Howard University Hospital, previously known as Freedmen's Hospital, is a major hospital located in Washington, D.C., built on the site of the previous Griffith Stadium. The hospital has served the African-American community in the area for over 150 years, having been established in 1862 to cater for the medical needs of the thousands of African Americans who came to Washington during the Civil War, seeking their freedom. The first hospital of its kind to provide medical treatment for former slaves, it later became the major hospital for the area's African American community.C.C.C.
BACKGROUND:The rostral ventromedial medulla (RVM) is a brainstem structure that integrates descending modulatory signaling and contains neurons highly responsive to opioid receptor activation. Despite the well-established effects of opioids in the RVM, the neurochemical adaptations following sustained morphine exposure remain poorly understood. In particular, the contribution of G-protein-coupled inwardly rectifying potassium type 2 (GIRK2) channels, key mediators of opioid receptor-dependent antinociception has not been fully characterized. We hypothesized that GIRK2 channels are essential for morphine-induced metabolic alterations in the RVM. METHODS:In vivo proton nuclear magnetic resonance spectroscopy (1H NMR) was used to examine metabolite responses to prolonged morphine exposure. Metabolite profiles were compared between wild-type and GIRK2 heterozygous mutant (GIRK2+/-) mice before and after four days of subcutaneous implantation with placebo or morphine pellets. RESULTS:In wild-type mice, morphine exposure significantly increased levels of phosphocreatine, total creatine, glutamine, glutathione, taurine, and glycerophosphocholine plus phosphocholine (GPC + PCh), while decreasing N-acetylaspartate (NAA). These changes suggest enhanced energy storage, activation of antioxidant pathways, increased membrane turnover, and alterations in neuronal integrity and excitatory neurotransmission. In contrast, GIRK2+/- mice exhibited attenuated or opposite responses to morphine, characterized by elevated glutamate and reductions in glutamine, GPC + PCh, and total creatine, with no change in NAA. These differential responses indicate that GIRK2 channels influence neurochemical adaptations to morphine in the RVM. CONCLUSION:These findings identify the GIRK2 channel as an important modulator of morphine-induced metabolic changes in the RVM. The observed neurochemical alterations likely reflect adaptive responses to sustained opioid exposure.
Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, liraglutide, and tirzepatide, are increasingly prescribed for weight management in patients with obesity. Given the intersection between obesity, asthma, and obstructive sleep apnea (OSA), we sought to evaluate the impact of GLP-1RA use on asthma severity and related outcomes in obese adults with asthma and OSA. Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with documented diagnoses of obesity (ICD-10: E66), asthma (ICD-10: J45), and OSA (ICD-10: G47.33) were identified. Patients prescribed GLP-1RAs (semaglutide [RxNorm: 1991302], liraglutide [RxNorm: 475968], or tirzepatide [RxNorm: 2601723]) formed the exposure cohort. A control group of non-GLP-1RA-users with similar clinical characteristics was selected using 1:1 propensity score matching. Key outcomes included asthma exacerbation, asthma severity progression, emergency department (ED) visits, hospitalizations, new OSA diagnoses, and all-cause mortality. Time-to-event analyses were performed using Cox proportional hazards models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. Results After propensity score matching, each cohort included 332,958 adults (mean age 54 years, 60% female, 69% White, and 20% Black or African American). GLP-1RA users experienced a significantly lower hazard of asthma exacerbation (HR 0.92, 95% CI 0.91-0.92), suggesting reduced flare-up frequency. Progression to more severe asthma phenotypes was also less common among GLP-1RA users (HR 0.78, 95% CI 0.77-0.79), indicating a potential disease-modifying effect. Reductions in healthcare utilization were observed, including lower risks of ED visits (HR 0.89, 95% CI 0.88-0.89) and hospitalizations (HR 0.58, 95% CI 0.58-0.59), reflecting improved disease control. All-cause mortality was significantly lower in the GLP-1RA group (HR 0.40, 95% CI 0.39-0.41), further underscoring the systemic benefit of these agents. Notably, a slight increase in the hazard of new OSA diagnosis was observed (HR 1.22, 95% CI 1.21-1.23), which may reflect increased diagnostic surveillance or unmasking of pre-existing but undiagnosed OSA. Conclusions Among obese adults with asthma and OSA, GLP-1RA use was associated with improved asthma outcomes, reduced healthcare utilization, and significantly lower mortality. These findings suggest GLP-1RAs may offer a therapeutic advantage beyond weight control in patients with respiratory comorbidities. Further prospective trials are warranted to confirm these findings and explore underlying mechanisms. This abstract is funded by: None
