The exposure of the developing human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the visual system. One common phenotype seen in humans exposed to ethanol in utero is microphthalmia. The objective of this study was to describe the effects of ethanol during retinal neurogenesis in a model organism, the zebrafish, and to pursue the potential mechanisms by which ethanol causes microphthalmia. Zebrafish embryos were exposed to 1% or 1.5% ethanol from 24 to 48 h after fertilization, a period during which the retinal neuroepithelium undergoes rapid proliferation and differentiation to form a laminated structure composed of different retinal cell types. Ethanol exposure resulted in significantly reduced eye size immediately following the treatment, and this microphthalmia persisted through larval development. This reduced eye size could not entirely be accounted for by the accompanying general delay in embryonic development. Retinal cell death was only slightly higher in ethanol-exposed embryos, although cell death in the lens was extensive in some of these embryos, and lenses were significantly reduced in size as compared to those of control embryos. The initiation of retinal neurogenesis was not affected, but the subsequent waves of cell differentiation were markedly reduced. Even cells that were likely generated after ethanol exposure-rod and cone photoreceptors and Müller glia-were delayed in their expression of cell-specific markers by at least 24 h. We conclude that ethanol exposure over the time of retinal neurogenesis resulted in persistent microphthalmia due to a combination of an overall developmental delay, lens abnormalities, and reduced retinal cell differentiation.

Background Microphthalmia (reduced eye size), generally accompanied by vision defects, is a hallmark of fetal alcohol spectrum disorder (FASD) in humans. In zebrafish, embryonic ethanol exposure over the time of retinal neurogenesis also results in microphthalmia. This microphthalmia is in part the consequence of reduced retinal cell differentiation, including photoreceptors. Here we pursue 2 signaling pathways implicated in other aspects of FASD pathogenesis: retinoic acid (RA) and Sonic hedgehog (Shh). Methods We evaluated markers for RA and Shh signaling within the eyes of embryos treated with ethanol during the period of retinal neurogenesis. We also perrormed rescue experiments using administration of exogenous RA and microinjection of cholesterol, which augments Shh signaling. Results Using sequential or co-treatments, RA did not rescue ethanol-induced microphthalmia at any concentration tested. In addition, RA itself caused microphthalmia, although the underlying mechanisms were distinct from those or ethanol. Interestingly, RA treatment appeared to recover photoreceptor differentiation in a concentration-dependent manner. This may be an independent effect or exogenous RA, as ethanol treatment alone did not alter RA signaling in the eye. Cholesterol injection also did not rescue ethanol-induced microphthalmia at any concentration tested, and ethanol treatments did not alter expression of shh, or of ptc-2, which is normally regulated by Shh signaling. Conclusions Together these findings indicate that, during the time of retinal neurogenesis, effects of ethanol on eye development are likely independent of the RA and Shh signaling pathways. These studies suggest that FASD intervention strategies based upon augmentation or RA or Shh signaling may not prevent ethanol-induced microphthalmia.

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Epidemiological studies provide strong evidence that obstructive sleep apnea (OSA) is associated with cardiovascular complications such as systemic hypertension, congestive heart failure, and atrial fibrillation. Successful OSA treatment with continuous positive airway pressure (CPAP) has resulted in coincident reductions in systemic hypertension, improvements in left ventricular systolic function, and reductions in sympathetic nervous activity. These data suggest that successful treatment of OSA may reduce cardiovascular morbidity in such patients. Although CPAP is the more successful treatment for OSA when used properly and consistently, its clinical success is often limited by poor patient and partner acceptance, which leads to suboptimal compliance. Oral appliances or upper airway surgeries are considered a second line of treatment for patients with mild to moderate OSA who do not comply with or refuse long-term CPAP treatment. Oral devices such as mandibular repositioning appliances were recently shown to improve arterial hypertension in OSA patients. Electrical stimulation of the hypoglossal nerve is a new investigational therapy for patients with moderate to severe OSA. This new treatment option, if proven effective, may provide cardiovascular benefits secondary to treating OSA.

BACKGROUND: The incidence rate of stroke in hospitalized patients ranges between 2% and 17% of all strokes—a higher rate than in the community. Delays in recognition and management of stroke in hospitalized patients lead to worse outcomes. At our hospital, the existing in-hospital stroke (IHS) code showed low usage and effectiveness. In a quality improvement (QI) project, we aimed to improve the identification of and the quality of care for inpatient strokes. METHODS: A nurse-driven IHS protocol was implemented, which alerted a specialized stroke team and cleared the computed tomography (CT) scanner. The protocol focused on prioritizing staff education, simplifying the process, empowering staff to activate an IHS code, ensuring adequate support and teamwork, identifying well-defined quality metrics (eg, time to CT and documentation tool use), and providing feedback communication. We analyzed 2 years of postimplementation IHS data for impact on stroke detection and outcomes. RESULTS: In the 2 years post QI, there was a more than 10-fold increase in IHS (pre-QI, n = 8; first year post QI, n = 94; second year post QI, n = 123). In the post-QI cohort, after excluding patients with missing information (n = 26), 69 cases had new stroke diagnoses (63 ischemic, 6 hemorrhagic), and 148 were stroke mimics. The mean (SD) time from IHS to CT was 18.7 (7.0) minutes. Of the 63 new ischemic stroke cases, 25 (39.7%) were treated with thrombolytic therapy and/or mechanical thrombectomy. CONCLUSION: The new IHS protocol has led to a marked increase in cases identified, rapid evaluation, and high utilization rate of acute stroke therapies.