Naturally Occurring Canine Glioma as a Model for Novel Therapeutics.

BACKGROUND: Current animal models of glioma are limited to small animal models, which are less predictive of treatment of human disease. Canines often develop gliomas de novo, but the natural history of the disease is not well described. OBJECTIVE: We provide data for naturally occurring canine gliomas; evaluating medical and surgical therapies. METHODS: We reviewed medical records of pet dogs with a presumptive diagnosis of glioma from MRI imaging that underwent surgery as part of the Canine Brain Tumor Clinical Trials Program. Breed, age, sex, median progression-free, and overall survival times and cause of death were recorded for multivariate analysis. RESULTS: Ninety five dogs (56 male; mean age = 8.3 years) were included, but nine were excluded as final pathology was non-neoplastic. Gross total resection was reported in 81 cases based on postoperative MRI. Seventy had high-grade tumors (grade III or IV). Eighty three dogs presented with seizures, being the most common presenting clinical sign. Median survival after surgery was 723 days (95% CI 343-1103) for grade II tumors, 301 days (197-404) for grade III and 200 days (126-274) for grade IV (p = .009 Kaplan-Meier survival analysis; Log Rank test). Age (cox regression, p = .14) or sex (Kaplan-Meier test, p = .22) did not predict survival. CONCLUSIONS: This study establishes normative data for a model exploiting dogs with naturally occurring glioma, which can be used to test novel therapies prior to translation to human trials. Further work will focus on the effects of different therapies, including chemotherapy, radiation therapy, and immunotherapy.

Creatine supplementation post-exercise does not enhance training-induced adaptations in middle to older aged males.

PURPOSE: The present study evaluated the effects of creatine monohydrate (CrM) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program. METHODS: In a double-blind, randomized trial, 20 males aged between 55 and 70 years were randomly assigned to consume either CrM-carbohydrate (CHO) [20 g days(-1) CrM + 5 g days(-1) CHO × 7 days, then 0.1 g kg(-1) CrM + 5 g CHO on training days (average dosage of ~8.8 g)] or placebo CHO (20 g days(-1) CHO × 7 days, 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 cross-sectional 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.

Cavernous Sinus Thrombosis.

Cavernous sinus thrombosis is a potentially lethal subset of cerebral venous sinus thrombosis that may occur as a result of septic and aseptic etiologies. The overall incidence is estimated to be between 0.2 and 1.6 per 100,000 persons; and treatments include antibiotics, anticoagulation, corticosteroids, and surgery. Recent morbidity and mortality estimates are approximately 15% and 11%, respectively. Rapid identification and treatment are essential and may reduce the risk of poor outcome or death.

Phase-Decorrelation Optical Coherence Tomography Measurement of Cold-Induced Nuclear Cataract.

Purpose: The purpose of this work is to determine the sensitivity of phase-decorrelation optical coherence tomography (OCT) to protein aggregation associated with cataracts in the ocular lens, as compared to OCT signal intensity. Methods: Six fresh porcine globes were held at 4°C until cold cataracts developed. As the globes were re-warmed to ambient temperature, reversing the cold cataract, each lens was imaged repeatedly using a conventional OCT system. Throughout each experiment, the internal temperature of the globe was recorded using a needle-mounted thermocouple. OCT scans were acquired, their temporal fluctuations were analyzed, and the rates of decorrelation were spatially mapped. Both decorrelation and intensity were evaluated as a function of recorded temperature. Results: Both signal decorrelation and intensity were found to change with lens temperature, a surrogate of protein aggregation. However, the relationship between signal intensity and temperature was not consistent across different samples. In contrast, the relationship between decorrelation and temperature was found to be consistent across samples. Conclusions: In this study, signal decorrelation was shown to be a more repeatable metric for quantification of crystallin protein aggregation in the ocular lens than OCT intensity-based metrics. Thus, OCT signal decorrelation measurements could enable more detailed and sensitive study of methods to prevent cataract formation. Translational Relevance: This dynamic light scattering-based approach to early cataract assessment can be implemented on existing clinical OCT systems without hardware additions, so it could quickly become part of a clinical study workflow or an indication for use for a pharmaceutical cataract intervention.

Mechanical Thrombectomy Versus Best Medical Management for Acute Ischemic Stroke in Elderly Patients: A Cost-Effectiveness Analysis.

OBJECTIVE: To determine the cost-effectiveness of mechanical thrombectomy (MT) versus best medical management (BMM) in patients aged ≥80 years. METHODS: We performed a systematic literature review to identify comparative studies of MT versus BMM with or without intravenous tissue-type plasminogen activator (IV tPA) in patients ≥80 years. Clinical data including outcomes and mortality categorized as modified Rankin scale scores 0-2, 3-5, and 6, were collected from identified studies, and effectiveness scores were assigned to each outcome. Costs associated with stroke outcomes were derived from previous literature, including costs associated with initial and follow-up imaging, hospitalization, physicians/associated personnel, and MT. TreeAge Pro software was used to construct a cost-effectiveness analysis model of clinical data from studies and costs derived from the literature. RESULTS: The review identified 1 relevant comparative study. The cost model demonstrated total annual cumulative overall per-patient costs of $30,064.21 for BMM with IV tPA and $21,940.36 for BMM without IV tPA. Overall effectiveness scores were 0.61 and 0.62, respectively. MT had a cumulative total annual per-patient cost of $47,849.54 and an overall effectiveness score of 0.40. The cost-effectiveness ratios of total cumulative patient cost to overall outcome effectiveness score for the 3 treatments were as follows: BMM with IV tPA = $49,285.59, BMM without IV tPA = $35,387.58, and MT = $119,623.85. BMM with or without IV tPA was found to be more cost-effective than MT. CONCLUSIONS: This study utilized stroke outcomes data for patients aged ≥80 years to conduct a cost-effectiveness analysis. MT was found to be less cost-effective than BMM with and without IV tPA.

Learning curves for transradial access versus transfemoral access in diagnostic cerebral angiography: a case series.

BACKGROUND: The perception of a steep learning curve associated with transradial access has resulted in its limited adoption in neurointervention despite the demonstrated benefits, including decreased access-site complications. OBJECTIVE: To compare learning curves of transradial versus transfemoral diagnostic cerebral angiograms obtained by five neurovascular fellows as primary operator. METHODS: The first 100-150 consecutive transradial and transfemoral angiographic scans performed by each fellow between July 2017 and March 2020 were identified. Mean fluoroscopy time per artery injected (angiographic efficiency) was calculated as a marker of technical proficiency and compared for every 25 consecutive procedures performed (eg, 1-25, 26-50, 51-75). RESULTS: We identified 1242 diagnostic angiograms, 607 transradial and 635 transfemoral. The radial cohort was older (64.3 years vs 62.3 years, p=0.01) and demonstrated better angiographic efficiency (3.4 min/vessel vs 3.7 min/vessel, p=0.03). For three fellows without previous endovascular experience, proficiency was obtained between 25 and 50 transfemoral angiograms. One fellow achieved proficiency after performing 25-50 transradial angiograms; and the two other fellows, in <25 transradial angiograms. The two fellows with previous experience had flattened learning curves for both access types. Two patients experienced transient neurologic symptoms postprocedure. Transradial angiograms were associated with significantly fewer access-site complications (3/607, 0.5% vs 22/635, 3.5%, p<0.01). Radial-to-femoral conversion occurred in 1.2% (7/607); femoral-to-radial conversion occurred in 0.3% (2/635). Over time, the proportion of transradial angiographic procedures increased. CONCLUSION: Technical proficiency improved significantly over time for both access types, typically requiring between 25 and 50 diagnostic angiograms to achieve asymptomatic improvement in efficiency. Reduced access-site complications and decreased fluoroscopy time were benefits associated with transradial angiography.

Optimizing thermal block length during infrared neural inhibition to minimize temperature thresholds.

Objective. Infrared neural inhibition (INI) is a method of blocking the generation or propagation of neural action potentials through laser heating with wavelengths strongly absorbed by water. Recent work has identified that the distance heated along axons, the block length (BL), modulates the temperature needed for inhibition; however, this relationship has not been characterized. This study explores how BL during INI can be optimized towards minimizing its temperature threshold.Approach. To understand the relationship between BL and the temperature required for INI, excised nerves fromAplysia californicawere laser-heated over different lengths of axon during electrical stimulation of compound action potentials. INI was provided by irradiation (λ= 1470 nm) from a custom probe (n= 6 nerves), and subsequent validation was performed by providing heat block using perfused hot media over nerves (n= 5 nerves).Main Results. Two BL regimes were identified. Short BLs (thermal full width at half maximum (tFWHM) = 0.81-1.13 mm) demonstrated that increasing the tFWHM resulted in lower temperature thresholds for INI (p< 0.0125), while longer BLs (tFWHM = 1.13-3.03 mm) showed no significant change between the temperature threshold and tFWHM (p> 0.0125). Validation of this longer regime was performed using perfused hot media over different lengths of nerves. This secondary heating method similarly showed no significant change (p> 0.025) in the temperature threshold (tFWHM = 1.25-4.42 mm).Significance. This work characterized how the temperature threshold for neural heat block varies with BL and identified an optimal BL around tFWHM = 1.13 mm which minimizes both the maximum temperature applied to tissue and the volume of tissue heated during INI. Understanding how to optimally target lengths of nerve to minimize temperature during INI can help inform the design of devices for longitudinal animal studies and human implementation.

Isotonic ion replacement can lower the threshold for selective infrared neural inhibition.

Significance: Infrared (IR) inhibition can selectively block peripheral sensory nerve fibers, a potential treatment for autonomic-dysfunction-related diseases (e.g., neuropathic pain and interstitial cystitis). Lowering the IR inhibition threshold can increase its translational potentials. Aim: Infrared induces inhibition by enhancing potassium channel activation. We hypothesized that the IR dose threshold could be reduced by combining it with isotonic ion replacement. Approach: We tested the IR inhibition threshold on the pleural-abdominal connective of Aplysia californica. Using a customized chamber system, the IR inhibition was applied either in normal saline or in isotonic ion-replaced saline, which could be high glucose saline, high choline saline, or high glucose/high choline saline. Each modified saline was at a subthreshold concentration for inhibiting neural conduction. Results: We showed that isotonically replacing ions in saline with glucose and/or choline can reduce the IR threshold and temperature threshold of neural inhibition. Furthermore, the size selectivity of IR inhibition was preserved when combined with high glucose/high choline saline. Conclusions: The present work of IR inhibition combined with isotonic ion replacement will guide further development of a more effective size-selective IR inhibition modality for future research and translational applications.

Dual Microwire Rail Technique to Advance a Microcatheter Past the Ostium of a Dissecting Carotid Artery Aneurysm for Flow Diverter Deployment: 2-Dimensional Operative Video.

Flow diversion using a Pipeline embolization device (PED; Medtronic, Dublin, Ireland) is an effective therapy for treating cavernous aneurysms. Currently, flow diverters require a 0.027-inch microcatheter for deployment. To navigate across these aneurysms, a 0.014-inch microwire is used, which often does not offer a sturdy enough rail to advance a 0.027-inch microcatheter past dissecting artery aneurysm ostia. We present a patient with a right cavernous dissecting carotid artery aneurysm. A step off between the 0.027-inch VIA microcatheter (MicroVention Terumo, Tustin, California) and 0.014-inch Synchro 2 microwire (Stryker Neurovascular, Fremont, California) resulted in difficulty with navigation of the microcatheter across the dissected portion of the aneurysm. A dual microwire rail technique involving two 0.014-inch Synchro 2 microwires was used to advance the VIA microcatheter past the dissecting artery aneurysm ostia for PED deployment. The introduction of the second microwire eliminated the step off between the microwire and microcatheter, providing a stronger rail and easier navigation of the microcatheter, without aggressive pushing. Postembolization runs showed optimal wall apposition and contrast stasis within the aneurysm, with successful flow diversion of the aneurysm. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary.

Genetically Encoded Calcium Indicators for In Situ Functional Studies of Corneal Nerves.

Purpose: Millions of people suffer from diseases that involve corneal nerve dysfunction, caused by various conditions, including dry eye syndrome, neurotrophic keratopathy, diabetes, herpes simplex, glaucoma, and Alzheimer's disease. The morphology of corneal nerves has been studied extensively. However, corneal nerve function has only been studied in a limited fashion owing to a lack of tools. Here, we present a new system for studying corneal nerve function. Methods: Optical imaging was performed on the cornea of excised murine globes taken from a model animal expressing a genetically encoded calcium indicator, GCaMP6f, to record calcium transients. A custom perfusion and imaging chamber for ex vivo murine globes was designed to maintain and stabilize the cornea, while allowing the introduction of chemical stimulation during imaging. Results: Imaging of calcium signals in the ex vivo murine cornea was demonstrated. Strong calcium signals with minimal photobleaching were observed in experiments lasting up to 10 minutes. Concentrated potassium and lidocaine solutions both modulated corneal nerve activity. Similar responses were observed in the same neurons across multiple chemical stimulations, suggesting the feasibility of using chemical stimulations to test the response of the corneal nerves. Conclusions: Our studies suggest that this tool will be of great use for studying functional changes to corneal nerves in response to disease and ocular procedures. This process will enable preclinical testing of new ocular procedures to minimize damage to corneal innervation and therapies for diminished neural function.

Transition to Transradial Access for Mechanical Thrombectomy-Lessons Learned and Comparison to Transfemoral Access in a Single-Center Case Series.

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.

Make Clipping Great Again: Microsurgery for Cerebral Aneurysms by Dual-Trained Neurosurgeons.

OBJECTIVE: Despite an increasing focus on endovascular treatment of cerebral aneurysms, microsurgical clipping remains an integral part of management. We evaluated the safety and effectiveness of microsurgical clipping performed by dual-trained neurosurgeons at our institute, which has adopted an endovascular first approach. METHODS: We retrospectively reviewed clinical and radiographic data of 412 aneurysms in 375 patients treated with microsurgical clipping. Univariate and multivariate analyses were performed to identify predictive outcome factors. We defined favorable outcome as a modified Rankin Scale (mRS) score of 0-2 at last clinical follow-up; unfavorable outcome was an mRS score of 3-6. We compared outcomes in our series with those of seminal aneurysm clipping series. RESULTS: Clipping of 330 of 351 unruptured aneurysms (94.01%) was associated with favorable outcome during the follow-up period (mean, 26.5 months). On univariate analysis, older patient age, intraoperative rupture, and higher baseline mRS scores were associated with unfavorable outcome in the unruptured cohort. On multivariate analysis, older age, higher baseline mRS scores, and posterior circulation aneurysm location were predictive of unfavorable outcome. Clipping of 46 of 61 ruptured aneurysms (75.4%) was associated with favorable outcome during the follow-up period (mean, 23.1 months). On univariate analysis, left-sided aneurysms, intraoperative rupture, and large aneurysm size were associated with unfavorable outcome in the ruptured cohort. On multivariate analysis, female sex was predictive of unfavorable outcome. CONCLUSIONS: Our ruptured and unruptured cohort results compared favorably with those in seminal series. Treatment by neurosurgeons adept at both endovascular and microsurgical techniques may improve clinical outcomes.

"Strokenomics": bending the cost curve in stroke care.

OBJECTIVE: The mortality rates for stroke are decreasing, yet it remains a leading cause of disability and the principal neurological diagnosis in patients discharged to nursing homes. The societal and economic burdens of stroke are substantial, with the total annual health care costs of stroke expected to reach $240.7 billion by 2030. Mechanical thrombectomy has been shown to improve functional outcomes compared to medical therapy alone. Despite an incremental cost of $10,840 compared to medical therapy, the improvement in functional outcomes and decreased disability have contributed to the cost-effectiveness of the procedure. In this study the authors describe a physician-led device bundle purchase program implemented for the delivery of stroke care. METHODS: The authors retrospectively reviewed the clinical and radiographic data and device-associated charges of 45 consecutive patients in whom a virtual "stroke bundle" model was used to purchase mechanical thrombectomy devices. RESULTS: Use of the stroke bundle to purchase mechanical thrombectomy devices resulted in an average savings per case of $2900.93. Compared to the traditional model of charging for devices à la carte, this represented an average savings of 25.2% per case. The total amount of savings for these initial 45 cases was $130,542.00. Thrombolysis in Cerebral Infarction scale grade 2b or 3 recanalization occurred in 38 patients (84.4%) using these devices. CONCLUSIONS: Purchasing devices through a bundled model resulted in substantial cost savings while maintaining the therapeutic efficacy of the procedure, further pushing the already beneficial long-term cost-benefit curve in favor of thrombectomy.

Endoscopic management of benign cystic lesions of the thalamus with fenestrated stent placement.

Benign intracranial cystic lesions of the thalamus are an uncommon clinical entity rarely requiring operative decompression. In combination with cyst fenestration, cerebrospinal fluid (CSF) flow diversion or fenestrated stent placement may be performed at the time of surgery. We describe a method of treatment of these cysts using endoscopic cyst fenestration with fenestrated transventricular stent placement. Three patients with benign cystic lesions were treated with stereotactic-guided, endoscopic fenestration and fenestrated stent placement. All 3 had radiographic and clinical improvement. There were no complications. Endoscopic fenestration and transventricular fenestrated stent placement is a minimally invasive, effective, and safe method to decompress benign, symptomatic cystic lesions of the thalamus.

Management of Iatrogenic Internal Carotid Artery Dissection and Middle Cerebral Artery Restenosis during Endovascular Treatment of Acute Stroke: Video Case.

Iatrogenic dissection of the internal carotid artery (ICA) during endovascular approaches is challenging. This video illustrates a case of iatrogenic ICA dissection at the skull base during mechanical thrombectomy for M1 occlusion. This case was further complicated by post-thrombectomy M1 restenosis that did not improve with submaximal angioplasty. ICA dissection occurred while navigating the guide catheter into the distal cervical ICA over a 0.38 inch Glidewire (MicroVention-Terumo, Aliso Viejo, California). The dissection flap was crossed with a SofiaPlus intermediate catheter (MicroVention-Terumo), Velocity microcatheter (Penumbra, Alameda, California), and double-ended 0.18 inch wire. The M1 occlusion was crossed and treated with Solumbra technique by pulling a Solitaire stent-retriever (Medtronic, Dublin, Ireland) through a SofiaPlus aspiration catheter (MicroVention). Post-recanalization M1 stenosis was noted, which was believed to be due to underlying intracranial atherosclerotic disease because of the appearance of platelet aggregation instead of a typical vasospasm response to a stent-retriever. A noncompliant Gateway 2 × 12 mm balloon catheter (Stryker Neurovascular, Kalamazoo, Michigan) was used to cross the lesion and perform submaximal angioplasty. Next, the dissection was treated by advancing a NeuronMAX guide catheter (Penumbra) over the SofiaPlus into the vertical petrous carotid artery beyond the dissection flap and unsheathing a Wallstent (Stryker Neurovascular) across the flap. Because of progressive M1 restenosis, a Wingspan stent (Stryker Neurovascular) was deployed. Final runs demonstrated Thrombolysis in Cerebral Infarction 2C recanalization. Pre-stenting thrombectomy was chosen because the duration of symptoms was >48 h; thus, determining the risk of reperfusion hemorrhage by evaluating intracranial shunting before stenting was prudent. Reperfusion hemorrhage would complicate the antiplatelet agent therapy necessary for stent placement. Consent was obtained from the patient prior to performing the procedure. Institutional review board approval is not required for the report of a single case.

Use of Intra-Arterial Tissue Plasminogen Activator in Acute Stroke: Video Case.

This video illustrates access to tortuous distal intracranial vasculature and the use of intra-arterial (IA) tissue plasminogen activator (tPA) for the revascularization of small vessel occlusion. IA tPA is a reasonable approach for distal arterial occlusion resistant to intravenous tPA or mechanical thrombectomy. In this video, the patient had a posterior circulation stroke with elevated time-to-peak in the cerebellar hemispheres. He had received intravenous tPA in the emergency room but ataxia and dysarthria symptoms persisted. Cerebral angiography showed right superior cerebellar artery (SCA) occlusion. Although his NIHSS score was low, his symptoms were disabling. While not standard of care, discussion with patients about potential options is crucial; and we believe that mechanical and localized therapies in these circumstances may be beneficial. A Velocity microcatheter (Penumbra, Alameda, California) was initially used to attempt SCA access but was unsuccessful. A second attempt was made with a Headway Duo (MicroVention, Aliso Viejo, California)-a smaller, more pliant microcatheter better suited to the acute turn in the SCA. A 2 mg IA tPA dose was administered at the occlusion site. A direct aspiration first-pass technique (ADAPT) and stent retriever were thought to be too aggressive in a small SCA. The proximal vessel was recanalized, and the microcatheter was advanced to the distal occlusion site before IA administration of another 2 mg of tPA. Post-tPA runs showed excellent SCA revascularization. For occlusion of small intracranial vessels where IV tPA is ineffective and mechanical thrombectomy is unsafe, local administration of IA tPA can be an effective therapy. Consent was obtained from the patient prior to performing the procedure. Institutional review board approval is not required for the report of a single case.

Voltage-gated potassium channels are critical for infrared inhibition of action potentials: an experimental study.

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 Prevalence of Burnout Among US Neurosurgery Residents.

BACKGROUND: Burnout is a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment. Its prevalence among US physicians exceeds 50% and is higher among residents/fellows. This is important to the practice of neurosurgery, as burnout is associated with adverse physical health, increased risk of substance abuse, and increased medical errors. To date, no study has specifically addressed the prevalence of burnout among neurosurgery residents. OBJECTIVE: To determine and compare the prevalence of burnout among US neurosurgery residents with published rates for residents/fellows and practicing physicians from other specialties. METHODS: We surveyed 106 US neurosurgery residency training programs to perform a descriptive analysis of the prevalence of burnout among residents. Data on burnout among control groups were used to perform a cross-sectional analysis. Nonparametric tests assessed differences in burnout scores among neurosurgery residents, and the 2-tailed Fisher's exact test assessed burnout between neurosurgery residents and control populations. RESULTS: Of approximately 1200 US neurosurgery residents, 255 (21.3%) responded. The prevalence of burnout was 36.5% (95% confidence interval: 30.6%-42.7%). There was no significant difference in median burnout scores between gender (P = .836), age (P = .183), or postgraduate year (P = .963) among neurosurgery residents. Neurosurgery residents had a significantly lower prevalence of burnout (36.5%) than other residents/fellows (60.0%; P < .001), early career physicians (51.3%; P < .001), and practicing physicians (53.5%; P < .001). CONCLUSION: 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.

An infrared optical pacing system for screening cardiac electrophysiology in human cardiomyocytes.

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.