Background: Methylmercury (MeHg) is a pollutant of global concern. While there is a need to gauge early-life exposures, there remain outstanding ethical, financial, and practical challenges with using the preferred biomarker, whole blood, notably in pregnant women, infants, toddlers, and children. Dried bloodspots (DBS) may help overcome some of these challenges. Notably DBS are collected from newborns in many jurisdictions offering an institutionalized platform to efficiently characterize exposures.
Objective: To develop, validate, and apply a new method to measure MeHg levels in DBS with a specific aim to use this method to increase understanding of newborn exposures.
Methods: Method development and validation was pursued by consulting U.S. EPA Method 1630 and other resources. The method was applied to measure MeHg levels in DBS from newborns (n = 675) from the Michigan BioTrust for Health program.
Results: The assay's detection limit (0.3μg/L), accuracy (96-115% of expected), precision, linearity, and range met performance criteria guidelines. In the newborn DBS samples, the mean (SD) and geometric mean values of MeHg were 1.46 (0.90) and 1.25μg/L respectively, and ranged from 0.09 to 9.97μg/L. The values we report here are similar to cord blood mercury values reported elsewhere.
Conclusions: This is the first characterization of MeHg exposure in newborns, and thus fills an important data gap as prior studies have focused on pregnant women, cord blood, or toddlers. This method helps overcome technical challenges associated with other proposed approaches, and moving ahead there is great promise for applying this DBS-based method for population-level surveillance, particularly in resource-limited settings and for children's health.
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http://dx.doi.org/10.1016/j.envres.2017.08.021 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
Background: Pharmacoepidemiologic studies assessing drug effectiveness for Alzheimer's disease and related dementias (ADRD) are increasingly popular given the critical need for effective therapies for ADRD. To meet the urgent need for robust dementia ascertainment from real-world data, we aimed to develop a novel algorithm for identifying incident and prevalent dementia in claims.
Method: We developed algorithm candidates by different timing/frequency of dementia diagnosis/treatment to identify dementia from inpatient/outpatient/prescription claims for 6,515 and 3,997 participants from Visits 5 (2011-2013; mean age 75.
Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFBackground: Availability of amyloid modifying therapies will dramatically increase the need for disclosure of Alzheimer's disease (AD) related genetic and/or biomarker test results. The 21st Century Cares Act requires the immediate return of most medical test results, including AD biomarkers. A shortage of genetic counselors and dementia specialists already exists, thus driving the need for scalable methods to responsibly communicate test results.
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