Impact of Virtual Reality on Pharmacology Education: A Pilot Study.

Introduction Virtual reality (VR) is a powerful tool in health professional education. It has been successfully implemented in various domains of education with positive learning outcomes. The three-dimensional (3D) visualization offered by VR can potentially be applied to learn complex pharmacology topics. This study aims to investigate whether VR technology can improve the learning of complex pharmacological concepts. Methods A VR learning module on cardiovascular drugs was developed using Kern's six-step framework. 32 medical students participated in the pilot study. Their pharmacology knowledge was assessed using pre- and post-intervention tests. Additionally, feedback from the participants were collected through a post-intervention survey that assessed learner satisfaction, ease of use, perceived usefulness, quality of visual elements, intention to use, and comfort level during the VR experience. Results Participants scored significantly higher in the post-intervention test than in the pre-intervention test (p <0.05). A majority of the participants (90%) were satisfied with the VR module, finding it easy to use, and time efficient. A minority of participants (15%) preferred a traditional learning format while some participants (20%) experienced discomfort in VR. Conclusion Our findings suggest that VR enhances pharmacology knowledge in medical students and is well-received as an innovative educational tool. By providing immersive 3D visualization of complex drug actions, VR has the potential to transform pharmacology education into an engaging and effective learning experience.

Frequently Used Conceptual Frameworks and Design Principles for Extended Reality in Health Professions Education.

Health professions education (HPE) has witnessed a dramatic increase in the use of extended reality (XR), but there is limited evidence that conceptual frameworks are being effectively employed in the design and implementation of XR. This paper introduces commonly utilized conceptual frameworks that can support the integration of XR into the learning process and design principles that can be helpful for the development and evaluation of XR educational applications. Each framework and design principle is summarized briefly, followed by a description of its applicability to XR for HPE and an example of such application.

Improving Summative Assessment Through a Resource-Efficient Faculty Review Process.

Committee reviews improve the quality of multiple-choice question (MCQ) exams; however, such review processes are typically highly resource-intensive and time-consuming. We report a review process that requires limited faculty time and administrative resources. A small committee reviewed selected items (14-20%) of the final exams of six independent block courses taken by first- and second-year medical students. This process resulted in a significant increase in the item discrimination of reviewed questions in all exams. Our findings support the utility of a review process and may offer health profession educators a more practical and efficient approach for improving the quality of in-house MCQ exams. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01631-9.

Implementing Rubric-Based Peer Review for Video Microlecture Design in Health Professions Education.

Efficient and effective instructional materials designed for asynchronous learning are increasingly important in health professions curricula. Video microlectures are an effective instructional method, but many faculty lack training in applying best-practice multimedia principles to development of their own recorded microlectures. Here we report a rubric designed for use in a peer-review process to evaluate and improve microlectures. The one-page rubric provides a framework for application of multimedia principles and cognitive load theory to microlecture design. Quality improvement of microlectures following redesign according to rubric elements is supported by increased student viewership, which coincided with higher rubric peer review scores.

Effect of Video Conferencing on Student Academic Performance: Evidence from Preclinical Summative Assessment Scores.

Anecdotal evidence suggests learners experience fatigue and burnout from multiple hours on virtual platforms. We compared summative exam performance data of second year preclinical medical students in a medical neuroscience course over consecutive years in which interactive synchronous activities occurred in-person (2019) or entirely online (2020). Exam items that assessed interactive, synchronously delivered content in 2020 had mean scores that were significantly lower than 2019. Interestingly, summative exam performance in the preceding course showed no appreciable difference. Taken together, our findings suggest that prolonged use of virtual platforms in preclinical medical education might negatively impact the efficacy of synchronous learning.

Dehydration: A Multidisciplinary Case-Based Discussion for First-Year Medical Students.

Introduction: As many medical school curricula shift to integrated learning of multiple basic science topics as well as clinical concepts, there is an increasing need for instructional materials that incorporate multiple topics yet are targeted to the knowledge basis of first-year medical students. This interactive case-based session for first-year medical students centers on the clinical presentation and initial evaluation of a patient experiencing dehydration after running a marathon in a high-altitude city. Methods: After completion of assigned out-of-class preparation, students followed the patient from a healthy state to moderate dehydration over the course of two 2-hour class sessions. Throughout discussion of the case, students answered questions requiring them to integrate elements of cell biology, biochemistry, physiology, and clinical reasoning with minimal faculty involvement. The learning activity was administered at University of Illinois College of Medicine campuses in both a small-group setting (10 students, one faculty facilitator) and a large-group format (55-90 students, multiple faculty facilitators). Following the activity, we assessed student perceptions of the design and implementation of the materials as well as effectiveness at meeting the learning goals. Results: Of 198 students who participated in the case discussions on dehydration, the majority rated the case positively, indicated by a rating of good or excellent. Discussion: This multidisciplinary case on dehydration can be used early in medical education to introduce students to clinical scenarios while learning fundamental science content. An integrated approach to medical content and versatility with regard to class size make this case a valuable teaching tool.

Human Schwann cells exhibit long-term cell survival, are not tumorigenic and promote repair when transplanted into the contused spinal cord.

The transplantation of rodent Schwann cells (SCs) provides anatomical and functional restitution in a variety of spinal cord injury (SCI) models, supporting the recent translation of SCs to phase 1 clinical trials for human SCI. Whereas human (Hu)SCs have been examined experimentally in a complete SCI transection paradigm, to date the reported behavior of SCs when transplanted after a clinically relevant contusive SCI has been restricted to the use of rodent SCs. Here, in a xenotransplant, contusive SCI paradigm, the survival, biodistribution, proliferation and tumorgenicity as well as host responses to HuSCs, cultured according to a protocol analogous to that developed for clinical application, were investigated. HuSCs persisted within the contused nude rat spinal cord through 6 months after transplantation (longest time examined), exhibited low cell proliferation, displayed no evidence of tumorigenicity and showed a restricted biodistribution to the lesion. Neuropathological examination of the CNS revealed no adverse effects of HuSCs. Animals exhibiting higher numbers of surviving HuSCs within the lesion showed greater volumes of preserved white matter and host rat SC and astrocyte ingress as well as axon ingrowth and myelination. These results demonstrate the safety of HuSCs when employed in a clinically relevant experimental SCI paradigm. Further, signs of a potentially positive influence of HuSC transplants on host tissue pathology were observed. These findings show that HuSCs exhibit a favorable toxicity profile for up to 6 months after transplantation into the contused rat spinal cord, an important outcome for FDA consideration of their use in human clinical trials.

Loss of central inhibition: implications for behavioral hypersensitivity after contusive spinal cord injury in rats.

Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.

Limitations of nerve repair of segmental defects using acellular conduits.

The authors present the case of a 20-year-old man who, 3 months after his initial injury, underwent repair of a 1.7-cm defect of the ulnar nerve at the wrist; repair was performed with an acellular nerve allograft. Given the absence of clinical or electrophysiological recovery at 8 months postrepair, the patient underwent reexploration, excision of the "regenerated cable," and rerepair of the ulnar nerve with sural nerve autografts. Histology of the cable demonstrated minimal axonal regeneration at the midpoint of the repair. At the 6- and 12-month follow-ups of the sural nerve graft repair, clinical and electrophysiological evidence of both sensory and motor reinnervation of the ulnar nerve and associated hand muscles was demonstrated. In this report, the authors describe a single case of failed acellular nerve allograft and correlate the results with basic science and human studies reporting length and diameter limitations in human nerve repair utilizing grafts or conduits devoid of viable Schwann cells.

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats.

OBJECT: Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. METHODS: The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/µl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only-filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. RESULTS: Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein-positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum-only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. CONCLUSIONS: The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

Review of the history and current status of cell-transplant approaches for the management of neuropathic pain.

Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant or replacement for current pharmacological treatments, cell therapy is a likely near future clinical tool for improved health care.

Potential for Cell-Transplant Therapy with Human Neuronal Precursors to Treat Neuropathic Pain in Models of PNS and CNS Injury: Comparison of hNT2.17 and hNT2.19 Cell Lines.

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate the potential of cell-based release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes-related injury) and CNS (spinal cord injury) damage in rat models. Both cell lines transplants potently and permanently reverse behavioral hypersensitivity without inducing tumors or other complications after grafting. Functioning as cellular minipumps for antinociception, human neuronal precursors, like these NT2-derived cell lines, would likely provide a useful adjuvant or replacement for current pharmacological treatments for neuropathic pain.

The combination of human neuronal serotonergic cell implants and environmental enrichment after contusive SCI improves motor recovery over each individual strategy.

A human neuronal cell line, hNT2.19, which secretes serotonin (5-HT) after differentiation, was used as a transplant source to improve motor dysfunction following severe contusive spinal cord injury (SCI). Also, environmental enrichment (EE) was added to the interspinal transplant treatment paradigm. Motor testing was performed weekly before and following SCI, with and without EE and/or cell transplant conditions. Motor recovery was maximal when both cell transplant and EE were used. Individual treatment paradigms also significantly improved foot rotation and reduced footfall errors but not stride length or base of support dysfunction. This recovery of motor function after SCI suggests that the combinatory use of serotonergic hNT2.19 cell grafts plus EE is a meaningful strategy to modestly improve motor dysfunction that accompanies contusive SCI.

Social and environmental enrichment improves sensory and motor recovery after severe contusive spinal cord injury in the rat.

Neuropathic pain and motor dysfunction are difficult problems following spinal cord injury (SCI). Social and environmental enrichment (SEE), which models much of the clinical rehabilitation environment for post-SCI persons, is the focus of the current investigation which examines the effects of multiple-housing and the addition of climbing spaces, improved bedding and crawl toys on the sensory and motor recovery following a severe contusive SCI. Efficacy was determined with sensory testing, open-field motor behavioral testing, lesion volume analysis and quantification of brain-derived neurotrophic factor (BDNF) in the lumbar spinal cord with and without SEE provided during the recovery period. Sensory and motor testing were performed weekly for 12 weeks following SCI. SEE significantly and permanently reversed cutaneous allodynia, but not thermal hyperalgesia, to near normal levels. The gross locomotor performance (BBB [Basso, Beattie, and Bresnahan] motor scores) significantly improved about two points. In addition, the BBB subscale scores were significantly improved nearly seven points by the end of the study. SEE also significantly improved foot rotation to normal levels and reduced gridwalk footfall errors nearly 50%, but had no effect on stride length or base of support dysfunctions. SEE significantly increased the total volume of a thoracic segment of cord encompassing the injury site at 12 weeks, by reducing cavitation and increasing both the volume of grey and white matter spared, compared to SCI alone. When BDNF levels were examined in the injured lumbar spinal cord, SEE significantly returned BDNF levels to near-normal. These data suggest that immediate use of SEE after contusive SCI is able to improve overall spinal cell survival and prevent much of the sensory and motor dysfunction that accompanies contusive SCI.

Optimizing the transplant dose of a human neuronal cell line graft to treat SCI pain in the rat.

Neuropathic pain is a prevalent and difficult problem in the setting of spinal cord injury (SCI). The use of cellular transplant therapy to treat this pain has been successful with the use of a human neuronal cell line, hNT2.17 [M.J. Eaton, S.Q. Wolfe, M.A. Martinez, M. Hernandez, C. Furst, J. Huang, B.R. Frydel, O. Gomez-Marin, Subarachnoid transplant of a human neuronal cell line attenuates chronic allodynia and hyperalgesia after excitotoxic SCI in the rat, J. Pain 8 (2007) 33-50]. Intrathecal transplant of these cells potently reverses behavioral hypersensitivity after excitotoxic spinal cord injury in the rat model. This study focuses on delineating the optimal dose of these cell grafts in the same model. Two weeks after intraspinal injection of quisqualic acid (QUIS) with subsequent behavioral hypersensitivity, terminally differentiated hNT2.17 cells were transplanted into 300 g Wistar-Furth rats in a logarithmic variation of doses: 10(6), 10(5) and 10(3) cells. Behavioral hypersensitivity testing was performed weekly for 6 weeks following transplant. The dose of 10(6) cells (or approximately 3 million/kg) potently and permanently reversed both cutaneous allodynia (CA) and thermal hyperalgesia (TH). Reduced transplant doses of the hNT2.17 cell line did not permanently reverse behavioral hypersensitivity, suggesting that there is an optimal dose that can be used as a clinical tool to treat SCI-associated neuropathic pain.

cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury.

Central neurons regenerate axons if a permissive environment is provided; after spinal cord injury, however, inhibitory molecules are present that make the local environment nonpermissive. A promising new strategy for inducing neurons to overcome inhibitory signals is to activate cAMP signaling. Here we show that cAMP levels fall in the rostral spinal cord, sensorimotor cortex and brainstem after spinal cord contusion. Inhibition of cAMP hydrolysis by the phosphodiesterase IV inhibitor rolipram prevents this decrease and when combined with Schwann cell grafts promotes significant supraspinal and proprioceptive axon sparing and myelination. Furthermore, combining rolipram with an injection of db-cAMP near the graft not only prevents the drop in cAMP levels but increases them above those in uninjured controls. This further enhances axonal sparing and myelination, promotes growth of serotonergic fibers into and beyond grafts, and significantly improves locomotion. These findings show that cAMP levels are key for protection, growth and myelination of injured CNS axons in vivo and recovery of function.