Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI. 

/pdf/activity-dependent-spinal-cord-neuromodulation-rapidly-2hpsfsa5.pdf

Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

A universal interface for plug-and-play assembly of stretchable devices

Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system. In the past few decades, researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling, but the results have not been ideal. Recently, new pathological mechanisms of SCI, especially the interactions between immune and neural cell responses, have been revealed by single-cell sequencing and spatial transcriptome analysis. With the development of bioactive materials and stem cells, more attention has been focused on forming intermediate neural networks to promote neural regeneration and neural circuit reconstruction than on promoting axonal regeneration in the corticospinal tract. Furthermore, technologies to control physical parameters such as electricity, magnetism and ultrasound have been constantly innovated and applied in neural cell fate regulation. Among these advanced novel strategies and technologies, stem cell therapy, biomaterial transplantation, and electromagnetic stimulation have entered into the stage of clinical trials, and some of them have already been applied in clinical treatment. In this review, we outline the overall epidemiology and pathophysiology of SCI, expound on the latest research progress related to neural regeneration and circuit reconstruction in detail, and propose future directions for SCI repair and clinical applications. 

/pdf/spinal-cord-injury-molecular-mechanisms-and-therapeutic-51h4g9ju.pdf

Spinal cord injury: molecular mechanisms and therapeutic interventions

Abstract A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord 1–3 applied during neurorehabilitation 4,5 (EES REHAB ) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EES REHAB in mice. We applied single-nucleus RNA sequencing 6–9 and spatial transcriptomics 10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type 12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EES REHAB , whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours. 

/pdf/the-neurons-that-restore-walking-after-paralysis-1k4t06ke.pdf

The neurons that restore walking after paralysis

Background 
Over the last three decades, various instruments were developed and employed to assess medical professionalism, but their measurement properties have yet to be fully evaluated. This study aimed to systematically evaluate these instruments’ measurement properties and the methodological quality of their related studies within a universally acceptable standardized framework and then provide corresponding recommendations.


Methods 
A systematic search of the electronic databases PubMed, Web of Science, and PsycINFO was conducted to collect studies published from 1990–2015. After screening titles, abstracts, and full texts for eligibility, the articles included in this study were classified according to their respective instrument’s usage. A two-phase assessment was conducted: 1) methodological quality was assessed by following the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist; and 2) the quality of measurement properties was assessed according to Terwee’s criteria. Results were integrated using best-evidence synthesis to look for recommendable instruments.


Results 
After screening 2,959 records, 74 instruments from 80 existing studies were included. The overall methodological quality of these studies was unsatisfactory, with reasons including but not limited to unknown missing data, inadequate sample sizes, and vague hypotheses. Content validity, cross-cultural validity, and criterion validity were either unreported or negative ratings in most studies. Based on best-evidence synthesis, three instruments were recommended: Hisar’s instrument for nursing students, Nurse Practitioners’ Roles and Competencies Scale, and Perceived Faculty Competency Inventory.


Conclusion 
Although instruments measuring medical professionalism are diverse, only a limited number of studies were methodologically sound. Future studies should give priority to systematically improving the performance of existing instruments and to longitudinal studies.

/pdf/assessing-medical-professionalism-a-systematic-review-of-496aaaih24.pdf

Assessing medical professionalism: A systematic review of instruments and their measurement properties.

Spinal cord injury (SCI) induces haemodynamic instability that threatens survival1–3, impairs neurological recovery4,5, increases the risk of cardiovascular disease6,7, and reduces quality of life8,9. Haemodynamic instability in this context is due to the interruption of supraspinal efferent commands to sympathetic circuits located in the spinal cord10, which prevents the natural baroreflex from controlling these circuits to adjust peripheral vascular resistance. Epidural electrical stimulation (EES) of the spinal cord has been shown to compensate for interrupted supraspinal commands to motor circuits below the injury11, and restored walking after paralysis12. Here, we leveraged these concepts to develop EES protocols that restored haemodynamic stability after SCI. We established a preclinical model that enabled us to dissect the topology and dynamics of the sympathetic circuits, and to understand how EES can engage these circuits. We incorporated these spatial and temporal features into stimulation protocols to conceive a clinical-grade biomimetic haemodynamic regulator that operates in a closed loop. This ‘neuroprosthetic baroreflex’ controlled haemodynamics for extended periods of time in rodents, non-human primates and humans, after both acute and chronic SCI. We will now conduct clinical trials to turn the neuroprosthetic baroreflex into a commonly available therapy for people with SCI. An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

/pdf/neuroprosthetic-baroreflex-controls-haemodynamics-after-5ecxe5ebvs.pdf

Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury

OBJECTIVE Residents must become proficient in a variety of procedures. The practice of learning procedural skills on patients has come under ethical scrutiny, giving rise to the concept of simulation-based medical education. Resident training in a simulated environment allows skill acquisition without compromising patient safety. We assessed the impact of a simulation-based procedural skills training course on residents' competence in the performance of critical resuscitation procedures. METHODS We solicited self-assessments of the knowledge and clinical skills required to perform resuscitation procedures from a cross-sectional multidisciplinary sample of 28 resident study participants. Participants were then exposed to an intensive 8-hour simulation-based training program, and asked to repeat the self-assessment questionnaires on completion of the course, and again 3 months later. We assessed the validity of the self-assessment questionnaire by evaluating participants' skills acquisition through an Objective Structured Clinical Examination station. RESULTS We found statistically significant improvements in participants' ratings of both knowledge and clinical skills during the 3 self-assessment periods ( p < 0.001). The participants' year of postgraduate training influenced their self assessment of knowledge ( F = 4.91, p< 0.01) and clinical 2,25 skills ( F = 10.89, p< 0.001). At the 3-month follow-up, junior 2,25 level residents showed consistent improvement from their baseline scores, but had regressed from their posttraining measures. Senior-level residents continued to show further increases in their assessments of both clinical skills and knowledge beyond the simulation-based training course. CONCLUSION Significant improvement in self-assessed theoretical knowledge and procedural skill competence for residents can be achieved through participation in a simulation-based resuscitation course. Gains in perceived competence appear to be stable over time, with senior learners gaining further confidence at the 3-month follow-up. Our findings support the benefits of simulation-based training for residents.

/pdf/simulation-based-training-in-critical-resuscitation-475sgd5iem.pdf

Simulation-based training in critical resuscitation procedures improves residents' competence.

Background There is a question of whether a single assessment tool can assess the key competencies of residents as mandated by the Royal College of Physicians and Surgeons of Canada CanMEDS roles framework. Objective The objective of the present study was to investigate the reliability and validity of an emergency medicine (EM) in-training evaluation report (ITER). Method ITER data from 2009 to 2011 were combined for residents across the 5 years of the EM residency training program. An exploratory factor analysis with varimax rotation was used to explore the construct validity of the ITER. A total of 172 ITERs were completed on residents across their first to fifth year of training. Results A combined, 24-item ITER yielded a five-factor solution measuring the CanMEDs role Medical Expert/Scholar, Communicator/Collaborator, Professional, Health Advocate and Manager subscales. The factor solution accounted for 79% of the variance, and reliability coefficients (Cronbach alpha) ranged from α = 0.90 to 0.95 for each subscale and α = 0.97 overall. The combined, 24-item ITER used to assess residents' competencies in the EM residency program showed strong reliability and evidence of construct validity for assessment of the CanMEDS roles. Conclusion Further research is needed to develop and test ITER items that will differentiate each CanMEDS role exclusively.

/pdf/validity-and-reliability-of-an-in-training-evaluation-report-24v5kk40u8.pdf

Validity and reliability of an in-training evaluation report to measure the CanMEDS roles in emergency medicine residents.

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Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury

Simulation-based training in critical resuscitation procedures improves residents' competence.

Validity and reliability of an in-training evaluation report to measure the CanMEDS roles in emergency medicine residents.