Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative stress, enhancing acute hepatotoxicity. Glycine supplementation or hepatocyte-specific ablation of the mitochondrial SHMT2 isoform in mice with hepatic steatosis mitigated acetaminophen-induced hepatotoxicity by supporting de novo glutathione synthesis. Thus, early metabolic changes in MASLD that limit glycine availability sensitize mice to xenobiotics even at the reversible stage of this disease.

Death and Dying: Tools to Help Respiratory Therapists Handle Frequent Exposure to End of Life Care.

Education and recognition of death anxiety are important for respiratory therapists. A vital component of respiratory therapy is managing mechanical ventilation and dealing with death and dying. For most institutions, respiratory therapy is a vital component of the rapid response team, code team, and trauma team. Removal of mechanical ventilation is a duty primarily bestowed upon the respiratory therapist. Exposure to death, on a frequent basis, can take an emotional toll and lead to burnout, stress, and increased turnover. Managers and leaders in the hospital must make efforts to provide counseling and education to support respiratory therapists and their ongoing exposure to death and dying. This paper examines coping mechanisms for physicians and paramedics, resulting in tools that can be used to provide support to the respiratory therapist.