8 ± 4.6 mg/100 g). Furthermore, we identified a significant cross-sectional association between plasma meglutol (per 1-standard deviation) and lower LDL cholesterol in two Hispanic adult cohorts (n = 1,628) (ß [standard error]: -5.5 (1.6) mg/dl, P = 0.0005). These findings highlight how multidisciplinary metabolomics can serve as a systematic tool for discovering and enhancing bioactive metabolites in food, such as meglutol, with potential applications in personalized dietary approaches for disease prevention.