The association between toenail metals and extracellular MicroRNAs (ex-miRNAs) among the participants of the Normative Aging study (NAS).

BACKGROUND: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression. METHODS: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses. We looked at associations between measured toenail metals: arsenic, cadmium, lead, manganese, and mercury and 282 ex-miRNAs in this population using canonical correlation analyses (CCAs) and longitudinal median regression. We adjusted for covariates such as age, education, body mass index, drinking and smoking behaviors, diabetes, and where available, seafood consumption. The p-values obtained from regression analyses were corrected for multiple comparisons. Ex-miRNAs identified to be associated with toenail metal levels were further examined using pathway analyses. RESULTS: Our dataset included 937 observations from 589 men with an average age of 72.9 years at baseline. Both our correlation and regression analyses identified lead and cadmium as exposures most strongly associated with ex-miRNA expression. Numerous ex-miRNAs were identified as being associated with toenail metal levels. miR-27b-3p, in particular, was found to have high correlation with the first canonical dimension in the CCA and was significantly associated with cadmium in the regression analysis. Pathway analyses revealed messenger RNA (mRNA) targets for the ex-miRNAs that were associated with a number of clinical disorders including cancer, cardiovascular disease, and neurological disorders, etc. CONCLUSION: Toenail metals were associated with changes in ex-miRNA levels in both correlational and regression analyses. The ex-miRNAs identified can be linked to a variety of clinical disorders. Further studies are required to validate these findings.

Extracellular vesicle-encapsulated microRNAs and respiratory health among American Indians in the Strong Heart Study.

BACKGROUND: American Indian populations have experienced marked disparities in respiratory disease burden. Extracellular vesicle-encapsulated microRNAs (EV-miRNAs) are a novel class of biomarkers that may improve recognition of lung damage in indigenous populations. RESEARCH QUESTION: Are plasma EV-miRNAs viable biomarkers of respiratory health in American Indian populations? STUDY DESIGN AND METHODS: The Strong Heart Study is a prospective cohort study that enrolled American Indians aged 45-74 years. EV-miRNA expression was measured in plasma (1993-1995). Respiratory health outcomes including pre-bronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and respiratory symptom burden were ascertained in the same study visit. Club cell secretory protein (CC-16), an anti-inflammatory pneumoprotein implicated in COPD pathogenesis, was measured in serum. Linear and logistic regression were used for statistical analyses. Biological pathway analyses were used to elucidate gene targets of significant EV-miRNAs. RESULTS: Among 853 American Indian adults, three EV-miRNAs were associated with FEV1, four EV-miRNAs were associated with FVC, and one EV-miRNA was associated with FEV1/FVC (P<0.05). Increased miR-1294 expression was associated with higher odds of airflow limitation (OR 1.29, 95% CI 1.07-1.55), while increased expression of miR-1294 (OR 1.32, 95% CI 1.07-1.63) and miR-532-5p (OR 1.57, 95% CI 1.02-2.40) was associated with higher odds of restriction. Increased miR-451a expression was associated with lower odds of exertional dyspnea (OR 0.71, 95% CI 0.59-0.85). Twenty-two EV-miRNAs were associated with serum CC-16 levels (q<0.05), suggesting EV-miRNAs may play a role in the pathway linking CC-16 to COPD pathogenesis. A pathway analysis showed key EV-miRNAs targeted biological pathways that modulate inflammation, immunity, and structural integrity in the lungs. INTERPRETATION: Circulating EV-miRNAs are novel mechanistic biomarkers of respiratory health and may facilitate the early detection and treatment of lung damage in American Indian populations that have been disproportionately affected by chronic lung diseases.

Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns.

Importance: Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations. Objective: To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth. Design, Setting, and Participants: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023. Exposures: A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure. Main Outcomes and Measures: Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes. Results: This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (ß, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (ß, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA. Conclusions and Relevance: The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

Extracellular microRNAs associated with psychiatric symptoms in the Normative Aging Study.

Earlier studies have revealed microRNAs (miRNAs) as potential biomarkers for neurological conditions, however, such evidence on psychiatric outcomes is limited. We utilized the Normative Aging Study (NAS) cohort to investigate the associations between extracellular miRNAs (ex-miRNA) and psychiatric symptoms among a group of older male adults, along with the targeted genes and biological pathways. We studied 569 participants with miRNA profile primarily measured in extracellular vesicles isolated from plasma, and psychiatric symptoms reported over 1996-2014 with repeated measures. Global and dimension scales of psychiatric symptoms were measured via the administration of Brief Symptom Inventory (BSI) per visit covering nine aspects of psychiatric health, such as anxiety, depression, hostility, psychoticism, etc. Ex-miRNAs were profiled using small RNA sequencing. Associations of expression of 395 ex-miRNAs (present in >70% samples) with current mental status were assessed using single-miRNA as well as Least Absolute Shrinkage and Selection Operator (LASSO)-based multi-miRNAs linear mixed effects models adjusting for key demographic and behavioral factors. Biological functions were explored using pathway analyses. We identified ex-miRNAs associated with each BSI scale. In particular, hsa-miR-320d was consistently identified for two global scales. Similar overlapping miRNAs across global and dimension scores included hsa-miR-379-3p, hsa-miR-1976, hsa-miR-151a-5p, hsa-miR-151b, hsa-miR-144-3p, etc. Top KEGG pathways for identified miRNAs included p53 signaling, Hippo signaling, FoxO signaling, protein processing in endoplasmic reticulum and several pathways related with cancer and neurological diseases. This study provided early evidence supporting the associations between extracellular miRNAs and psychiatric conditions. MiRNAs may serve as biomarkers of subclinical psychiatric illness in older adults.

Precision public health in the era of genomics and big data.

Precision public health (PPH) considers the interplay between genetics, lifestyle and the environment to improve disease prevention, diagnosis and treatment on a population level-thereby delivering the right interventions to the right populations at the right time. In this Review, we explore the concept of PPH as the next generation of public health. We discuss the historical context of using individual-level data in public health interventions and examine recent advancements in how data from human and pathogen genomics and social, behavioral and environmental research, as well as artificial intelligence, have transformed public health. Real-world examples of PPH are discussed, emphasizing how these approaches are becoming a mainstay in public health, as well as outstanding challenges in their development, implementation and sustainability. Data sciences, ethical, legal and social implications research, capacity building, equity research and implementation science will have a crucial role in realizing the potential for 'precision' to enhance traditional public health approaches.

Metabolism-Disrupting Chemical Mixtures during Pregnancy, Folic Acid Supplementation, and Liver Injury in Mother-Child Pairs.

Background and Aims: Scarce knowledge about the impact of metabolism-disrupting chemicals (MDCs) on liver injury limits opportunities for intervention. We evaluated pregnancy MDC-mixture associations with liver injury and effect modification by folic acid (FA) supplementation in mother-child pairs. Methods: We studied ∼200 mother-child pairs from the Mexican PROGRESS cohort, with measured 43 MDCs during pregnancy (estimated air pollutants, blood/urine metals or metalloids, urine high- and low-molecular-weight phthalate [HMWPs, LMWPs] and organophosphate-pesticide [OP] metabolites), and serum liver enzymes (ALT, AST) at ∼9 years post-parturition. We defined liver injury as elevated liver enzymes in children, and using established clinical scores for steatosis and fibrosis in mothers (i.e., AST:ALT, FLI, HSI, FIB-4). Bayesian Weighted Quantile Sum regression assessed MDC-mixture associations with liver injury outcomes. We further examined chemical-chemical interactions and effect modification by self-reported FA supplementation. Results: In children, many MDC-mixtures were associated with liver injury outcomes. Per quartile HMWP-mixture increase, ALT increased by 10.1% (95%CI: 1.67%, 19.4%) and AST by 5.27% (95% CI: 0.80%, 10.1%). LMWP-mixtures and air pollutant-mixtures were associated with higher AST and ALT, respectively. Air pollutant and non-essential metal/element associations with liver enzymes were attenuated by maternal cobalt blood concentrations ( p -interactions<0.05). In mothers, only the LMWP-mixture was associated with liver injury [OR=1.53 (95%CI: 1.01, 2.28) for HSI>36, and OR=1.62 (95%CI: 1.05, 2.49) for AST:ALT<1]. In mothers and children, most associations were attenuated (null) at FA supplementation≥600mcg/day ( p -interactions<0.05). Conclusions: Pregnancy MDC exposures may increase liver injury risk, particularly in children. These associations may be attenuated by higher FA supplementation and maternal cobalt levels.

Exposome Profiling of Environmental Pollutants in Seminal Plasma and Novel Associations with Semen Parameters.

Indicators of male fertility are in decline globally, but the underlying causes, including the role of environmental exposures, are unclear. This study aimed to examine organic chemical pollutants in seminal plasma, including both known priority environmental chemicals and less studied chemicals, to identify uncharacterized male reproductive environmental toxicants. Semen samples were collected from 100 individuals and assessed for sperm concentration, percent motility, and total motile sperm. Targeted and nontargeted organic pollutant exposures were measured from seminal plasma using gas chromatography, which showed widespread detection of organic pollutants in seminal plasma across all exposure classes. We used principal component pursuit (PCP) on our targeted panel and derived one component (driven by etriadizole) associated with total motile sperm (p < 0.001) and concentration (p = 0.03). This was confirmed by the exposome-wide association models using individual chemicals, where etriadizole was negatively associated with total motile sperm (FDR q = 0.01) and concentration (q = 0.07). Using PCP on 814 nontargeted spectral peaks identified a component that was associated with total motile sperm (p = 0.001). Bayesian kernel machine regression identified one principal driver of this association, which was analytically confirmed to be N-nitrosodiethylamine. These findings are promising and consistent with experimental evidence showing that etridiazole and N-nitrosodiethylamine may be reproductive toxicants.

Endocrine-disrupting chemical concentrations in follicular fluid and follicular reproductive hormone levels.

PURPOSE: To determine correlations between chemicals in follicular fluid (FF) and follicular reproductive hormone levels. METHODS: The analysis was part of a larger cohort study to determine associations between exposure to EDCs and in vitro fertilization (IVF) outcomes. FF was aspirated from a single leading follicle per participant. Demographics and data on exposure to EDCs were self-reported by the participants using a questionnaire. The concentrations of estradiol (E2), progesterone (PG), anti-Mullerian hormone (AMH), and inhibin B, as well as that of 12 phthalate metabolites and 12 phenolic chemicals were measured in each FF sample. Multivariate linear regression model was used to identify the drivers of hormone levels based on participant's age, BMI, smoking status, and chemical exposure for the monitored chemicals detected in more than 50% of the samples. Benjamini-Hochberg false discovery rate (FDR) correction was applied on the resulting p values (q value). RESULTS: FF samples were obtained from 72 women (mean age 30.9 years). Most of the phthalates and phenolic substances monitored (21/24, 88%) were identified in FF. Ten compounds (7 phthalate metabolites, 3 phenols) were found in more than 50% of samples. In addition, there were positive associations between E2 levels and mono-n-butyl phthalate (MnBP) (beta = 0.01) and mono-isobutyl phthalate (MiBP) (beta = 0.03) levels (q value < 0.05). CONCLUSION: Higher concentrations of several phthalate metabolites, present among others in personal care products, were associated with increased E2 levels in FF. The results emphasize the need to further investigate the mechanisms of action of such EDCs on hormonal cyclicity and fertility in women.

Inverse associations of cord blood mitochondrial DNA copy number with childhood adiposity.

OBJECTIVE: The objective of this study was to examine associations between umbilical cord mitochondrial DNA copy number (mtDNAcn) and adiposity across childhood. METHODS: In a prospective birth cohort of Dominican and African American children from New York City, New York (1998-2006), mtDNAcn was measured in cord blood. Children (N = 336) were evaluated for their height, weight, and bioimpedance at age 5, 7, 9, and 11 years. We used linear mixed-effects models to assess associations of mtDNAcn tertiles in cord blood with child BMI, BMI z scores, fat mass index, and body fat percentage. Latent class growth models and interactions between mtDNAcn and child age or child age2 were used to assess associations between age and adiposity trajectories. RESULTS: BMI was, on average, 1.5 kg/m2 higher (95% CI: 0.58, 2.5) in individuals with mtDNAcn in the low- compared with the middle-mtDNAcn tertile. Results were similar for BMI z score, fat mass index, and body fat percentage. Moreover, children in the low-mtDNAcn group had increased odds of being in an "increasing" or "high-stable" adiposity class. CONCLUSIONS: Lower mtDNAcn at birth may predict greater childhood adiposity, highlighting the potential key role of perinatal mitochondrial function in adiposity during development.

Associations of prenatal one-carbon metabolism nutrients and metals with epigenetic aging biomarkers at birth and in childhood in a US cohort.

Epigenetic gestational age acceleration (EGAA) at birth and epigenetic age acceleration (EAA) in childhood may be biomarkers of the intrauterine environment. We investigated the extent to which first-trimester folate, B12, 5 essential, and 7 non-essential metals in maternal circulation are associated with EGAA and EAA in early life. Bohlin EGAA and Horvath pan-tissue and skin and blood EAA were calculated using DNA methylation measured in cord blood (N=351) and mid-childhood blood (N=326; median age = 7.7 years) in the Project Viva pre-birth cohort. A one standard deviation increase in individual essential metals (copper, manganese, and zinc) was associated with 0.94-1.2 weeks lower Horvath EAA at birth, and patterns of exposures identified by exploratory factor analysis suggested that a common source of essential metals was associated with Horvath EAA. We also observed evidence nonlinear associations of zinc with Bohlin EGAA, magnesium and lead with Horvath EAA, and cesium with skin and blood EAA at birth. Overall, associations at birth did not persist in mid-childhood; however, arsenic was associated with greater EAA at birth and in childhood. Prenatal metals, including essential metals and arsenic, are associated with epigenetic aging in early life, which might be associated with future health.

Associations between individual and structural level racism and gestational age at birth in the Nulliparous Pregnancy Outcomes Study: Monitoring mothers-to-be.

The purpose of this study was to investigate the associations between multilevel racism and gestational age at birth among nulliparous non-Hispanic Black, non-Hispanic White and Hispanic women. We conducted a secondary analysis of data of the nuMoM2b Study (2010-2013) to examine the associations between individual and structural-level experiences of racism and discrimination and gestational age at birth among nulliparous women (n=7,732) at eight sites across the U.S. Measures included the individual Experiences of Discrimination (EOD) scale and the Index of Concentration (ICE) at the Extremes to measure structural racism. After adjustment,we observed a significant individual and structural racism interaction on gestational length (p=0.03). In subgroup analyses, we found that among these with high EOD scores, women who were from households concentrated in the more privileged group had significantly longer gestations (ß = 1.07, 95% CI: 0.24, 1.90). Women who reported higher EOD scores and more economic privilege had longer gestations, demonstrating the moderating effect of ICE as a measure of structural racism. In conclusion, ICE may represent a modifiable factor in the prevention of adverse birth outcomes in nulliparas.

Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging.

BACKGROUND: People living with HIV (PLHIV) on effective antiretroviral therapy are living near-normal lives. Although they are less susceptible to AIDS-related complications, they remain highly vulnerable to non-communicable diseases. In this exploratory study of older PLHIV (OPLHIV) in Eswatini, we investigated whether epigenetic aging (i.e., the residual between regressing epigenetic age on chronological age) was associated with HIV-related parameters, and whether lifestyle factors modified these relationships. We calculated epigenetic aging focusing on the Horvath, Hannum, PhenoAge and GrimAge epigenetic clocks, and a pace of biological aging biomarker (DunedinPACE) among 44 OPLHIV in Eswatini. RESULTS: Age at HIV diagnosis was associated with Hannum epigenetic age acceleration (EAA) (ß-coefficient [95% Confidence Interval]; 0.53 [0.05, 1.00], p = 0.03) and longer duration since HIV diagnosis was associated with slower Hannum EAA (- 0.53 [- 1.00, - 0.05], p = 0.03). The average daily dietary intake of fruits and vegetables was associated with DunedinPACE (0.12 [0.03, 0.22], p = 0.01). The associations of Hannum EAA with the age at HIV diagnosis and duration of time since HIV diagnosis were attenuated when the average daily intake of fruits and vegetables or physical activity were included in our models. Diet and self-perceived quality of life measures modified the relationship between CD4+ T cell counts at participant enrollment and Hannum EAA. CONCLUSIONS: Epigenetic age is more advanced in OPLHIV in Eswatini in those diagnosed with HIV at an older age and slowed in those who have lived for a longer time with diagnosed HIV. Lifestyle and quality of life factors may differentially affect epigenetic aging in OPLHIV. To our knowledge, this is the first study to assess epigenetic aging in OPLHIV in Eswatini and one of the few in sub-Saharan Africa.

Cumulative Stress Across the Life Course and Biological Aging in Adulthood.

OBJECTIVE: Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies have examined stressors across the life course in relation to biological aging. METHODS: In 359 individuals (57% White, 34% Black) from the Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) and traumatic (death of a sibling or child, violence exposure) stressors were assessed at multiple time points (birth and ages 9, 15, and 50 years). Experiences of major discrimination were assessed at age 50. Life period stress scores were then assessed as childhood (birth-age 15 years) and adulthood (age 50 years). At age 50 years, participants provided blood samples, and DNA methylation was assessed with the EPIC BeadChip. Epigenetic age was estimated using six epigenetic clocks (Horvath, Hannum, Skin and Blood age, PhenoAge, GrimAge, Dunedin Pace of Aging). Age acceleration was determined using residuals from regressing chronologic age on each of the epigenetic age metrics. Telomere length was assessed using the quantitative polymerase chain reaction-based methods. RESULTS: In linear regression models adjusted for race and gender, total life stress, and childhood and adult stress independently predicted accelerated aging based on GrimAge and faster pace of aging based on the DunedinPace. Associations were attenuated after adjusting for smoking status. In sex-stratified analyses, greater childhood stress was associated with accelerated epigenetic aging among women but not men. No associations were noted with telomere length. CONCLUSIONS: We found that cumulative stressors across the life course were associated with accelerated epigenetic age, with differences by sex (e.g., accelerated among women). Further research of this association in large and diverse samples is needed.

Psychosocial Stress and MicroRNA Expression Profiles in Myometrial Tissue of Women Undergoing Surgical Treatment for Uterine Fibroids.

Uterine leiomyomas (fibroids) are the most common non-cancerous tumors affecting women. Psychosocial stress is associated with fibroid risk and severity. The relationship between psychosocial stress and fibroid pathogenesis may involve alterations in microRNAs (miRNAs) although this has yet to be examined. We investigated associations between two psychosocial stress measures, a composite measure of recent stressful life events and perceived social status, with expression levels of 401 miRNAs in myometrium (n = 20) and fibroids (n = 44; 20 with paired fibroid and myometrium samples) among pre-menopausal women who underwent surgery for fibroid treatment. We used linear regressions to identify psychosocial stressors associated with miRNAs, adjusting for covariates (age, body mass index, race/ethnicity, and oral contraceptive use). The association between psychosocial stressors and miRNAs was considered statistically significant at an FDR p < 0.10 and showed a monotonic response (nominal p-trend < 0.05). In the myometrium, 21 miRNAs were significantly associated with a composite measure of recent stressful events, and two miRNAs were associated with perceived social status. No fibroid miRNAs were associated with either stress measure. Pathway analyses revealed miRNA-mRNA targets were significantly enriched (FDR p < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids, miR-27a-5p and miR-301b were also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with myometrial miRNA expression and, thus, may have a role in the pathogenesis of fibroids from healthy myometrium.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents. AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD. METHODS: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD. RESULTS: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B. CONCLUSION: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Indoor environment, physiological factors, and diet as predictors of halogenated flame retardant levels in stool and plasma of children from a Canadian cohort.

Exposure to halogenated flame retardants (HFRs) has been associated with various adverse effects on human health. Human exposure to HFRs mainly occurs through diet, ingesting contaminated dust, and inhaling contaminated air. Understanding and characterizing the variables linked to these exposure pathways is essential for developing effective risk assessment and mitigation strategies. We investigated indoor environment quality, physiological factors, and diet as potential predictors of HFRs concentration in children's plasma and stool. A selected number of HFRs, including polybrominated diphenyl ethers (PBDEs), Dechlorane-like compounds, and emerging halogenated flame retardants, were measured in children from eastern Quebec (Canada). Information on indoor environment quality, physiological factors, and diet was obtained through self-report questionnaires. Our results show that lower brominated compounds, which are more volatile, were primarily correlated to indoor environment quality. Notably, the use of air purifiers was associated with lower BDE47 and BDE100 levels in blood and newer residential buildings were associated with higher concentrations of BDE47. A significant seasonal variation was found in stool samples, with higher levels of lower brominated PBDEs (BDE47 and BDE100) in samples collected during summer. No association between household income or maternal education degree and HFRs was found. Among emerging compounds, Dec602 and Dec603 were associated with the most variables, including the use of air dehumidifiers, air conditioning, and air purifiers, and the child's age and body fat percentage.

Establishing non-fasting reference values for plasma lipids levels based on age, sex, and puberty stage in a French-Canadian pediatric population.

BACKGROUND: Dyslipidemias, including familial hypercholesterolemia (FH), are a significant risk factor for cardiovascular diseases. FH is a genetic disorder resulting in elevated levels of low-density lipoprotein cholesterol (LDL-C) and an increased probability of early cardiovascular disorders. Heterozygous familial hypercholesterolemia (HeFH) is the most common form, affecting approximately 1 in 250 individuals worldwide, with a higher prevalence among the French-Canadian population. Childhood is a critical period for screening risk factors, but the recommendation for non-fasting screening remains controversial due to a lack of specific reference values for this state. This study aims to establish reference values for lipid levels in non-fasting children from Sherbrooke, Quebec, Canada, that will be specific for sex, age, and pubertal stages. METHODS: Blood samples and corresponding anthropometric data were collected from 356 healthy children aged from 6 to 13. They were categorized either into two age groups: Cohort 6-8 and Cohort 9-13, or into pubertal stages. Reference values, specifically the 2.5th, 5th, 10th, 50th, 90th, 95th, and 97.5th percentiles were determined using the CLSI C28-A3 guidelines. RESULTS: Lipid profiles did not significantly differ between sexes, except for higher levels of high-density lipoprotein (HDL-C) in boys within Cohort 6-8. HDL-C levels significantly increased, while LDL-C and non-HDL-C levels significantly decreased in both sexes with age. Non-fasting age- and pubertal stages-specific reference values were established. CONCLUSION: This study established reference intervals for lipid markers in non-fasting state within the pediatric French-Canadian population. These findings could be used in dyslipidemia screening in daily practice.

Diet Quality and Epigenetic Aging in the Women's Health Initiative.

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 (ß ± 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.