Tire-derived contaminants 6PPD and 6PPD-Q: Analysis, sample handling, and reconnaissance of United States stream exposures.

The environmental ubiquity of tire and road wear particles (TRWP) underscores the need to understand the occurrence, persistence, and environmental effects of tire-related chemicals in aquatic ecosystems. One such chemical is 6PPD-quinone (6PPD-Q), a transformation product of the tire antioxidant 6PPD. In urban stormwater runoff 6PPD-Q can exceed acute toxicity thresholds for several salmonid species and is being implicated in significant coho salmon losses in the Pacific Northwest. There is a critical need to understand the prevalence of 6PPD-Q across watersheds to identify habitats heavily affected by TRWPs. We conducted a reconnaissance of 6PPD and 6PPD-Q in surface waters across the United States from sites (N = 94) with varying land use (urban, agricultural, and forested) and streamflow to better understand stream exposures. A rapid, low-volume direct-inject, liquid chromatography mass spectrometry method was developed for the quantitation of 6PPD-Q and screening for 6PPD. Laboratory holding times, bottle material, headspace, and filter materials were investigated to inform best practices for 6PPD-Q sampling and analysis. Glass bottles with PTFE-lined caps minimized sorption and borosilicate glass fiber filters provided the highest recovery. 6PPD-Q was stable for at least 5 months in pure laboratory solutions and for 75 days at 5 °C with minimal headspace in the investigated surface water and stormwaters. Results also indicated samples can be frozen to extend holding times. 6PPD was not detected in any of the 526 analyzed samples and there were no detections of 6PPD-Q at agricultural or forested sites. 6PPD-Q was frequently detected in stormwater (57%, N = 90) and from urban impacted sites (45%, N = 276) with concentrations ranging from 0.002 to 0.29 µg/L. The highest concentrations, above the lethal level for coho salmon, occurred during stormwater runoff events. This highlights the importance of capturing episodic runoff events in urban areas near ecologically relevant habitat or nursery grounds for sensitive species.

Efficacy of addition of the anti-inflammatory, IV glutathione to standard ketamine IV therapy in major depressive disorder.

Ketamine, a N-methyl-D-aspartate (NMDA) antagonist, is used for treatment-resistant depression (TRD). Recent studies have shown that there are increased levels of pro-inflammatory cytokines in individuals with major depressive disorder (MDD) and those with higher levels of oxidative stress markers have a decreased or null response to conventional antidepressants. Glutathione (GSH) as an antioxidant adjuvant to ketamine has not been well studied. This double-blind study with 30 patients divided into 2 groups of 15 each, aimed to determine if GSH, added to standard ketamine infusion (GSH+K), rendered better outcomes in MDD patients versus patients receiving ketamine infusions with a normal saline placebo (K+NS). There were significant drops in BDI-II scores from day 1 to day 14, PHQ- scores from day 1 to day 14 and PHQ-9 scores day 14 to day 28, suggesting the overall treatment was effective. There were no statistically significant differences between the groups over time. However, a sustained improvement in depressive symptoms was observed for 14 days post-infusion in both groups.

Per- and polyfluoroalkyl substances (PFAS) in United States tapwater: Comparison of underserved private-well and public-supply exposures and associated health implications.

Drinking-water quality is a rising concern in the United States (US), emphasizing the need to broadly assess exposures and potential health effects at the point-of-use. Drinking-water exposures to per- and poly-fluoroalkyl substances (PFAS) are a national concern, however, there is limited information on PFAS in residential tapwater at the point-of-use, especially from private-wells. We conducted a national reconnaissance to compare human PFAS exposures in unregulated private-well and regulated public-supply tapwater. Tapwater from 716 locations (269 private-wells; 447 public supply) across the US was collected during 2016-2021 including three locations where temporal sampling was conducted. Concentrations of PFAS were assessed by three laboratories and compared with land-use and potential-source metrics to explore drivers of contamination. The number of individual PFAS observed ranged from 1 to 9 (median: 2) with corresponding cumulative concentrations (sum of detected PFAS) ranging from 0.348 to 346 ng/L. Seventeen PFAS were observed at least once with PFBS, PFHxS and PFOA observed most frequently in approximately 15% of the samples. Across the US, PFAS profiles and estimated median cumulative concentrations were similar among private wells and public-supply tapwater. We estimate that at least one PFAS could be detected in about 45% of US drinking-water samples. These detection probabilities varied spatially with limited temporal variation in concentrations/numbers of PFAS detected. Benchmark screening approaches indicated potential human exposure risk was dominated by PFOA and PFOS, when detected. Potential source and land-use information was related to cumulative PFAS concentrations, and the number of PFAS detected; however, corresponding relations with specific PFAS were limited likely due to low detection frequencies and higher detection limits. Information generated supports the need for further assessments of cumulative health risks of PFAS as a class and in combination with other co-occurring contaminants, particularly in unmonitored private-wells where information is limited or not available.

Estrogenic activity response to best management practice implementation in agricultural watersheds in the Chesapeake Bay watershed.

Best management practices (BMPs) have been predominantly used throughout the Chesapeake Bay watershed (CBW) to reduce nutrients and sediments entering streams, rivers, and the bay. These practices have been successful in reducing loads entering the estuary and have shown the potential to reduce other contaminants (pesticides, hormonally active compounds, pathogens) in localized studies and modeled load estimates. However, further understanding of relationships between BMPs and non-nutrient contaminant reductions at regional scales using sampled data would be beneficial. Total estrogenic activity was measured in surface water samples collected over a decade (2008-2018) in 211 undeveloped NHDPlus V2.1 watersheds within the CBW. Bayesian hierarchical modeling between total estrogenic activity and landscape predictors including landcover, runoff, BMP intensity, and a BMP*agriculture intensity interaction term indicates a 96% posterior probability that BMP intensity on agricultural land is reducing total estrogenic activity. Additionally, watersheds with high agriculture and low BMPs had a 49% posterior probability of exceeding an effects-based threshold in aquatic organisms of 1 ng/L but only a 1% posterior probability of exceeding this threshold in high-agriculture, high-BMP watersheds.

Bottled water contaminant exposures and potential human effects.

BACKGROUND: Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW. METHODS: BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity. Health-benchmark-weighted cumulative hazard indices and ratios of organic-contaminant in vitro exposure-activity cutoffs were assessed for detected regulated and unregulated inorganic and organic contaminants. RESULTS: 48 inorganics and 45 organics were detected in sampled BW. No enforceable chemical quality standards were exceeded, but several inorganic and organic contaminants with maximum contaminant level goal(s) (MCLG) of zero (no known safe level of exposure to vulnerable sub-populations) were detected. Among these, arsenic, lead, and uranium were detected in 67 %, 17 %, and 57 % of BW, respectively, almost exclusively in spring-sourced samples not treated by advanced filtration. Organic MCLG exceedances included frequent detections of disinfection byproducts (DBP) in tapwater-sourced BW and sporadic detections of DBP and volatile organic chemicals in BW sourced from tapwater and springs. Precautionary health-based screening levels were exceeded frequently and attributed primarily to DBP in tapwater-sourced BW and co-occurring inorganic and organic contaminants in spring-sourced BW. CONCLUSION: The results indicate that simultaneous exposures to multiple drinking-water contaminants of potential human-health concern are common in BW. Improved understandings of human exposures based on more environmentally realistic and directly comparable point-of-use exposure characterizations, like this BW study, are essential to public health because drinking water is a biological necessity and, consequently, a high-vulnerability vector for human contaminant exposures.

A case study: temporal trends of environmental stressors and reproductive health of smallmouth bass (Micropterus dolomieu) from a site in the Potomac River Watershed, Maryland, USA.

Decades of poor reproductive success and young-of-the-year survival, combined with adult mortality events, have led to a decline in the smallmouth bass (SMB; Micropterus dolomieu) population in sections of the Potomac River. Previous studies have identified numerous biologic and environmental stressors associated with negative effects on SMB health. To better understand the impact of these stressors, this study was conducted at the confluence of Antietam Creek and the Potomac River from 2013 to 2019 to identify temporal changes associated with SMB reproductive health. Surface water samples were collected and analyzed for over 300 organic contaminants, including pesticides, phytoestrogens, pharmaceuticals, hormones and total estrogenicity (E2Eq). Adult SMB were collected and sampled for multiple endpoints, including gene transcripts associated with reproduction (molecular), histopathology (cellular), and organosomatic indices (tissue). In males, biomarkers of estrogenic endocrine disruption, including testicular oocytes (TO) and plasma vitellogenin (Vtg) were assessed. Numerous agriculture-related contaminants or land use patterns were associated with gene transcript abundance in both male and female SMB. Positive associations between pesticides in the immediate catchment with TO severity and E2Eq with plasma Vtg in males were identified. In males, the prevalence of TO and detectable levels of plasma Vtg, liver vitellogenin transcripts (vtg) and testis vtg were high throughout the study. Peaks of complex mixtures of numerous contaminants occurred during the spring/early summer when spawning and early development occurs and to a lesser extent in fall/winter during recrudescence. Management practices to reduce exposure during these critical and sensitive periods may enhance reproductive health of these economically important sportfishes.

The statistical power to detect regional temporal trends in riverine contaminants in the Chesapeake Bay Watershed, USA.

Chemical contamination of riverine ecosystems is largely a result of urbanization, industrialization, and agricultural activities occurring on adjacent terrestrial landscapes. Land management activities (e.g., Best Management Practices) are an important tool used to reduce point and non-point sources of pollution. However, the ability to confidently make inferences about the efficacy of land management activities on reducing in-stream chemical concentrations is poorly understood. We estimated regional temporal trends and components of variation for commonly used herbicides (atrazine and metolachlor), total estrogenicity, and riverine sediment concentrations of total PCBs for rivers in the Chesapeake Bay Watershed, USA. We then used the estimated variance components to perform a power analysis and evaluated the statistical power to detect regional temporal trends under different monitoring scenarios. Scenarios included varying the magnitude of the annual contaminant decline, the number of sites sampled each year, the number of years sampled, and sampling frequency. Monitoring for short time periods (e.g., 5 years) was inadequate for detecting regional temporal trends, regardless of the number of sites sampled or the magnitude of the annual declines. Even when monitoring over a 20-year period, sampling a relatively large number of sites each year was required (e.g., >50 sites) to achieve adequate statistical power for smaller trend magnitudes (declines of 5-7%/year). Annual sampling frequency had little impact on power for any monitoring scenario. All sampling scenarios were underpowered for sediment total PCBs. Power was greatest for total estrogenicity, suggesting that this aggregate measure of estrogenic activity may be a useful indicator. This study provides information that can be used to help (1) guide the development of monitoring programs aimed at detecting regional declines in riverine chemical contaminant concentrations in response to land management actions, and (2) set expectations for the ability to detect changes over time.

Reproductive health and endocrine disruption in smallmouth bass (Micropterus dolomieu) from the Lake Erie drainage, Pennsylvania, USA.

Smallmouth bass Micropterus dolomieu were sampled from three sites within the Lake Erie drainage (Elk Creek, Twentymile Creek, and Misery Bay, an embayment in Presque Isle Bay). Plasma, tissues for histopathological analyses, and liver and testes preserved in RNALater® were sampled from 30 smallmouth bass (of both sexes) at each site. Liver and testes samples were analyzed for transcript abundance with Nanostring nCounter® technology. Evidence of estrogenic endocrine disruption was assessed by the presence and severity of intersex (testicular oocytes; TO) and concentrations of plasma vitellogenin in male fish. Abundance of 17 liver transcripts associated with reproductive function, endocrine activity, and contaminant detoxification pathways and 40 testes transcripts associated with male and female reproductive function, germ cell development, and steroid biosynthesis were also measured. Males with a high rate of TO (87-100%) and plasma vitellogenin were noted at all sites; however, TO severity was greatest at the site with the highest agricultural land cover. Numerous transcripts were differentially regulated among the sites and patterns of transcript abundance were used to better understand potential risk factors for estrogenic endocrine disruption. The results of this study suggest endocrine disruption is prevalent in this region and further research would benefit to identify the types of contaminants that may be associated with the observed biological effects.

Perfluoroalkyl Substances in Plasma of Smallmouth Bass from the Chesapeake Bay Watershed.

Smallmouth bass Micropterus dolomieu is an economically important sportfish and within the Chesapeake Bay watershed has experienced a high prevalence of external lesions, infectious disease, mortality events, reproductive endocrine disruption and population declines. To date, no clear or consistent associations with contaminants measured in fish tissue or surface water have been found. Therefore, plasma samples from two sites in the Potomac River and two in the Susquehanna River drainage basins, differing in land-use characteristics, were utilized to determine if perfluoroalkyl substances were present. Four compounds, perfluorooctane sulphonic acid (PFOS), perfluoroundecanoic acid (PFUnA), perfluorodecanoic acid (PFDA) and perfluorododecanoic acid (PFDoA), were detected in every fish. Two additional compounds, perfluorooctane sulphonamide (PFOSA) and perfluorononanoic acid (PFNA), were less commonly detected at lower concentrations, depending on the site. Concentrations of PFOS (up to 574 ng/mL) were the highest detected and varied significantly among sites. No seasonal differences (spring versus fall) in plasma concentrations were observed. Concentrations of PFOS were not significantly different between the sexes. However, PFUnA and PFDoA concentrations were higher in males than females. Both agricultural and developed land-use appeared to be associated with exposure. Further research is needed to determine if these compounds could be affecting the health of smallmouth bass and identify sources.

Environmental and anthropogenic drivers of contaminants in agricultural watersheds with implications for land management.

If not managed properly, modern agricultural practices can alter surface and groundwater quality and drinking water resources resulting in potential negative effects on aquatic and terrestrial ecosystems. Exposure to agriculturally derived contaminant mixtures has the potential to alter habitat quality and negatively affect fish and other aquatic organisms. Implementation of conservation practices focused on improving water quality continues to increase particularly in agricultural landscapes throughout the United States. The goal of this study was to determine the consequences of land management actions on the primary drivers of contaminant mixtures in five agricultural watersheds in the Chesapeake Bay, the largest watershed of the Atlantic Seaboard in North America where fish health issues have been documented for two decades. Surface water was collected and analyzed for 301 organic contaminants to determine the benefits of implemented best management practices (BMPs) designed to reduce nutrients and sediment to streams in also reducing contaminants in surface waters. Of the contaminants measured, herbicides (atrazine, metolachlor), phytoestrogens (formononetin, genistein, equol), cholesterol and total estrogenicity (indicator of estrogenic response) were detected frequently enough to statistically compare to seasonal flow effects, landscape variables and BMP intensity. Contaminant concentrations were often positively correlated with seasonal stream flow, although the magnitude of this effect varied by contaminant across seasons and sites. Land-use and other less utilized landscape variables including biosolids, manure and pesticide application and percent phytoestrogen producing crops were inversely related with site-average contaminant concentrations. Increased BMP intensity was negatively related to contaminant concentrations indicating potential co-benefits of BMPs for contaminant reduction in the studied watersheds. The information gained from this study will help prioritize ecologically relevant contaminant mixtures for monitoring and contributes to understanding the benefits of BMPs on improving surface water quality to better manage living resources in agricultural landscapes inside and outside the Chesapeake Bay watershed.

Modeling estrogenic activity in streams throughout the Potomac and Chesapeake Bay watersheds.

Endocrine-disrupting compounds (EDCs), specifically estrogenic endocrine-disrupting compounds, vary in concentration and composition in surface waters under the influence of different landscape sources and landcover gradients. Estrogenic activity in surface waters may lead to adverse effects in aquatic species at both individual and population levels, often observed through the presence of intersex and vitellogenin induction in male fish. In the Chesapeake Bay Watershed, located on the mid-Atlantic coast of the USA, intersex has been observed in several sub-watersheds where previous studies have identified specific landscape sources of EDCs in tandem with observed fish health effects. Previous work in the Potomac River Watershed (PRW), the largest basin within the Chesapeake Bay Watershed, was leveraged to build random forest regression models to predict estrogenic activity at unsampled reaches in both the Potomac River and larger Chesapeake Bay Watersheds (CBW). Model outputs including important variables, partial dependence plots, and predicted values of estrogenic activity at unsampled reaches provide insight into drivers of estrogenic activity at different seasons and scales. Using the US Environmental Protection Agency effects-based threshold of 1.0 ng/L 17 ß-estradiol equivalents, catchments predicted to exceed this value were categorized as at risk for adverse effects from exposure to estrogenic compounds and evaluated relative to healthy watersheds and recreation access locations throughout the PRW. Results show immediate catchment scale models are more reliable than upstream models, and the best predictive variables differ by season and scale. A small percentage of healthy watersheds (< 13%) and public access sites were classified as at risk using the "Total" (annual) model in the CBW. This study is the first Potomac River Watershed assessment of estrogenic activity, providing a new foundation for future risk assessment and management design efforts, with additional context provided for the entire Chesapeake Bay Watershed.

Retrospective analysis of estrogenic endocrine disruption and land-use influences in the Chesapeake Bay watershed.

The Chesapeake Bay is the largest estuary in the United States and its watershed includes river drainages in six states and the District of Columbia. Sportfishing is of major economic interest, however, the rivers within the watershed provide numerous other ecological, recreational, cultural and economic benefits, as well as serving as a drinking water source for millions of people. Consequently, major fish kills and the subsequent finding of estrogenic endocrine disruption (intersex or testicular oocytes and plasma vitellogenin in male fishes) raised public and management concerns. Studies have occurred at various sites within the Bay watershed to document the extent and severity of endocrine disruption, identify risk factors and document temporal and spatial variability. Data from these focal studies, which began in 2004, were used in CART (classification and regression trees) analyses to better identify land use associations and potential management practices that influence estrogenic endocrine disruption. These analyses emphasized the importance of scale (immediate versus upstream catchment) and the complex mixtures of stressors which can contribute to surface water estrogenicity and the associated adverse effects of exposure. Both agricultural (percent cultivated, pesticide application, phytoestrogen cover crops) and developed (population density, road density, impervious surface) land cover showed positive relationships to estrogenic indicators, while percent forest and shrubs generally had a negative association. The findings can serve as a baseline for assessing ongoing restoration and management practices.

Cognitive Fitness to Drive in Huntington's Disease: Assessing the Clinical Utility of DriveSafe DriveAware.

BACKGROUND: DriveSafe DriveAware (DSDA) has been validated as an off-road screening tool for predicting on-road driving performance in clinical populations, but its utility in people with Huntington's disease (HD) is unknown. OBJECTIVE: Our aim was to evaluate the utility of DSDA in people with HD by demonstrating sensitivity of DSDA scores to HD progression and exploring associations between DSDA performance and cognitive functions that are essential to driving and impaired in people with HD. METHODS: We administered the iPad application version of DSDA to 26 pre-symptomatic and symptomatic participants with HD. Disease progression was assessed via measures of motor impairment, disease burden and functional capacity. Standardised neuropsychological tests were used to assess cognitive function across several domains including attention, processing speed, planning, and visuoperception. RESULTS: Results underscore the sensitivity of DSDA to HD progression and cognitive impairment; that is, poorer DSDA performance was associated with greater HD severity and poorer cognitive ability across the domains of attention, processing speed, and planning. Nevertheless, we identified a proportion of participants with HD who were predicted to pass on-road testing based on DSDA, but scored in the impaired range on multiple cognitive tests. These participants tended to score closer to the cut-off score used by DSDA to categorise pass/fail outcomes. CONCLUSIONS: Our findings demonstrate potential for use of DSDA in the HD population, however, significant variability in cognitive performance among those predicted to 'pass' on-road driving assessment suggests the screening tool requires further development for use with HD drivers.

RNA-Dependent Epigenetic Silencing Directs Transcriptional Downregulation Caused by Intronic Repeat Expansions.

Transcriptional downregulation caused by intronic triplet repeat expansions underlies diseases such as Friedreich's ataxia. This downregulation of gene expression is coupled with epigenetic changes, but the underlying mechanisms are unknown. Here, we show that an intronic GAA/TTC triplet expansion within the IIL1 gene of Arabidopsis thaliana results in accumulation of 24-nt short interfering RNAs (siRNAs) and repressive histone marks at the IIL1 locus, which in turn causes its transcriptional downregulation and an associated phenotype. Knocking down DICER LIKE-3 (DCL3), which produces 24-nt siRNAs, suppressed transcriptional downregulation of IIL1 and the triplet expansion-associated phenotype. Furthermore, knocking down additional components of the RNA-dependent DNA methylation (RdDM) pathway also suppressed both transcriptional downregulation of IIL1 and the repeat expansion-associated phenotype. Thus, our results show that triplet repeat expansions can lead to local siRNA biogenesis, which in turn downregulates transcription through an RdDM-dependent epigenetic modification.

A method to quantify and value floodplain sediment and nutrient retention ecosystem services.

Floodplains provide critical ecosystem services to local and downstream communities by retaining floodwaters, sediments, and nutrients. The dynamic nature of floodplains is such that these areas can both accumulate sediment and nutrients through deposition, and export material downstream through erosion. Therefore, estimating floodplain sediment and nutrient retention should consider the net flux of both depositional and erosive processes. An ecosystem services framework was used to quantify and value the sediment and nutrient ecosystem service provided by floodplains in the Difficult Run watershed, a small (151 km2) suburban watershed located in the Piedmont of Virginia (USA). A sediment balance was developed for Difficult Run and two nested watersheds. The balance included upland sediment delivery to streams, stream bank flux, floodplain flux, and stream load. Upland sediment delivery was estimated using geospatial datasets and a modified Revised Universal Soil Loss Equation. Predictive models were developed to extrapolate field measurements of the flux of sediment, sediment-bound nitrogen (N), and sediment-bound phosphorus (P) from stream banks and floodplains to 3232 delineated stream segments in the study area. A replacement cost approach was used to estimate the economic value of the sediment and nutrient retention ecosystem service based on estimated net stream bank and floodplain flux of sediment-bound N for all streams in the study area. Results indicated the net fluvial fluxes of sediment, sediment-bound N, and sediment-bound P were -10,439 Mg yr-1 (net export), 57,300 kg-N yr-1 (net trapping), and 98 kg-P yr-1(net trapping), respectively. For sediment, floodplain retention was offset by substantial losses from stream bank erosion, particularly in headwater catchments, resulting in a net export of sediment. Nutrient retention in the floodplain exceeded that lost through stream bank erosion resulting in net retention of nutrients (TN and TP). Using a conservative cost estimate of $12.69 (USD) per kilogram of nitrogen, derived from wastewater treatment costs, the estimated annual value for sediment and nutrient retention on Difficult Run floodplains was $727,226 ±â€¯194,220 USD/yr. Values and differences in floodplain nitrogen retention among stream reaches can be used to target areas for floodplain conservation and stream restoration. The methods presented are scalable and transferable to other areas if appropriate datasets are available for validation.