Metal Exposure During Pregnancy: Trends, Predictors, Associations with Birth Outcomes and the Modifying Effect of Maternal Psychosocial Stress

Preterm birth is a significant public health concern as a leading cause of infant mortality; it also contributes substantially to childhood and adult morbidity. Other adverse birth outcomes including low birthweight are associated with later comorbidities. There is growing evidence that the underlying contributors to adverse birth outcomes may include environmental contaminants (like metals), but these factors are understudied. Puerto Rico has one of the highest preterm birth rates of all U.S. states and territories. Moreover, the population in Puerto Rico is exposed to higher levels of many environmental chemicals because of heavily contaminated hazardous industrial sites. Even though prenatal exposure to heavy metals has been well investigated, our knowledge of the threats to the fetus at low levels of exposure remains rather limited. From animal studies, few data are available on the effects of excessive exposure from essential trace elements on adverse pregnancy outcomes. As humans are continuously exposed to a mixture of environmental toxicants, and typically not to single agents in isolation, there is a pressing need to study the relationship of exposures both individually and as mixtures. This dissertation investigates the predictors of environmental metal exposures among pregnant women, and the potential of metal exposures measured in different media to increase the risk of adverse birth outcomes. The interactions between psychosocial stress and the exposure biomarkers on adverse birth outcomes are also explored. The four aims of this dissertation examine a subset of participants from the “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)” cohort. Aim 1 of this dissertation identifies levels, trend, and predictors of prenatal exposure for 14 metals. Aim 2 investigates the individual and collective effects of metals on adverse birth outcomes. Of all the metals assessed, blood lead at low levels, and potentially below current reference levels, was the most strongly associated with increased risk of preterm birth and decreased gestational length. Findings in Aim 2 also showed that lead, zinc, and manganese may contribute to adverse birth outcomes. Aim 3 explores the modifying effect of maternal psychosocial stress on the association between the metal exposure biomarkers and adverse birth outcomes. Presence of “poor” psychosocial status strengthened the adverse associations between Mn and preterm birth, indicating that prenatal psychosocial stress may modify vulnerability to metal exposure. Finally, Aim 4 examines the mixture predictive performance of urine and blood metal biomarkers, and integrated multimedia biomarkers incorporating both matrices, in association with preterm birth. Metal mixtures measured in urine (specific gravity corrected), blood, and integrated biomarkers had comparable performance in associations with preterm birth, indicating that using urine or blood may be an equally good approach to evaluate the metals as a mixture, but only when urine measurements of metal account for urinary dilution. Overall, these results broaden our understanding of the effects of metal mixtures on birth outcomes. We identify dietary and behavioral predictors of metal exposures which could inform exposure reduction strategies, and potentially result in an eventual reduction in preterm birth rates. Furthermore, our novel study design underscores the importance of considering the performance of exposure biomarkers measured in different media, and modifying effects of non-chemical exposures, when evaluating the relationship between chemical exposures and birth outcomes. Further studies are needed to substantiate these findings to advance our knowledge on the impact of environmental chemicals on pregnancy.PHDEnvironmental Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/168064/1/pahriya_1.pd

The NIEHS Superfund Research Program: 25 Years of Translational Research for Public Health

BACKGROUND: The Superfund Research Program (SRP) is an academically based, multidisciplinary, translational research program that for 25 years has sought scientific solutions to health and environmental problems associated with hazardous waste sites. SRP is coordinated by the National Institute of Environmental Health Sciences (NIEHS). It supports multi-project grants, undergraduate and postdoctoral training programs, individual research grants, and Small Business Innovation Research (SBIR) and Technology Transfer Research (STTR) grants. RESULTS: SRP has had many successes: discovery of arsenic\u27s toxicity to the developing human central nervous system; documentation of benzene toxicity to hematologic progenitor cells in human bone marrow; development of novel analytic techniques such as the luciferase expression assay and laser fragmentation fluorescence spectroscopy; demonstration that PCBs can cause developmental neurotoxicity at low levels and alter the genomic characteristics of sentinel animals; elucidation of the neurodevelopmental toxicity of organophosphate insecticides; documentation of links between antimicrobial agents and alterations in hormone response; discovery of biological mechanisms through which environmental chemicals may contribute to obesity, atherosclerosis, diabetes, and cancer; tracking the health and environmental effects of the attacks on the World Trade Center and Hurricane Katrina; and development of novel biological and engineering techniques to facilitate more efficient and lower-cost remediation of hazardous waste sites. CONCLUSION: SRP must continue to address the legacy of hazardous waste in the United States, respond to new issues caused by rapid advances in technology, and train the next generation of leaders in environmental health science while recognizing that most of the world\u27s worst toxic hot spots are now located in low- and middle-income countries

Integrated application of genomic, biochemical and cultivation approaches to characterize 1,2-dichloropropane dichloroelemination in organohalide respiring Chloroflexi

Chlorinated solvents are among the most encountered groundwater pollutants. These toxic compounds cause harm to ecosystem functioning and human health. 1,2-Dichloropropane (1,2-D) was used in a variety of industrial and agricultural applications until it was banned in the U.S. in the 1970s. Only a handful of bacteria have been described to reductively dechlorinate 1,2-D to innocuous propene and inorganic chloride, among these the Dehalococcoides (Dhc) strains RC and KS. In order to shed light into the genetic basis of 1,2-D dechlorination, efforts focused in identifying the gene encoding the enzyme system (i.e., reductive dehalogenase) responsible for 1,2-D to propene transformation. To accomplish this goal, a multiple lines of evidence approach combining gene cloning, transcriptional studies, and enzyme activity assays implicated the dcpA gene in 1,2-D reductive dechlorination in Dhc strains RC and KS. This gene was also identified in Dehalogenimonas lykanthroporepellens (Dhgm) strain BL-DC-9, another member of the organohalide-respiring Chloroflexi group, and also capable of growth with 1,2-D as electron acceptor. Propene-producing enrichment cultures were derived from a variety of environments and the presence of dcpA correlated with 1,2-D reductive dechlorination observed in situ and/or in microcosms. Nested PCR and qPCR assays were designed and validated to detected and quantify the gene in laboratory cultures and in environmental samples. These surveys shed light into the distribution of this gene in diverse environments including pristine environments. Genomic and bioinformatics tools explored the gene neighborhood of dcpA and revealed a genomic island shared between Dhc and Dhgm indicative of a horizontal gene transfer event. Metagenome analysis of consortia RC and KS enabled the draft genome assemblies of these two Dhc strains. This analysis revealed that the Dhc strain RC and strain KS harbor at least 34 and 31 reductive dehalogenase genes, including genes implicated in PCB reductive dechlorination. These findings reveal broad reductive dechlorination potential and emphasize that such dedicated dechlorinators (i.e., Dhc strain FL2) occur in pristine environments and are members of natural microbial assemblages that have not been exposed to anthropogenic contamination

Building Industries at Sea - ‘Blue Growth’ and the New Maritime Economy

Throughout the world there is evidence of mounting interest in marine resources and new maritime industries to create jobs, economic growth and to help in the provision of energy and food security. Expanding populations, insecurity of traditional sources of supply and the effects of climate change add urgency to a perceived need to address and overcome the serious challenges of working in the maritime environment. Four promising areas of activity for ‘Blue Growth’ have been identified at European Union policy level including Aquaculture; Renewable Energy (offshore wind, wave and tide); Seabed Mining; and Blue Biotechnology. Work has started to raise the technological and investment readiness levels (TRLs and IRLs) of these prospective industries drawing on the experience of established maritime industries such as Offshore Oil and Gas; Shipping; Fisheries and Tourism. An accord has to be struck between policy makers and regulators on the one hand, anxious to direct research and business incentives in effective and efficient directions, and developers, investors and businesses on the other, anxious to reduce the risks of such potentially profitable but innovative investments.The EU H2020 MARIBE (Marine Investment for the Blue Economy) funded project was designed to identify the key technical and non-technical challenges facing maritime industries and to place them into the social and economic context of the coastal and ocean economy. MARIBE went on to examine with companies, real projects for the combination of marine industry sectors into multi-use platforms (MUPs). The purpose of this book is to publish the detailed analysis of each prospective and established maritime business sector. Sector experts working to a common template explain what these industries are, how they work, their prospects to create wealth and employment, and where they currently stand in terms of innovation, trends and their lifecycle. The book goes on to describe progress with the changing regulatory and planning regimes in the European Sea Basins including the Caribbean where there are significant European interests. The book includes:• Experienced chapter authors from a truly multidisciplinary team of sector specialisms• First extensive study to compare and contrast traditional Blue Economy with Blue Growth• Complementary to EU and National policies for multi-use of maritime spac

Building Industries at Sea - ‘Blue Growth’ and the New Maritime Economy

Throughout the world there is evidence of mounting interest in marine resources and new maritime industries to create jobs, economic growth and to help in the provision of energy and food security. Expanding populations, insecurity of traditional sources of supply and the effects of climate change add urgency to a perceived need to address and overcome the serious challenges of working in the maritime environment. Four promising areas of activity for ‘Blue Growth’ have been identified at European Union policy level including Aquaculture; Renewable Energy (offshore wind, wave and tide); Seabed Mining; and Blue Biotechnology. Work has started to raise the technological and investment readiness levels (TRLs and IRLs) of these prospective industries drawing on the experience of established maritime industries such as Offshore Oil and Gas; Shipping; Fisheries and Tourism. An accord has to be struck between policy makers and regulators on the one hand, anxious to direct research and business incentives in effective and efficient directions, and developers, investors and businesses on the other, anxious to reduce the risks of such potentially profitable but innovative investments.The EU H2020 MARIBE (Marine Investment for the Blue Economy) funded project was designed to identify the key technical and non-technical challenges facing maritime industries and to place them into the social and economic context of the coastal and ocean economy. MARIBE went on to examine with companies, real projects for the combination of marine industry sectors into multi-use platforms (MUPs). The purpose of this book is to publish the detailed analysis of each prospective and established maritime business sector. Sector experts working to a common template explain what these industries are, how they work, their prospects to create wealth and employment, and where they currently stand in terms of innovation, trends and their lifecycle. The book goes on to describe progress with the changing regulatory and planning regimes in the European Sea Basins including the Caribbean where there are significant European interests. The book includes:• Experienced chapter authors from a truly multidisciplinary team of sector specialisms• First extensive study to compare and contrast traditional Blue Economy with Blue Growth• Complementary to EU and National policies for multi-use of maritime spac