Predicting Human Health Effects from Environmental Exposures: Applying Translatable and Accessible Biomarkers of Effect Proceedings of a Workshop–in Brief (2020) / Chapter Skim
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Proceedings of a Workshop IN BRIEF October 2020 Predicting Human Health Effects from Environmental Exposures: Applying Translatable and Accessible Biomarkers of Effect Proceedings of a Workshop -- in Brief Biomarkers of effect are measurable changes in an individual that indicate health impairment or disease. Although biomarkers have long been a crucial part of medical practice -- blood pressure is a simple example -- researchers have recently identified a variety of new biomarkers that signal the presence of conditions such as nervous system damage, autoimmune disorders, and cancer.
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Two other important terms are validation and qualification, which some people use interchangeably, but Sauer drew a distinction between them. Validation is "a process to establish that the performance of a test, tool, or instrument is acceptable for its intended purpose," he said.
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protection against tumors, and the body's response to various injuries. Exogenous agents, including pathogens and environmental toxicants, can trigger immune system actions, and immunotoxicity is defined as the ability of a substance to cause the immune system to behave inappropriately.
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In other Native American communities, a high prevalence of autoantibodies was linked with fish consumption and proximity to an arsenic-contaminated river, said Erdei. She added that more generally, there have been significant increases in ANA prevalence in younger adults across the United States over the past 25 years.
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What makes TSPO particularly useful is that it can be bound to high-affinity ligands that can be labeled with radioisotopes, and this makes it possible to use such imaging techniques as positron emission tomography (PET) and singlephoton-emission computed tomography (SPECT)
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a functional change in mRNA expression, 7 of which were associated with low birth weight in the infants. One of them was KCNQ1, a potassium channel–related gene, which has been associated with intrauterine growth depression as well as later-life metabolic health.
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As background, he noted that carcinogenicity assays have a variety of disadvantages. They are done in mice and rats, their cost is typically in the millions of dollars, and they may take a couple of years to complete.
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cohorts after PFAS exposure. Woychik emphasized that new approaches "hold the promise to detect variation between individuals" that could be "enormously helpful" for future precision health efforts.
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McMullen next discussed the context in which biomarkers are used. He offered a list of categories into which biomarkers might be classified: diagnostic, monitoring, predictive, prognostic, pharmacodynamic/response, safety, and susceptibility/ risk.
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As newer technologies and new knowledge have appeared, a variety of novel biomarkers have come under discussion, Chorley said, and he pointed to miRNAs as a particularly promising example. These are markers of gene expression, not just of one gene but of multiple genes.
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Evaluating and Improving the Biomarker Pipeline In the second presentation session, Joshua Wallach of Yale University spoke about evaluating and improving the biomarker pipeline. He explained that he is not a biomarker expert but rather carries out research on research -- a "meta-researcher," as he termed it -- who studies how research is conducted and how it can be improved.
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biomarkers, but there should be continuing evaluation for all. Sauer said that this approach is being encouraged in the pharmaceutical world -- collecting data on safety biomarkers after they have been implemented.
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to keep this context in mind, Jackson said, because the internal biological signals that are the subject of biomarkers of effect are often influenced by external environmental factors. In short, she added, researchers interested in the effects of chemical or non-chemical stressors on health should move beyond an oversimplified reductionist approach and take into account the more complex systems and complete picture that includes multiple levels of influences that play a role in health outcomes.
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For instance, researchers need to consider how to incorporate factors such as socioeconomic stress and its biological effects into their models. Fry said that her group is beginning work in which they take blood cells from genetically diverse populations and transform those into human pluripotent stem cells that can then be cultured into various body cell types.
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context of use for the biomarker, because the radar plot can change depending on the context. Reza Rasoulpour of Corteva Agriscience added that it is not just the context that must be taken into account, but the radar plot for γH2AX should be compared with radar plots for other choices of biomarkers.
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DISCLAIMER: This Proceedings of a Workshop -- in Brief was prepared by Robert Poole, Fran Sharples, and Keegan Sawyer as a factual summary of what occurred at the workshop. The planning committee's role was limited to planning the workshop.
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