Evaluation of sleep medicine fellowship program websites.

STUDY OBJECTIVES: Sleep fellowship program websites likely serve as a preliminary source of information for prospective fellows. Arguably, applicants have likely become even more reliant on program websites during the COVID-19 pandemic due to travel restrictions and social-distancing measures limiting in-person interviews. In this study, we evaluated the content and comprehensiveness of sleep medicine fellowship websites to identify areas of improvement. METHODS: A list of sleep medicine fellowship programs in the United States participating in the 2021 match cycle was compiled using the Electronic Residency Application Service (ERAS) and Fellowship and Residency Electronic Interactive database (FREIDA) websites. Twenty-two prespecified content criteria related to education, recruitment, and compensation were used to evaluate each program website. Sleep programs' website comprehensiveness were compared based on US location, type, matching status, core specialty, and size of programs. RESULTS: Seventy-eight US sleep fellowship program websites were evaluated. Most program websites had a working hyperlink on ERAS or FREIDA. There was considerable variability in content reported across program websites, with a mean of 56.8% of content items reported per program. There was a greater educational website content comprehensiveness for internal medicine compared with other specialty-based sleep programs. There was no difference in sleep programs' website comprehensiveness based on US location, type, matching status, or size of programs. CONCLUSIONS: Website content comprehensiveness among sleep fellowship programs is variable. There is opportunity for all sleep fellowship programs to improve their websites to better inform prospective trainees. CITATION: Shenoy S, Akberzie W, Landeo-Gutierrez JS, Leon Guerrero CR, Karroum EG. Evaluation of sleep medicine fellowship program websites. J Clin Sleep Med. 2023;19(6):1083-1088.

Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture.

BACKGROUND: Isoflurane causes long-term hippocampal-dependent learning deficits in rats despite limited isoflurane-induced hippocampal cell death, raising questions about the causality between isoflurane-induced cell death and isoflurane-induced cognitive function. Neurogenesis in the dentate gyrus is required for hippocampal-dependent learning and thus constitutes a potential alternative mechanism by which cognition can be altered after neonatal anesthesia. The authors tested the hypothesis that isoflurane alters proliferation and differentiation of hippocampal neural progenitor cells. METHODS: Multipotent neural progenitor cells were isolated from pooled rat hippocampi (postnatal day 2) and grown in culture. These cells were exposed to isoflurane and evaluated for cell death using lactate dehydrogenase release, caspase activity, and immunocytochemistry for nuclear localization of cleaved caspase 3. Growth was assessed by cell counting and BrdU incorporation. Expression of markers of stemness (Sox2) and cell division (Ki67) were determined by quantitative polymerase chain reaction. Cell fate selection was assessed using immunocytochemistry to stain for neuronal and glial markers. RESULTS: Isoflurane did not change lactate dehydrogenase release, activity of caspase 3/7, or the amount of nuclear cleaved caspase 3. Isoflurane decreased caspase 9 activity, inhibited proliferation, and decreased the proportion of cells in s-phase. messenger ribonucleic acid expression of Sox2 (stem cells) and Ki67 (proliferation) were decreased. Differentiating neural progenitor cells more often select a neuronal fate after isoflurane exposure. CONCLUSIONS: The authors conclude that isoflurane does not cause cell death, but it does act directly on neural progenitor cells independently of effects on the surrounding brain to decrease proliferation and increase neuronal fate selection. These changes could adversely affect cognition after isoflurane anesthesia.

The role of Akt/protein kinase B subtypes in retinal ischemic preconditioning.

Potent endogenous protection from ischemia can be induced in the retina by ischemic preconditioning (IPC). Protein kinase B/Akt is a cellular survival factor. We hypothesized that Akt was integral to IPC based upon differential effects of Akt subtypes. Rats were subjected to retinal ischemia after IPC or IPC-mimicking by the opening of mitochondrial KATP (mKATP) channels. The effects of blocking Akt using wortmannin, API-2, or small interfering RNA (siRNA) were examined. Electroretinography assessed functional recovery after ischemia, and TUNEL examined retinal ganglion cell apoptosis. We studied the relationship between Akt activation and known initiators of IPC, including adenosine receptor stimulation and the opening of mKATP channels. The PI-3 kinase inhibitor wortmannin 1 or 4 mg/kg (i.p.), the specific Akt inhibitor API-2, 5-500 microM in the vitreous, or intravitreal siRNA directed against Akt2 or -3, but not Akt1, significantly attenuated the neuroprotective effect of IPC. Interfering RNA against any of the three Akt subtypes significantly but time-dependently attenuated mKATP channel opening to mimic IPC. Adenosine A1 receptor blockade (DPCPX), A2a blockade (CSC), or the mKATP channel blocker 5-hydroxydecanoic acid significantly attenuated Akt activation after IPC. Interfering RNA directed against Akt subtypes prevented the ameliorative effect of IPC on post-ischemic apoptosis. All three Akt subtypes are involved in functional retinal neuroprotection by IPC or IPC-mimicking. Akt is downstream of adenosine A1 and A2a receptors and mKATP channel opening. The results indicate the presence in the retina of robust and redundant endogenous neuroprotection based upon subtypes of Akt.

Protein kinase C subtypes and retinal ischemic preconditioning.

The purpose of our study was to determine the specific subtypes of protein kinase C involved in the neuroprotection afforded by retinal ischemic preconditioning (IPC), their relationship to the opening of mitochondrial KATP (mKATP) channels, and their role in apoptosis after preconditioning and ischemia. Rats were subjected to retinal ischemia after IPC, or retinas were rendered ischemic after pharmacological opening of mKATP channels. Using immunohistochemistry and image analysis, we determined cellular localization of PKC subtypes. We blocked PKC-delta and -epsilon to study the effect on protection with IPC or with IPC-mimicking by the opening of mKATP channels. PKC subtypes were inhibited pharmacologically or with interfering RNA. Electroretinography assessed functional recovery after ischemia. IPC was effectively mimicked by injection of diazoxide to open the mKATP channel. IPC and/or its mimicking were attenuated by the PKC-delta inhibitor rottlerin and by interfering RNA targeting PKC-delta or -epsilon. Using TUNEL staining and Western blotting for caspase-3 and fodrin breakdown we assessed apoptosis. The injection of interfering RNA to PKC-delta and -epsilon before preconditioning significantly enhanced TUNEL staining as well as the cleavage of caspase-3 and fodrin after ischemia. In summary, our experiments have shown that both PKC-delta and -epsilon subtypes are involved in the cellular signaling that results in neuroprotection from IPC and that both are downstream of the opening of mKATP channels.