BDNF-mediated restoration of KCC2 expression underlies the suppression of spasticity and allodynia caused by rehabilitation.

Most studies targeting chronic spinal cord injury (SCI) have concluded that neural stem/progenitor cell (NS/PC) transplantation exerts only a subclinical recovery; this in contrast to its remarkable effect on acute and subacute SCI. To determine whether the addition of rehabilitative intervention enhances the effect of NS/PC transplantation for chronic SCI, we used thoracic SCI mouse models to compare manifestations secondary to both transplantation and treadmill training, and the two therapies combined, with a control group. Significant locomotor recovery in comparison with the control group was only achieved in the combined therapy group. Further investigation revealed that NS/PC transplantation improved spinal conductivity and central pattern generator activity, and that treadmill training promoted the appropriate inhibitory motor control. The combined therapy enhanced these independent effects of each single therapy, and facilitated neuronal differentiation of transplanted cells and maturation of central pattern generator activity synergistically. Our data suggest that rehabilitative treatment represents a therapeutic option for locomotor recovery after NS/PC transplantation, even in chronic SCI.

There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injury (SCI). Our multicenter team is currently planning to launch a first‐in‐human clinical study of an induced pluripotent stem cell (iPSC)‐based cell transplant intervention for subacute SCI. This trial was conducted as class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine, using neural stem/progenitor cells derived from a clinical‐grade, integration‐free human “iPSC stock” generated by the Kyoto University Center for iPS Cell Research and Application. In the present article, we describe how we are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. stem cells 2019;37:6–13

Background This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. Methods We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). Results Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47–0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15–20 μg/mL (OR 2.39, 95% CI 1.78–3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18–0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13–3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28–1.01); however, it was not significant in the analysis of mortality. Conclusions We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

No abstract

Background: Factors that govern peripheral neuropathy associated with Schwann cell dysfunction are not fully understood. Results: Under hyperglycemic conditions, Schwann cells de-differentiate into immature cells via sorbitol accumulation and Igf1 down-regulation. Conclusion: Schwann cell de-differentiation promotes neuropathy development under hyperglycemic conditions. Significance: These findings reveal new mechanisms underlying neuropathy seen in diabetes mellitus via Schwann cell de-differentiation leading to de-myelination.

Background:Somatosensory function has been frequently overlooked in clinics and research in the field of chronic stroke. The effects of neurorehabilitation interventions on sensory processing have still to be investigated using electrophysiological means.This study investigated the effect of hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy utilizing closed-loop electromyography-controlled neuromuscular electrical stimulation (NMES), on sensory changes and cortical plasticity among patients with chronic stroke.Methods:This study was a prespecified analysis of 23 participants involved in an ongoing large interventional study. Patients with severe upper limb hemiplegia dues to chronic stroke underwent 3 weeks of inpatient HANDS therapy, where daily treatment consisted of 8 h of NMES combined with wrist splinting, 90 min of comprehensive occupational therapy, and the practice of bimanual activities of daily living. Somatosensory evoked potentials (SEPs) and functional sensory assessments, including the Semmes–Weinstein monofilament test (SWMT) and thumb localizing test (TLT), were compared pre and post-treatment.Results:While no significant recovery of tactile sensation was observed, significant improvements in proprioception and motor function were induced. The number of cortical peaks significantly increased in the median nerve, but not in the tibial nerve. A total of 9 out of 11 participants who initially lacked certain peaks responded to treatment. Further analysis revealed a significant improvement in latency and amplitude of SEP peaks.Conclusions:Our results suggest that NMES-based neurorehabilitation induces certain plastic changes in the primary sensory cortex and in cortices associated with sensorimotor processing in people with chronic stroke sequelae, which may explain the observed improvements in proprioception.

No abstract