Neurosurgery residents have a significantly lower prevalence of burnout than other residents/fellows and practicing physicians. The underlying causes for these findings were not assessed and are likely multifactorial. Future studies should address possible causes of these findings.
Thermal block of unmyelinated axons may serve as a modality for control, suggesting a means for providing therapies for pain. Computational modeling predicted that potassium channels are necessary for mediating thermal block of propagating compound action potentials (CAPs) with infrared (IR) light. Our study tests that hypothesis. Results suggest that potassium channel blockers disrupt the ability of IR to block propagating CAPs in Aplysia californica nerves, whereas sodium channel blockers appear to have no significant effect. These observations validate the modeling results and suggest potential applications of thermal block to many other unmyelinated axons. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
A-to-I RNA editing is a post-transcriptional modification of single nucleotides in RNA by adenosine deamination, which thereby diversifies the gene products encoded in the genome. Thousands of potential RNA editing sites have been identified by recent studies (e.g. see Li et al, Science 2009); however, only a handful of these sites have been independently confirmed. Here, we systematically and quantitatively examined 109 putative coding region A-to-I RNA editing sites in three sets of normal human brain samples by ultra-high-throughput sequencing (uHTS). Forty of 109 putative sites, including 25 previously confirmed sites, were validated as truly edited in our brain samples, suggesting an overestimation of A-to-I RNA editing in these putative sites by Li et al (2009). To evaluate RNA editing in human disease, we analyzed 29 of the confirmed sites in subjects with major depressive disorder and schizophrenia using uHTS. In striking contrast to many prior studies, we did not find significant alterations in the frequency of RNA editing at any of the editing sites in samples from these patients, including within the 5HT2C serotonin receptor (HTR2C). Our results indicate that uHTS is a fast, quantitative and high-throughput method to assess RNA editing in human physiology and disease and that many prior studies of RNA editing may overestimate both the extent and disease-related variability of RNA editing at the sites we examined in the human brain.
then 5 g cHO on training days) while participating in a high intensity resistance training program [3 sets × 10 repetitions at 75 % of 1 repetition maximum (1rM)], 3 days weeks −1 for 12 weeks. Following the initial 7-day "loading" phase, participants were instructed to ingest their supplement within 60 min post-exercise. Body composition and muscle strength measurements, blood collection and vastus lateralis muscle biopsy were completed at 0, 4, 8 and 12 weeks of the supplement and resistance training program. Results A significant time effect was observed for 1rM bench press (p = 0.016), leg press (p = 0.012), body mass (p = 0.03), fat-free mass (p = 0.005) and total myofibrillar protein (p = 0.005). A trend for larger muscle fiber crosssectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training (p = 0.08). no supplement interaction effects were observed. Conclusion Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males. crM + 5 g days −1 cHO × 7 days, then 0.1 g kg KeywordscrM + 5 g cHO on training days (average dosage of ~8.8 g)] or placebo cHO (20 g days −1 cHO × 7 days, communicated by Michael lindinger.
Background The relationship between changes in endocardial cushion and resultant congenital heart diseases (CHD) has yet to be established. It has been shown that increased regurgitant flow early in embryonic heart development leads to endocardial cushion defects, but it remains unclear how abnormal endocardial cushions during the looping stages might affect the fully septated heart. The goal of this study was to reproducibly alter blood flow in vivo and then quantify the resultant effects on morphology of endocardial cushions in the looping heart and on CHDs in the septated heart. Methods Optical pacing was applied to create regurgitant flow in embryonic hearts, and optical coherence tomography (OCT) was utilized to quantify regurgitation and morphology. Embryonic quail hearts were optically paced at 3 Hz (180bpm, well above intrinsic rate 60–110bpm) at stage 13 of development (3–4 wks human) for 5 min. Pacing fatigued the heart and led to at least 1 hr of increased regurgitant flow. Resultant morphological changes were quantified with OCT imaging at stage 19 (cardiac looping – 4–5 wks human) or stage 35 (4 chambered heart – 8 wks human). Results All paced embryos imaged at stage 19 displayed structural changes in cardiac cushions. The amount of regurgitant flow immediately after pacing was inversely correlated with cardiac cushion size 24-hrs post pacing (p-value < 0.01). The embryos with the most regurgitant flow and smallest cushions after pacing had a decreased survival rate at 8 days (p<0.05), indicating that those most severe endocardial cushion defects were lethal. Of the embryos that survived to stage 35, 17/18 exhibited CHDs including valve defects, ventricular septal defects, hypoplastic ventricles, and common AV canal. Conclusion The data illustrate a strong inverse relationship in which regurgitant flow precedes abnormal and smaller cardiac cushions, resulting in the development of CHDs.
Human cardiac myocytes derived from pluripotent stem cells (hCM) have invigorated interest in genetic disease mechanisms and cardiac safety testing; however, the technology to fully assess electrophysiological function in an assay that is amenable to high throughput screening has lagged. We describe a fully contactless system using optical pacing with an infrared (IR) laser and multi-site high fidelity fluorescence imaging to assess multiple electrophysiological parameters from hCM monolayers in a standard 96-well plate. Simultaneous multi-site action potentials (FluoVolt) or Ca2+ transients (Fluo4-AM) were measured, from which high resolution maps of conduction velocity and action potential duration (APD) were obtained in a single well. Energy thresholds for optical pacing were determined for cell plating density, laser spot size, pulse width, and wavelength and found to be within ranges reported previously for reliable pacing. Action potentials measured using FluoVolt and a microelectrode exhibited the same morphology and rate of depolarization. Importantly, we show that this can be achieved accurately with minimal damage to hCM due to optical pacing or fluorescence excitation. Finally, using this assay we demonstrate that hCM exhibit reproducible changes in repolarization and impulse conduction velocity for Flecainide and Quinidine, two well described reference compounds. In conclusion, we demonstrate a high fidelity electrophysiological screening assay that incorporates optical pacing with IR light to control beating rate of hCM monolayers.
BACKGROUND Trends in mechanical thrombectomy have emphasized larger bore aspiration catheters that may be difficult to deploy from a radial access point due to size constraints or need to obtain sheathless access. As such, many neurointerventionists are reticent to attempt thrombectomy through transradial access (TRA) for fear of worse outcomes. OBJECTIVE To explore whether mechanical thrombectomy could be achieved safely and effectively through the transradial route. METHODS We retrospectively analyzed the records of patients undergoing mechanical thrombectomy at our academic institute between January 2018 and January 2019, which corresponded to a time when we began to transition to TRA for neurointerventions, including mechanical thrombectomy. We compared the procedural details and clinical outcomes of patients undergoing mechanical thrombectomy using TRA with those using transfemoral access (TFA). RESULTS During the study period, 44 patients underwent mechanical thrombectomy with TRA and 129 with TFA. There was no statistically significant difference in door-to-access time, door-to-reperfusion time, or first-pass recanalization rate. There was no significant difference in modified Rankin Scale (mRS) score at discharge, mRS score at last follow-up, or length of stay. There were 7 access-site complications in the TFA group and none in the TRA group. One patient in the TRA group required crossover to TFA. CONCLUSION Mechanical thrombectomy can be performed safely and effectively from a TRA site without compromising recanalization times or rates. TRA has superior access-site complication profiles compared to TFA.
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