The WD40 Repeat Protein WDR-23 Functions with the CUL4/DDB1 Ubiquitin Ligase To Regulate Nuclear Abundance and Activity of SKN-1 in Caenorhabditis elegans▿

The transcription factor SKN-1 protects Caenorhabditis elegans from stress and promotes longevity. SKN-1 is regulated by diverse signals that control metabolism, development, and stress responses, but the mechanisms of regulation and signal integration are unknown. We screened the C. elegans genome for regulators of cytoprotective gene expression and identified a new SKN-1 regulatory pathway. SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23, which interacts with the CUL-4/DDB-1 ubiquitin ligase to presumably target the transcription factor for proteasomal degradation. WDR-23 regulates SKN-1 target genes downstream from p38 mitogen-activated protein kinase, glycogen synthase kinase 3, and insulin-like receptor pathways, suggesting that phosphorylation of SKN-1 may function to modify its interaction with WDR-23 and/or CUL-4/DDB-1. These findings define the mechanism of SKN-1 accumulation in the cell nucleus and provide a new mechanistic framework for understanding how phosphorylation signals are integrated to regulate stress resistance and longevity

Knowledge Gaps in Anesthetic Gas Utilization in a Large Academic Hospital System: A Multicenter Survey

Inhaled anesthetics account for a significant portion of the greenhouse gases generated by perioperative services within the healthcare systems. This cross-sectional study aimed to identify knowledge gaps and practice patterns related to carbon dioxide (CO2) absorbents and intraoperative delivery of fresh gas flows (FGF) for future sustainability endeavors. Secondary aims focused on differences in these knowledge gaps based on the level of training. Surveys were distributed at five large academic medical centers. In addition to site-specific CO2 absorbent use and practice volume and experience, respondents at each institution were queried about individual practice with FGF rates during anesthetic maintenance as well as the cost-effectiveness and environmental impact of different volatile anesthetics. Results were stratified and analyzed by the level of training. In total, 368 (44% physicians, 30% residents, and 26% nurse anesthetists) respondents completed surveys. Seventy-six percent of respondents were unaware or unsure about which type of CO2 absorbent was in use at their hospital. Fifty-nine percent and 48% of respondents used sevoflurane and desflurane with FGF ≥1 L/min, respectively. Most participants identified desflurane as the agent with the greatest environmental impact (89.9%) and a greater proportion of anesthesiologists correctly identified isoflurane as a cost-effective anesthetic (78.3%, p=0.02). Knowledge gaps about in-use CO2 absorbent and optimal FGF usage were identified within the anesthesia care team. Educational initiatives to increase awareness about the carbon emissions from anesthesia and newer CO2 absorbents will impact the environmental and economic cost per case and align anesthesia providers toward healthcare decarbonization