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INTRODUCTION: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimers disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS: Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION: The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Prenatal first-trimester essential metals were associated with lower childhood adiposity, whereas nonessential metals were associated with higher adiposity into adolescence.

The perforant path, the white matter bundle connecting the entorhinal cortex (ERC) with the hippocampal formation deteriorates with age-related cognitive decline. Previous investigations using diffusion-weighted MRI to quantify perforant path integrity in-vivo have been limited due to image resolution or have quantified the perforant path using methods susceptible to partial volume effects such as the tensor model and without consideration of its 3-dimensional morphology. In this investigation, we use quantitative-anisotropy informed tractography derived from ultra-high resolution diffusion imaging (ZOOMit) to investigate structural connectivity of the perforant path and other medial temporal lobe (MTL) pathways in older adults (63 to 98 years old, n = 51). We show that graph density within the MTL declines with age and is associated with lower delayed recall performance. We also show that older age and poorer delayed recall are associated with reduced streamlines connecting the ERC and dentate gyrus of the hippocampus (the putative perforant path). This work suggest that intra-MTL connectivity may new candidate biomarkers for age-related cognitive decline.

Epigenome-wide association studies (EWAS) are widely implemented in epidemiology, and the Illumina HumanMethylationEPIC BeadChip (EPIC) DNA microarray is the most-used technology. Recently, next-generation sequencing (NGS)-based methods, which assess DNA methylation at single-base resolution, have become more affordable and technically feasible. While the content of microarray technology is fixed, NGS-based approaches, such as the Roche Nimblegen, SeqCap Epi Enrichment System (SeqCap), offer the flexibility of targeting most CpGs in a gene. With the current usage of microarrays and emerging NGS-based technologies, it is important to establish whether data generated from the two platforms are comparable. We harnessed 112 samples from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort study and compared DNA methylation between the EPIC microarray and SeqCap for PON1 and nine additional candidate genes, by evaluating epigenomic coverage and correlations. We conducted multivariable linear regression and principal component analyses to assess the ability of the EPIC array and SeqCap to detect biological differences in gene methylation by the PON1-108 single nucleotide polymorphism. We found an overall high concordance (r = 0.84) between SeqCap and EPIC DNA methylation, among highly methylated and minimally methylated regions. However, substantial disagreement was present between the two methods in moderately methylated regions, with SeqCap measurements exhibiting greater within-site variation. Additionally, SeqCap did not capture PON1 SNP associated differences in DNA methylation that were evident with the EPIC array. Our findings indicate that microarrays perform well for analysing DNA methylation in large cohort studies but with limited coverage.

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. https://doi.org/10.1289/EHP9934.

Medial temporal lobe (MTL) atrophy is a core feature of age-related cognitive decline and Alzheimer's disease (AD). While regional volumes and thickness are often used as a proxy for neurodegeneration, they lack the sensitivity to serve as an accurate diagnostic test and indicate advanced neurodegeneration. Here, we used a submillimeter resolution diffusion weighted MRI sequence (ZOOMit) to quantify microstructural properties of hippocampal subfields in older adults (63-98 years old) using tensor derived measures: fractional anisotropy (FA) and mean diffusivity (MD). We demonstrate that the high-resolution sequence, and not a standard resolution sequence, identifies dissociable profiles for CA1, dentate gyrus (DG), and the collateral sulcus. Using ZOOMit, we show that advanced age is associated with increased MD of the CA1 and DG as well as decreased FA of the DG. Increased MD of the DG, reflecting decreased cellular density, mediated the relationship between age and word list recall. Further, increased MD in the DG, but not DG volume, was linked to worse spatial pattern separation. Our results demonstrate that ultrahigh-resolution diffusion imaging enables the detection of microstructural differences in hippocampal subfield integrity and will lead to novel insights into the mechanisms of age-related memory loss.

BackgroundPhthalates and bisphenol A (BPA) are endocrine disrupting chemicals used in consumer products, building materials, and food processing and packaging materials. They are associated with adverse health outcomes, especially when exposure occurs during heightened windows of susceptibility.ObjectiveWe evaluated the relationship between housing and dietary characteristics and the concentration of several high-molecular-weight (HMW) phthalate metabolites and BPA in a cohort of Latina adolescents.MethodsWe collected information on recent food consumption and housing characteristics and quantified the concentration of HMW phthalate and BPA metabolites in urine collected at two different time points. We used generalized estimating equations (GEE) to assess predictors of each metabolite.ResultsNo significant associations were observed between housing and dietary characteristics and metabolites of di(2-ethylhexyl) phthalate (DEHP) or BPA. In contrast, higher urinary monobenzyl phthalate (MBzP) concentration was associated with living in a home with vinyl or linoleum flooring (66.7% change, p-value

BackgroundHundreds of thousands of biodigesters have been constructed in Nepal. These household-level systems use human and animal waste to produce clean-burning biogas used for cooking, which can reduce household air pollution from woodburning cookstoves and prevent respiratory illnesses. The biodigesters, typically operated by female caregivers, require the handling of animal waste, which may increase domestic fecal contamination, exposure to diarrheal pathogens, and the risk of enteric infections, especially among young children.ObjectiveWe estimated the effect of daily reported biogas cookstove use on incident diarrhea among children

BackgroundMetal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants.ObjectivesWe evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress.MethodsWe measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn (n=898) and TL (n=893) in second-trimester maternal blood and mtDNAcn (n=419) and TL (n=408) in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions.ResultsA 2-fold increase in maternal magnesium was associated with lower maternal [β=-0.07, 95% confidence interval (CI): -0.10, -0.01] and cord blood (β=-0.08, 95% CI: -0.20, -0.01) mtDNAcn. Lead was associated with higher maternal mtDNAcn (β=0.04, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (β=0.30, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (β=0.04, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium.DiscussionMaternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294.

ObjectivesThe US National Toxicology Program (NTP) recently recommended in its Report on Carcinogens Monograph for Antimony Trioxide that antimony trioxide be listed as 'reasonably anticipated to be a human carcinogen' based on sufficient evidence of carcinogenicity in experimental animals and supporting evidence from mechanistic studies. Our goal was to estimate the possible human cancer risk from occupational exposure to antimony trioxide.MethodsWe selected data from 2-year inhalation studies in male and female mice conducted by the NTP and performed cancer dose-response analyses using cancer models and benchmark dose methods developed by the US Environmental Protection Agency. In these analyses, we generated benchmark doses and cancer slope factors for antimony trioxide, and then estimated human cancer risk under various exposure scenarios. Typical and worst-case inhalation scenarios in multiple occupational settings were used in risk estimation.ResultsIn typical case scenarios, the occupational cancer risk from antimony trioxide was estimated to be 0.025 (25 in 1000) for persons working with flame retardants in plastics and textiles for 40 years. Under worst-case scenarios, the occupational cancer risk was estimated to be 0.11 (110 in 1000) for persons working with flame retardants in plastics and textiles. At the current Occupational Safety and Health Administration Permissible Exposure Limit, the cancer risk for occupational inhalation exposure of antimony trioxide was estimated to be 0.096 (96 in 1000).ConclusionThe risk estimates calculated in this study suggest that exposure to antimony trioxide at levels present in certain occupational settings results in a large increase in the risk of developing cancer.

Background and Objectives: Exclusive breastfeeding is recommended for most newborns. However, exclusively breastfed newborns sometimes experience excess weight loss (EWL, loss ≥10% of birth weight) while lactation is being established. Our primary objective was to evaluate the sensitivity and specificity of the Newborn Weight Loss Tool (NEWT) in early identification of exclusively breastfed newborns who develop EWL; and secondarily, identify breastfeeding variables associated with an at-risk NEWT trajectory. Materials and Methods: We conducted a secondary analysis of prospective data from mother-infant dyads screened for inclusion in the U.S. site of the WHO Growth Reference Study. We excluded records if: NEWT-specific criteria not met, missing key data, or >60 mL formula consumed. We defined NEWT "test-positive" based on an in-hospital weight at about 24 hours falling within the NEWT trajectory consistent with eventual EWL. We defined cases as true EWL based on weight measured at home on day of life 4 (DoL4). Results: Of 280 original records, 60 were excluded (n = 27, NEWT-specific exclusion; n = 15, missing data; n = 18, >60 mL formula), resulting in 220 paired newborn weights measured in-hospital (17 ± 8 hours), and at DoL4 (84 ± 8 hours). NEWT status correctly identified 6/28 EWL cases (21% sensitivity [95% confidence interval, CI, 8-34%]), and 158/192 noncases (82% specificity [95% CI, 75-89%]). NEWT test-positive status was associated with greater weight loss, lower perceived breastfeeding support, and infant less often showing feeding cues on DoL4 (p

Purpose of reviewCannabis exposure during critical windows of development may have intergenerational physiological consequences disrupting epigenetic programming and marks. This review examines the literature relating to pre-gestational and prenatal cannabinoid exposure and its effect on genes and molecular pathways related to the development of psychiatric disease.Recent findingsDevelopmental cannabis exposure alters epigenetic processes with functional gene consequences. These include potentially heritable alterations in genes and molecular pathways critical for brain development and associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, addiction, and other psychiatric diseases. Cannabis consumption and mental health illness in adolescents and young adults are increasing in the United States (U.S.), and recent studies suggest that cannabis consumption during critical periods of brain development could contribute to mental health illness through epigenetic mechanisms. These findings warrant future studies and consideration by regulators and health communicators.

Pregnancy is a unique period when biological changes can increase sensitivity to chemical exposures. Pregnant women are exposed to multiple environmental chemicals via air, food, water, and consumer products, including flame retardants, plasticizers, and pesticides. Lead exposure increases risk of pregnancy-induced hypertensive disorders, although women's health risks are poorly characterized for most chemicals. Research on prenatal exposures has focused on fetal outcomes and less on maternal outcomes. We reviewed epidemiologic literature on chemical exposures during pregnancy and three maternal outcomes: preeclampsia, gestational diabetes, and breast cancer. We found that pregnancy can heighten susceptibility to environmental chemicals and women's health risks, although variations in study design and exposure assessment limited study comparability. Future research should include pregnancy as a critical period for women's health. Incorporating biomarkers of exposure and effect, deliberate timing and method of measurement, and consistent adjustment of potential confounders would strengthen research on the exposome and women's health.

Environmental Health (EH) is an essential profession for protecting human health and yet as a discipline it is under-recognised, overlooked and misunderstood. Too few students undertake EH studies, culminating in a dearth of qualified Environmental Health Officers (EHOs) in Australia. A major deterrent to students enrolling in EH courses is a lack of appreciation of the relevance to their own lives. This is symptomatic of a wider problem of scientific literacy: the relevance gap and how to bridge it. Employing a cultural hook offers a means to connect students to science and the fundamental elements of EH. Zombies feature prominently in the contemporary cultural landscape--movies, TV, gaming, music, cosplay, 'Zombie Marches'. A Zombie Apocalypse provides an engaging platform to convey key EH concepts such as microbes and toxins, whilst improving the scientific literacy skills of both science and non-science students. Engaging students through this cultural hook bridged the relevance gap, connected students to science, and inspired an increased interest in EH.

The Connected Learning Massive Open Online Collaboration (CLMOOC) is an online professional development experience designed as an openly networked, production-centered, participatory learning collaboration for educators. Addressing the paucity of research that investigates learning processes in MOOC experiences, this paper examines the situated literacy practices that emerged as educators in CLMOOC composed, collaborated, and distributed multimediated artifacts. Using a collaborative, interactive visual mapping tool as participant-researchers, we analyzed relationships between publically available artifacts and posts generated in one week through a transliteracies framework. Culled data included posts on Twitter (n = 678), a Google+ Community (n = 105), a Facebook Group (n = 19), a blog feed (n = 5), and a "make" repository (n = 21). Remix was found to be a primary form of interaction and mediator of learning. Participants not only iterated on each others' artifacts, but on social processes and shared practices as well. Our analysis illuminated four distinct remix mobilities and relational tendencies--"bursting," "drifting," "leveraging," and "turning." "Bursting" and "drifting" characterize the paces and proximities of remixing while "leveraging" and "turning" are activities more obviously disruptive of social processes and power hierarchies. These mobilities and tendencies revealed remix as an emergent, iterative, collaborative, critical practice with transformative possibilities for openly networked web-mediated professional learning.