Introduction: Spinal cord injury (SCI) is associated with microenvironment imbalance, thereby resulting in poor regeneration and recovery of the spinal cord. Gene therapy can be used to balance the inflammatory response, however target genes cannot exist in localized injured areas. Methods: A genetically engineered electrospun scaffold (GEES) to achieve long-term immunoregulation and nerve repair was constructed. By combining the microfluidic and electrospinning techniques, interleukin-10 plasmid (pIL10) was loaded into lipid nanoparticles (LNPs) (pIL10-LNP), which was encapsulated to the nerve growth factor (NGF). Immunofluorescence staining, qRT-PCR, ELISA, flow cytometry, and other tests were employed to comprehensively assess the role of GEES in modulating macrophage polarization and facilitating neural repair. Results: The results showed that the scaffold released >70% of the pIL10-LNP within 10 d and continued slow release within 30 d. In vitro cell experiments have demonstrated that GEES effectively stimulates macrophages to secrete anti-inflammatory cytokines and facilitates the differentiation of neural stem cells into neuronal cells. In rat T9 SCI model, the GEES significantly inhibited the inflammatory response in the acute and chronic phases of SCI by transfecting local tissues with slow-release pIL10-LNP to promote the release of the anti-inflammatory factor IL10, thereby creating a favorable microenvironment. With the addition of NGF, the repair and regeneration of nerve tissues was effectively promoted, and the post-SCI motor function of rats improved. Discussion: GEES can regulate post-SCI immune responses through continuous and effective gene delivery, providing a new strategy for the construction of electrospun scaffolds for nerve repair in gene therapy.

UNASSIGNED: Physical and occupational therapists provide routine care for manual wheelchair users and are responsible for training and assessing the quality of transfers. These transfers can produce large loads on the upper extremity joints if improper sitting-pivot-technique is used. Methods to assess quality of transfers include the Transfer Assessment Instrument, a clinically validated tool derived from quantitative biomechanical features; however, adoption of this tool is low due to the complex usage requirements and speed of typical transfers.
UNASSIGNED: The objective of this study is to develop and validate a computer vison and machine learning solution to better implement the Transfer Assessment Instrument in clinical settings.
UNASSIGNED: The prototype system, TransKinect, consists of an infrared depth sensor and a custom software application; usability testing was carried out with fifteen therapists who performed two transfer assessments with the TransKinect. Proficiency in using features, usability, acceptability and satisfaction were analysed with validated surveys and themes were extracted from the qualitative feedback.
UNASSIGNED: The therapists were able to successfully complete the transfer quality assessments with 86.7 ± 5.4% proficiency. Total scores for System Usability Scale (77.6 ± 14.7%) and Questionnaire for User Interface Satisfaction (83.5 ± 8.7%) indicated that the system was usable and satisfactory. Qualitative feedback indicated that TransKinect was user-friendly, easy to learn, and had high potential.
UNASSIGNED: The results support TransKinect as a potential clinical decision support system for therapists for the comprehensive assessment of independent transfer technique. Future research is needed to investigate the utility and acceptance of TransKinect in real clinical environments. Implications for RehabilitationMachine learning and computer vision can be used to analyze transfer techniqueTransKinect is a usable and user-friendly means for therapists to automate analysisSummary reports and videos of transfers show high potential for clinical useAdoption of TransKinect can increase quality of care for manual wheelchair users.

For individuals with spinal cord injuries (SCIs) above the midthoracic level, a common complication is the partial or complete loss of trunk stability in the seated position. Functional neuromuscular stimulation (FNS) can restore seated posture and other motor functions after paralysis by applying small electrical currents to the peripheral motor nerves. In particular, the Networked Neuroprosthesis (NNP) is a fully implanted, modular FNS system that is also capable of capturing information from embedded accelerometers for measuring trunk tilt for feedback control of stimulation. The NNP modules containing the accelerometers are located in the body based on surgical constraints. As such, their exact orientations are generally unknown and cannot be easily assessed. In this study, a method for estimating trunk tilt that employed the Gram-Schmidt method to reorient acceleration signals to the anatomical axes of the body was developed and deployed in individuals with SCI using the implanted NNP system. An anatomically realistic model of a human trunk and five accelerometer sensors was developed to verify the accuracy of the reorientation algorithm. Correlation coefficients and root mean square errors (RMSEs) were calculated to compare target trunk tilt estimates and tilt estimates derived from simulated accelerometer signals under a variety of conditions. Simulated trunk tilt estimates with correlation coefficients above 0.92 and RMSEs below 5° were achieved. The algorithm was then applied to accelerometer signals from implanted sensors installed in three NNP recipients. Error analysis was performed by comparing the correlation coefficients and RMSEs derived from trunk tilt estimates calculated from implanted sensor signals to those calculated via motion capture data, which served as the gold standard. NNP-derived trunk tilt estimates exhibited correlation coefficients between 0.80 and 0.95 and RMSEs below 13° for both pitch and roll in most cases. These findings suggest that the algorithm is effective at estimating trunk tilt with the implanted sensors of the NNP system, which implies that the method may be appropriate for extracting feedback signals for control systems for seated stability with NNP technology for individuals who have reduced control of their trunk due to paralysis.

Seat pressure measurements in wheelchair users have been available for some time; however, repeated measurements from a commercially available pressure mat over 90 min did not differ in the pressure-loaded measurement area or the coordinates of the center of pressure, even in participants who were able to reposition themselves in the wheelchair. The question therefore arises: to what extent are there other parameters that reflect the activity of wheelchair users with the pressure mat? To investigate this, a commercial pressure mat (BodiTrak®) was used to perform the measurements of pressure of 33 adult wheelchair-dependent people with spinal cord injury after 30 and 90 min sitting on the cushion. In addition to the standard output of the pressure mat, graph-based surface analyses (calculation of the area of maximum pressure, calculation of the pressure-loaded measurement area, and pressure-area ratio) was performed retrospectively using Python 3.7. The analysis of the measurements after 30 and 90 min was performed by distinguishing the participants between those who could actively change their position (N = 24) and those who could not (N = 9). The parameters of the pressure mat and the graph-based analyses remained unchanged for active participants. In participants who were unable to actively change their position, the area of maximum pressure and the pressure-area ratio (ratio of maximum pressure area and total pressure-loaded area) increased. Significant differences between minutes 30 and 90 are only found for the pressure-area ratio. Thus, when measuring the seat pressure of wheelchair users, the pressure-area ratio should be taken into account as it reflects the daily relief activities of wheelchair users.

Background and Objectives: The discharge destination of patients with advanced cancer correlates with their quality of life. Patients with bone metastases often undergo lifestyle changes owing to pain and activity limitations. However, there are few reports on factors related to the discharge destination of patients with bone metastases. This study aimed to elucidate the factors associated with the discharge destination of patients with bone metastases. Methods: This study included 278 patients diagnosed with bone metastases who were admitted to the University of Tsukuba Hospital between April 2015 and March 2020. This study examined discharge destination, occurrence of skeletal-related events (SREs), primary lesions, locations of bone metastases, functional ambulation categories (FAC), age, and length of hospital stay. A binomial logistic regression analysis was conducted to compare the home and non-home discharge groups. Results: Of the 278 patients, 142 were discharged to home, 89 were discharged to somewhere other than home (non-home), and 47 died. The discharge destination was associated with spinal cord compression (SCC) (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.35-8.43), hypercalcemia (OR 6.84, 95% CI 1.09-42.76), and FAC at admission (OR 0.45, 95% CI 0.35-0.58). The admission FAC cut-off value for discharge to home was determined to be 1.5 (area under the curve [AUC] 0.79, sensitivity 77.5%, specificity 68.5%). Conclusions: Factors associated with discharge destination were identified. The walking ability required for discharge to home was FAC 1.5, meaning that the patient needed one person to assist in preventing falls when walking on level ground. A cut-off value for FAC on admission for predicting outcomes was identified, suggesting the importance of gait ability assessment on admission.

Older patients with spinal cord injury (SCI) have different features with regard to neurological characteristics after injury. Recent large-scale longitudinal population-based studies showed that individuals with SCI are at a higher risk of developing dementia than non-SCI patients, indicating that SCI is a potential risk factor for dementia. Aging is known to potentiate inflammation and neurodegeneration at the injured site leading to impaired recovery from SCI. However, no research has been aimed at studying the mechanisms of SCI-mediated cognitive impairment in the elderly. The present study examined neurobehavioral and molecular changes in the brain and the underlying mechanisms associated with brain dysfunction in aged C57BL/6 male mice using a contusion SCI model. At 2 months post-injury, aged mice displayed worse performance in locomotor, cognitive and depressive-like behavioral tests compared to young adult animals. Histopathology in injured spinal cord tissue was exacerbated in aged SCI mice. In the brain, transcriptomic analysis with NanoString neuropathology panel identified activated microglia and dysregulated autophagy as the most significantly altered pathways by both age and injury. These findings were further validated by flow cytometry, which demonstrated increased myeloid and lymphocytes infiltration at both the injured site and brain of aged mice. Moreover, SCI in aged mice altered microglial function and dysregulated autophagy in microglia, resulting in worsened neurodegeneration. Taken together, our data indicate that old age exacerbates neuropathological changes in both the injured spinal cord and remote brain regions leading to poorer functional outcomes, at least in part, through altered inflammation and autophagy function.

The aim of this work is to determine the effect of upper-body high intensity interval training (HIIT) on cardiometabolic risks in individuals with chronic paraplegia. Twenty-seven individuals (14 females, 13 males, mean ± SD age: 46 ± 9 years) with chronic paraplegia (spinal cord injury between T2 and L5 >1-year post-injury) took part in a randomized controlled trial and were included in the final analysis. Participants in the HIIT group (n = 18) performed ∼30 min of arm crank exercise (60 s intervals at 80%-90% peak heart rate) four times per week, for 6 weeks. Participants in the control (CON) group (n = 9) were asked to maintain their habitual diet and physical activity patterns over the study period. Outcome measures were taken at baseline and follow-up. The primary outcome measures were fasting insulin, peak power output (PPO) and peak aerobic capacity ( V ̇ O 2 peak ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}{\\mathrm{peak}}}}$ ). Secondary outcome measures included body composition, postprandial glycaemic control, fasting blood lipids, inflammatory biomarkers and resting blood pressure. Differences between groups were assessed by ANCOVA, using baseline values as a covariate. PPO was higher in the HIIT (101 W, 97-106) compared to the CON (90 W, 83-96) group at follow-up (P = 0.006). There were no differences in fasting insulin (P = 0.415) or relative V ̇ O 2 peak ${{\\dot{V}}_{{{{\\mathrm{O}}}_{\\mathrm{2}}}{\\mathrm{peak}}}}$ (P = 0.417). Postprandial Matsuda insulin sensitivity index (ISIMatsuda) was higher in the HIIT (5.42, 4.69-6.15) compared to the CON (3.75, 2.46-5.04) group at follow-up (P = 0.036). Six weeks of upper-body HIIT increased PPO and ISIMatsuda, with no other beneficial effect on cardiometabolic component risks in persons with chronic paraplegia. HIGHLIGHTS: What is the central question of this study? What is the effect of upper-body high intensity interval training (HIIT) on cardiometabolic component risks in individuals with chronic paraplegia? What is the main finding and its importance? Six weeks of upper-body HIIT increased PPO and improved insulin sensitivity, but had no beneficial effect on other cardiometabolic component risks in persons with chronic paraplegia. The large effect size observed for insulin sensitivity may be important in terms of reducing the risk of type-2 diabetes in this population.

OBJECTIVE: The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation.
METHODS: Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined.
RESULTS: In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls ( p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls ( p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs ( p > 0.05 for all) bilaterally.
CONCLUSIONS: Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.

As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.

Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.