Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin-A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin-A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage-dependent manner. In mice lacking ephrin-A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus.Ephrin-A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin-A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.
Introduction With changes in insurance coverage after the implementation of the Affordable Care Act (ACA) in 2014, we aim to analyze the impact of Medicaid expansion on clinical outcomes and patient disposition after burn injury. We hypothesize that with increased insurance coverage, more patients are discharged to a skilled nursing facility (SNF) or rehabilitation center. Methods Under IRB approval, we reviewed trauma registry data for patients with burn injuries admitted to a regional burn center from 2011 to 2018. Patients were grouped into two categories: before (2011–2014) and after (2015–2018) ACA; we excluded data from 2014 to serve as a washout period. Outcomes of interest were length of hospital stay controlled for burn size (LOS/TBSA), number of complications, patient disposition (Home, SNF, or Rehab), and mortality. Chi square analysis and student t-tests were performed to determine differences between the two groups. Multivariate logistic regression including age, sex, race, distance from medical center, burn size, and etiology of the burn as covariates were used to determine the impact of ACA implementation on patient disposition. Results Inpatient mortality rates did not change following ACA implementation. Average LOS/TBSA and number of complications increased, which may be due to increased average age, burn size, and distance from the burn center after ACA. Fewer patients were discharged home and more patients were sent to rehabilitation centers and SNF, which may relate to more patients being insured. Even after adjusting for covariates, discharge to inpatient rehabilitation was significantly increased and discharge to a SNF approached significance. Conclusions Since ACA implementation, there has been no change in mortality after a burn injury, but an increase in average LOS and complication rates, consistent with increased injury severity. Rates of discharge to rehab centers and SNF improved with the increase in overall insurance coverage in the burn population. Applicability of Research to Practice This work highlights changes in patient outcomes with ACA implementation and can help to guide understanding of health disparity and resource utilization in this population.
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