Kaycee E. Faunce

Managing per- and polyfluoroalkyl substances (PFAS) in water resources requires a basin-scale approach. Predicted environmental concentrations (PEC) and stream-vulnerability scores for PFAS were determined for the Potomac River watershed in the eastern United States. Approximately 15% of stream reaches contained municipal and/or industrial wastewater treatment plant (WWTP) discharges that are presumptive PFAS sources, comprising from 90% of streamflow. Mean annual PEC, based on the summed concentrations of eight PFAS detected in WWTP effluents (ΣPFAS_PEC), for all stream reaches in the watershed was 3.8 ng L^-1, and stream reaches impacted by WWTP had perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) PEC of 0.39 and 0.14 ng L^-1. For locations where measured-environmental concentrations (MEC) were determined, municipal and industrial WWTP contributed 7.8% (0 to 65%) of the total annual streamflow and MEC were greater than PEC in 99% of the samples, indicating additional potential PFAS sources. The mean ΣPFAS_PEC was 9.1 ng L^-1 compared to a mean sum of PFAS MEC of 34 ng L^-1. Under mean-August low-flow, 17% and 9.4% of the water-supply intakes had maximum PFOA and PFOS PEC exceeding drinking water maximum contaminant levels.

A wastewater model was applied to the Potomac River watershed to provide (i) a means to identify streams with a high likelihood of carrying elevated effluent‐derived contaminants and (ii) risk assessments to aquatic life and drinking water. The model linked effluent discharges along stream networks, accumulated wastewater, and predicted contaminant loads of municipal wastewater constituents while accounting for instream dilution and attenuation. Simulations using 2016 data suggested that nearly 30% (8281 km) of streams were wastewater impacted. Low‐ to medium‐order streams had the largest range of accumulated wastewater (ACCWW%) values. ACCWW% exceeded a 1% threshold at >39% of drinking‐water intakes (varied by temporal condition). Risk assessments of municipal wastewater‐contaminant mixtures indicated that 22% (1479 km) of streams impacted by municipal wastewater (5.5% of all reaches modeled) may pose high risk to aquatic organisms under mean‐annual conditions, with fish more susceptible to chronic‐exposure effects relative to other taxa. Risk varied temporally and by stream order, with the greatest risk occurring in the summer in small streams. These findings suggest that wastewater may be an important factor contributing to environmental degradation in the Potomac River watershed.

Water withdrawn from rivers and streams accounts for approximately 80 percent of the public water supply in West Virginia. Localized and (or) seasonal droughts may threaten future water availability in the state, particularly in rural communities located in the headwaters of unregulated watersheds. Monthly water withdrawal data obtained from the West Virginia Department of Environmental Protection’s Large Quantity User program’s regulatory database was used to calculate all-time, seasonal, and monthly 75th quantile withdrawal rates for 109 public water system (PWS) intakes withdrawing from surface waters in West Virginia. A drought-vulnerability assessment value was calculated by comparing PWS withdrawal rates to the 1-day, 10-year hydrologically based streamflow statistic (1Q10) for 71 of the 109 PWS in locations with valid streamflow statistics. Withdrawal rates were evaluated against thresholds representing different levels of drought-related impacts from the West Virginia interagency drought plan and ecological-flow literature. The drought-vulnerability assessment found 33 of 71 PWS have 75th quantile withdrawal rates greater than 100 percent of 1Q10 streamflow. Forty-five of 71 PWS have 75th quantile withdrawal rates more than 10 percent of 1Q10 streamflow, suggesting some level of ecological impairment during severe drought. Additionally, a publicly available, near real-time drought-awareness web tool was created to compare the estimated withdrawal rate for 109 PWS to forecast streamflows from the National Water Model to support decision-making for emergency and water managers.

Temporal variations of de facto wastewater reuse are relevant to public drinking water systems (PWSs) that obtain water from surface sources. Variations in wastewater discharge flows, streamflow, de facto reuse, and disinfection by-products (DBPs – trihalomethane-4 [THM4] and haloacetic acid-5 [HAA5]) over an 18-year period were examined at 11 PWSs in the Shenandoah River watershed, using more than 25,000 data records, in gaged and ungaged reaches. The relationship of de facto reuse with DBPs by year and quarter at the PWSs was examined. A linear relationship was found between THM4 and de facto reuse on an annual average basis (p = 0.050), as well as in quarters 3 (July – September) (p = 0.032) and 4 (October – December) (p = 0.031). Using a t-test (p < 0.05), the study also showed that there were significant differences in DBP levels for PWSs relative to 1% de facto reuse. This was found for THM4 based on annual average and quarter 1 (January – March) data, and for HAA5 based on quarter 3 data during the period of record.

Opioid-targeted vaccines represent an emerging treatment strategy for Opioid Use Disorder. To determine whether concurrent vaccination against two commonly abused opioids (fentanyl and heroin) would confer broader spectrum opioid coverage, the current study evaluated dual fentanyl/heroin conjugate vaccine effectiveness using a warm-water tail-withdrawal and a fentanyl/heroin-vs.-food choice procedure in male and female rats across a 105-day observation period. Vaccine administration generated titers of high-affinity antibodies to both fentanyl and heroin sufficient to decrease the antinociceptive potency of fentanyl (25-fold), heroin (4.6-fold), and a 1:27 fentanyl/heroin mixture (7.5-fold). Vaccination did not alter the antinociceptive potency of the structurally dissimilar opioid agonist methadone. For comparison, continuous treatment with a naltrexone dose (0.032 mg/kg/h) shown previously to produce clinically relevant plasma-naltrexone levels decreased the antinociceptive potency of fentanyl, heroin, and the 1:27 fentanyl/heroin mixture by approximately 20-fold. Naltrexone treatment also shifted the potency of 1:27 fentanyl/heroin mixture in a drug-vs.-food choice self-administration procedure 4.3-fold. In contrast, vaccination did not attenuate 1:27 fentanyl/heroin mixture self-administration in the drug-vs.-food choice procedure. These data demonstrate that a vaccine can simultaneously attenuate the thermal antinociceptive effects of two structurally dissimilar opioids. However, the vaccine did not attenuate fentanyl/heroin mixture self-administration, suggesting a greater magnitude of vaccine responsiveness is required to decrease opioid reinforcement relative to antinociception.

Repeated drug administration results in sensitization, tolerance, or no change in subsequent drug-induced alterations of motivated behaviors, such as intracranial self-stimulation (ICSS). For example, repeated mu-opioid agonist administration results in increased expression of mu agonist-induced facilitation of ICSS. Acute kappa-opioid receptor (KOR) agonist administration depresses ICSS; however, effects of repeated KOR agonist administration on ICSS are unknown. This study determined effects of daily KOR agonist U-50488 administration and subsequent termination on ICSS in male and female rats. Female (n = 5) and male (n = 6) Sprague-Dawley rats were trained to respond for electrical brain stimulation under a frequency-rate ICSS procedure. Sequential U-50488 dose-effect functions (1-5.6 mg/kg, intraperitoneal) were determined every 7 days over a 21-day experimental period during which saline and increasing U-50488 doses (3.2-5.6 mg/kg, intraperitoneal) were administered on intervening days. Sequential U-50488 dose-effect functions were also determined 7 and 28 days after termination of repeated U-50488 administration. U-50488 dose-dependently depressed ICSS in both female and male rats. There were no sex differences on either initial or repeated U-50488 treatment effects. Repeated 5.6 mg/kg U-50488 administration produced selective tolerance to the rate-decreasing, but not threshold-altering, effects of 5.6 mg/kg U-50488 during sequential dose-effect test sessions. Neither repeated U-50488 administration nor termination of U-50488 significantly altered baseline ICSS. Overall, these results suggest neither tolerance nor sensitization develops to the depressive-like effects of repeated KOR agonist activation. Selective tolerance to the rate-decreasing effects of repeated KOR agonist administration may have implications for elucidating the neurobiological processes involved in long-term abused drug self-administration.

The current opioid crisis remains a significant public health issue and there is a critical need for biomedical research to develop effective and easily deployable candidate treatments. One emerging treatment strategy for opioid use disorder includes immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness of a fentanyl-tetanus toxoid conjugate vaccine to alter fentanyl self-administration using a fentanyl-vs.-food choice procedure in male and female rats under three experimental conditions. For comparison, continuous 7-day naltrexone (0.01–0.1 mg/kg/h) and 7-day clonidine (3.2–10 μg/kg/h) treatment effects were also determined on fentanyl-vs.-food choice. Male and female rats responded for concurrently available 18% diluted Ensure® (liquid food) and fentanyl (0–10 μg/kg/infusion) infusions during daily sessions. Under baseline and saline treatment conditions, fentanyl maintained a dose-dependent increase in fentanyl-vs.-food choice. First, fentanyl vaccine administration significantly blunted fentanyl reinforcement and increased food reinforcement for 15 weeks in non-opioid dependent rats. Second, surmountability experiments by increasing the unit fentanyl dose available during the self-administration session 10-fold empirically determined that the fentanyl vaccine produced an approximate 22-fold potency shift in fentanyl-vs.-food choice that was as effective as the clinically approved treatment naltrexone. Clonidine treatment significantly increased fentanyl-vs.-food choice. Lastly, fentanyl vaccine administration prevented the expression of withdrawal-associated increases in fentanyl-vs.-food choice following introduction of extended 12 h fentanyl access sessions. Overall, these results support the potential and further consideration of immunopharmacotherapies as candidate treatments to address the current opioid crisis.