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Prenatal nonessential metals may contribute to postnatal adiposity, whereas essential metals may have metabolic benefits. We evaluated joint and individual associations between prenatal metals and childhood adiposity.We measured concentrations of six nonessential (arsenic, barium, cadmium, cesium, lead, and mercury) and four essential (magnesium, manganese, selenium, and zinc) metals in first trimester maternal blood from a prebirth cohort. We collected anthropometric measures in early childhood, mid-childhood, and early adolescence including subscapular+tricep skinfold thickness (mm) (N = 715-859), waist circumference (cm) (N = 717-882), and body mass index (BMI) (z-score) (N = 716-875). We measured adiposity in mid-childhood and early adolescence using bone densitometry total- and trunk- fat mass index (kg/m 2 ) (N = 511-599). We estimated associations using adjusted quantile g-computation and linear regression.The nonessential metal mixture was associated with higher total (β = 0.07, 95% CI = 0.01, 0.12) and trunk fat mass index (β = 0.12, CI = 0.02, 0.22), waist circumference (β = 0.01, CI = 0.00, 0.01), and BMI (β = 0.24, CI = 0.07, 0.41) in mid-childhood, and total fat mass index (β = 0.07, CI = 0.01, 0.14), and BMI (β = 0.19, CI = 0.02, 0.37) in early adolescence. The essential metal mixture was associated with lower early adolescence total-(β = -0.11, CI = -0.17, -0.04) and trunk- fat mass index (β = -0.13, CI = -0.21, -0.05), subscapular+tricep skinfold thickness (β = -0.02, CI = -0.03, -0.00), waist circumference (β = -0.003, CI = -0.01, -0.00), and BMI (β = -0.16, CI = -0.28, -0.04). Cadmium and cesium were individually associated with childhood adiposity at different timepoints.Prenatal first-trimester essential metals were associated with lower childhood adiposity, whereas nonessential metals were associated with higher adiposity into adolescence.

Sufficient evidence supports a relationship between certain myeloid neoplasms and exposure to benzene or formaldehyde. DNA methylation could underlie benzene- and formaldehyde-induced health outcomes, but data in exposed human populations are limited. We conducted two cross-sectional epigenome-wide association studies (EWAS), one in workers exposed to benzene and another in workers exposed to formaldehyde. Using HumanMethylation450 BeadChips, we investigated differences in blood cell DNA methylation among 50 benzene-exposed subjects and 48 controls, and among 31 formaldehyde-exposed subjects and 40 controls. We performed CpG-level and regional-level analyses. In the benzene EWAS, we found genome-wide significant alterations, i.e., FWER-controlled

It is expected that the communication fabric and the way network services are consumed will evolve towards 6G, building on and extending capabilities of 5G and Beyond networks. Service APIs, Operation APIs, Network APIs are different aspects of the network exposure, which provides the communication service providers a way to monetize the network capabilities. Allowing the developer community to use network capabilities via APIs is an emerging area for network monetization. Thus, it is important that network exposure caters for the needs of developers serving different markets, e.g., different vertical industry segments. The concept of “Network Applications” is introduced following this idea. It is defined as a set of services that provides certain functionalities to verticals and their associated use cases. The Network Applications is more than the introduction of new vertical applications that have interaction capabilities. It refers to the need for a separate middleware layer to simplify the implementation and deployment of vertical systems on a large scale. Specifically, third parties or network operators can contribute to Network Applications, depending on the level of interaction and trust. In practice, a Network Application uses the exposed APIs from the network and can either be integrated with (part of) a vertical application or expose its APIs (e.g., service APIs) for further consumption by vertical applications. This paper builds on the findings of the white paper released in 2022. It targets to go into details about the implementations of the two major Network Applications class: “aaS” and hybrid models. It introduces the Network Applications marketplace and put the light on technological solution like CAMARA project, as part of the standard landscape.

The prenatal environment may program health and disease susceptibility via epigenetic mechanisms. We evaluated associations of maternal trimester-specific intake of micronutrients with global DNA methylation (%5mC) and 5-hydroxymethylation (%5hmC) at birth in cord blood and tested for persistence into childhood. We quantified global %5mC and %5hmC in cord blood cells (n= 434) and in leukocytes collected in early (n= 108) and mid-childhood (n= 390) from children in Project Viva, a pre-birth cohort from Boston, MA. Validated food frequency questionnaires estimated maternal first- and second-trimester intakes of vitamin B2, vitamin B6, vitamin B12, folate, betaine, choline, methionine, iron, and zinc. Mean (SD) cord blood %5mC and %5hmC was 5.62% (2.04) and 0.25% (0.15), respectively. Each μg increase in first-trimester B12intake was associated with 0.002 lower %5hmC in cord blood (95% CI: −0.005, −0.0003), and this association persisted in early childhood (β= −0.007; 95% CI: −0.01, −0.001) but not mid-childhood. Second-trimester iron (mg) was associated with 0.01 lower %5mC (95% CI: −0.02, −0.002) and 0.001 lower %5hmC (95% CI: −0.01, −0.00001) in cord blood only. Increased second-trimester zinc (mg) intake was associated with 0.003 greater %5hmC in early childhood (β= 0.003; 95% CI: 0.0004, 0.006). Second-trimester folate was positively associated with %5hmC in early childhood only (β= 0.08, 95% CI: 0.003, 0.16). Associations did not survive multiple testing adjustment; future replication is needed. Trimester-specific nutrients may impact various sensitive windows of epigenetic programming some with lasting effects in childhood. Further research is needed to understand the role of gene-specific epigenetic changes and how global DNA methylation measures relate to child health.

ObjectiveThe aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length.MethodsThe study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States.ResultsIncumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality.ConclusionsLong-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.

Introduction: The developing kidney is vulnerable to pre- and postnatal environmental stressors. Suboptimal environmental conditions during early life, such as exposure to toxic metals and deficiency in essential metals, can alter the risk of kidney dysfunction later in life. In this pilot study, we aimed to examine the relationship between prenatal exposure to metals and adolescent kidney function using data from Project Viva, a Boston-area prospective pre-birth cohort. Hypothesis: Prenatal exposure to higher metal concentrations, both individually and as mixtures, will be associated with altered kidney function in mid-adolescence. Methods: We assessed the following metals in erythrocyte samples collected during pregnancy: 1 st -trimester [arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), mercury (Hg), lead (Pb), copper (Cu), magnesium (Mg), manganese (Mn), selenium (Se), and Zinc (Zn)]; 2 nd -trimester (Pb, Mn, Hg, and Se). We measured plasma cystatin C and creatinine from blood samples collected in mid-adolescence (mean age 18 years) in a sub-sample of Project Viva participants. We calculated the estimated glomerular filtrate rate (eGFR) using a cystatin C-based equation for children. We examined associations of prenatal metal exposure and mid-adolescent eGFR using linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses. In all models, we adjusted for maternal education level, annual household income, race/ethnicity, child sex, and age at eGFR assessment. Results: A total of 146 participants had complete data for 1 st -trimester erythrocyte metals and mid-adolescent eGFR, and 105 participants had complete data for 2 nd -trimester blood metals and mid-adolescent eGFR. All children had eGFR values in the normal range (i.e., >60 mL/min/1.73m 2 ); the mean (SD) eGFR was 92.0 (13.7) mL/min/1.73m 2 . Most pairwise metal-eGFR relationships were statistically null; however, a 2-fold increase in 1 st -trimester Zn was associated with higher eGFR (β 7.25 mL/min/1.73m 2 ; 95% CI 0.33, 14.16), while a 2-fold increase in 2 nd -trimester Pb was associated with lower eGFR (β -4.90 mL/min/1.73m 2 ; 95% CI -8.32, -1.48). Mixture analyses did not identify statistically significant findings but suggested some non-linear associations and interactions between metals. Conclusions: Preliminary evidence suggests that prenatal Zn exposure is associated with higher kidney function while prenatal Pb exposure is associated with lower kidney function in mid-adolescence. We plan to assess eGFR in additional participants to increase the power of the analyses.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by the BBSRC (BBI025751/1 and BB/I025263/1). GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. DCa is funded by the MRC (MC_UU_00011/1 and MC_UU_00011/5). GS is financially supported by the MRC [New Investigator Research Grant, MR/S009310/1] and the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1]. AH is supported by the South-Eastern Norway Regional Health Authority (2020022) and the Research Council of Norway (274611 and 288083). The POSEIDON work was supported by the German Research Foundation [DFG; grant FOR2107; RI908/11-2 and WI3429/3-2], the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent, under the auspices of the e:Med Programme [01ZX1314G; 01ZX1614G] through grants 01EE1406C, 01EE1409C and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” [01EW1810], through ERA-NET NEURON “Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention” [01EW1904] and by a grant of the Dietmar-Hopp Foundation. The general design of the Generation R Study is made possible by financial support from Erasmus Medical Center, Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw) and the Ministry of Health, Welfare and Sport. The EWAS data were funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). AN and HT are supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). AN is also supported by a Canadian Institutes of Health Research team grant. The work of HT is further supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). JFF has received funding from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no. 529051022) and the European Union’s Horizon 2020 research and innovation programme (733206, LifeCycle; 633595, DynaHEALTH). The work of CAMC, JF and RM has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 848158 (EarlyCause Project). Main funding of the epigenetic studies in INMA were grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CP18/00018), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615) Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness (IJCI-2017-34068). The Project Viva work was supported by the US National Institutes of Health grants R01 HD034568, UH3 OD023286 and R01 ES031259. The CHAMACOS project was supported by grants from the Environmental Protection Agency [R82670901 and RD83451301], the National Institute of Environmental Health Science (NIEHS) [P01 ES009605, R01ES021369, R01ES023067, R24ES028529, F31ES027751], the National Institute on Drug Abuse (NIDA) [R01DA035300], the National Institutes of Health (NIH) [UG3OD023356] and the National Institute of Mental Health (NIMH) [T32MH112510]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the EPA, NIEHS, or NIH. We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for medical research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris–Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programs (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale complementary health insurance (MGEN), French national agency for food security, French speaking association for the study of diabetes and metabolism (ALFEDIAM), grant # 2012/51290-6 Sao Paulo Research Foundation (FAPESP), EU funded MeDALL project. PREDO: The PREDO Study has been funded by the Academy of Finland (JL: 311617 and 269925, KR: 1312670 ja 128789 1287891), EraNet Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki and Sakari Sohlberg Foundation, Juho Vainio foundation, Yrjö Jahnsson foundation, Jalmari and Rauha Ahokas foundation, Sigrid Juselius Foundation granted to members of the Predo study board. Methylation assays were funded by the Academy of Finland (269925). SJL is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

Higher optimism is associated with reduced mortality and a lower risk of age-related chronic diseases. DNA methylation (DNAm) may provide insight into mechanisms underlying these relationships. We hypothesized that DNAm would differ among older individuals who are more versus less optimistic.Using cross-sectional data from two population-based cohorts of women with diverse races/ethnicities ( n = 3816) and men (only White, n = 667), we investigated the associations of optimism with epigenome-wide leukocyte DNAm. Random-effects meta-analyses were subsequently used to pool the individual results. Significantly differentially methylated cytosine-phosphate-guanines (CpGs) were identified by the "number of independent degrees of freedom" approach: effective degrees of freedom correction using the number of principal components (PCs), explaining95% of the variation of the DNAm data (PC-correction). We performed regional analyses using comb-p and pathway analyses using the Ingenuity Pathway Analysis software.We found that essentially all CpGs (total probe N = 359,862) were homogeneous across sex and race/ethnicity in the DNAm-optimism association. In the single CpG site analyses based on homogeneous CpGs, we identified 13 significantly differentially methylated probes using PC-correction. We found four significantly differentially methylated regions and two significantly differentially methylated pathways. The annotated genes from the single CpG site and regional analyses are involved in psychiatric disorders, cardiovascular disease, cognitive impairment, and cancer. Identified pathways were related to cancer, and neurodevelopmental and neurodegenerative disorders.Our findings provide new insights into possible mechanisms underlying optimism and health.

BackgroundKey characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents.ObjectivesThe goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs.MethodsA committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity.DiscussionKCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800.

Background Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)—the discrepancy between chronological and epigenetic ages. Methods We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. DNA methylation was measured using Illumina arrays, personal/parental SES by questionnaire and neighbourhood disadvantage from geocoded address. In CARDIA, we examined the most strongly associated personal, parental and neighbourhood SES measures with EAA (Hannum’s method) at study years 15 and 20 separately and combined using a generalized estimating equation (GEE) and compared with other EAA measures (Horvath’s EAA, PhenoAge and GrimAge calculators, and DunedinPoAm). Results EAA was associated with paternal education in CARDIA [GEEs: βsome college = −1.01 years (−1.91, −0.11) and β Conclusions These findings suggest that EAA captures epigenetic impacts of paternal education independently of personal SES later in life. Longitudinal studies should explore these associations at different life stages and link them to health outcomes. EAA could be a useful biomarker of SES-associated health and provide important insight into the pathogenesis and prevention of chronic disease.

DNA methylation (DNAm) is one of the most studied epigenetic modifications. DNAm has emerged as a key biological mechanism and biomarkers to test associations between environmental exposure and outcomes in epidemiological studies. Although previous studies have focused on associations between DNAm and either exposure/outcomes, it is useful to test for mediation of the association between exposure and outcome by DNAm. The purpose of this scoping review is to introduce the methodological essence of statistical mediation analysis and to examine emerging epidemiological research applying mediation analyses. We conducted this scoping review for published peer-reviewed journals on this topic using online databases (PubMed, Scopus, Cochrane, and CINAHL) ending in December 2020. We extracted a total of 219 articles by initial screening. After reviewing titles, abstracts, and full texts, a total of 69 articles were eligible for this review. The breakdown of studies assigned to each category was 13 for smoking (18.8%), 8 for dietary intake and famine (11.6%), 6 for other lifestyle factors (8.7%), 8 for clinical endpoints (11.6%), 22 for environmental chemical exposures (31.9%), 2 for socioeconomic status (SES) (2.9%), and 10 for genetic factors and race (14.5%). In this review, we provide an exposure-wide summary for the mediation analysis using DNAm levels. However, we found heterogenous methods and interpretations in mediation analysis with typical issues such as different cell compositions and tissue-specificity. Further accumulation of evidence with diverse exposures, populations and with rigorous methodology will be expected to provide further insight in the role of DNAm in disease susceptibility.

Background Dietary sources of metals are not well established among pregnant women in the United States. Objective We aimed to perform a diet-wide association study (DWAS) of metals during the first trimester of pregnancy. Methods In early pregnancy (11.3 ± 2.8 weeks of gestation), 1196 women from Project Viva (recruited 1999-2002 in eastern Massachusetts) completed a validated FFQ (135 food items) and underwent measurements of erythrocyte metals [arsenic (As), barium, cadmium, cesium (Cs), copper, mercury (Hg), magnesium, manganese, lead (Pb), selenium (Se), zinc]. The DWAS involved a systematic evaluation and visualization of all bivariate relations for each food-metal combination. For dietary items with strong associations with erythrocyte metals, we applied targeted maximum likelihood estimations and substitution models to evaluate how hypothetical dietary interventions would influence metals' concentrations. Results Participants' mean ± SD age was 32.5 ± 4.5 y and prepregnancy BMI was 24.8 ± 5.4 kg/m2; they were mostly white (75.9%), college graduates (72.4%), married or cohabitating (94.6%), had a household income >$70,000/y (63.5%), and had never smoked (67.1%). Compared with other US-based cohorts, the overall diet quality of participants was above average, and concentrations of erythrocyte metals were lower. The DWAS identified significant associations of several food items with As, Hg, Pb, Cs, and Se; for example, As was higher for each SD increment in fresh fruit (11.5%; 95% CI: 4.9%, 18.4%), white rice (17.9%; 95% CI: 9.4%, 26.9%), and seafood (50.9%; 95% CI: 42.8%, 59.3%). Following the guidelines for pregnant women to consume ≤3 servings/wk of seafood was associated with lower As (-0.55 ng/g; 95% CI: -0.82, -0.28 ng/g) and lower Hg (-2.67 ng/g; 95% CI: -3.55, -1.80 ng/g). Substituting white rice with bread, pasta, tortilla, and potato was also associated with lower As (35%-50%) and Hg (35%-70%). Conclusions Our DWAS provides a systematic evaluation of diet-metals relations. Prenatal diet may be an important source of exposures to metals.

Maternal fat intake during pregnancy affects fetal growth, but mechanisms underlying this relationship are unclear. We performed an exploratory study of the associations of fat consumption during pregnancy with cord blood DNA methylation of the insulin-like growth factor 2 (IGF2) and H19 genes. We used data from 96 uncomplicated full-term pregnancies of mothers of whom majority had normal body mass index (BMI) (66%) in Project Viva, a prospective pre-birth cohort. We assessed maternal diet with validated food frequency questionnaires during the first and second trimesters and measured DNA methylation in segments of the IGF2- and H19-differentially methylated regions (DMRs) by pyrosequencing DNA extracted from umbilical cord blood samples. Mean (SD) age was 32.8 (4.1) years and prepregnancy BMI was 24.0 (4.4) kg/m2 . Mean DNA methylation was 56.3% (3.9%) for IGF2-DMR and 44.6% (1.9%) for H19-DMR. Greater first trimester intake of omega-6 polyunsaturated fat (effect per 1% of calories at the expense of carbohydrates) was associated with lower DNA methylation of IGF2-DMR (-1.2%; 95% confidence interval [CI]: -2.2%, -0.2%) and higher DNA methylation at H19-DMR (0.8%; 95% CI: 0.3%, 1.3%). On the other hand, greater first trimester intake of omega-3 polyunsaturated fat was associated with lower DNA methylation of the H19-DMR (-4.3%; 95% CI: -7.9%, -0.8%). We did not find significant associations of IGF2 and H19 methylation with IGF2 cord blood levels. Our findings suggest that early prenatal fat intake (omega-3, omega-6, and saturated fatty acids) may influence DNA methylation at the IGF2 and H19 locus, which could impact fetal development and long-term health.

BACKGROUND: Multiple epidemiological studies have shown that exposure to pesticides is associated with adverse health outcomes. However, the literature on pesticide-related health effects in the Latin American and the Caribbean (LAC) region, an area of intensive agricultural and residential pesticide use, is sparse. We conducted a scoping review to describe the current state of research on the health effects of pesticide exposure in LAC populations with the goal of identifying knowledge gaps and research capacity building needs. METHODS: We searched PubMed and SciELO for epidemiological studies on pesticide exposure and human health in LAC populations published between January 2007 and December 2021. We identified 233 publications from 16 countries that met our inclusion criteria and grouped them by health outcome (genotoxicity, neurobehavioral outcomes, placental outcomes and teratogenicity, cancer, thyroid function, reproductive outcomes, birth outcomes and child growth, and others). RESULTS: Most published studies were conducted in Brazil (37%, n = 88) and Mexico (20%, n = 46), were cross-sectional in design (72%, n = 167), and focused on farmworkers (45%, n = 105) or children (21%, n = 48). The most frequently studied health effects included genotoxicity (24%, n = 62) and neurobehavioral outcomes (21%, n = 54), and organophosphate (OP) pesticides were the most frequently examined (26%, n = 81). Forty-seven percent (n = 112) of the studies relied only on indirect pesticide exposure assessment methods. Exposure to OP pesticides, carbamates, or to multiple pesticide classes was consistently associated with markers of genotoxicity and adverse neurobehavioral outcomes, particularly among children and farmworkers. DISCUSSION: Our scoping review provides some evidence that exposure to pesticides may adversely impact the health of LAC populations, but methodological limitations and inconsistencies undermine the strength of the conclusions. It is critical to increase capacity building, integrate research initiatives, and conduct more rigorous epidemiological studies in the region to address these limitations, better inform public health surveillance systems, and maximize the impact of research on public policies., Fil: Zúñiga-Venegas, Liliana A. Universidad Católica del Maule. Centro de Investigaciones de Estudios Avanzados del Maule; Chile, Fil: Hyland, Carly. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Hyland, Carly. Boise State University. School of Public Health and Population Science; Estados Unidos, Fil: Muñoz-Quezada, María Teresa. Universidad Católica del Maule. Facultad de Ciencias de la Salud. Centro de Investigación en Neuropsicología y Neurociencias Cognitivas; Chile, Fil: Quirós-Alcalá, Lesliam. John Hopkins University. Bloomberg School of Public Health. Department of Environmental Health and Engineering; Estados Unidos, Fil: Quirós-Alcalá, Lesliam. University of Maryland. School of Public Health. Maryland Institute of Applied Environmental Health; Estados Unidos, Fil: Butinof, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina, Fil: Buralli, Rafael. Universidade de São Paulo. Faculdade de Saúde Pública. Departamento de Saúde Ambiental; Brasil, Fil: Cardenas, Andres. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Fernandez, Ricardo A. Universidad Católica de Córdoba. Facultad de Ciencias de la Salud; Argentina, Fil: Foerster, Claudia. Universidad de O’Higgins. Instituto de Ciencias de la Agroalimentarias, Animales y Ambientales; Chile, Fil: Gouveia, Nelson. Universidade de São Paulo. Faculdade de Medicina. Departamento de Medicina Preventiva; Brasil, Fil: Jara, Juan P. Gutiérrez. Universidad Católica del Maule. Centro de Investigaciones de Estudios Avanzados del Maule; Chile, Fil: Lucero, Boris A. Universidad Católica del Maule. Facultad de Ciencias de la Salud. Centro de Investigación en Neuropsicología y Neurociencias Cognitivas; Chile, Fil: Muñoz, María Pía. Universidad de Chile. Facultad de Medicina. Escuela de Salud Pública; Chile, Fil: Ramírez-Santana, Muriel. Universidad Católica del Norte. Facultad de Medicina. Departamento de Salud Pública; Chile, Fil: Smith, Anna R. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Tirado, Noemi. Universidad Mayor de San Andrés. Facultad de Medicina. Instituto de Genética; Bolivia, Fil: de Joode, Berna van Wendel. Universidad Nacional. Central American Institute for Studies on Toxic Substances. Infants’ Environmental Health Study; Costa Rica, Fil: Calaf, Gloria M. Universidad de Tarapacá. Instituto de Alta Investigación; Chile, Fil: Calaf, Gloria M. Columbia University Medical Center; Estados Unidos, Fil: Handal, Alexis J. University of Michigan School of Public Health. Department of Epidemiology; Estados Unidos, Fil: da Silva, Agnes Soares. Pan American Health Organization. Estados Unidos, Fil: Cortés, Sandra. Pontificia Universidad Católica de Chile. Departamento de Salud Pública. Centro de Desarrollo Urbano Sustentable. Centro Avanzado de Enfermedades Crónicas (ACCDiS); Chile, Fil: Mora, Ana M. University of California. School of Public Health. Center for Environmental Research and Community Health; Estados Unidos, Fil: Mora, Ana M. Universidad Nacional. Central American Institute for Studies on Toxic Substances. Infants’ Environmental Health Study; Costa Rica

Leukocyte telomere length (LTL) may be a biomarker for chronic disease susceptibility, but no work has tested this hypothesis directly. Our study investigated associations of LTL at birth with markers of adiposity growth that are linked with cardiometabolic health later in life.Participants were 375 children in Project Viva (48% female, 71% White). Body mass index (BMI) trajectories from birth to 18 years were tracked using repeated measures of BMI collected in physical examinations and via medical records, then used to predict age (months) and magnitude (kg/mLTL was unrelated to BMI at peak or rebound, but associations were apparent with the timing of BMI growth milestones. Short LTL was related to a later age of peak for females (β = 0.99, 95% CI = 0.16, 1.82; pLTL at birth may be an early biomarker of altered adiposity growth. Newborn telomere biology may shed new insight into the developmental origins of health and disease.

Household air pollution (HAP) from indoor combustion of solid fuel is a global health burden that has been linked to lung cancer. A striking example occurs in Xuanwei, China where the lung cancer rate for never smoking women is among the highest in the world and largely attributed to high levels of various toxic constituents, including polycyclic aromatic hydrocarbons (PAHs), a combustion product of smoky (bituminous) coal used for cooking and heating. Several air pollution constituents have been associated with epigenetic accelerated aging (EAA) derived from DNA methylation (DNAm)-based biomarkers that are highly correlated with biological processes underlying aging-related diseases. We aim to assess the association between HAP exposure and EAA in Xuanwei, China. We analyzed 106 never smoking women in an exposure assessment study in Xuanwei, China with a repeat DNA sample from 23 subjects. Household fuel type used for cooking and heating (smoky vs. smokeless coal) was collected using a questionnaire, and exposure models were used to predict levels of 43 individual HAP constituents for current and childhood exposure. Leukocyte DNAm was measured using Illumina EPIC array. EAA was derived for five clocks using the Horvath calculator and defined as the residuals resulting from regressing each clock on chronological age. We used generalized estimating equations to assess the associations between fuel type, clusters derived from predicted levels of HAP exposure, and ambient 5-methylchrysene (5-MC), a carcinogenic PAH previously associated with lung cancer in Xuanwei and selected a priori for analyses, as independent variables and EAA clocks as dependent variables, while accounting for repeated-measurements. We observed a significant increase in GrimAge EAA among smoky coal users compared to smokeless coal users for current (β=1.84 years (y), 95% confidence interval (CI): 0.59, 3.09, P-value=0.004) and childhood (β=4.14 y, 95% CI: 1.63, 6.64, P-value=0.001) exposures. We also observed a monotonic increase in GrimAge EAA for a cluster of 31 PAHs reflecting current exposure (β=0.77 y, 95% CI: 0.36, 1.19, P-value=3 × 10−4) and for a cluster of 33 PAHs reflecting childhood exposure (β=0.92 y, 95% CI: 0.40, 1.45, P-value=0.001). Ambient 5-MC, one of the constituents within the PAH clusters, was found to have an increasing monotonic relationship with GrimAge EAA for current (β=0.15 y, 95% CI: 0.05, 0.25, P-value=0.003) and childhood (β=0.30 y, 95% CI: 0.13, 0.47, P-value=4.7 × 10−4) exposures. Our findings suggest that exposure to PAH from indoor smoky coal combustion is associated with EAA, particularly for the GrimAge clock, a strong biomarker of mortality. This finding is consistent with our recent observation linking accelerated GrimAge to increased risk of lung cancer in a prospective study of never smoking women in China. Additionally, our study provides further support for 5-MC as a prominent carcinogenic component of smoky coal emissions. Citation Format: Batel Blechter, Andres Cardenas, Seraphina (Junming) Shi, Mohammad L. Rahman, Jason Y.Y. Wong, Wei Hu, George S. Downward, Lutzen Portengen, Richard Cawthon, H. Dean Hosgood, Jihua Li, Debra T. Silverman, Yunchao Huang, Roel Vermeulen, Nathaniel Rothman, Qing Lan. Smoky coal exposure is associated with epigenetic accelerated aging. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4219.

Background: The etiology of lung cancer among never-smokers has not been adequately elucidated despite that globally15% of lung cancer cases in men and 53% in women are not smoking-related. Epigenetic modifications, including changes in DNA methylation (DNAm), have been suggested as possible underlying mechanisms. However, only a few prospective epigenome-wide association studies (EWAS) of lung cancer incidence have been conducted, all exclusively focused on DNAm in peripheral blood cells and included a minimal number of never-smokers. We aimed to investigate genome-wide DNAm associations and epigenetic age acceleration with future risk of lung cancer among never-smokers using pre-diagnostic oral rinse samples. Methods: We conducted a case-control study of 80 never-smoking incident lung cancer cases and 83 comparable never-smoking controls nested in two large prospective cohorts: the Shanghai Women’s Health Study and Shanghai Men’s Health Study. DNAm was measured using the Illumina EPIC array. The top 50 differentially methylated positions (DMPs) were identified from a discovery sample and tested for replication in a validation sample using robust linear regression models. We also conducted an EWAS in the pooled sample. We examined functional overlap enrichment across chromatin states and histone mark broadPeaks for the top 1000 DMPs using eFORGE and constructed enrichment biological pathways analyses. Results: Across discovery and pooled EWAS, we identified four DMPs associated with lung cancer at the epigenome-wide significance level of P Conclusions: To our knowledge, this is the first prospective EWAS of lung cancer among never-smokers using oral rinse samples. Our results show that DNAm in pre-diagnostic oral rinse samples can provide new insights into lung cancer etiology and risk factors. Citation Format: Mohammad L. Rahman, Charles E. Breeze, Xiao-Ou Shu, Jason YY Wong, Andres Cardenas, Xuting Wang, Bu-Tian Ji, Wei Hu, Batel Blechter, Qiuyin Cai, H Dean Hosgood, Gong Yang, Jianxin Shi, Jirong Long, Yu-Tang Gao, Douglas Bell, Wei Zheng, Qing Lan, Nathaniel Rothman. Epigenome-wide association study of lung cancer among never-smokers in two prospective cohorts in Shanghai [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3483.

This article studies the spatial evolution of mergers and acquisitions (M&A) in Canada to investigate the path dependence process of corporate control geography. The analysis is based on network an...