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Nonalcoholic fatty liver disease (NAFLD) is a known outcome of hepatosteatosis. Free fatty acids (FFA) induce the unfolded protein response (UPR) or endoplasmic reticulum (ER) stress that may induce apoptosis. Recent data indicate ER stress to be a major player in the progression of fatty liver to more aggressive lesions. Autophagy on the other hand has been demonstrated to be protective against ER stress-induced cell death. We hypothesized that exendin-4 (GLP-1 analog) treatment of fat loaded hepatocytes can reduce steatosis by autophagy which leads to reduced ER stress-related hepatocyte apoptosis. Primary human hepatocytes were loaded with saturated, cis- and trans-unsaturated fatty acids (palmitic, oleic and elaidic acid respectively). Steatosis, induced with all three fatty acids, was significantly resolved after exendin-4 treatment. Exendin-4 sustained levels of GRP78 expression in fat-loaded cells when compared to untreated fat-loaded cells alone. In contrast, CHOP (C/EBP homologous protein); the penultimate protein that leads to ER stress-related cell death was significantly decreased by exendin-4 in hepatocytes loaded with fatty acids. Finally, exendin-4 in fat loaded hepatocytes clearly promoted gene products associated with macroautophagy as measured by enhanced production of both Beclin-1 and LC3B-II, markers for autophagy; and visualized by transmission electron microscopy (TEM). Similar observations were made in mouse liver lysates after mice were fed with high fat high fructose diet and treated with a long acting GLP-1 receptor agonist, liraglutide. GLP-1 proteins appear to protect hepatocytes from fatty acid-related death by prohibition of a dysfunctional ER stress response; and reduce fatty acid accumulation, by activation of both macro-and chaperone-mediated autophagy. These findings provide a novel role for GLP-1 proteins in halting the progression of more aggressive lesions from underlying steatosis in humans afflicted with NAFLD.

Respiratory syncytial virus (RSV), the leading cause of hospitalization among U.S. infants, results in 50,000-80,000 associated hospitalizations and 100-300 deaths among children aged <5 years each year (1). In 2023, the Advisory Committee on Immunization Practices (ACIP) recommended two options for preventing severe RSV in infants: maternal RSV vaccination during pregnancy (2) or administration of nirsevimab, a long-acting monoclonal antibody to infants (1). Nirsevimab is recommended for infants aged <8 months during their first RSV season (October-March in most of the United States); ideally, it should be administered during the birth hospitalization or within the first week of life. In September 2023, ACIP passed a resolution to add nirsevimab to the Vaccines for Children (VFC) Program, a public-private partnership that provides CDC-purchased vaccines to VFC-eligible children (those who are uninsured or underinsured, insured through Medicaid, or who are American Indian or Alaska Native) at no cost. Approximately one half (52.2%) of U.S. children aged 19-35 months are VFC-eligible, and among those, 93.4% are insured by Medicaid (3). Medicaid-insured infants have a higher incidence of severe RSV infection than do privately insured infants (4). Providers enrolled in the VFC program are able to administer nirsevimab at no cost to eligible children. Enrollment of birthing hospitals in VFC thus has the potential to expand infant immunization against RSV. This report describes enrollment of U.S. birthing hospitals (those with more than one birth during the previous year or at least one registered maternity bed) in the VFC program since the introduction of nirsevimab.