There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy. Normal brain function relies on a precise and delicate balance of chemical signaling mediated by the release of specific neurotransmitters. When this balance is disrupted by disease or injury, the results can be devastating. For example, decreased dopamine release is associated with anxiety, depression, cognitive impairment, fatigue, balance difficulties, and tremor [1][2][3][4][5][6]

Neurochemical changes evoked by electrical stimulation of the nervous system have been linked to both therapeutic and undesired effects of neuromodulation therapies used to treat obsessive-compulsive disorder, depression, epilepsy, Parkinson’s disease, stroke, hypertension, tinnitus, and many other indications. In fact, interest in better understanding the role of neurochemical signaling in neuromodulation therapies has been a focus of recent government- and industry-sponsored programs whose ultimate goal is to usher in an era of personalized medicine by creating neuromodulation therapies that respond to real-time changes in patient status. A key element to achieving these precision therapeutic interventions is the development of mathematical modeling approaches capable of describing the nonlinear transfer function between neuromodulation parameters and evoked neurochemical changes. Here, we propose two computational modeling frameworks, based on artificial neural networks (ANNs) and Volterra kernels, that can characterize the input/output transfer functions of stimulation-evoked neurochemical release. We evaluate the ability of these modeling frameworks to characterize subject-specific neurochemical kinetics by accurately describing stimulation-evoked dopamine release across rodent (R2 = 0.83 Volterra kernel, R2 = 0.86 ANN), swine (R2 = 0.90 Volterra kernel, R2 = 0.93 ANN), and non-human primate (R2 = 0.98 Volterra kernel, R2 = 0.96 ANN) models of brain stimulation. Ultimately, these models will not only improve understanding of neurochemical signaling in healthy and diseased brains but also facilitate the development of neuromodulation strategies capable of controlling neurochemical release via closed-loop strategies.

Background: The lack of consensus regarding optimal nonoperative management of idiopathic toe walking (ITW) results in wide variation in treatment across providers and institutions. Untreated toe walking can cause persistence of abnormal gait and symptomatic foot deformity in adulthood. Objective: To examine the outcomes of multiple commonly used nonoperative treatment techniques in a large cohort of children with ITW to better inform management of this condition. Design: Retrospective cohort study. Setting: Single tertiary care children's hospital from 2008 to 2015. Patients: Two hundred four children with ITW, aged 4 to 7 years at time of diagnosis, nonoperatively managed in orthopedic surgery, rehabilitation medicine, neurodevelopmental medicine, neurology, or physical therapy clinics. Interventions: Nonoperative techniques included observation, home stretching program, physical therapy program, use of anklefoot orthoses (AFOs), and serial casting. Main Outcome Measures: Greater than or equal to 10 of ankle dorsiflexion with the knee extended or walking on toes less than 25% of the time at last visit. Failure of treatment was defined as not achieving resolution criteria or requiring surgical intervention following failed nonoperative management. Results: Only 121 children (59.3%) attended at least one follow-up visit. Of those, 55 (45.5%) had a successful outcome. Increasing severity of ITW was associated with increased rate of follow-up (P = .03) and lower rates of successful treatment (P = .03). The use of AFOs was the only treatment modality associated with a successful outcome (unadjusted/adjusted odds ratio 3.97; [95% confidence interval, 1.80-8.74] and 4.81 [95% confidence interval, 1.91-12.1], respectively; P = .001). Conclusions: Loss to follow-up is common in children with ITW. Of those children who returned to clinic, less than half had a successful outcome. The only treatment technique statistically associated with short-term resolution of toe walking was the use of AFOs.

We aimed to evaluate the effectiveness of a single institution’s hand surgery clinical care guidelines at preventing the transmission of COVID-19. This is an anonymous survey study distributed to all employees within the division of hand surgery at a single quaternary-care academic medical facility. The primary outcome measure was the result of their employee surveillance and/or symptom initiated COVID-19 antibody (prior transmission) or polymerase chain reaction test (active infection) after institution of a COVID-19 exposure and transmission mitigating clinical care protocol. Employees were also asked multiple questions regarding their perceived and actual risk of exposure to COVID-19 while performing their clinical duties. Fifty-five of 69 (79.7%) hand clinic personnel employed during the COVID-19 surge from March 23, 2020 to May 18, 2020 (therapist: 15/19; consulting physicians: 11/16, nurses: 10/11; hand surgery residents: 6/6; hand surgery fellows: 4/5; physician assistant/nurse practitioners: 4/7; clinical desk operations specialists 3/4) responded to the survey. Forty-two employees were tested and all were negative for COVID-19 antibodies (42/42). Seventeen (17/55, 30.9%) employees had a known exposure to COVID-19 of which 13 of the 17 (76.5%) were from patients. Ten of these 17 (58.8%) employees were tested for COVID-19 antibodies and were negative. Twenty four of the 55 (43.6%) respondents felt they were at high risk for transmission of COVID-19. These data support ongoing care of emergent and urgent hand surgery patients during the COVID-19 surge and safe operation of an elective hand surgery practice amidst the ongoing pandemic through a multimodal approach.

Purpose In response to the COVID-19 pandemic, many post-graduate medical education lectures and conferences have been moved to a virtual platform. Questions remain regarding the effectiveness of virtual education, what types of educational offerings can be transitioned to a virtual format, and what types of curricula should still take place in person. Methods This study surveyed trainees from the United States who participated in a single institution’s hand surgery virtual flipped classroom curriculum consisting of six, week-long modules. Demographics, pre- and post- module achieved level of learning based on Bloom’s taxonomy, technology usage, and preferences were surveyed. Results Forty one of 65 (63.1%) participants responded to the survey. Trainees included hand surgery fellows (27/41,65.9%), orthopedic surgery residents (11/41,26.8%), and plastic surgery residents (3/41,7.3%). Participants primarily utilized a laptop to access articles (31/41,75.6%), view lectures (29/41,70.7%), and observe conferences (32/41,78.0%). On average, the majority of trainees read, viewed, and participated in more than half of the articles (28/41,68.3%), electronic videos (31/41,75.6%), and conferences (35/41,85.4%) per week. Median level of achieved learning increased from “I can apply” to “I can analyze” for all modules. Self-directed learning was preferred for basic fact and knowledge (26/41,63.4%) and faculty-directed learning was preferred to review and practice advanced concepts (34/41,82.9%). Participants perceived benefits of the virtual curriculum to include increased scheduling flexibility (8/41,19.5%), expert opinions (7/41,17.1%), and diversity of educational formats (3/41,7.3%). Perceived drawbacks included decreased interaction (8/41,19.5%), technical difficulties (6/41,14.6%), excessive detail (3/41,7.3%), and single institution bias (2/41,4.9%). Conclusions The flipped virtual classroom model is a highly effective and preferred method of instruction for trainees. Trainees achieved a higher level of learning following completion of each week long modules. Three considerations for implementation of a virtual curriculum include content quality, quantity, and reducing single-institution bias. Clinical Relevance Implementation of virtual learning can enhance hand surgery education for the modern learner.