Assessing Metabolic Differences Associated with Exposure to Polybrominated Biphenyl and Polychlorinated Biphenyls in the Michigan PBB Registry.

BACKGROUND: Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. OBJECTIVES: In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. METHODS: HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB in utero or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and ΣPCB (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. RESULTS: Mean levels were 1.75 ng/mL [standard deviation (SD): 13.9] for PBB-153 and 1.04 ng/mL (SD: 0.788) for ΣPCB. Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) p<0.2], respectively. There were 2,861 features associated with ΣPCB (FDR p<0.2). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with ΣPCB in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with ΣPCB levels (level 1 evidence). CONCLUSIONS: Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that ΣPCB was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.

A Collaborative Approach to Address Racism in a Community-Academic Partnership.

The HERCULES Exposome Research Center at Emory University uses an exposome approach to study the environment's effect on health and community well-being. HERCULES is guided by a Stakeholder Advisory Board (SAB) that includes representatives of neighborhoods, nonprofit organizations, government agencies, and academic institutions in the Atlanta metropolitan region. This region (and the SAB) has a large proportion of Black residents, many of whom live in areas experiencing environmental injustices. Historic and current racial injustices in Atlanta and public health research made it imperative to initiate dialogue and implement actions to address racism and power dynamics that may impact research and partnerships between affected communities and our institution.After initial discussion, the HERCULES Community Engagement Core and SAB members formed a workgroup to develop an internal anti-racism process. The workgroup drafted an Anti-Racism Commitment, hosted a Racism and Equity Dialogue Series, and initiated a strategic planning process to implement the resulting recommendations, which fell into the following categories: anti-racist guidance/policies and recommendations for research, community engagement, and the department. Center leadership and the SAB were engaged throughout the iterative process.This deliberate and ongoing process allows HERCULES to identify and begin implementing action items that go beyond a written proclamation to address racialized power imbalances and systemic inequities. HERCULES is committed to working collaboratively to earn community trust while addressing systemic issues, recognizing that these are essential to forming research partnerships that address health inequities.

"They Kept Going for Answers": Knowledge, Capacity, and Environmental Health Literacy in Michigan's PBB Contamination.

The Michigan PBB Oral History Project documented community residents' descriptions of a large-scale chemical contamination-the PBB contamination-that occurred in Michigan in 1973. These oral histories document residents' and others' experiences during and after the contamination. We conducted a grounded theory qualitative analysis of 31 oral histories to examine the experiences of community members, researchers, lawyers, and others who actively sought out and contributed essential information about the contamination and its impacts. Our findings highlight several challenges encountered in the development of this knowledge including four central themes-contested knowledge, community skills, inaction, and uncertainty. Integrating environmental health literacy, community capacity, and contested illness frameworks, we examine the contributions of community residents, scientists (from inside and outside the community), and others to the development of knowledge to inform decisions and sustain action regarding this large-scale contamination. We close with a discussion of lessons learned regarding efforts to build environmental health knowledge within uncertain and often contested contexts and for promoting environmental health and action related to large-scale chemical contaminations. Our findings suggest the importance of integrated frameworks for examining and promoting the critical role of community skills, leadership, participation, sense of community, and community power in promoting environmental health.

Birth outcomes associated with paternal polybrominated and polychlorinated biphenyl exposure.

In 1973-74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds and is now led by a community-academic partnership. PBB exposure is associated with altered DNA methylation in sperm, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB). Paternal PBB and PCB levels of men enrolled in the Michigan PBB Registry (n = 155) were analyzed against matched offspring birthweight and gestational age (n = 336). Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks, respectively, and paternal PBB and PCB levels were examined as continuous measures and divided into tertiles. Associations of offspring birthweight and gestational age with paternal PBB and PCB serum concentrations were modeled using multivariable linear spline and log-risk regression, adjusting for family clustering, paternal health and lifestyle factors, maternal PBB, and PCB serum concentrations, sex, and offspring gestational age (for birthweight). Fathers in the middle and upper PBB and PCB tertiles had increased risks for lowest quartile birthweight compared to the first tertile, with adjusted risk ratios (aRR) = 1.67 (95% CI: 0.93, 2.99) and aRR = 2.06 (95% CI: 1.12, 3.79) for PBB, and aRR = 1.47 (95% CI: 0.79, 2.75) and aRR = 1.34 (95% CI: 0.70, 2.54) for PCB, respectively. Elevated paternal PBB levels were not associated with an increased risk for preterm birth, while PCB levels were associated with a small, but not significant, decrease in gestational age, ß = -0.37 (95% CI: -0.76, 0.03) weeks per log unit increase PCB. The findings suggest that increased paternal PBB and PCB levels negatively impact offspring birthweight, and paternal PCB levels may negatively impact gestational age.

Defining the Exposome Using Popular Education and Concept Mapping With Communities in Atlanta, Georgia.

Introduction: The exposome concept provides a framework to better incorporate the environment into the study of health and disease and has been defined by academics to encompass all lifetime exposures including toxicants, diet, and lifestyle choices. However, initial applications of the exposome concept have been less apt at measuring social determinants of health, focusing primarily on conventional environmental exposures and lifestyle choices that do not reflect the complex lived experience of many communities. To bring community voice into the exposome concept, the HERCULES Exposome Research Center and its Stakeholder Advisory Board co-developed the Exposome Roadshow. We present and discuss the resulting community-exposome definition to inform and improve exposome research. Materials and Methods: Four communities from distinct areas across metro-Atlanta participated in separate 2-day Exposome Roadshow workshops with concept mapping. Aligned with a popular education approach in which community knowledge is used to work collectively for change, concept mapping provided a systematic method to collect and visualize community members' knowledge and create a shared understanding to take action. Community members brainstormed, sorted, and rated their responses to the prompt: "What in your environment is affecting your and your community's health?" Responses were analyzed and visually depicted by concept maps consisting of separate but interrelated clusters of ideas. Community members discussed and validated the maps, selecting a final map illustrating their community's exposome. Results: A total of 118 community members completed concept mapping. On average communities identified 7 clusters to define their exposome. The resulting concept maps offer a community definition of the exposome. Five major themes arose across all four communities: conventional environmental concerns, built environment, social relationships, crime and safety, and individual health and behaviors. Discussion: The resulting community-exposome definition demonstrates the importance of expanding the scope of exposures beyond traditional environmental influences to include the lived experience of individuals and communities. While newer exposome definitions align more closely with this community definition, traditional exposome methods do not routinely include these factors. To truly capture the totality of lifetime exposures and improve human health, researchers should incorporate community perspectives into exposome research.

Identifying Issues and Priorities in Reporting Back Environmental Health Data.

Experts recommend reporting environmental exposure results back to research participants and communities, yet environmental health researchers need further guidance to improve the practice of reporting back. We present the results of a workshop developed to identify pertinent issues and areas for action in reporting back environmental health research results. Thirty-five attendees participated, brainstorming responses to the prompt: "What are some specific issues that are relevant to reporting back research results to individuals or the larger community?", and then grouping responses by similarity and rating their importance. Based on a combined theoretical foundation of grounded theory and qualitative content analysis, we used concept mapping to develop a collective understanding of the issues. Visual maps of the participants' responses were created using nonmetric multidimensional scaling and hierarchical cluster analysis. The resulting concept map provided a spatial depiction of five issue areas: Effective Communication Strategies, Community Knowledge and Concerns, Uncertainty, Empowering Action, and Institutional Review and Oversight (listed from highest to lowest rating). Through these efforts, we disentangled the complex issues affecting how and whether environmental health research results are reported back to participants and communities, by identifying five distinct themes to guide recommendations and action. Engaging community partners in the process of reporting back emerged as a unifying global theme, which could improve how researchers report back research results by understanding community context to develop effective communication methods and address uncertainty, the ability to act, and institutional concerns about beneficence and justice.

Neurovascular coupling in normal aging: a combined optical, ERP and fMRI study.

Brain aging is characterized by changes in both hemodynamic and neuronal responses, which may be influenced by the cardiorespiratory fitness of the individual. To investigate the relationship between neuronal and hemodynamic changes, we studied the brain activity elicited by visual stimulation (checkerboard reversals at different frequencies) in younger adults and in older adults varying in physical fitness. Four functional brain measures were used to compare neuronal and hemodynamic responses obtained from BA17: two reflecting neuronal activity (the event-related optical signal, EROS, and the C1 response of the ERP), and two reflecting functional hemodynamic changes (functional magnetic resonance imaging, fMRI, and near-infrared spectroscopy, NIRS). The results indicated that both younger and older adults exhibited a quadratic relationship between neuronal and hemodynamic effects, with reduced increases of the hemodynamic response at high levels of neuronal activity. Although older adults showed reduced activation, similar neurovascular coupling functions were observed in the two age groups when fMRI and deoxy-hemoglobin measures were used. However, the coupling between oxy- and deoxy-hemoglobin changes decreased with age and increased with increasing fitness. These data indicate that departures from linearity in neurovascular coupling may be present when using hemodynamic measures to study neuronal function.

Dietary patterns among the Metro Atlanta Cohort: implications for population-based longitudinal dietary pesticide exposure and risk assessment.

Characterizing dietary consumption patterns is critical to dietary pesticide exposure assessment. We compared consumption patterns between adults (age 18-60) in the Metro Atlanta Cohort (MAC), a longitudinal study of pesticide exposure among Atlanta residents, and US National Health and Nutrition Examination Survey (NHANES) adults. We focused on foods commonly eaten by US adults and foods likely to contain certain pesticide residues. MAC participants provided consumption data for 6 days per month for 1 year using a web-based data collection tool. We defined "percent eaters" as the percent of participants who reported eating a particular food in 24 h. We computed the NHANES weighted percent eaters and 95% confidence limits (CLs) using the 24-h dietary recall data. We calculated the MAC percent eaters for each sampling day and the percent of days this number fell below, within, or above the NHANES 95% CLs. We also re-sampled the MAC percent eaters across sampling days to find whether the resulting distribution resembled the NHANES estimate, and used the Kruskal-Wallis test to evaluate whether season affected the number of MAC eaters of a particular food on a given sampling day. In general, across all sampling days, a greater proportion of MAC participants reported eating banana, broccoli, cream, grapes, lettuce, onion, peach, pear, peas, strawberries, string beans, and tomatoes than the national estimate, whereas the proportion of apple, spinach, ketchup and white bread/roll eaters was similar, and the proportion of milk drinkers was lower. Season predicted the number of MAC peach and strawberry eaters but not other foods. The data show how a higher proportion of Atlanta adults may eat certain foods (e.g., peaches in summer or strawberries in spring) than the national average depending on season or other factors. An exposure assessment that ignored this difference could underestimate dietary pesticide intakes.

Assessing children's dietary pesticide exposure: direct measurement of pesticide residues in 24-hr duplicate food samples.

BACKGROUND: The data presented here are a response to calls for more direct measurements of pesticide residues in foods consumed by children and provide an opportunity to compare direct measures of pesticide residues in foods representing actual consumption with those reported by the U.S. Department of Agriculture Pesticide Data Program. OBJECTIVE: We measured pesticide residues in 24-hr duplicate food samples collected from a group of 46 young children participating in the Children's Pesticide Exposure Study (CPES). METHODS: Parents were instructed to collect 24-hr duplicate food samples of all conventional fruits, vegetables, and fruit juices equal to the quantity consumed by their children, similarly prewashed/ prepared, and from the same source or batch. Individual or composite food items were analyzed for organophosphate (OP) and pyrethroid insecticide residues. RESULTS: We collected a total of 239 24-hr duplicate food samples collected from the 46 CPES children. We found 14% or 5% of those food samples contained at least one OP or pyrethroid insecticide, respectively. We measured a total of 11 OP insecticides, at levels ranging from 1 to 387 ng/g, and three pyrethroid insecticides, at levels ranging from 2 to 1,133 ng/g, in children's food samples. We found that many of the food items consumed by the CPES children were also on the list of the most contaminated food commodities reported by the Environmental Working Group. CONCLUSIONS: The frequent consumption of food commodities with episodic presence of pesticide residues that are suspected to cause developmental and neurological effects in young children supports the need for further mitigation.

Comparison of food consumption frequencies among NHANES and CPES children: implications for dietary pesticide exposure and risk assessment.

Characterizing food consumption patterns among children is critical to dietary pesticide exposure assessment. We have used public release data from the US National Health and Nutrition Examination Survey (NHANES) and the longitudinal Children's Pesticide Exposure Study (CPES) to illustrate the magnitude of potential error introduced by using national-scale, cross-sectional data to estimate the consumption frequencies for smaller cohorts. We focused on foods commonly consumed by children in the target CPES age and income group (3-11 years; annual household income >$75,000) and foods likely to contain organophosphorus or pyrethroid pesticide residues. We defined "percent eaters" as the percentage of study participants who reported eating a particular food in a 24-h period. We computed the weighted percent eaters and 95% confidence limits (CL) for the target age/income group using the NHANES 24-h dietary recall data and compared these with the CPES percent eaters by sampling day and season. For certain foods, particularly the seasonally available produce (for example, apples, peaches/nectarines, melon, grapes, pears, strawberries), soy milk, and peanut butter, the CPES percent eaters fell outside the NHANES 95% CLs on many sampling days. For other foods (for example, orange juice and cow's milk), differences were not readily apparent. Although the differences we observed for certain foods may be, in part, because of measurement error, they also likely reflect seasonal and geographic patterns among the CPES data that the public release NHANES data do not capture. Using NHANES data to estimate pesticide intakes from strawberries, for example, may underestimate the exposure of the CPES children, as significantly more CPES than NHANES children ate strawberries on many sampling days. For other sampling days or other foods, overestimation is also possible.

Evaluation of physiological measures for correcting variation in urinary output: Implications for assessing environmental chemical exposure in children.

Urinary contaminant concentrations are commonly adjusted by creatinine to account for the variability in urinary output. This approach may not be optimal among children due to developmental growth of muscle mass and the associated increase in creatinine formation. An alternative approach is to measure the specific gravity of the urine sample, which reflects the solute concentration of the urine. We compare the appropriateness of urinary creatinine and urinary-specific gravity as factors for correcting morning and evening spot urine samples collected from 23 children (3-11 years) for a total of 41 days in four different seasons. Two linear mixed-effects models were fit using age, sex, season, and sample collection time (morning/evening) as predictors with specific gravity and creatinine as dependent variables. Specific gravity was significantly associated with the sample collection time (P<0.001) with morning samples higher than evening samples. Creatinine was significantly associated with season (P<0.05), sample collection time (P<0.0001), and age (P<0.0001). Creatinine levels were higher during the summer compared to the other seasons, higher in the morning compared to the evening, and higher with increases in children's age. Normalizing the children's spot urine samples using creatinine would introduce bias to the data analysis. Whereas using specific gravity to correct for variable urinary output would be more robust. In addition, measuring specific gravity is relatively easy, does not require the use of chemicals, and the results are available instantaneously.

The attribution of urban and suburban children's exposure to synthetic pyrethroid insecticides: a longitudinal assessment.

Despite the widespread use of synthetic pyrethroid insecticides that led to common exposure in the population, very few studies have been conducted to quantitatively assess human, particularly, children's, long-term exposures to pyrethroid insecticides. The objective of the Children Pesticide Exposure Study - Washington (CPES-WA) was to establish the longitudinal exposure profiles for pyrethroid insecticides in a cohort of children living in an urban and suburban community using urinary pyrethroid metabolites as exposure biomarkers. The results from this analysis will allow us to examine potential risk factors in relation to the elevated pyrethroid insecticide exposure in children. A total of 23 children, aged 3-11 years, who only consumed conventional diets were enrolled in this 1-year study. We provided organic food items to children for 5 consecutive days in the summer and fall sampling seasons. We measured urinary metabolites for the synthetic pyrethroid insecticides in urine samples that were collected twice daily during each of the four sampling seasons. 3-phenoxybenzoic acid was frequently detected in the urine samples with mean and median daily volume-weighted average levels of 1.5 and 1.2 microg/l, followed by trans-2,2-(dichloro)-2-dimethylvinylcyclopropane carboxylic acid (1.4 and 1.0 microg/l) and cis-2,2-(dichloro)-2-dimethylvinylcyclopropane carboxylic acid (0.5 microg/l, and non-detected). When we took into account season, age, sex, diet, and self-reported residential use of pyrethroid insecticides in a linear mixed-effects model, the results suggested that the combination of the use of pyrethroid insecticides in the household, dietary intake, and seasonal differences play a significant role in predicting children's exposure to synthetic pyrethroid insecticides. We found CPES-WA children were continuously exposed to pyrethroid insecticides through their diets all year long, and this chronic exposure pattern was periodically modified by episodes of relatively high exposures from residential uses. Future research should be devoted to enhancing our understanding of the complexity of pyrethroid insecticide exposure patterns.

Dietary intake and its contribution to longitudinal organophosphorus pesticide exposure in urban/suburban children.

BACKGROUND: The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further. OBJECTIVES: We assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure. METHODS: Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. RESULTS: By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to non-detected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. CONCLUSIONS: The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.

Estimating dietary consumption patterns among children: a comparison between cross-sectional and longitudinal study designs.

Estimating dietary intake for children is an essential component of conducting pesticide exposure assessments given the fact that children are predominantly exposed to certain pesticides, such as organophosphorus pesticide, through dietary intake. Different study designs and their respective sampling methodology utilized to estimate food consumption patterns can significantly alter the parameter estimates and the variability in the values obtained. This study investigated the impacts of study design on overall estimates of dietary intake by applying the temporal sampling characteristics used in cross-sectional approaches, as in The Continuing Survey of Food for Intakes by Individuals (CSFII), to food consumption data collected in a longitudinal manner via a bootstrap sampling technique. We examined the precision of time-averaged dietary intake estimates under various sampling schemes and explored the contribution of seasonality toward the dietary patterns. A comparison between the estimates of food consumption obtained from the bootstrap replicates and the longitudinal study estimates indicate that variability is significantly decreased when employing a longitudinal study design. Moreover, both between and within-subject variability decreases when individuals are followed over an increasing number of days. Finally, within the longitudinal study cohort, we observed a seasonal component to dietary intake for fruits and grains. Our findings suggest that longitudinal dietary surveys offer substantial improvements for exposure assessment compared to a standard cross-sectional design.

Effects of measurement method, wavelength, and source-detector distance on the fast optical signal.

Fast optical signals can be used to study the time course of neuronal activity in localized cortical areas. The first report of such signals [Gratton, G., Corballis, P. M., Cho, E., Fabiani, M., Hood, D., 1995a. Shades of gray matter: Noninvasive optical images of human brain responses during visual stimulation. Psychophysiol, 32, 505-509.] was based on photon delay measures. Subsequently, other laboratories have also measured fast optical signals, but a debate still exists about how these signals are generated and optimally recorded. Here we report data from a visual stimulation paradigm in which different parameters (continuous: DC intensity; modulated: AC intensity and photon delay), wavelengths (shorter and longer than the hemoglobin isosbestic point), and source-detector distances (shorter and longer than 22.5 mm) were used to record fast signals. Results indicate that a localized fast signal (peak latency=80 ms) can be detected with both delay and AC intensity measures in visual cortex, but not with unmodulated DC measures. This is likely due to the fact that differential measures (delay and AC intensity) are less sensitive to superficial noise sources, which heavily influence DC intensity. The fast effect had similar sign at wavelengths shorter and longer than the hemoglobin isosbestic point, consistent with light scattering but not rapid deoxygenation accounts of this phenomenon. Finally, the fast signal was only measured at source-detector distances greater than 22.5 mm, consistent with the intracranial origin of the signal, and providing indications about the minimum distance for recording. These data address some of the open questions in the field and provide indications about the optimal recording methods for fast optical signals.

Strategic control and medial frontal negativity: beyond errors and response conflict.

Errors in timed choice tasks typically produce an error-related negativity (ERN) in the event-related potential (ERP). The error specificity of the ERN has been challenged by studies showing a correct response negativity (CRN). Forty-five participants engaged in a flanker task in which both compatibility between flankers and target and the probability of compatible flankers were manipulated. Correct responses elicited a CRN, the amplitude of which increased with the degree of mismatch between the presence of conflict and conflict probability, even on low-conflict (compatible) trials. The fronto-central N2 component was larger on high-conflict (incompatible) correct response trials. However, in contrast to some recent accounts, this N2 was largest for highly probable stimuli. These findings suggest revision to models of the effects of conflict on response-related negativity to account for strategic adjustments made in preparation for the response.

Effects of alcohol on person perception: a social cognitive neuroscience approach.

The acute effects of alcohol on cognitive processing of expectancy violations were investigated using event-related brain potentials and a cued recall task to index attentional and working memory processes associated with inconsistency resolution. As predicted, expectancy-violating behaviors elicited larger late positive potentials (LPP) and were recalled better than expectancy-consistent behaviors. These effects were moderated by alcohol and the valence of initial expectancies. For placebo group participants, positive targets performing negative behaviors elicited the largest LPP responses and were recalled best. For those in the alcohol groups, negative targets behaving positively elicited the largest LPP and recall responses. These findings suggest that alcohol does not globally impair working memory processes in person perception but instead changes the nature of valenced information processing. Findings are discussed in the context of alcohol's effects on working memory processes, reward sensitivity, and the prefrontal cortical structures thought to mediate them.