Dolutegravir-induced neural tube defects in mice are folate responsive.

OBJECTIVES: In 2018, the Botswana Tsepamo Study reported a nine-fold increased risk of neural tube defects in infants whose mothers were treated with dolutegravir (DTG) from the time of conception. As maternal folate supplementation and status is a well known modifier of neural tube defect (NTD) risk, we sought to evaluate birth outcomes in mice fed normal and low folic acid diets treated with DTG during pregnancy. DESIGN: DTG was evaluated for developmental toxicity using pregnant mice fed normal or low folic acid diet. METHODS: CD-1 mice were provided diet with normal (3 mg/kg) or low (0.3 mg/kg) folic acid. They were treated with water, a human therapeutic-equivalent dose, or supratherapeutic dose of DTG from mouse embryonic day E6.5 to E12.5. Pregnant dams were sacrificed at term (E18.5) and fetuses were inspected for gross, internal, and skeletal defects. RESULTS: Fetuses with exencephaly, an NTD, were present in both therapeutic human equivalent and supratherapeutic exposures in dams fed low folic acid diet. Cleft palates were also found under both folate conditions. CONCLUSIONS: Recommended dietary folic acid levels during mouse pregnancy ameliorate developmental defects that arise from DTG exposure. Since low folate status in mice exposed to DTG increases the risk for NTDs, it is possible that DTG exposures in people living with HIV with low folate status during pregnancy may explain, at least in part, the elevated NTD risk signal observed in Botswana. Based on these results, future studies should consider folate status as a modifier for DTG-associated NTD risk.

Impact of sediment parameters in the prediction of benthic microbial fuel cell performance.

The benthic microbial fuel cell (BMFC) is a promising technology for harvesting renewable energy from marine littoral environments. The scientific community has researched BMFC technology for well over a decade, but the in situ performance remains challenging. To address this challenge, BMFC power experiments were performed on sediment collected from San Diego Bay (CA, USA), La Spezia (Italy) and Honolulu (HI, USA) in the ever-changing littoral environment. Analysis of BMFC laboratory data found the power density varied substantially across 11 sites in San Diego Bay. In addition, data from experiments repeated at four locations in San Diego Bay showed significant differences between experiments performed in 2014, 2016 and 2019. Multivariable linear analysis showed BMFC 90 day cumulative power density was positively correlated with the total organic carbon (p < 0.05) and negatively correlated with the black carbon in the sediment (p < 0.05). Regression coefficients trained on the San Diego Bay data from 2014 facilitated accurate predictions of BMFC performance in 2016 and 2019. The modeling paradigm accurately explained variations in BMFC power performance in La Spezia and showed sediment parameters can impact BMFC performance differently across geographic regions. The results demonstrate a great potential to use sediment parameters and statistical modeling to predict BMFC power performance prior to deployment in oceanographic environments, thereby reducing cost, work force and resources.