Faculty Bibliography

Background/UNASSIGNED:Although the incidence of radiographic Adjacent Segment Disease (ASD) following anterior cervical diskectomy/fusion (ACDF) or cervical disc arthroplasty (CDA) typically ranges from 2-4%/year, reportedly fewer patients are symptomatic, and even fewer require secondary surgery. Methods/UNASSIGNED:Multiple studies have documented a 2-4% incidence of radiographic ASD following either ACDF or CDA per year. However, fewer are symptomatic from ASD, and even fewer require additional surgery/reoperations. Results/UNASSIGNED:In a meta-analysis (2016) involving 83 papers, the incidence of radiographic ASD per year was 2.79%, but symptomatic disease was present in just 1.43% of patients with only 0.24% requiring secondary surgery. In another study (2019) involving 38,149 patients undergoing ACDF, 2.9% (1092 patients; 0.62% per year) had radiographic ASD within an average of 4.66 postoperative years; the younger the patient at the index surgery, the higher the reoperation rate (i.e. < 40 years of age 4.56 X reoperations vs. <70 at 2.1 X reoperations). In a meta-analysis of 32 articles focusing on ASD 12-24 months following CDA, adjacent segment degeneration (ASDeg) occurred in 5.15% of patients, but adjacent segment disease (AS Dis) was noted in just 0.2%/ year. Further, AS degeneration occurred in 7.4% of patients after 1-level vs. 15.6% following 2 level fusions, confirming that CDA's "motion-sparing" design did not produce the "anticipated" beneficial results. Conclusion/UNASSIGNED:The incidence of radiographic ASD ranges from 2-4% per year for ACDF and CDA. Additionally, both demonstrate lesser frequencies of symptomatic ASD, and the need for secondary surgery. Further, doubling the frequency of ASD following 2 vs. 1-level CDA, should prompt surgeons to limit surgery to only essential levels.

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic.

Background/UNASSIGNED:gene have recently been linked to a spectrum of phenotypes including epilepsy, cerebellar ataxia, cortical myoclonus and intellectual disability (ID), and primary congenital defects of glycosylation. Case Report/UNASSIGNED:-associated clinical phenotypes. Discussion/UNASSIGNED:should be included in the genetic screening of undiagnosed forms of myoclonus, myoclonus-ataxia, and progressive myoclonus epilepsies.

Prediction of blood transfusion after adult spinal deformity (ASD) surgery can identify at-risk patients and potentially reduce its utilization and the complications associated with it. The use of artificial neural networks (ANNs) offers the potential for high predictive capability. A total of 1173 patients who underwent surgery for ASD were identified in the 2017-2019 NSQIP databases. The data were split into 70% training and 30% testing cohorts. Eighteen patient and operative variables were used. The outcome variable was receiving RBC transfusion intraoperatively or within 72 h after surgery. The model was assessed by its sensitivity, positive predictive value, F1-score, accuracy (ACC), and area under the curve (AUROC). Average patient age was 56 years and 63% were female. Pelvic fixation was performed in 21.3% of patients and three-column osteotomies in 19.5% of cases. The transfusion rate was 50.0% (586/1173 patients). The best model showed an overall ACC of 81% and 77% on the training and testing data, respectively. On the testing data, the sensitivity was 80%, the positive predictive value 76%, and the F1-score was 78%. The AUROC was 0.84. ANNs may allow the identification of at-risk patients, potentially decrease the risk of transfusion via strategic planning, and improve resource allocation.

BACKGROUND:Improving confidence in and uptake of the COVID-19 vaccines and boosters among long-term care workers (LTCWs) is a crucial public health goal, given their role in the care of the elderly and people at risk. While difficult to reach with workplace communication interventions, most LTCWs regularly use social media and smartphones. Various social media interventions have improved attitudes and uptake for other vaccines and hold promise for the LTCW population. OBJECTIVE:e aimed to develop a curated social web app (interactive website) to increase COVID-19 vaccine confidence (three-arm randomized trial underway). METHODS:Following user-centric design and participatory research approaches, we undertook three steps: 1) content identification, 2) platform development, and 3) community building. A LTCW and stakeholder advisory group provided iterative input. For content identification, we identified topics of concern about COVID-19 vaccines via desktop research (published literature, public opinion polls and social media monitoring), refined by interviewing and polling LTCWs. We also conducted a national online panel survey. We curated and fact-checked posts from popular social media platforms that addressed the identified concerns. During platform development, we solicited preferences for design and functionality via interviews and user experience (UX) testing with LTCWs. We also identified best practices for online community building, like comment moderation. RESULTS:In the interviews (n=9), we found three themes: LTCWs 1) are proud of their work but feel undervalued; 2) have varying levels of trust in COVID-19 related information, and 3) would welcome a curated COVID-19 resource that is easy to understand and use. Desktop research, LTCW interviews and our national online panel survey (n=592) found participants are interested in information about COVID-19 in general, vaccine benefits, vaccine risks, and vaccine development. Content identification resulted in 434 posts addressing these topic areas, with 209 uploaded to the final web app. Our LTCW poll (n=8) revealed preferences for personal stories and video content. The platform we developed is an accessible WordPress-based social media web app, refined through formal (n=3) and informal UX testing. Users can sort posts by topic or subtopic and react to or comment on them. To build an online community, we recruited three LTCW 'community ambassadors' and instructed them to encourage discussion, acknowledge concerns and offer factual information on COVID-19 vaccines. We also set 'community standards' for the web app. CONCLUSIONS:An iterative, user-centric, participatory approach led to the launch of an accessible social media web app with curated content for COVID-19 vaccines targeting LTCWs in the U.S. Through our trial, we will determine if this approach successfully improves vaccine confidence. If so, a similar social media resource could be used to develop curated social media interventions in other populations and with other public health goals. CLINICALTRIAL/BACKGROUND:This effort is part of a broader clinical trial; ClinicalTrials.gov NCT05168800.

HNRNPU encodes the heterogeneous nuclear ribonucleoprotein U, which participates in RNA splicing and chromatin organization. Microdeletions in the 1q44 locus encompassing HNRNPU and other genes and point mutations in HNRNPU cause brain disorders, including early-onset seizures and severe intellectual disability. We aimed to understand HNRNPU's roles in the developing brain. Our work revealed that HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with an apparent higher sensitivity of the latter. Further, expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu's conditional truncation. Finally, we identified pharmaceutical and genetic agents that can partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains, ameliorate radial neuronal migration defects and rescue cultured neural progenitors' cell death.

OBJECTIVE/UNASSIGNED:Studies have observed variable associations of prior contact sport participation with subjective and objective measures of cognitive function. This study directly investigated the association between subjective self-report and objective performance-based cognition among former collegiate football players, as well as its relationship to self-reported concussion history. METHODS/UNASSIGNED: = 1.49]) retired from sport 15-years prior were enrolled. Linear regression models examined associations between subjective cognition (Quality of Life in Neurological Disorders Cognitive Functioning-Short Form), and performance on a neuropsychological battery. Domain specific (executive function) metrics of subjective (Behavior Rating Inventory of Executive Function-Adult) and objective cognition were also exclusively examined. Associations between self-reported concussion history with subjective and objective measures were tested. Potential influential factors (sleep quality and distress) were included as covariates. RESULTS/UNASSIGNED:= .033). CONCLUSIONS/UNASSIGNED:Reliance on self-reported measures of cognitive functioning alone is insufficient when assessing cognition in former contact sport athletes. Assessment of other factors known to influence subjective cognitive complaints should also be examined in determining the presence of cognitive deficits.

Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive method for stimulating the brain that is rapidly developing into a treatment method for various neurological and psychiatric conditions. In particular, there is growing evidence of a therapeutic role for tDCS in ameliorating or delaying the cognitive decline in Alzheimer's disease (AD). We provide a brief overview of the current development and application status of tDCS as a nonpharmacological therapeutic method for AD and mild cognitive impairment (MCI), summarize the levels of evidence, and identify the improvements needed for clinical applications. We also suggest future directions for large-scale controlled clinical trials of tDCS in AD and MCI, and emphasize the necessity of identifying the mechanistic targets to facilitate clinical applications.