National Institute Of Environmental Health Sciences Research Articles

Ethical, Legal, and Social Implications of Gene-Environment Interaction Research.

Many complex disorders are impacted by the interplay of genetic and environmental factors. In gene-environment interactions (GxE), an individual's genetic and epigenetic makeup impacts the response to environmental exposures. Understanding GxE can impact health at the individual, community, and population levels. The rapid expansion of GxE research in biomedical studies for complex diseases raises many unique ethical, legal, and social implications (ELSIs) that have not been extensively explored and addressed. This review article builds on discussions originating from a workshop held by the National Institute of Environmental Health Sciences (NIEHS) and the National Human Genome Research Institute (NHGRI) in January 2022, entitled: "Ethical, Legal, and Social Implications of Gene-Environment Interaction Research." We expand upon multiple key themes to inform broad recommendations and general guidance for addressing some of the most unique and challenging ELSI in GxE research. Key takeaways include strategies and approaches for establishing sustainable community partnerships, incorporating social determinants of health and environmental justice considerations into GxE research, effectively communicating and translating GxE findings, and addressing privacy and discrimination concerns in all GxE research going forward. Additional guidelines, resources, approaches, training, and capacity building are required to further support innovative GxE research and multidisciplinary GxE research teams.

Combined Exposures and Mixtures Research: An Enduring NIEHS Priority.

The National Institute of Environmental Health Sciences (NIEHS) continues to prioritize research to better understand the health effects resulting from exposure to mixtures of chemical and nonchemical stressors. Mixtures research activities over the last decade were informed by expert input during the development and deliberations of the 2011 NIEHS Workshop "Advancing Research on Mixtures: New Perspectives and Approaches for Predicting Adverse Human Health Effects." NIEHS mixtures research efforts since then have focused on key themes including a) prioritizing mixtures for study, b) translating mixtures data from in vitro and invivo studies, c) developing cross-disciplinary collaborations, d) informing component-based and whole-mixture assessment approaches, e) developing sufficient similarity methods to compare across complex mixtures, f) using systems-based approaches to evaluate mixtures, and g) focusing on management and integration of mixtures-related data. We aimed to describe NIEHS driven research on mixtures and combined exposures over the last decade and present areas for future attention. Intramural and extramural mixtures research projects have incorporated a diverse array of chemicals (e.g., polycyclic aromatic hydrocarbons, botanicals, personal care products, wildfire emissions) and nonchemical stressors (e.g., socioeconomic factors, social adversity) and have focused on many diseases (e.g., breast cancer, atherosclerosis, immune disruption). We have made significant progress in certain areas, such as developing statistical methods for evaluating multiple chemical associations in epidemiology and building translational mixtures projects that include both in vitro and invivo models. Moving forward, additional work is needed to improve mixtures data integration, elucidate interactions between chemical and nonchemical stressors, and resolve the geospatial and temporal nature of mixture exposures. Continued mixtures research will be critical to informing cumulative impact assessments and addressing complex challenges, such as environmental justice and climate change. https://doi.org/10.1289/EHP14340.

Epigenetic age acceleration in follicular fluid and markers of ovarian response among women undergoing IVF.

Are markers of epigenetic age acceleration in follicular fluid associated with outcomes of ovarian stimulation? Increased epigenetic age acceleration of follicular fluid using the Horvath clock, but not other epigenetic clocks (GrimAge and Granulosa Cell), was associated with lower peak estradiol levels and decreased number of total and mature oocytes. In granulosa cells, there are inconsistent findings between epigenetic age acceleration and ovarian response outcomes. Our study included 61 women undergoing IVF at an academic fertility clinic in the New England area who were part of the Environment and Reproductive Health Study (2006-2016). Participants provided a follicular fluid sample during oocyte retrieval. DNA methylation of follicular fluid was assessed using a genome-wide methylation screening tool. Three established epigenetic clocks (Horvath, GrimAge, and Granulosa Cell) were used to predict DNA-methylation-based epigenetic age. To calculate the age acceleration, we regressed epigenetic age on chronological age and extracted the residuals. The association between epigenetic age acceleration and ovarian response outcomes (peak estradiol levels, follicle stimulation hormone, number of total, and mature oocytes) was assessed using linear and Poisson regression adjusted for chronological age, three surrogate variables (to account for cellular heterogeneity), race, smoking status, initial infertility diagnosis, and stimulation protocol. Compared to the median chronological age of our participants (34 years), the Horvath clock predicted, on an average, a younger epigenetic age (median: 24.2 years) while the GrimAge (median: 38.6 years) and Granulosa Cell (median: 39.0 years) clocks predicted, on an average, an older epigenetic age. Age acceleration based on the Horvath clock was associated with lower peak estradiol levels (-819.4 unit decrease in peak estradiol levels per standard deviation increase; 95% CI: -1265.7, -373.1) and fewer total (% change in total oocytes retrieved per standard deviation increase: -21.8%; 95% CI: -37.1%, -2.8%) and mature oocytes retrieved (% change in mature oocytes retrieved per standard deviation increase: -23.8%; 95% CI: -39.9%, -3.4%). The age acceleration based on the two other epigenetic clocks was not associated with markers of ovarian response. Our sample size was small and we did not specifically isolate granulosa cells from follicular fluid samples so our samples could have included mixed cell types. Our results highlight that certain epigenetic clocks may be predictive of ovarian stimulation outcomes when applied to follicular fluid; however, the inconsistent findings for specific clocks across studies indicate a need for further research to better understand the clinical utility of epigenetic clocks to improve IVF treatment. The study was supported by grants ES009718, ES022955, ES000002, and ES026648 from the National Institute of Environmental Health Sciences (NIEHS) and a pilot grant from the NIEHS-funded HERCULES Center at Emory University (P30 ES019776). RBH was supported by the Emory University NIH Training Grant (T32-ES012870). N/A.

Abstract 859: Development of non-smoking lung cancers by indoor carcinogenic aerosols through epigenetic reprogramming of lung stem cells: Bioinformatics and artificial intelligence analysis

Abstract Several scientific studies discovered the toxic effects of indoor aerosols on different organs’ adult stem cells of the human body. The most importantly, the indoor toxic aerosols comprised of numerous carcinogens namely, sodium dodecyl sulfate, phthalic acids from floor cleaners, formaldehyde, acetaldehyde, benzene, toluene, ethyl benzene, xylenes, from air fresheners, Hydramethylnon, Pyrethrins, imiprothrin, cypermethrin, tetramethrin, prallethrin and permethrin from ant and roach Killer. However, there was a lack of analysis revealing the mechanism of toxic effects and epigenetic reprogramming of human lung stem cells and development of non-smoking lung cancers. In this study, we analyzed the toxic effects of these chemicals and the mechanism of epigenetic reprograming on lung epithelial cells using Comparative Toxico-genomics Database (CTD), database of Environmental Health Perspectives (EHP), National Institute of Environmental Health Sciences (NIEHS), Google search browser with generative artificial intelligence (AI) and other biological informatics methods (Reactome, Cytoscape PSICQUIC services, and ChEMBL database). We observed from CTD analysis that the chemical gene interactions as risk factors from indoor aerosols showed transcriptionally highly expressed of 31 common genes, by phthalic acids, sodium dodecyl sulfate, from the total of 1347 genes, 107 common genes by formaldehyde, acetaldehyde from the total of 4193 genes and all other toxic ingredients of indoor aerosols. The epigenetic mechanism of histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac, H3K36me3, H3K4me1, Hsa-mir-1301 of lung epithelial, and miRNAs have been revealed by NIH Roadmap Epigenomics Mapping Consortium and the lung tissue arrays were analyzed with AI and matplotlib program. The heterogenic adult stem cell reprogramming is regulated by epigenetic bivalent histone modifications at transcript starts sequences (TSS) of target genes and our current study revealed that CD44, CD80, ALDH2, ALDH3A1, ALDH3B2 are epigenetically reprogrammed with close interaction of other genes by these toxic ingredients of indoor aerosols. Therefore, our results are significant for the carcinogenic effects of indoor aerosols causing for development of lung cancer epigenetically, which may give a clue for the prevention and treatment of nonsmoking lung cancer. Citation Format: Juan Anderson, Mariah Delgado, Malcolm Lovett, Maya Saunders, Geovannie Lake, Samuel Darko, Rose M. Stiffin, Ayivi Huisso, Marilyn Sherman, Latoya Appleton, Amalya Mihnea, Swarnava Das, Mohammad M. Algahtani, Ravi Vadapalli, Biswarup Basu, Arunima Biswas, Noor Neha, Madhumita Das, Marco A. Ruiz, Mayur Doke, Jayanta K. Das. Development of non-smoking lung cancers by indoor carcinogenic aerosols through epigenetic reprogramming of lung stem cells: Bioinformatics and artificial intelligence analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 859.

Broadening the Environmental Lens to Include Social and Structural Determinants of Women's Health Disparities.

Due to the physical, metabolic, and hormonal changes before, during, and after pregnancy, women-defined here as people assigned female at birth-are particularly susceptible to environmental insults. Racism, a driving force of social determinants of health, exacerbates this susceptibility by affecting exposure to both chemical and nonchemical stressors to create women's health disparities. To better understand and address social and structural determinants of women's health disparities, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop focused on the environmental impacts on women's health disparities and reproductive health in April 2022. This commentary summarizes foundational research and unique insights shared by workshop participants, who emphasized the need to broaden the definition of the environment to include upstream social and structural determinants of health. We also summarize current challenges and recommendations, as discussed by workshop participants, to address women's environmental and reproductive health disparities. The challenges related to women's health equity, as identified by workshop attendees, included developing research approaches to better capture the social and structural environment in both human and animal studies, integrating environmental health principles into clinical care, and implementing more inclusive publishing and funding approaches. Workshop participants discussed recommendations in each of these areas that encourage interdisciplinary collaboration among researchers, clinicians, funders, publishers, and community members. https://doi.org/10.1289/EHP12996.

Seminar: Extracellular Vesicles as Mediators of Environmental Stress in Human Disease.

Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress. This seminar addresses the application of new tools and approaches for EV research, developed in part through the National Institutes of Health (NIH) Extracellular RNA Communication Program, and reflects presentations and discussions from a workshop held 27-28 September 2021 by the National Institute of Environmental Health Sciences (NIEHS) and the National Center for Advancing Translational Sciences (NCATS) on "Extracellular Vesicles, Exosomes, and Cell-Cell Signaling in Response to Environmental Stress." The panel of experts discussed current research on EVs and environmental exposures, highlighted recent advances in EV isolation and characterization, and considered research gaps and opportunities toward identifying and characterizing the roles for EVs in environmentally related diseases, as well as the current challenges and opportunities in this field. The authors discuss the application of new experimental models, particularly organ-on-chip (OOC) systems and in vitro approaches and how these have the potential to extend findings in population-based studies of EVs in exposure-related diseases. Given the complex challenges of identifying cell-specific EVs related to environmental exposures, as well as the general heterogeneity and variability in EVs in blood and other accessible biological samples, there is a critical need for rigorous reporting of experimental methods and validation studies. The authors note that these efforts, combined with cross-disciplinary approaches, would ensure that future research efforts in environmental health studies on EV biomarkers are rigorous and reproducible. https://doi.org/10.1289/EHP12980.

Tox21Enricher-Shiny: an R Shiny application for toxicity functional annotation analysis.

Inference of toxicological and mechanistic properties of untested chemicals through structural or biological similarity is a commonly employed approach for initial chemical characterization and hypothesis generation. We previously developed a web-based application, Tox21Enricher-Grails, on the Grails framework that identifies enriched biological/toxicological properties of chemical sets for the purpose of inferring properties of untested chemicals within the set. It was able to detect significantly overrepresented biological (e.g., receptor binding), toxicological (e.g., carcinogenicity), and chemical (e.g., toxicologically relevant chemical substructures) annotations within sets of chemicals screened in the Tox21 platform. Here, we present an R Shiny application version of Tox21Enricher-Grails, Tox21Enricher-Shiny, with more robust features and updated annotations. Tox21Enricher-Shiny allows users to interact with the web application component (available at http://hurlab.med.und.edu/Tox21Enricher/) through a user-friendly graphical user interface or to directly access the application's functions through an application programming interface. This version now supports InChI strings as input in addition to CASRN and SMILES identifiers. Input chemicals that contain certain reactive functional groups (nitrile, aldehyde, epoxide, and isocyanate groups) may react with proteins in cell-based Tox21 assays: this could cause Tox21Enricher-Shiny to produce spurious enrichment analysis results. Therefore, this version of the application can now automatically detect and ignore such problematic chemicals in a user's input. The application also offers new data visualizations, and the architecture has been greatly simplified to allow for simple deployment, version control, and porting. The application may be deployed onto a Posit Connect or Shiny server, and it uses Postgres for database management. As other Tox21-related tools are being migrated to the R Shiny platform, the development of Tox21Enricher-Shiny is a logical transition to use R's strong data analysis and visualization capacities and to provide aesthetic and developmental consistency with other Tox21 applications developed by the Division of Translational Toxicology (DTT) at the National Institute of Environmental Health Sciences (NIEHS).

Natural mineral fibers: conducting inhalation toxicology studies—part B: development of a nose-only exposure system for repeat-exposure in vivo study of Libby amphibole aerosol

Background Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. Results The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. Conclusion The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.

Responding to Disasters: Training Can Overcome Issues in Disaster Response.

Training can assist in overcoming gaps in disaster response. The National Institute of Environmental Health Sciences (NIEHS) Worker Training Program (WTP) funds a network of nonprofit organizations, or grantees, that deliver peer-reviewed safety and health training curricula to workers across a variety of occupational sectors. Grantees' experiences providing training for recovery workers after numerous disasters show the following issues need to be addressed to better protect the safety and health of recovery workers: (1) regulations and guidance documents not sufficient to protect workers; (2) protecting responders' health and safety which is a core value; (3) improving communication between responders and communities to assist in decision-making and guiding safety and health planning; (4) partnerships critical for disaster response; and (5) greater attention to protecting communities disproportionately affected by disasters. This article provides insight into addressing these recurring issues and utilizes them as part of a continuous quality improvement process for disaster responders that may help to reduce responder injuries, illness, and death during future disasters.

Health Research in the Wake of Disasters: Challenges and Opportunities for Sensor Science.

Disaster events adversely affect the health of millions of individuals each year. They create exposure to physical, chemical, biological, and psychosocial hazards while simultaneously exploiting community and individual-level vulnerabilities that allow such exposures to exert harm. Since 2013, the National Institute of Environmental Health Sciences (NIEHS) has led the development of the Disaster Research Response (DR2) program and infrastructure; however, research exploring the nature and effects of disasters on human health is lacking. One reason for this research gap is the challenge of developing and deploying cost-effective sensors for exposure assessment during disaster events. The objective of this commentary is to synergize the consensus findings and recommendations from a panel of experts on sensor science in support of DR2. The NIEHS convened the workshop, "Getting Smart about Sensors for Disaster Response Research" on 28 and 29 July 2021 to discuss current gaps and recommendations for moving the field forward. The workshop invited full discussion from multiple viewpoints, with the goal of identifying recommendations and opportunities for further development of this area of research. The panel of experts included leaders in engineering, epidemiology, social and physical sciences, and community engagement, many of whom had firsthand experience with DR2. The primary finding of this workshop is that exposure science in support of DR2 is severely lacking. We highlight unique barriers to DR2, such as the need for time-sensitive exposure data, the chaos and logistical challenges that ensue from a disaster event, and the lack of a robust market for sensor technologies in support of environmental health science. We highlight a need for sensor technologies that are more scalable, reliable, and versatile than those currently available to the research community. We also recommend that the environmental health community renew efforts in support of DR2 facilitation, collaboration, and preparedness. https://doi.org/10.1289/EHP12270.

Electronic cigarettes exposures modulate Heart Rate and Heart Rate Variability

Background: Despite a lack of empirical data, an unprecedented rise in electronic cigarettes (ECs) has been widely perceived as safe. Multiple studies support a causal link between tobacco cigarette (TC) use and cardiovascular (CV) diseases; however, there is a lack of data with EC use. We have previously shown that chronic and acute EC use decreases heart rate variability (HRV) in humans, likely via increased sympathetic nervous system activation. Objective: We aimed to evaluate HRV effects induced by brief EC exposures utilizing an in-vivo model for freely moving C57BL/6 mice. Methods and Results: Telemetry devices were implanted in the abdomen of six 10-week-old C57BL/6 male mice to monitor electrocardiographic activity continuously. Mice underwent an exposure protocol designed to reflect human vaping topography with two EC exposures, each lasting 15-minutes (4-sec puff/ 26-sec Air) followed by 45-min post-exposure periods. Air (primary control) and PBS (secondary control) were also included, each with their own post-exposure events. During EC exposures, we observed bradycardic effects in heart rate (HR) with the standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and the proportion of adjacent normalized RR intervals that differed by more than 6 ms (pNN 6 ) significantly (p< 0.05) altered as compared to Air exposures. After EC exposures, SDNN, RMSSD and pNN 6 parameters significantly decreased compared to Air. No significant differences between Air and PBS were observed in these parameters. Frequency domain parameters also indicated significant changes in HRV; the low frequency (LF) and high frequency (HF) bands showed marked increases during and after the EC exposures, while the log (LF/HF) ratio remained relatively unchanged, suggesting a possible coactivation of both parasympathetic and sympathetic branches of the autonomic nervous system. Conclusion: Short-term EC exposures lower heart rate and altered HRV in mice in an acute manner, suggesting that ECs may not be safe as previously assumed. This work was funded by the Tobacco-Related Disease Research Program (TRDRP) which included the High Impact Pilot Research Award [28IP-0036], the Cornelius Hopper Diversity Award Supplement and the Student Research Award Supplement, the UCLA Center for Occupational and Environmental Health (COEH) Student Project Award, and in part by the National Institute of Environmental Health Sciences (NIEHS) via the Student-to-Scientist Bridge program at California State University, Northridge [5R25ES025507]. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 6584: Potential carcinogenic effects of electronic nicotine delivery systems through epigenetic reprogramming in oral, brain, and lung stem cells

Abstract Recent scientific studies exhibited that the electronic nicotine delivery systems (ENDS) aerosols comprise numerous carcinogens namely propylene glycol, diacetyl, formaldehyde, acetaldehyde, crotonaldehyde (2-butenal), acetone, acetyl propionyl (2,3-pentanedione), acrolein, nicotine, arsenic, cadmium and radioisotopes, such as Polonium-210 and lead-210. However, there was no such investigation for clarifying the mechanism of carcinogenic effects and epigenetic reprogramming of human oral, brain, and lung stem cells. In this study, we investigated the carcinogenic effects of ENDS aerosols, and the mechanism of epigenetic reprogramming using the Comparative Toxico-genomics Database (CTD), NIH Toxicology Data Network (TOXNET), the database of the National Institute of Environmental Health Sciences (NIEHS), AACR Genomics Evidence Neoplasia Information Exchange (GENIE) database, and other bioinformatics databases. We found from CTD analysis that the chemical gene interactions showed approximately 3% of genes highly expressed by propylene glycol and diacetyl from a total of 98 genes. The AACR GENIE database analysis showed EGFR, is associated with gliomas (191 clinical data, DFCI glioma cohort), found among 98 genes regulated by propylene glycol and diacetyl. The CTD analysis also exhibited the chemical gene interactions of highly expressed 9 common genes (with miR140 by propylene glycol, and formaldehyde from a total of 3983 genes; 5 common genes by propylene glycol, acetaldehyde, from a total of 275 genes; 1 common gene by propylene glycol, crotonaldehyde (2-butenal), from a total of 227 genes; 7 common genes by propylene glycol, acrolein from total 2185 genes; 18 common genes by propylene glycol, and nicotine from total 1244 genes; 11 common genes by propylene glycol, and arsenic from total 4983 genes; 9 common genes with HDAC4, CD86, miR21 by propylene glycol, and cadmium from total 5242 genes. The ENDs aerosols contain Polonium-210 and lead-210 (concentration; 13 ± 2 Bq/kg), which have been reported as Group 1 human carcinogens and emit alpha particles. We found that alpha particles caused DNA lesions, and gene mutations in human oral, brain, and lung stem cells and resulted in long-term chromosomal instability in primary human T lymphocytes by analyzing recent works of literature. The epigenetic mechanisms of histone modifications and these potential carcinogens have been revealed by the database of NIH Roadmap Epigenomics Mapping Consortium and our analysis discovered that Mitogen-activated protein kinase 1(MAPK1) is epigenetically reprogrammed with close interaction of teen genes. Therefore, it is important to find the actual epigenetic mechanism of transcriptional regulation by these potential carcinogens on oral, lung, and brain stem cells, and our current study revealed this important relationship. Citation Format: Akilah Shepard, Oneilia Yearde, Juan Sanchez, Ryan Amador, Gabriel Xirinachs, Erika Hernandez, Elizabeth Corrales, Swarnava Das, Marco Ruiz, Madhumita Das, Rose M. Stiffin, Marilyn Sherman, Alessandra Manzon, Ayivi Huisso, Jayanta K. Das. Potential carcinogenic effects of electronic nicotine delivery systems through epigenetic reprogramming in oral, brain, and lung stem cells. [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 6584.

Government Program Celebrates 25 Years of Commitment to Environmental Justice Movement.

For over 25 years, the National Institute of Environmental Health Sciences (NIEHS) Environmental Career Worker Training Program (ECWTP) has advanced principles of environmental justice by funding nonprofit organizations, or grantees, to deliver health, safety, and job training for individuals from disadvantaged communities. This article provides a brief background of the environmental justice movement and examines the efforts of grantees to demonstrate how the ECWTP model can serve as a pathway for advancing environmental justice in disadvantaged and underserved communities.

Integrating Multiscale Geospatial Environmental Data into Large Population Health Studies: Challenges and Opportunities.

Quantifying the exposome is key to understanding how the environment impacts human health and disease. However, accurately, and cost-effectively quantifying exposure in large population health studies remains a major challenge. Geospatial technologies offer one mechanism to integrate high-dimensional environmental data into epidemiology studies, but can present several challenges. In June 2021, the National Institute of Environmental Health Sciences (NIEHS) held a workshop bringing together experts in exposure science, geospatial technologies, data science and population health to address the need for integrating multiscale geospatial environmental data into large population health studies. The primary objectives of the workshop were to highlight recent applications of geospatial technologies to examine the relationships between environmental exposures and health outcomes; identify research gaps and discuss future directions for exposure modeling, data integration and data analysis strategies; and facilitate communications and collaborations across geospatial and population health experts. This commentary provides a high-level overview of the scientific topics covered by the workshop and themes that emerged as areas for future work, including reducing measurement errors and uncertainty in exposure estimates, and improving data accessibility, data interoperability, and computational approaches for more effective multiscale and multi-source data integration, along with potential solutions.

The Impact of Natural Disasters on Maternal Health: Hurricanes Irma and María in Puerto Rico.

The PROTECT research Center funded by the NIH’s National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program was launched in 2010 to explore the impact of exposure to pollutants on the high rate of premature births in Puerto Rico. In September 2017, Hurricanes Irma and María devastated the archipelago, which caused: collapse of the electrical system, collapse of the communication system, limited access to clean water, food, gas, and health services, destruction of public (e.g., hospitals) and private property (e.g., houses) and more than 4500 deaths. Pregnant and postpartum individuals are especially vulnerable to natural disasters. They face difficulty obtaining adequate pre- and post-natal care, are exposed to increased risk of miscarriage, premature delivery, and giving birth to low birth weight babies during and after disasters and are also more likely to suffer physical and mental health problems compared to the general population during and after disasters. A face-to-face questionnaire was administered to PROTECT participants who were pregnant during hurricanes Irma or Maria or who became pregnant shortly after in order to identify hurricane-related sources of stress and other adverse effects. This paper is based on the answers to the open-ended question at the end of the questionnaire where participants were asked to share their experiences during and after the hurricanes. Among the 375 participants who completed the survey, 76 answers to the open-ended question were considered due to data saturation. The answers to the open-ended question were transcribed into a document in order to facilitate the coding process. The transcribed text was analyzed first to identify emerging categories and then coded to identify common themes as well as divergence among participants. The following themes were identified: pregnancy and birth challenges, lack of access to basic services, housing conditions, stressful working conditions, concerns about health, concerns about their children, and positive or protective aspects. The results indicate how the disruption in access to basic services has a unique impact on the physical and mental health of pregnant and post-partum women in an emergency situation. These findings point to the potential benefit of developing specific protocols designed for emergency preparedness aimed at this population, which can inform healthcare providers and community organizations in case of future events.

Abstract 5830: Carcinogenic effects of metal and metalloids through epigenetic reprogramming of human bone marrow stem cells: The bioinformatics database analysis

Abstract Many scientific studies showed that the carcinogenic effects of environmental contamination of several metal and metalloids on bone marrow stem cells of human body. These carcinogens include, Cadmium, Mercury, Chromium, Aluminum, Nickel and Arsenic. However, there was no such analysis for elucidating the mechanism of carcinogenic effects and epigenetic reprogramming of human bone marrow stem cells. In this study, we analyzed the carcinogenic effects of mentioned carcinogens, and the mechanism of epigenetic reprogramming using NIH Toxicology Data Network (TOXNET), Comparative Toxico-genomics Database (CTD), AACR Genomics Evidence Neoplasia Information Exchange (GENIE) database, database of Environmental Health Perspectives (EHP), National Institute of Environmental Health Sciences (NIEHS), and other bioinformatics database. We found from CTD analysis that the chemical gene interactions showed highly expressed of 272 common genes with miR140 by Cadmium, Mercury from total 3704 genes (approximately 7% affected genes). The AACR GENIE database analysis showed CDKN3, is associated with bone cancer (2 clinical data), HDAC7, TP53, MAPK3K1, MAP2K2 (8 clinical data) found among 272 genes regulated by Cadmium and Mercury. The CTD analysis showed the chemical gene interactions of highly expressed of 102 common genes with miR140 by Chromium, Mercury from a total of 1406 genes; 268 common genes with CD84, CD226 by Mercury, Nickel from a total of 5032 genes; 103 common genes with CD226 by Aluminum, Mercury from a total of 2556 genes; 248 common genes by Arsenic, Mercury from total 5508 genes. Among these 5508 genes, 248 common genes with ALDHA1, 247 common genes with CD40, 248 common genes with CD44, 247 common genes with CD423, 247 common genes with miR10A by Arsenic, Mercury from total 2556 genes. The epigenetic mechanisms of histone modifications (H3K9me3, H3K27me3, H3K27ac, H3K36me3, H3K4me1, H3K4me3 of B cells, hemopoietic stem cells, mesenchymal bone marrow, and chondrocyte stem cells and miRNAs) and these carcinogens have been revealed by the database of EHP, NIEHS, the NIH Roadmap Epigenomics Mapping Consortium, the National Center for Biotechnology Information (NCBI), and U.S. National Library of Medicine (NLM) database. Our previous study reported that the regulation of epigenetic bivalent histone modifications at transcript starts sequences (TSS) of target genes for heterogenic adult stem cells (CSCs)reprogramming and our current bioinformatics analysis revealed that TP53 is epigenetically reprogrammed with close interaction of thirteen genes by these carcinogens. Therefore, it is important to find the actual epigenetic mechanism both genomic and epigenomic transcriptional regulation and carcinogenic effects of these carcinogens on bone marrow stem cells, and our current study revealed this important relationship. Citation Format: Benedrica Solomon, Richgena Sturrup, Jada Dixon, Kiyona Jackson, Biancaliz Cruz, Charlissia Ferguson, Taylor Walker, Ralph Elisson, Nathan Harris, Jesennia Bonilla, Rose Mary Stiffin, Marilyn Sherman, Alessandra Manzon, Swarnava Das, Madhumita Das, Jayanta Kumar Das. Carcinogenic effects of metal and metalloids through epigenetic reprogramming of human bone marrow stem cells: The bioinformatics database analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5830.

Understanding exposures and latent disease risk within the National Institute of Environmental Health Sciences Superfund Research Program.

Understanding the health effects of exposures when there is a lag between exposure and the onset of disease is an important and challenging topic in environmental health research. The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) is a National Institutes of Health (NIH) grant program that uses a multidisciplinary approach to support biomedical and environmental science and engineering research. Because of the multidisciplinary nature of the program, SRP grantees are well-positioned to study exposure and latent disease risk across humans, animal models, and various life stages. SRP-funded scientists are working to address the challenge of connecting exposures that occur early in life and prior to conception with diseases that manifest much later, including developing new tools and approaches to predict how chemicals may affect long-term health. Here, we highlight research from the SRP focused on understanding the health effects of exposures with a lag between exposure and the onset of the disease as well as provide future directions for addressing knowledge gaps for this highly complex and challenging topic. Advancing the knowledge of latency to disease will require a multidisciplinary approach to research, the need for data sharing and integration, and new tools and computation approaches to make better predications about the timing of disease onset. A better understanding of exposures that may contribute to later-life diseases is essential to supporting the implementation of prevention and intervention strategies to reduce or modulate exposures to reduce disease burden.

Exposure to Metal Mixtures in Association with Cardiovascular Risk Factors and Outcomes: A Scoping Review.

Since the National Institute of Environmental Health Sciences (NIEHS) declared conducting combined exposure research as a priority area, literature on chemical mixtures has grown dramatically. However, a systematic evaluation of the current literature investigating the impacts of metal mixtures on cardiovascular disease (CVD) risk factors and outcomes has thus far not been performed. This scoping review aims to summarize published epidemiology literature on the cardiotoxicity of exposure to multiple metals. We performed systematic searches of MEDLINE (PubMed), Scopus, and Web of Science to identify peer-reviewed studies employing statistical mixture analysis methods to evaluate the impact of metal mixtures on CVD risk factors and outcomes among nonoccupationally exposed populations. The search was limited to papers published on or after 1998, when the first dedicated funding for mixtures research was granted by NIEHS, through 1 October 2021. Twenty-nine original research studies were identified for review. A notable increase in relevant mixtures publications was observed starting in 2019. The majority of eligible studies were conducted in the United States (n = 10) and China (n = 9). Sample sizes ranged from 127 to 10,818. Many of the included studies were cross-sectional in design. Four primary focus areas included: (i) blood pressure and/or diagnosis of hypertension (n = 15), (ii) risk of preeclampsia (n = 3), (iii) dyslipidemia and/or serum lipid markers (n = 5), and (iv) CVD outcomes, including stroke incidence or coronary heart disease (n = 8). The most frequently investigated metals included cadmium, lead, arsenic, and cobalt, which were typically measured in blood (n = 15). The most commonly utilized multipollutant analysis approaches were Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQSR), and principal component analysis (PCA). To our knowledge, this is the first scoping review to assess exposure to metal mixtures in relation to CVD risk factors and outcomes. Recommendations for future studies evaluating the associations of exposure to metal mixtures with risk of CVDs and related risk factors include extending environmental mixtures epidemiologic studies to populations with wider metals exposure ranges, including other CVD risk factors or outcomes outside hypertension or dyslipidemia, using repeated measurement of metals to detect windows of susceptibility, and further examining the impacts of potential effect modifiers and confounding factors, such as fish and seafood intake.

Biosafety and infectious disease occupational health training from the NIEHS Worker Training Program: A historical look at capacity building that supported a COVID-19 response.

The COVID-19 pandemic demonstrated that large segments of the workforce–many of which were not previously considered or valued–are needed to keep the economy moving and critical societal functions going. From first responders to bus drivers, this expanded essential workforce needed training to build a solid knowledge of infectious disease protection practices. However, most workplaces had no existing plan or training for infectious disease exposure control. The National Institute of Environmental Health Sciences (NIEHS) Worker Training Program (WTP) was able to immediately respond with health and safety curricula, resources, and course delivery based on decades of building capacity for disaster and infectious disease response.

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease

2021 Workshop: Neurodegenerative Diseases in the Gut-Brain Axis—Parkinson's Disease