RESUMEN
Opioid receptors within the CNS regulate pain sensation and mood and are key targets for drugs of abuse. Within the adult rodent hippocampus (HPC), µ-opioid receptor agonists suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting the circuit. However, it is uncertain if this disinhibitory motif is conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition is robustly suppressed by opioids in HPC but not neocortex in mice and nonhuman primates, with spontaneous inhibitory tone in resected human tissue also following a consistent dichotomy. This hippocampal disinhibitory motif was established in early development when immature PV-INs and opioids already influence primordial network rhythmogenesis. Acute opioid-mediated modulation was partially occluded with morphine pretreatment, with implications for the effects of opioids on hippocampal network activity during circuit maturation as well as learning and memory. Together, these findings demonstrate that PV-INs exhibit a divergence in opioid sensitivity across brain regions that is remarkably conserved across evolution and highlights the underappreciated role of opioids acting through immature PV-INs in shaping hippocampal development.
RESUMEN
Background: The critical care resuscitation unit (CCRU) facilitates interhospital transfer (IHT) of critically ill patients for immediate interventions. Due to these patients' acuity, it is uncommon for patients to be directly discharged home from this unit, but it does happen on occasion. Since there is no literature regarding outcomes of patients being discharged from a resuscitation unit, our study investigated these patients' outcome at greater than 12 months after being discharged directly from the CCRU. Methods: We performed a retrospective cohort study of all adult patients directly discharged from the CCRU between January 01, 2017, and December 31, 2020. The primary outcome was number of ED visits or hospitalizations within 6 months. Secondary outcomes were number of ED visits or hospitalizations within 6, 12, and >12 months from CCRU discharge. Results: We analyzed 145 patients' records. Mean age was 56 (standard deviation [SD] ± 19), with a majority being male (72%) and Caucasian (58%). The most common discharge destination was home (139 patients, 96% of total subjects) versus hospice (2%) or nursing facilities (2%). Most patients (55%) did not have any hospital revisits within the first 6 months of discharge, while 31% had 1-2 revisits, and 14% had ≥3 revisits. The most common discharge diagnoses were soft tissue infection (16.5%), aortic dissection (14%), and stroke (11%). Factors which were associated with a greater likelihood of any return hospital visit within 6 months receiving mechanical ventilation during CCRU stay (coefficient -2.23, 95% CI 0.01-0.87, P=0.036), while high hemoglobin on CCRU discharge was associated with no ED revisit (coeff. 0.42, 95% CI 1.15-2.06, P=0.004). Conclusions: Most patients who were discharged from the CCRU did not require any hospital revisits in the first 6 months. Requiring mechanical ventilation and having soft tissue infection were associated with high unplanned hospital revisits following discharge. Further research is needed to validate these findings.