Impaired Dendritic Expression and Plasticity Of H-Channels in the fmr1(-/Y) Mouse Model of Fragile X Syndrome

Despite extensive research into both synaptic and morphological changes, surprisingly little is known about dendritic function in fragile X syndrome (FXS). We found that the dendritic input resistance of CA1 neurons was significantly lower in fmr1(-/y) versus wild-type mice. Consistent with elevated dendritic I-h, voltage sag, rebound, and resonance frequency were significantly higher and temporal summation was lower in the dendrites of fmr1(-/y) mice. Dendritic expression of the h-channel subunit HCN1, but not HCN2, was higher in the CA1 region of fmr1(-/y) mice. Interestingly, whereas mGluR-mediated persistent decreases in Ih occurred in both wildtype and fmr1(-/y) mice, persistent increases in Ih that occurred after LTP induction in wild-type mice were absent in fmr1(-/y) mice. Thus, chronic upregulation of dendritic Ih in conjunction with impairment of homeostatic h-channel plasticity represents a dendritic channelopathy in this model of mental retardation and may provide a mechanism for the cognitive impairment associated with FXS.FRAXAUniversity of Texas Austin Undergraduate Research FellowshipNational Institutes of Health Grant MH048432Center for Learning and Memor

Risk Stratification of COVID-19 Patients Using Ambulatory Oxygen Saturation in the Emergency Department

Introduction: It is difficult to determine illness severity for coronavirus disease 2019 (COVID-19) patients, especially among stable-appearing emergency department (ED) patients. We evaluated patient outcomes among ED patients with a documented ambulatory oxygen saturation measurement.Methods: This was a retrospective chart review of ED patients seen at New York University Langone Health during the peak of the COVID-19 pandemic in New York City. We identified ED patients who had a documented ambulatory oxygen saturation. We studied the outcomes of high oxygen requirement (defined as >4 liters per minute) and mechanical ventilation among admitted patients and bounceback admissions among discharged patients. We also performed logistic regression and compared the performance of different ambulatory oxygen saturation cutoffs in predicting these outcomes.Results: Between March 15–April 14, 2020, 6194 patients presented with fever, cough, or shortness of breath at our EDs. Of these patients, 648 (11%) had a documented ambulatory oxygen saturation, of which 165 (24%) were admitted. Notably, admitted and discharged patients had similar initial vital signs. However, the average ambulatory oxygen saturation among admitted patients was significantly lower at 89% compared to 96% among discharged patients (p<0.01). Among admitted patients with an ambulatory oxygen saturation, 30% had high oxygen requirements and 8% required mechanical ventilation. These rates were predicted by low ambulatory oxygen saturation (p<0.01). Among discharged patients, 50 (10%) had a subsequent ED visit resulting in admission. Although bounceback admissions were predicted by ambulatory oxygen saturation at the first ED visit (p<0.01), our analysis of cutoffs suggested that this association may not be clinically useful.Conclusion: Measuring ambulatory oxygen saturation can help ED clinicians identify patients who may require high levels of oxygen or mechanical ventilation during admission. However, it is less useful for identifying which patients may deteriorate clinically in the days after ED discharge and require subsequent hospitalization.