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Penetrating traumatic brain injury (pTBI) is increasingly survivable, but permanently disabling as adult mammalian nervous system does not regenerate. Recently, our group demonstrated transplant location-dependent neuroprotection and safety of clinical trial-grade human neural stem cell (hNSC) transplantation in a rodent model of acute pTBI. To evaluate whether longer injury-transplantation intervals marked by chronic inflammation impede engraftment, 60 male Sprague-Dawley rats were randomized to three sets. Each set was divided equally into two groups: 1) with no injury (sham) or 2) pTBI. After either 1 week (groups 1 and 2), 2 weeks (groups 3 and 4), or 4 weeks after injury (groups 5 and 6), each animal received 0.5 million hNSCs perilesionally. A seventh group of pTBI animals treated with vehicle served as the negative control. All animals were allowed to survive 12 weeks with standard chemical immunosuppression. Motor capacity was assessed pre-transplant to establish injury-induced deficit and followed by testing at 8 and 12 weeks after transplantation. Animals were euthanized, perfused, and examined for lesion size, axonal degeneration, and engraftment. Compared to vehicle, transplanted groups showed a trend for reduced lesion size and axonal injury across intervals. Remote secondary axonal injury was significantly reduced in groups 2 and 4, but not in group 6. The majority of animals showed robust engraftment independent of the injury-transplant time interval. Modest amelioration of motor deficit paralleled the axonal injury trend. In aggregate, pTBI-induced remote secondary axonal injury was resolved by early, but not delayed, hNSC transplantation., Competing Interests: The human neural stem cells (GFP labeled NSI-566 RSC) were provided by Dr. Karl Johe and Dr. Thomas G. Hazel, employees of NeuralStem Inc. (Germantown, MD). Dr. Gajavelli is an employee of Lacerta Therapeutics, a company developing viral vector-based gene therapies for central nervous system disorders., (© MaryLourdes Andreu et al., 2023; Published by Mary Ann Liebert, Inc.)

Purpose: This study describes and examines the short- and longer-term impact of a required longitudinal medical Spanish curriculum on physician assistant student preparedness and ability to communicate with patients in Spanish during clinical rotations., Methods: Fifty-eight preclinical students participated in an 80-hour curriculum delivered weekly over 3 semesters. Teaching followed a framework of second-language acquisition and included structured grammar and medical vocabulary practice with didactic, interactive, and group assignments. Vocabulary and grammar were assessed with quizzes. Oral proficiency was assessed by faculty with Spanish Objective Structured Clinical Examination (OSCE) stations at midpoint and end using the Interagency Language Roundtable (ILR), a 6-level scale (immediate outcome). Students self-rated proficiency and confidence and evaluated curriculum effectiveness for preparing them to care for Spanish-speaking patients (longer-term outcomes)., Results: All students passed the written and oral quizzes. Faculty-scored ILR verbal proficiency at the OSCEs increased by a mean level of 0.5 over 6 months. Student self-assessed proficiency improved on average by one level from baseline to 24 months later. Students rated highly curriculum effectiveness, preparedness to communicate in Spanish during clinical rotations, ability to judge when an interpreter was needed, and the importance of medical Spanish to future practice., Conclusions: A required integrated longitudinal medical Spanish curriculum was well received. Physician assistant students demonstrated short-term interval progression in Spanish proficiency, with improvements in both faculty and self-rating scores, and readiness to apply the skill to practice. They valued active learning associated with repeated practice with feedback, role playing, and interval assessments throughout the curriculum.

Traumatic brain injury (TBI) is the largest cause of death and disability of persons under 45 years old, worldwide. Independent of the distribution, outcomes such as disability are associated with huge societal costs. The heterogeneity of TBI and its complicated biological response have helped clarify the limitations of current pharmacological approaches to TBI management. Five decades of effort have made some strides in reducing TBI mortality but little progress has been made to mitigate TBI-induced disability. Lessons learned from the failure of numerous randomized clinical trials and the inability to scale up results from single center clinical trials with neuroprotective agents led to the formation of organizations such as the Neurological Emergencies Treatment Trials (NETT) Network, and international collaborative comparative effectiveness research (CER) to re-orient TBI clinical research. With initiatives such as TRACK-TBI, generating rich and comprehensive human datasets with demographic, clinical, genomic, proteomic, imaging, and detailed outcome data across multiple time points has become the focus of the field in the United States (US). In addition, government institutions such as the US Department of Defense are investing in groups such as Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug-screening consortium to address the barriers in translation. The consensus from such efforts including "The Lancet Neurology Commission" and current literature is that unmitigated cell death processes, incomplete debris clearance, aberrant neurotoxic immune, and glia cell response induce progressive tissue loss and spatiotemporal magnification of primary TBI. Our analysis suggests that the focus of neuroprotection research needs to shift from protecting dying and injured neurons at acute time points to modulating the aberrant glial response in sub-acute and chronic time points. One unexpected agent with neuroprotective properties that shows promise is transplantation of neural stem cells. In this review we present (i) a short survey of TBI epidemiology and summary of current care, (ii) findings of past neuroprotective clinical trials and possible reasons for failure based upon insights from human and preclinical TBI pathophysiology studies, including our group's inflammation-centered approach, (iii) the unmet need of TBI and unproven treatments and lastly, (iv) present evidence to support the rationale for sub-acute neural stem cell therapy to mediate enduring neuroprotection.