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Spinal cord (SC) reconstruction (process to reestablish the severed neural continuity at the injury site) may provide better recovery from blunt SC injury (SCI). A miniature swine model of blunt SC compression was used to test the hypothesis that reconstruction of the SC with sural nerve in combination with surgical decompression and stabilization improves functional, macro- and microstructural recovery compared to decompression and stabilization alone. Following blunt T9-T11 SC compression injury, five adult Yucatan gilts randomly received laminectomy and polyethylene glycol (as fusogen) with (n = 3) or without (n = 2) sural nerve graft SC reconstruction. Fusogens are a heterogeneous collection of chemicals that fuse the axon membrane and are currently used to augment epineural coaptation during peripheral nerve graft reconstruction. Outcome measures of recovery included weekly sensory and motor assessments, various measurements obtained from computed tomography (CT) myelograms up to 12 weeks after injury Measurements from postmortem magnetic resonance imaging (MRI) and results from spinal cord histology performed 12 weeks after injury were also reported. Vertebral canal (VC), SC and dural sac (DS) dimensions and areas were quantified on 2-D CT images adjacent to the injury. Effort to stand and response to physical manipulation improved 7 and 9 weeks and 9 and 10 weeks, respectively, after injury in the reconstruction group. Myelogram measures indicated greater T13-T14 VC, smaller SC, and smaller DS dimensions in the reconstruction cohort, and increased DS area increased DS/VC area ratio, and higher contrast migration over time. Spinal cord continuity was evident in 2 gilts in the reconstruction cohort with CT and MRI imaging. At the SCI, microstructural alterations included axonal loss and glial scarring. Better functional outcomes were observed in subjects treated with sural nerve SC reconstruction. Study results support the use of this adult swine model of blunt SCI. Long-term studies with different nerve grafts or fusogens are required to expand upon these findings. [ABSTRACT FROM AUTHOR]

Importance: Spinal cord injury is a lifelong disability necessitating early management of falls during inpatient admissions. However, there is a paucity of research on fall prevention and management in Spinal cord injury rehabilitation. Objective(s): This study aimed at developing a fall prevention program in an inpatient rehabilitation Spinal cord injury unit. Method: A participatory action research approach utilizing a before-and-after, mixed-method design was employed for this study. The study was performed at Rofaydeh Rehabilitation Hospital in Tehran, Iran, from 2021 to 2022. the study implemented Cohen's four-stage model, encompassing the design of a change program, action, observation and evaluation, and feedback stages. A purposeful sampling method was utilized to select 19 nurses and members of the rehabilitation team from the hospital, ensuring maximum diversity. Data collection involved semi-structured interviews, focus groups, and a checklist for fall prevention measures. Qualitative content analysis, alongside descriptive (frequency, mean, and standard deviation) and inferential statistics (paired t-tests and Chi-square tests), were employed for data analysis. The study adhered to COREQ guidelines. Results: Falls were most common among patients aged fifty years or older (P = 0.026). Throughout the study period, men were more likely to experience falls than women (P = 0.01). Preventive interventions have led to significant improvements in indicators of patient monitoring and care, patient education, and environmental safety, as demonstrated by a paired-sample t-test (P<0.001). Moreover, factors contributing to patients' falls included "shortcomings in fall prevention policies" and "lack of knowledge and participation among patients and caregivers." Changes implemented in the Spinal Cord Injury unit involved enhancing interprofessional interactions, conducting educational workshops for patients and their companions, and identifying high-risk patients. These findings indicate a significant decrease in the incidence of falls following the intervention (P = 0.02). Conclusions: The study found that a multifaceted intervention can increase knowledge about fall risks and substantially reduce both falls and associated minor injuries. [ABSTRACT FROM AUTHOR]

People with spinal cord injury (SCI) experience respiratory dysfunctions which include hypersecretions, bronchospasm, and respiratory muscles weakness. Singing therapy has been implemented as part of respiratory muscle training (RMT) to improve their muscle strength. Singing different types and genres of songs may elicit specific recruitment of respiratory muscles, attributed to the variation of the songs' characteristics including tempo, pitch, and rhythmic complexity. This study aims to determine the effect of singing songs with different characteristics on the accessory respiratory muscle performance among people with SCI. Thirteen male SCI participants of ASIA A and B (C4 –T11) were recruited. Respiratory muscle signals were retrieved by placing two mechanomyography (MMG) sensors on the sternocleidomastoid (SCM) and rectus abdominis (RA) muscles. Eight music experts categorized several songs into four categories based on their pitch, tempo, and rhythmic complexity. Each participant sang one song from each category. Findings showed statistically significant difference in RA and SCM responses among all categories (P < 0.01). The SCM muscle is most active while singing high pitch songs. While the RA is most active during slow tempo and easy rhythmic complexity. This shows that different accessory respiratory muscle is activated by people with SCI while singing songs with different characteristics. Clinicians could benefit from this knowledge while prescribing singing therapy or exercise among people with SCI in the future. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a consequence of significant disability and health issues globally, and long COVID represents the symptoms of neuro-musculoskeletal, cardiovascular and respiratory complications. Purpose: This study aimed to identify the symptom responses and disease burden of long COVID in individuals with spinal cord injury. Methods: This case-control study was conducted on patients with SCI residing at a specialised rehabilitation centre in Bangladesh. Forty patients with SCI with and without long COVID symptoms (LCS) were enrolled in this study at a 1:1 ratio according to WHO criteria. Result: Twelve LCS were observed in patients with SCI, including fatigue, musculoskeletal pain, memory loss, headache, respiratory problems, anxiety, depression, insomnia, problem in ADL problem in work, palpitation, and weakness. The predictors of developing long COVID include increasing age (p<0.002), increasing BMI (p<0.03), and longer duration of spinal cord injury (p<0.004). A significant difference (p<0.01) in overall years of healthy life lost due to disability (YLD) for non-long COVID cases was 2.04±0.596 compared to long COVID (LC) cases 1.22±2.09 was observed. Conclusion: Bangladeshi patients of SCI presented 12 long COVID symptoms and have a significant disease burden compared to non long COVID cases. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (TSCI) causes an insult to the central nervous system, often resulting in devastating temporary or permanent neurological impairment and disability, which places a substantial financial burden on the health-care system. This study aimed to clarify the up-to-date epidemiology and demographics of patients with TSCI treated at the largest SCI center in Japan. Data on all patients admitted to the Spinal Injuries Center with TSCI between May 2005 and December 2021 were prospectively collected using a customized, locally designed SCI database named the Japan Single Center Study for Spinal Cord Injury Database (JSSCI-DB). A total of 1152 patients were identified from the database. The study period was divided into the four- or five-year periods of 2005–2009, 2010–2013, 2014–2017, and 2018–2021 to facilitate the observation of general trends over time. Our results revealed a statistically significant increasing trend in age at injury. Since 2014, the average age of injury has increased to exceed 60 years. The most frequent spinal level affected by the injury was high cervical (C1-C4: 45.8%), followed by low cervical (C5-C8: 26.4%). Incomplete tetraplegia was the most common cause or etiology category of TSCI, accounting for 48.4% of cases. As the number of injuries among the elderly has increased, the injury mechanisms have shifted from high-fall trauma and traffic accidents to falls on level surfaces and downstairs. Incomplete tetraplegia in the elderly due to upper cervical TSCI has also increased over time. The percentage of injured patients with an etiology linked to alcohol use ranged from 13.2% (2005–2008) to 19% (2014–2017). Given that Japan has one of the highest aging populations in the world, epidemiological studies in this country will be very helpful in determining health insurance and medical costs and deciding strategies for the prevention and treatment of TSCI in future aging populations worldwide. [ABSTRACT FROM AUTHOR]

Considering the growing interest in clinical applications of neuromodulation, assessing effects of various modulatory approaches is increasingly important. Monosynaptic spinal reflexes undergo depression following repeated activation, offering a means to quantify neuromodulatory influences. Following spinal cord injury (SCI), changes in reflex modulation are associated with spasticity and impaired motor control. To assess disrupted reflex modulation, low-frequency depression (LFD) of Hoffman (H)-reflex excitability is examined, wherein the amplitudes of conditioned reflexes are compared to an unconditioned control reflex. Alternatively, some studies utilize paired-pulse depression (PPD) in place of the extended LFD train. While both protocols induce similar amounts of H-reflex depression in neurologically intact individuals, this may not be the case for persons with neuropathology. We compared the H-reflex depression elicited by PPD and by trains of 3–10 pulses to an 11-pulse LFD protocol in persons with incomplete SCI. The amount of depression produced by PPD was less than an 11-pulse train (mean difference = 0.137). When compared to the 11-pulse train, the 5-pulse train had a Pearson's correlation coefficient (R) of 0.905 and a coefficient of determination (R2) of 0.818. Therefore, a 5-pulse train for assessing LFD elicits modulation similar to the 11-pulse train and thus we recommend its use in lieu of longer trains. [ABSTRACT FROM AUTHOR]

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes—Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3—were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Patient and public involvement in research (PPI) has many benefits including increasing relevance and impact. While using PPI in clinical research is now an established practice, the involvement of patients and the public in pre-clinical research, which takes place in a laboratory setting, has been less frequently described and presents specific challenges. This study aimed to explore the perspectives of seriously injured rugby players' who live with a spinal cord injury on PPI in pre-clinical research. Methods: Semi-structured interviews were conducted via telephone with 11 seriously injured rugby players living with spinal cord injury on the island of Ireland. A purposive sampling approach was used to identify participants. Selected individuals were invited to take part via gatekeeper in a charitable organisation that supports seriously injured rugby players. Interviews were transcribed verbatim and analysed thematically. Findings: Six themes were identified during analysis: 'appreciating potential benefits of PPI despite limited knowledge', 'the informed perspectives of people living with spinal cord injury can improve pre-clinical research relevance', 'making pre-clinical research more accessible reduces the potential for misunderstandings to occur', 'barriers to involvement include disinterest, accessibility issues, and fear of losing hope if results are negative', 'personal contact and dialogue helps people feel valued in pre-clinical research, and 'PPI can facilitate effective dissemination of pre-clinical research as desired by people living with spinal cord injury.' Conclusion: People affected by spinal cord injury in this study desire further involvement in pre-clinical spinal cord injury research through dialogue and contact with researchers. Sharing experiences of spinal cord injury can form the basis of PPI for pre-clinical spinal cord injury research. [ABSTRACT FROM AUTHOR]

Background: SCI is a time-sensitive debilitating neurological condition without treatment options. Although the central nervous system is not programmed for effective endogenous repairs or regeneration, neuroplasticity partially compensates for the dysfunction consequences of SCI. Objective and hypothesis: The purpose of our study is to investigate whether early induction of hypothermia impacts neuronal tissue compensatory mechanisms. Our hypothesis is that although neuroplasticity happens within the neuropathways, both above (forelimbs) and below (hindlimbs) the site of spinal cord injury (SCI), hypothermia further influences the upper limbs' SSEP signals, even when the SCI is mid-thoracic. Study design: A total of 30 male and female adult rats are randomly assigned to four groups (n = 7): sham group, control group undergoing only laminectomy, injury group with normothermia (37°C), and injury group with hypothermia (32°C +/-0.5°C). Methods: The NYU-Impactor is used to induce mid-thoracic (T8) moderate (12.5 mm) midline contusive injury in rats. Somatosensory evoked potential (SSEP) is an objective and non-invasive procedure to assess the functionality of selective neuropathways. SSEP monitoring of baseline, and on days 4 and 7 post-SCI are performed. Results: Statistical analysis shows that there are significant differences between the SSEP signal amplitudes recorded when stimulating either forelimb in the group of rats with normothermia compared to the rats treated with 2h of hypothermia on day 4 (left forelimb, p = 0.0417 and right forelimb, p = 0.0012) and on day 7 (left forelimb, p = 0.0332 and right forelimb, p = 0.0133) post-SCI. Conclusion: Our results show that the forelimbs SSEP signals from the two groups of injuries with and without hypothermia have statistically significant differences on days 4 and 7. This indicates the neuroprotective effect of early hypothermia and its influences on stimulating further the neuroplasticity within the upper limbs neural network post-SCI. Timely detection of neuroplasticity and identifying the endogenous and exogenous factors have clinical applications in planning a more effective rehabilitation and functional electrical stimulation (FES) interventions in SCI patients. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate the ARM (arm repetitive movement) algorithm using inertial measurement unit (IMU) data to assess repetitive arm motion in manual wheelchair (MWC) users in real-world settings. The algorithm was tested on community data from four MWC users with spinal cord injury and compared with video-based analysis. Additionally, the algorithm was applied to in-home and free-living environment data from two and sixteen MWC users, respectively, to assess its utility in quantifying differences across activities of daily living and between dominant and non-dominant arms. The ARM algorithm accurately estimated active and resting times (>98%) in the community and confirmed asymmetries between dominant and non-dominant arm usage in in-home and free-living environment data. Analysis of free-living environment data revealed that the total resting bout time was significantly longer (P = 0.049) and total active bout time was significantly shorter (P = 0.011) for the non-dominant arm. Analysis of active bouts longer than 10 seconds showed higher total time (P = 0.015), average duration (P = 0.026), and number of movement cycles per bout (P = 0.020) for the dominant side. These findings support the feasibility of using the IMU-based ARM algorithm to assess repetitive arm motion and monitor shoulder disorder risk factors in MWC users during daily activities. [ABSTRACT FROM AUTHOR]

Study design: Single-cohort longitudinal survey design. Objectives: To identify what ongoing impact the COVID-19 pandemic has on functioning and health in individuals with SCI. Using the ICF model as a guide, outcome measures were chosen to explore potential constructs and aspects of health and functioning which may have been affected by regulations. Setting: Online, Canada. Methods: Participants provided demographic and clinical characteristics at baseline. They completed standardized online measures at three time points, each roughly one month apart (June, July, and August of 2020). The measures assessed mental health, resilience, boredom, social support, technology use, life space, and participation. Repeated measures ANOVAs were used to identify longitudinal changes for each measure. Results: We collected data from 21 participants with SCI (mean age 54 years, 12 male). We found a large effect size for participation (η2 = 0.20), which increased over time. We also found medium effect sizes in both anxiety (η2 = 0.12) and social network usage (η2 = 0.12). Anxiety decreased over time and social networking usage fluctuated slightly but with an increase from time point one to time point two. Conclusion: The results indicate that individuals with spinal cord injury appear to be staying relatively stable during the pandemic with improvements in a few key aspects, such as potentially increased participation and decreased anxiety. The results also suggest that it is important to continue fostering ways for individuals with spinal cord injury to stay connected, engaged, and informed. [ABSTRACT FROM AUTHOR]

Background: Intentional and unintentional injuries are a leading cause of death and disability globally. International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes are used to classify injuries in administrative health data and are widely used for health care planning and delivery, research, and policy. However, a systematic review of their overall validity and reliability has not yet been done. Objective: To conduct a systematic review of the validity and reliability of external cause injury ICD-10 codes. Methods: MEDLINE, EMBASE, COCHRANE, and SCOPUS were searched (inception to April 2023) for validity and/or reliability studies of ICD-10 external cause injury codes in all countries for all ages. We examined all available data for external cause injuries and injuries related to specific body regions. Validity was defined by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Reliability was defined by inter-rater reliability (IRR), measured by Krippendorff's alpha, Cohen's Kappa, and/or Fleiss' kappa. Results: Twenty-seven published studies from 2006 to 2023 were included. Across all injuries, the mean outcome values and ranges were sensitivity: 61.6% (35.5%-96.0%), specificity: 91.6% (85.8%-100%), PPV: 74.9% (58.6%-96.5%), NPV: 80.2% (44.6%-94.4%), Cohen's kappa: 0.672 (0.480–0.928), Krippendorff's alpha: 0.453, and Fleiss' kappa: 0.630. Poisoning and hand and wrist injuries had higher mean sensitivity (84.4% and 96.0%, respectively), while self-harm and spinal cord injuries were lower (35.5% and 36.4%, respectively). Transport and pedestrian injuries and hand and wrist injuries had high PPVs (96.5% and 92.0%, respectively). Specificity and NPV were generally high, except for abuse (NPV 44.6%). Conclusions and significance: The validity and reliability of ICD-10 external cause injury codes vary based on the injury types coded and the outcomes examined, and overall, they only perform moderately well. Future work, potentially utilizing artificial intelligence, may improve the validity and reliability of ICD codes used to document injuries. [ABSTRACT FROM AUTHOR]

Background: Individuals with spinal cord injuries or disease (SCI/D) require frequent healthcare services. The COVID-19 pandemic may have impacted healthcare. Furthermore, due to secondary health conditions and comorbidities persons with SCI/D are at increased risk of experiencing severe symptoms or outcomes if infected with the COVID-19 virus. It is unclear to what extent research has investigated the pandemic and virus impacts on the SCI/D population. Objective: To identify and summarize what is reported in the literature on the impact the COVID-19 virus and pandemic had on healthcare, health outcomes, and experiences in the adult SCI/D population. Methods: Electronic databases and grey literature were searched for articles that included an adult population with a SCI/D and investigated the impact the COVID-19 virus and pandemic had on healthcare-related outcomes and experiences. Articles were double screened, and data were extracted, and synthesized to provide a descriptive summary of the findings. Results: Twenty-four studies were included in this review with eight qualitative, fifteen quantitative, and one mixed methods study. Sixteen studies investigated healthcare utilization/access; nine investigated care delivery, nine investigated patient outcomes, and eight investigated patient experiences, with multiple studies spanning different categories of investigation. The pandemic was detrimental to healthcare utilization, access, and outcomes, but no studies quantified these changes. Virtual care was well-received by the SCI/D population to maintain continuity of care. The SCI/D population had issues with maintaining caregiving support. It was unclear if the COVID-19 virus infection impacted individuals with SCI/D differently than the general population. Conclusions: This scoping review found the pandemic negatively impacted multiple aspects of healthcare in individuals with SCI/D, however further investigation on health outcomes is required. More research, particularly large-scale quantitative studies, investigating healthcare access, utilization, and delivery, as well as patient outcomes and experiences is needed to improve care in the SCI/D population post-pandemic onset. [ABSTRACT FROM AUTHOR]

Information about an individual's functioning and its longitudinal development is key to informing clinical rehabilitation. However, the description and understanding of the detailed longitudinal course of functioning, i.e., functioning trajectories, is rare in the current SCI literature. The aim of this study was to re-estimate previously identified functioning trajectories of individuals with spinal cord injury (SCI) undergoing initial rehabilitation in Switzerland using trajectory analysis, and to identify highly influential functioning domains that could become trajectory-specific targets for clinical interventions using network analysis. The study was based on data from the Swiss SCI Cohort Study and included individuals with SCI (N = 1099) who completed their rehabilitation in one of four collaborating centers between May 2013 and March 2022. For the trajectory analysis, functioning was operationalized using the total sum score of the Spinal Cord Independence Measure version III (SICM III), which was assessed at up to four time points (T1-T4) during rehabilitation. For the network analysis, individual SCIM III items were used to operationalize relevant functioning problems at T1 (admission) and T4 (discharge). The re-estimation of trajectory analysis confirmed the previously identified mean functioning trajectory classes of stable high functioning (N = 239; 21.75%), early (N = 33; 3.00%), moderate (N = 753; 68.52%), and slow (N = 74; 6.73%) functioning improvement. The network analysis revealed highly connected functioning problems at T1 for the moderate functioning improvement class, including "Feeding", "Dressing upper body", and "Dressing lower body", "Mobility in bed", and "Use of toilet". These functioning domains might indicate potential trajectory-specific targets for clinical interventions. This study has increased our knowledge about functioning trajectories of individuals with SCI undergoing initial rehabilitation in Switzerland and its findings may inform discussions about the application and use of functioning trajectories in clinical practice. Due to the exploratory nature of this study, further research is needed to confirm the findings presented. [ABSTRACT FROM AUTHOR]

Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics. [ABSTRACT FROM AUTHOR]

Following a spinal cord injury (SCI), secondary damage mechanisms are triggered that cause inflammation and cell death. A key component of this secondary damage is a reduction in local blood flow that initiates a well-characterised ischemic cascade. Downstream hypoxia and acidosis activate acid sensing ion channel 1a (ASIC1a) to trigger cell death. We recently showed that administration of a potent venom-derived inhibitor of ASIC1a, Hi1a, leads to tissue sparing and improved functional recovery when delivered up to 8 h after ischemic stroke. Here, we use whole-cell patch-clamp electrophysiology in a spinal cord slice preparation to assess the effect of acute ASIC1a inhibition, via a single dose of Hi1a, on intrinsic membrane properties and excitatory synaptic transmission long-term after a spinal cord hemisection injury. We focus on a population of interneurons (INs) in the deep dorsal horn (DDH) that play a key role in relaying sensory information to downstream motoneurons. DDH INs in mice treated with Hi1a 1 h after a spinal cord hemisection showed no change in active or passive intrinsic membrane properties measured 4 weeks after SCI. DDH INs, however, exhibit significant changes in the kinetics of spontaneous excitatory postsynaptic currents after a single dose of Hi1a, when compared to naive animals (unlike SCI mice). Our data suggest that acute ASIC1a inhibition exerts selective effects on excitatory synaptic transmission in DDH INs after SCI via specific ligand-gated receptor channels, and has no effect on other voltage-activated channels long-term after SCI. [ABSTRACT FROM AUTHOR]

Artificial intelligence and machine learning (AI/ML) is becoming increasingly more accessible to biomedical researchers with significant potential to transform biomedicine through optimization of highly-accurate predictive models and enabling better understanding of disease biology. Automated machine learning (AutoML) in particular is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed. However, successful translation of AI/ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards establishing reproducible clinical and biological inferences. This is especially challenging for clinical studies on rare disorders where the smaller patient cohorts and corresponding sample size is an obstacle for reproducible modeling results. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics to assess model reproducibility. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication to optimize the intraoperative hemodynamic range during injury-related surgery and additionally identified a strong detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured how evolving clinical practices such as faster time-to-surgery and blood pressure management affect clinical model development. Altogether, we illustrate how expert-augmented AutoML improves inferential reproducibility for biomedical discovery and can ultimately build trust in AI processes towards effective clinical integration.

Background: Therapeutic rebound exercise is gaining popularity among the general population, but its effectiveness in individuals with neurological impairments remains uncertain. To shed light on this, a systematic review was conducted between November 2021 and March 2023 to study the impact of rebound exercise on balance and mobility in this group. Methods: Six databases were searched. Studies were included if written in English, peer-reviewed, had original research data and assessed the effect of rebound exercise in adults with neurological disorders. The outcomes measured were balance and mobility. Two reviewers independently appraised study quality using the Critical Appraisal Skills Program for Randomized Controlled Trials. Finally, a meta-summary of the included studies was completed, and a meta-analysis was performed using RevMan software version 5.3 to determine the effectiveness of the intervention. Results: Five studies were included comprising 130 participants aged 31.32±7.67 to 58±12 years, 72% male and 28% female. Participants were in-patients with stroke (49%), multiple sclerosis (24%), Parkinson's disease (15%) and spinal cord injury (12%). The included papers had moderate to high methodological quality. The timed up-and-go test revealed that the rebound group participants could walk 6.08 seconds quicker over three to eight weeks. Pooled results show that rebound exercise significantly improves mobility (-0.53[-0.94, -0.11], p = 0.01), but no significant improvement was observed in balance. Conclusion: Rebound exercise has shown the potential to improve mobility in people with neurological disorders. However, the findings should be in the context that the included studies are few and participants were in in-patient settings. PROSPERO registration: CRD42021298030. [ABSTRACT FROM AUTHOR]

Introduction: Sleep-related breathing disorders (SRBDs), neuropathic pain, spasticity and cardiovascular autonomic dysfunction are common after spinal cord injury (SCI). Prior studies suggest that systemic inflammation following SCI may be implicated in the development of neuropathic pain, spasticity and cardiovascular dysfunction. Given that SRBDs also cause a systemic inflammatory response, we hypothesized that individuals with SCI who develop more severe SRBDs would experience more intense neuropathic pain, more severe spasticity and more significant cardiovascular autonomic dysfunction. Methods: This cross-sectional prospective study will explore the previously understudied hypothesis that SRBDs are associated with increased neuropathic pain, spasticity, and cardiovascular autonomic dysfunction in adult individuals with low-cervical/high-thoracic (injury level at C5 to T6), complete/incomplete (ASIA Impairment Scale A, B, C or D) SCI. Discussion: To our knowledge, no prior study has addressed this clinically relevant question on whether the degree of SRBDs affects the intensity of neuropathic pain, spasticity, and cardiovascular autonomic dysfunction in individuals with SCI. We anticipate that the results of this original study will provide key information for a future clinical trial on the use of continuous positive airway pressure (CPAP) therapy for moderate-to-severe SRBDs, which may better control neuropathic pain, spasticity, and cardiovascular autonomic dysfunction among individuals with SCI. Trial registration: The research protocol for this study was registered in the ClinicalTrials.gov website (NCT05687097). https://clinicaltrials.gov/ct2/show/NCT05687097. [ABSTRACT FROM AUTHOR]

There are approximately 1.2 million people currently living with spinal cord injury (SCI), with a majority of cases at the cervical level and half involving incomplete injuries. Yet, as most preclinical research has been focused on bilateral thoracic models, there remains a disconnect between bench and bedside that limits translational success. Here, we profile a clinically relevant model of unilateral cervical contusion injury in the mouse (30kD with 0, 2, 5, or 10 second dwell time). We demonstrate sustained behavioral deficits in performance on grip strength, cylinder reaching, horizontal ladderbeam and CatWalk automated gait analysis tasks. Beyond highlighting reliable parameters for injury assessment, we also explored the effect of mouse strain and age on injury outcome, including evaluation of constitutively immunodeficient mice relevant for neurotransplantation and cellular therapy testing. Comparison of C57Bl/6 and immunodeficient Rag2gamma(c)-/- as well as Agouti SCIDxRag2Gamma(c)-/- hybrid mouse strains revealed fine differences in post-injury ipsilateral grip strength as well as total number of rearings on the cylinder task. Differences in post-SCI contralateral forepaw duty cycle and regularity index as measured by CatWalk gait analysis between the two immunodeficient strains were also observed. Further, assessment of young (3-4 months old) and aging (16-17 months old) Rag2gamma(c)-/- mice identified age-related pre-injury differences in strength and rearing that were largely masked following cervical contusion injury; observations that may help interpret previous results in aged rodents as well as human clinical trials. Collectively, the work provides useful insight for experimental design and analysis of future pre-clinical studies in a translational unilateral cervical contusion injury model.

Background: Spinal cord injury (SCI) often leaves affected persons with a lifelong demand for care. As a result, the effect of the condition goes beyond the injured person to affect family members and significant others who have to adjust their lives to provide care and support. However, little is known about the experiences of these family caregivers regarding the care of people with SCI in Ghana. Exploring their experiences would enhance the understanding of family caregiving of people with SCI and contribute to policy intervention. Methods: This qualitative descriptive phenomenology study used the purposive sampling method to select 10 family caregivers. Data were collected using a semi-structured interview guide through individual in-depth interviews. Written informed consent was obtained and interviews were audio-recorded and transcribed verbatim. Data were manually analysed following Colaizzi's method of data analysis. Results: In all, 4 main themes emerged from the analysis of data (1) becoming a caregiver, (2) roles of the caregiver, (3) the burden of caregiving, and (4) coping strategies. The family caregivers provided vital assistance to their relatives with SCI and experienced physical and financial burdens as a result of the care. Due to the strains involved in the caregiving process, family caregivers adopted various strategies to cope with the situation. Conclusion: This study has provided evidence of the lived experiences of family caregivers of people with SCI in the Ghanaian context and further supports the findings of previous studies. Measures including training, counselling, and instituting social support services for family caregivers should be considered by the management of healthcare institutions to enhance the experiences of family caregivers. [ABSTRACT FROM AUTHOR]

Background: As the European population with Spinal Cord Injury (SCI) is expected to become older, a better understanding of ageing with SCI using functioning, the health indicator used to model healthy ageing trajectories, is needed. We aimed to describe patterns of functioning in SCI by chronological age, age at injury and time since injury across eleven European countries using a common functioning metric, and to identify country-specific environmental determinants of functioning. Methods: Data from 6'635 participants of the International Spinal Cord Injury Community Survey was used. The hierarchical version of Generalized Partial Credit Model, casted in a Bayesian framework, was used to create a common functioning metric and overall scores. For each country, linear regression was used to investigate associations between functioning, chronological age, age at SCI or time since injury for persons with para- and tetraplegia. Multiple linear regression and the proportional marginal variance decomposition technique were used to identify environmental determinants. Results: In countries with representative samples older chronological age was consistently associated with a decline in functioning for paraplegia but not for tetraplegia. Age at injury and functioning level were associated, but patterns differed across countries. An association between time since injury and functioning was not observed in most countries, neither for paraplegia nor for tetraplegia. Problems with the accessibility of homes of friends and relatives, access to public places and long-distance transportation were consistently key determinants of functioning. Conclusions: Functioning is a key health indicator and the fundament of ageing research. Enhancing methods traditionally used to develop metrics with Bayesian approach, we were able to create a common metric of functioning with cardinal properties and to estimate overall scores comparable across countries. Focusing on functioning, our study complements epidemiological evidence on SCI-specific mortality and morbidity in Europe and identify initial targets for evidence-informed policy-making. [ABSTRACT FROM AUTHOR]

Background: Persons with traumatic spinal cord injury (SCI) use multiple medications (polypharmacy) to manage the high number of secondary complications and concurrent conditions. Despite the prevalence of polypharmacy and challenges associated with managing medications, there are few tools to support medication self-management for persons with SCI. Objective: The purpose of this scoping review was to identify and summarize what is reported in the literature on medication self-management interventions for adults with traumatic SCI. Methods: Electronic databases and grey literature were searched for articles that included an adult population with a traumatic SCI and an intervention targeting medication management. The intervention was required to incorporate a component of self-management. Articles were double screened and data were extracted and synthesized using descriptive approaches. Results: Three studies were included in this review, all of which were quantitative. A mobile app and two education-based interventions to address self-management of SCI, medication management, and pain management, respectively, were included. Only one of the interventions was co-developed with patients, caregivers, and clinicians. There was minimal overlap in the outcomes measured across the studies, but learning outcomes (e.g., perceived knowledge and confidence), behavioural outcomes (e.g., management strategies, data entry), and clinical outcomes (e.g., number of medications, pain scores, functional outcomes) were evaluated. Results of the interventions varied, but some positive outcomes were noted. Conclusions: There is an opportunity to better support medication self-management for persons with SCI by co-designing an intervention with end-users that comprehensively addresses self-management. This will aid in understanding why interventions work, for whom, in what setting, and under what circumstances. [ABSTRACT FROM AUTHOR]

Purpose: The postural transition from sitting to standing is a moment of dysautonomic occurrence in individuals with Spinal Cord Injury (SCI). Different tools can be used to minimize this event, such as virtual reality. Thus, we aimed to analyze cardiac autonomic modulation in individuals with SCI during postural transition from the sitting to orthostatism position using a cognitive virtual reality (VR) task. Methods: Individuals with and without SCI were positioned on the Easy Stand® device, sitting at rest, at 0° considering the angle between the seat and the floor, elevation at 45°, and orthostatism at 90°, for 5 minutes in each position. Heart rate variability (HRV) measures of sympathovagal balance were collected (heart rate receiver: Polar V800). The groups were subdivided into two groups, one that performed VR as an intervention during the postural angle changes and another group that did not perform VR. Results: We evaluated 76 individuals, 40 with a medical diagnosis of SCI and 36 who composed the able-bodied control group without SCI, matched by age and sex. The HRV results showed that the SCI group who performed the task in VR demonstrated no significant difference in parasympathetic activation and global variability between the sitting versus 90° positions. There was better sympathovagal balance in SCI and able-bodied control groups who performed the VR task between the sitting versus 90° positions. Conclusion: The use of a VR task seems to contribute to better sympathovagal balance, with the potential to reduce dysautonomia during postural changes. [ABSTRACT FROM AUTHOR]

Introduction: There is a considerably large group of community-dwelling spinal cord injury (SCI) survivors living with low quality of life. Physical inactivity, depression, and chronic pain are major problems faced by SCI survivors discharged from the acute phase of treatment or inpatient rehabilitation. This study aims to evaluate the feasibility, acceptability, and preliminary effects of a Physical-Psychological Integrative (PPI) online group intervention on community-dwelling SCI survivors' physical activity, depression, and chronic pain. Methods: This is a two-arm pilot randomized controlled trial with repeated measures (pre-, post-intervention, and 3-month follow-up) design. Seventy-two participants will be randomly assigned to two study groups. The PPI intervention group will receive a video program for physical activity training and eight-week online group psychological interventions using skills of group-based motivational interviewing and mindfulness-based stress reduction. The control group will receive an eight-week online didactic education programed. Focus-group interviews will be conducted post-intervention to explore their views about acceptance and suggested improvements to the intervention. The feasibility of study procedures and the acceptability of interventions will be evaluated. The effectiveness of the PPI intervention will be evaluated by leisure-time physical activity, depression, chronic pain, exercise efficacy, mindfulness, and quality of life. We will use the generalized estimating equation to assess intervention effects and content analysis for interview data. This study has received ethical approval from the Hong Kong Polytechnic University (HSEARS20210705004) and was registered in ClinicalTrials.gov (NCT05535400). Discussion: This study will be the first to provide empirical data on the evaluation of an online-group intervention integrating both physical activity promotion and psychological approaches, aimed at reducing physical inactivity, depression, and chronic pain for community-dwelling SCI survivors in Hong Kong. The findings could provide evidence supporting the use of PPI intervention as a novel online group support, in addressing both the physical and psychological needs of community-dwelling SCI survivors. [ABSTRACT FROM AUTHOR]

The most frequently reported use of medical marijuana is for pain relief. However, its psychoactive component Δ9-tetrahydrocannabinol (THC) causes significant side effects. Cannabidiol (CBD) and β-caryophyllene (BCP), two other cannabis constituents, possess more benign side effect profiles and are also reported to reduce neuropathic and inflammatory pain. We evaluated the analgesic potential of CBD and BCP individually and in combination in a rat spinal cord injury (SCI) clip compression chronic pain model. Individually, both phytocannabinoids produced dose-dependent reduction in tactile and cold hypersensitivity in male and female rats with SCI. When co-administered at fixed ratios based on individual A50s, CBD and BCP produced enhanced dose-dependent reduction in allodynic responses with synergistic effects observed for cold hypersensitivity in both sexes and additive effects for tactile hypersensitivity in males. Antinociceptive effects of both individual and combined treatment were generally less robust in females than males. CBD:BCP co-administration also partially reduced morphine-seeking behavior in a conditioned place preference (CPP) test. Minimal cannabinoidergic side effects were observed with high doses of the combination. The antinociceptive effects of the CBD:BCP co-administration were not altered by either CB2 or μ-opioid receptor antagonist pretreatment but, were nearly completely blocked by CB1 antagonist AM251. Since neither CBD or BCP are thought to mediate antinociception via CB1 activity, these findings suggest a novel CB1 interactive mechanism between these two phytocannabinoids in the SCI pain state. Together, these findings suggest that CBD:BCP co-administration may provide a safe and effective treatment option for the management of chronic SCI pain. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are a contributing factor to impaired function and pathology after spinal cord injury (SCI). The NADPH oxidase (NOX) enzyme is a key source of ROS; there are several NOX family members, including NOX2 and NOX4, that may play a role in ROS production after SCI. Previously, we showed that a temporary inhibition of NOX2 by intrathecal administration of gp91ds-tat immediately after injury improved recovery in a mouse SCI model. However, chronic inflammation was not affected by this single acute treatment, and other NOX family members were not assessed. Therefore, we aimed to explore the effect of genetic knockout (KO) of NOX2 or acute inhibition of NOX4 with GKT137831. A moderate SCI contusion injury was performed in 3 month old NOX2 KO and wild-type (WT) mice, who received no treatment or GKT137831/vehicle 30 minutes post-injury. Motor function was assessed using the Basso Mouse Scale (BMS), followed by evaluation of inflammation and oxidative stress markers. NOX2 KO mice, but not GKT137831 treated mice, demonstrated significantly improved BMS scores at 7, 14, and 28 days post injury (DPI) in comparison to WT mice. However, both NOX2 KO and GKT137831 significantly reduced ROS production and oxidative stress markers. Furthermore, a shift in microglial activation toward a more neuroprotective, anti-inflammatory state was observed in KO mice at 7 DPI and a reduction of microglial markers at 28 days. While acute alterations in inflammation were noted with GKT137831 administration, this was not sustained through 28 days. In vitro analysis also showed that while GKT137831 reduced ROS production by microglia, it did not translate to changes in pro-inflammatory marker expression within these cells. These data demonstrate that NOX2 and NOX4 play a role in post-injury ROS, but a single dose of NOX4 inhibitor fails to enhance long-term recovery. [ABSTRACT FROM AUTHOR]

Background: Satisfactory treatment is often lacking for spasticity, a highly prevalent motor disorder in patients with spinal cord injury (SCI). Low concentrations of riluzole potently reduce the persistent sodium current, the post-SCI increase in which contributes to spasticity. The repurposing of this drug may therefore constitute a useful potential therapeutic option for relieving SCI patients suffering from chronic traumatic spasticity. Objective: RILUSCI is a phase 1b–2b trial designed to assess whether riluzole is a safe and biologically effective means of managing spasticity in adult patients with traumatic chronic SCI. Methods: In this multicenter double-blind trial, adults (aged 18–65 years) suffering from spasticity after SCI (target enrollment: 90 participants) will be randomly assigned to be given either a placebo or a recommended daily oral dose of riluzole for two weeks. The latter dose will be previously determined in phase 1b of the study by performing double-blind dose-finding tests using a Bayesian continuous reassessment method. The primary endpoint of the trial will be an improvement in the Modified Ashworth Score (MAS) or the Numerical Rating Score (NRS) quantifying spasticity. The secondary outcomes will be based on the safety and pharmacokinetics of riluzole as well as its impact on muscle spasms, pain, bladder dysfunction and quality of life. Analyses will be performed before, during and after the treatment and the placebo-controlled period. Conclusion: To the best of our knowledge, this clinical trial will be the first to document the safety and efficacy of riluzole as a means of reducing spasticity in patients with chronic SCI. Trial registration: The clinical trial, which is already in progress, was registered on the ClinicalTrials.gov website on August 9, 2016 under the registration number NCT02859792. Trial sponsor: Assistance Publique–Hôpitaux de Marseille. [ABSTRACT FROM AUTHOR]

Introduction: Electrical spinal cord neuromodulation has emerged as a leading intervention for restoring autonomic functions, such as blood pressure, lower urinary tract (LUT), bowel, and sexual functions, following spinal cord injury (SCI). While a few preliminary studies have shown the potential effect of non-invasive transcutaneous spinal cord stimulation (tSCS) on autonomic recovery following SCI, the optimal stimulation parameters, as well as real-time and long-term functional benefits of tSCS are understudied. This trial entitled "Non-invasive Neuromodulation to Treat Bladder, Bowel, and Sexual Dysfunction following Spinal Cord Injury" is a pilot trial to examine the feasibility, dosage effect and safety of tSCS on pelvic organ function for future large-scale randomized controlled trials. Methods and analysis: Forty eligible participants with chronic cervical or upper thoracic motor-complete SCI will undergo stimulation mapping and assessment batteries to determine the real-time effect of tSCS on autonomic functions. Thereafter, participants will be randomly assigned to either moderate or intensive tSCS groups to test the dosage effect of long-term stimulation on autonomic parameters. Participants in each group will receive 60 minutes of tSCS per session either twice (moderate) or five (intensive) times per week, over a period of six weeks. Outcome measures include: (a) changes in bladder capacity through urodynamic studies during real-time and after long-term tSCS, and (b) resting anorectal pressure determined via anorectal manometry during real-time tSCS. We also measure assessments of sexual function, neurological impairments, and health-related quality of life using validated questionnaires and semi-structured interviews. Ethics and dissemination: Ethical approval has been obtained (CREB H20-01163). All primary and secondary outcome data will be submitted to peer-reviewed journals and disseminated among the broader scientific community and stakeholders. [ABSTRACT FROM AUTHOR]

Background: In Taiwan, physical restraint is commonly used in institutions to protect residents from falling or injury. However, physical restraint should be used cautiously to avoid side effects, such as worse cognition, mobility, depression, and even death. Objectives: To identify the rate of physical restraint and the associated risk factors in institutionalized residents in Taiwan. Methods: A community-based epidemiological survey was conducted from July 2019 to February 2020 across 266 residential institutions. Among the estimated 6,549 residents being surveyed, a total of 5,752 finished the study. The questionnaires were completed by residents, his/her family or social workers. The cognition tests were conducted by specialists and a multilevel analysis approach was used to identify cognition/disability/medical history/special nursing care/BPSD risk factors for physical restraints. Results: Of the 5,752 included institutionalized residents, 30.2% (1,737) had been previously restrained. Older age, lower education level, lower cognitive function, higher dependence, residents with cerebrovascular disease, pulmonary disease, dementia, and intractable epilepsy, all contributed to a higher physical restraint rate, while orthopedic disease and spinal cord injury were associated with a lower physical restraint rate. Furthermore, residents with special nursing care had a higher restraint rate. Residents with most of the behavior and psychological symptoms were also associated with an increased restraint rate. Conclusions: We studied the rate of physical restraint and associated risk factors in institutionalized residents in Taiwan. The benefits and risks of physical restraint should be evaluated before application, and adjusted according to different clinical situations. [ABSTRACT FROM AUTHOR]

Background: Stem cell transplantation therapy is a potential approach for the repair of spinal cord injuries and other neurodegenerative diseases, but its effectiveness is hampered by the low rate of targeted migration of cells to the area of injury. The aim of this study was to investigate the effects of miR-31 on the migration of bone marrow mesenchymal stem cells (BMSCs) and the regulation of MMP-2 and CXCR4 expression in vitro and in vivo. Methods: eGFP-expressing BMSCs were isolated and cultured for subsequent experiments. The experiments were divided into three groups: control group, miR-31agomir group, and miR-31antagomir group. Proliferation was analyzed using CCK-8 and flow cytometry; cell migration in vitro was analyzed using wound-healing and transwell assays. The mouse SCI model was prepared by the impact method, and cells were transplanted (3 groups, 12 per group). Relevant inflammatory factors were detected by ELISA. The BMS score was used to evaluate the functional recovery of the mouse spinal cord and the frozen section was used to analyze the cell migration ability in vivo. The in vitro and in vivo expression levels of MMP-2 and CXCR4 were evaluated by Western blot and immunohistochemical staining. Results: In vitro experiments showed that cells in the miR-31agomir group exhibited enhanced cell proliferation (P<0.05, P<0.001) and migration (P<0.001) and upregulated protein expression levels of CXCR4 (P<0.01) and MMP-2 (P<0.001) compared with cells in the control group. The results of in vivo experiments showed that the expression of pro-inflammatory factors was reduced after cell transplantation treatment. Cells in the miR-31agomir group showed enhanced cell-targeted migration ability (P<0.001), improved the function of damaged tissues (P<0.001), and upregulated CXCR4 and MMP-2 expression compared to the control group (P<0.001). Conclusion: Our experiment demonstrated that miR-31 could promote the migration of BMSCs and miR-31 could repair and improve the function of damaged tissues in SCI. [ABSTRACT FROM AUTHOR]

Adverse effects of morphine on locomotor function after moderate to severe spinal cord injury (SCI) have been reported; however, the effects after mild SCI without damage of lumbar α-motoneurons have not been investigated. We investigated the effects of lumbar intrathecal morphine on locomotor function after mild thoracic SCI and the involvement of classic opioid receptor activation. A mild thoracic contusive SCI was induced in adult rats at the T9-T10 spine level under sevoflurane anesthesia. We evaluated the effects of single doses of intrathecal morphine and selective μ-, δ-, and κ-opioid receptor agonists, continuous infusion of intrathecal morphine for 72 hours, and administration of physiological saline on locomotor function and muscle tone in the hindlimbs. The numbers of damaged and total α-motoneurons in the lumbar spinal cord were also investigated. Single doses of morphine aggravated residual locomotor function after SCI but did not affect functional recovery. Single doses of morphine and μ- and δ-opioid receptor agonists significantly aggravated residual locomotor function with increases in muscle tone after SCI, and the effects of the drugs were reversed by naloxone. In contrast, continuous infusion of morphine led to persistent decline in locomotor function with increased muscle tone, which was not reversed by naloxone, but did not increase the number of damaged lumbar α-motoneurons. These results indicate that a single dose of morphine at an analgesic dose transiently increases muscle tone of the hindlimbs via activation of spinal μ- and δ- opioid receptors, resulting in further deterioration of locomotor function in the acute phase of mild SCI. Our results also suggest that an increased dose of morphine with prolonged administration leads to persistent decline in locomotor function with increased muscle tone via mechanisms other than direct activation of classical opioid receptors. Morphine should be used cautiously even after mild SCI. [ABSTRACT FROM AUTHOR]

Precise evaluation of motor functions using simple and reproducible tests for mouse models of spinal cord injury (SCI) are required. Overground walking of SCI mice has been tested by Basso Mouse Scale for locomotion (BMS). In contrast, only a few works quantify walking performances of SCI mice on narrow beams, a different task. Here, we established a novel scoring system using a single beam walking apparatus for SCI mice. The scoring system uses binary judgments of values such as retention, moving forward and reaching the goal on a beam for rating. In addition, high score was given to SCI mouse when the mouse efficiently used hindlimbs for locomotion on the beam. A high rate of concordance of the score derived from positions of hindlimbs between two observers was obtained. Mice displayed the lowest total score on the beam immediately after the SCI, then the score gradually increased like time course of BMS score. Furthermore, the total scores reflected gradation of severity of SCI in 2 strains of mice. The beam walking score proved to be strongly correlated with that of BMS score, indicating that performances between overground walking and beam walking are partly correlated in SCI mice. Collectively, the novel scoring system offers an opportunity to easily evaluate motor performances of mice with SCI. [ABSTRACT FROM AUTHOR]

Transcranial electrically stimulated motor-evoked potentials (tcMEPs) are widely used to evaluate motor function in humans and animals. However, the relationship between tcMEPs and the recovery of paralysis remains unclear. We previously reported that transplantation of mesenchymal stem cells to a spinal cord injury (SCI) rat model resulted in various degrees of recovery from paraplegia. As a continuation of this work, in the present study, we aimed to establish the longitudinal electrophysiological changes in this SCI rat model after mesenchymal stem cell transplantation. SCI rats were established using the weight-drop method. The model rats were transvenously transplanted with two types of mesenchymal stem cells (MSCs), one derived from rat cranial bones and the other from the bone marrow of the femur and tibia bone, 24 h after SCI. A phosphate-buffered saline (PBS) group that received only PBS was also created for comparison. The degree of paralysis was evaluated over 28 days using the Basso–Beattie–Bresnahan (BBB) scale and inclined plane task score. Extended tcMEPs were recorded using a previously reported bone-thinning technique, and the longitudinal electrophysiological changes in tcMEPs were investigated. In addition, the relationship between the time course of recovery from paralysis and reappearance of tcMEPs was revealed. The appearance of the tcMEP waveform was earlier in MSC-transplanted rats than in PBS-administered rats (earliest date was 7 days after SCI). The MEP waveforms also appeared at approximately the same level on the BBB scale (average score, 11 points). Ultimately, this study can help enhance our understanding of the relationship between neural regeneration and tcMEP recording. Further application of tcMEP in regenerative medicine research is expected. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is often accompanied by gastrointestinal dysfunction due to the disconnection of the spinal autonomic nervous system. Gastrointestinal dysfunction reportedly upregulates intestinal permeability, leading to bacterial translocation of the gut microbiome to the systemic circulation, which further activates systemic inflammation, exacerbating neuronal damage. Mesenchymal stem cells (MSC) reportedly ameliorate SCI. Here, we aimed to investigate their effect on the associated gastrointestinal dysfunction. Human amnion-derived MSC (AMSCs) were intravenously transplanted one day after a rat model of midthoracic SCI. Biodistribution of transplanted cells, behavioral assessment, and histological evaluations of the spinal cord and intestine were conducted to elucidate the therapeutic effect of AMSCs. Bacterial translocation of the gut microbiome was examined by in situ hybridization and bacterial culture of the liver. Systemic inflammations were examined by blood cytokines, infiltrating immune cells in the spinal cord, and the size of the peripheral immune tissue. AMSCs released various neurotrophic factors and were mainly distributed in the liver and lung after transplantation. AMSC-transplanted animals showed smaller spinal damage and better neurological recovery with preserved neuronal tract. AMSCs transplantation ameliorated intestinal dysfunction both morphologically and functionally, which prevented translocation of the gut microbiome to the systemic circulation. Systemic inflammations were decreased in animals receiving AMSCs in the chronic phase. Intravenous AMSC administration during the acute phase of SCI rescues both spinal damage and intestinal dysfunction. Reducing bacterial translocation may contribute to decreasing systemic inflammation. [ABSTRACT FROM AUTHOR]

Background: Individuals living with chronic spinal cord injury or disease (SCI/D) are at an increased risk of falling. However, little is known about the impact of falls and fall risk in the subacute phase of SCI/D, despite this being a time when fall prevention initiatives are delivered. Hence, we explored the impact of falls and fall risk in individuals with subacute SCI/D as they transitioned from inpatient rehabilitation to community living. Methods: This qualitative photo-elicitation study used an inductive thematic analysis. Eight individuals (7 male) undergoing inpatient rehabilitation at a Canadian tertiary rehabilitation hospital due to a new SCI/D participated. Six months following discharge, photo-elicitation interviewing was used to understand the impact of falls and fall risk. Over 7–14 days, participants completed a photo-assignment that involved taking photographs in response to questions, such as what increases/decreases your likelihood of falling? A semi-structured interview followed, in which participants described their photographs and discussed their experiences with falls, fall risk and fall prevention training. Results: Four themes were identified. 1) Risk factors and strategies identified through lived experience. Participants discovered their fall risk factors and fall prevention strategies through "trial and error". 2) Influences on the individual's perception of their fall risk. Prior experience with falls, including falls experienced by themselves as well as friends and family, influenced their perception of fall risk. 3) Experiencing life differently due to increased fall risk. A high fall risk reduced participation, increased negative emotions and decreased independence and quality of life. 4) Falls training in rehabilitation can be improved. Prior experiences with falls training varied; however, participants expressed a desire for comprehensive and individualized training. Conclusion: Although participants' experiences with falls and fall prevention varied, falls and the risk of falling can have a significant impact on the first year of living with a SCI/D. [ABSTRACT FROM AUTHOR]

Introduction: As technological advances allow the use of robotic exoskeleton devices with gait training, there is a critical need to establish a robotic gait training (RGT) program to meet the needs of people with spinal cord injury (SCI) during inpatient rehabilitation. The purposes of this study are to prospectively examine the efficacy of a stakeholder informed RGT program compared to usual care gait training (UC) during inpatient rehabilitation in people with incomplete SCI and compare the intensity of RGT and UC gait training during inpatient rehabilitation. Study design: 128 patients with incomplete SCI admitted to our inpatient rehabilitation facility will be screened for eligibility and randomized to either the RGT or UC group. RGT sessions will use the Ekso robotic exoskeleton [class II medical device (United States FDA)]. UC sessions will use traditional gait training approaches such as manually assisted overground gait training with walkers and orthotics and body weight–supported treadmill training (BWSTT). Our primary outcome is gait function as characterized by the Walking Index for Spinal Cord Injury–II (WISCI-II). Secondary outcomes are gait speed, Spinal Cord Independence Measure (SCIM), Numeric Pain Rating Scale (NPRS), Fatigue Severity Scale (FSS), Penn Spasm Frequency Scale (PSFS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder– 7 (GAD-7), International Spinal Cord Injury Quality of Life Basic Data Set, and a Qualitative Questionnaire. Assessments of primary and secondary outcomes will occur at admission and discharge from inpatient rehabilitation. General or generalized linear models will be used to analyze differences between groups for all measures. Clinical impact: Successful completion of this study will provide a usable, replicable, stakeholder informed RGT intervention for use with individuals with incomplete SCI during inpatient rehabilitation. [ABSTRACT FROM AUTHOR]

Spasticity is a frequent chronic complication in individuals with spinal cord injury (SCI). However, the severity of spasticity varies in patients with SCI. Therefore, an evaluation method is needed to determine the severity of spasticity. We used a contusive SCI model that is suitable for clinical translation. In this study, we examined the feasibility of the swimming test and an EMG for evaluating spasticity in a contusive SCI rat model. Sprague-Dawley rats received an injury at the 8th thoracic vertebra. Swimming tests were performed 3 to 6 weeks after SCI induction. We placed the SCI rats into spasticity-strong or spasticity-weak groups based on the frequency of spastic behavior during the swimming test. Subsequently, we recorded the Hoffman reflex (H-reflex) and examined the immunoreactivity of serotonin (5-HT) and its receptor (5-HT2A) in the spinal tissues of the SCI rats. The spasticity-strong group had significantly decreased rate-dependent depression of the H-reflex compared to the spasticity-weak group. The area of 5-HT2A receptor immunoreactivity was significantly increased in the spasticity-strong group. Thus, both electrophysiological and histological evaluations indicate that the spasticity-strong group presented with a more severe upper motor neuron syndrome. We also observed the groups in their cages for 20 hours. Our results suggest that the swimming test provides an accurate evaluation of spasticity in this contusive SCI model. We believe that the swimming test is an effective method for evaluating spastic behaviors and developing treatments targeting spasticity after SCI.

Thrombin-induced secondary injury is mediated through its receptor, protease activated receptor-1 (PAR-1), by "biased agonism." Activated protein C (APC) acts through the same PAR-1 receptor but functions as an anti-coagulant and anti-inflammatory protein, which counteracts many of the effects of thrombin. Although the working mechanism of PAR-1 is becoming clear, the functional role of PAR-1 and its correlation with APC in the injured spinal cord remains to be elucidated. Here we investigated if PAR-1 and APC are determinants of long-term functional recovery after a spinal cord contusive injury using PAR-1 null and wild-type mice. We found that neutrophil infiltration and disruption of the blood-spinal cord barrier were significantly reduced in spinal cord injured PAR-1 null mice relative to the wild-type group. Both locomotor recovery and ability to descend an inclined grid were significantly improved in the PAR-1 null group 42 days after injury and this improvement was associated with greater long-term sparing of white matter and a reduction in glial scarring. Wild-type mice treated with APC acutely after injury showed a similar level of improved locomotor recovery to that of PAR-1 null mice. However, improvement of APC-treated PAR-1 null mice was indistinguishable from that of vehicle-treated PAR-1 null mice, suggesting that APC acts through PAR-1. Collectively, our findings define a detrimental role of thrombin-activated PAR-1 in wound healing and further validate APC, also acting through the PAR-1 by biased agonism, as a promising therapeutic target for spinal cord injury.

Background: Acquired brain injury and spinal cord injury are leading causes of severe motor disabilities impacting a person's autonomy and social life. Enhancing neurological recovery driven by neurogenesis and neuronal plasticity could represent future solutions; however, at present, recovery of activities employing assistive technologies integrating artificial intelligence is worthy of examining. MAIA (Multifunctional, adaptive, and interactive AI system for Acting in multiple contexts) is a human-centered AI aiming to allow end-users to control assistive devices naturally and efficiently by using continuous bidirectional exchanges among multiple sensorimotor information. Methods: Aimed at exploring the acceptability of MAIA, semi-structured interviews (both individual interviews and focus groups) are used to prompt possible end-users (both patients and caregivers) to express their opinions about expected functionalities, outfits, and the services that MAIA should embed, once developed, to fit end-users needs. Discussion: End-user indications are expected to interest MAIA technical, health-related, and setting components. Moreover, psycho-social issues are expected to align with the technology acceptance model. In particular, they are likely to involve intrinsic motivational and extrinsic social aspects, aspects concerning the usefulness of the MAIA system, and the related ease to use. At last, we expect individual factors to impact MAIA: gender, fragility levels, psychological aspects involved in the mental representation of body image, personal endurance, and tolerance toward AT-related burden might be the aspects end-users rise in evaluating the MAIA project. [ABSTRACT FROM AUTHOR]

Lifestyle physical activity following spinal cord injury (SCI) is critical for functional independence, mental wellness, and social participation, yet nearly 50% of individuals with SCI report no regular exercise. The objective of this study was to better understand factors leading to this participation gap by capturing the physical activity perspectives of individuals living with SCI. We completed small group interviews with nine individuals living with SCI across the United States. Iterative thematic analysis systematically revealed meaningful core concepts related to physical activity engagement with SCI. Emergent themes revealed challenges to lifestyle physical activity behavior including gaps in physical activity education, isolation during psychological adjustment, and knowledge limitations in community exercise settings. A secondary theme related to the COVID-19 pandemic emerged, highlighting additional environmental constraints affecting participation. Our findings suggest that most physical activity education is delivered during inpatient rehabilitation and is related to physical function. Lifetime physical activity strategies are achieved through self-education and peer networking. Personal motivators for physical activity include secondary condition prevention, while social and emotional barriers prevent regular adherence. These findings can inform the development and delivery of physical activity programs to maximize physical activity engagement in individuals living with chronic SCI. [ABSTRACT FROM AUTHOR]

Purpose: Muscle biopsies are the gold standard to assess mitochondrial respiration; however, biopsies are not always a feasible approach in persons with spinal cord injury (SCI). Peripheral blood mononuclear cells (PBMCs) and near-infrared spectroscopy (NIRS) may alternatively be predictive of mitochondrial respiration. The purpose of the study was to evaluate whether mitochondrial respiration of PBMCs and NIRS are predictive of respiration of permeabilized muscle fibers after SCI. Methods: Twenty-two individuals with chronic complete and incomplete motor SCI between 18–65 years old were recruited to participate in the current trial. Using high-resolution respirometry, mitochondrial respiratory capacity was measured for PBMCs and muscle fibers of the vastus lateralis oxidizing complex I, II, and IV substrates. NIRS was used to assess mitochondrial capacity of the vastus lateralis with serial cuff occlusions and electrical stimulation. Results: Positive relationships were observed between PBMC and permeabilized muscle fibers for mitochondrial complex IV (r = 0.86, P < 0.0001). Bland-Altman displayed agreement for complex IV (MD = 0.18, LOA = -0.86 to 1.21), between PBMCs and permeabilized muscles fibers. No significant relationships were observed between NIRS mitochondrial capacity and respiration in permeabilized muscle fibers. Conclusions: This is the first study to explore and support the agreement of less invasive clinical techniques for assessing mitochondrial respiratory capacity in individuals with SCI. The findings will assist in the application of PBMCs as a viable alternative for assessing mitochondrial health in persons with SCI in future clinical studies. [ABSTRACT FROM AUTHOR]

Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease. [ABSTRACT FROM AUTHOR]

Objectives: To determine the Effect of Hybrid functional electrically stimulated (FES) Exercise on Body Composition during the Sub-acute Phase of Spinal Cord Injury (SCI). Design: Randomized Clinical Trial. Setting: Rehabilitation Hospital. Participants: Patients within sub-acute phase (3–24 months) of SCI. Interventions: We investigated if high-intensity exercise training via the addition of functional electrically stimulated (FES) leg muscles, provides sufficient stimulus to mitigate against body composition changes in the sub-acute phase after SCI. Main outcome measures: We explored potential effects of FES row training (FESRT) on body fat gain, lean mass loss, and cardiometabolic parameters and compared the effects of 6-month of FESRT (n = 18) to standard of care (SOC, n = 13). Those in SOC were crossed over to FESRT. Results: FESRT resulted in greater exercise capacity and a tendency for lesser total body fat accumulation with a significant increase in total and leg lean mass (p<0.05). In addition pelvis and total bone mineral density declines were significantly less (p<0.05). Compared to SOC, FESRT did not lead to any significant difference in insulin sensitivity or serum lipids. However, HbA1C levels were significantly decreased in SOC participants who crossed over to 6-month FESRT. Conclusion: FESRT early after SCI provides a sufficient stimulus to mitigate against detrimental body composition changes. This may lead to prevention of losses in lean mass, including bone. [ABSTRACT FROM AUTHOR]

The circadian gene expression rhythmicity drives diurnal oscillations of physiological processes that may determine the injury response. While outcomes of various acute injuries are affected by the time of day at which the original insult occurred, such influences on recovery after spinal cord injury (SCI) are unknown. We report that mice receiving moderate, T9 contusive SCI at ZT0 (zeitgeber time 0, time of lights on) and ZT12 (time of lights off) showed similar hindlimb function recovery in the Basso mouse scale (BMS) over a 6 week post-injury period. In an independent study, no significant differences in BMS were observed after SCI at ZT18 vs. ZT6. However, the ladder walking test revealed modestly improved performance for ZT18 vs. ZT6 mice at week 6 after injury. Consistent with those minor effects on functional recovery, terminal histological analysis revealed no significant differences in white matter sparing at the injury epicenter. Likewise, blood-spinal cord barrier disruption and neuroinflammation appeared similar when analyzed at 1 week post injury at ZT6 or ZT18. Therefore, locomotor recovery after thoracic contusive SCI is not substantively modulated by the time of day at which the neurotrauma occurred. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous spinal cord stimulation (tSCS) is a non-invasive modality in which electrodes can stimulate spinal circuitries and facilitate a motor response. This review aimed to evaluate the methodology of studies using tSCS to generate motor activity in persons with spinal cord injury (SCI) and to appraise the quality of included trials. Methods: A systematic search for studies published until May 2021 was made of the following databases: EMBASE, Medline (Ovid) and Web of Science. Two reviewers independently screened the studies, extracted the data, and evaluated the quality of included trials. The electrical characteristics of stimulation were summarised to allow for comparison across studies. In addition, the surface electromyography (EMG) recording methods were evaluated. Results: A total of 3753 articles were initially screened, of which 25 met the criteria for inclusion. Studies were divided into those using tSCS for neurophysiological investigations of reflex responses (n = 9) and therapeutic investigations of motor recovery (n = 16). The overall quality of evidence was deemed to be poor-to-fair (10.5 ± 4.9) based on the Downs and Black Quality Checklist criteria. The electrical characteristics were collated to establish the dosage range across stimulation trials. The methods employed by included studies relating to stimulation parameters and outcome measurement varied extensively, although some trends are beginning to appear in relation to electrode configuration and EMG outcomes. Conclusion: This review outlines the parameters currently employed for tSCS of the cervicothoracic and thoracolumbar regions to produce motor responses. However, to establish standardised procedures for neurophysiological assessments and therapeutic investigations of tSCS, further high-quality investigations are required, ideally utilizing consistent electrophysiological recording methods, and reporting common characteristics of the electrical stimulation administered. [ABSTRACT FROM AUTHOR]

Intervertebral disc herniation (IVDH) is a frequently occurring neurological disease of dogs and the most common reason for spinal cord injury (SCI). Clinical signs are variable thus a reliable prognosis is crucial for further treatment decisions. Currently, the prognosis of IVDH primarily depends on presence or absence of deep pain perception. The purpose of this study was to investigate if Th17-cells could serve as a potential, prognostic biomarker for IVDH. We investigated a possible role of the adaptive immune system in the pathophysiology of IVDH in dogs. The investigation was performed by analyzing the influence of Th17-cells in blood and cerebrospinal fluid (CSF) of sixty-two dogs suffering from IVDH. In addition, we examined if Th17-cells might influence the course of this disease. As controls, paired blood and CSF samples of ten healthy clinic-owned dogs were examined and the values were compared to those of the IVDH group. Isolated lymphocytes were analyzed after stimulation by using multicolour flow cytometry to measure the number of Th17-cells. IL-17 levels were measured in paired serum and CSF samples by Enzyme‐linked Immunosorbent Assays (ELISA). Highly significant differences of stimulated Th17-cells in EDTA-blood samples could be determined between Th17-cell levels of dogs suffering from IVDH and the healthy control group and also between three sampling time points: preoperative, after clinical improvement and after six months. Preoperatively, Th17-cell levels were strongly decreased in contrast to the healthy controls. The decreased amount of Th17-cell levels recovered postoperatively so that Th17-cell levels of the last follow-up examinations were comparable to the control group after six months. At the same time IL-17 measured in serum preoperatively was significantly higher in dogs with IVDH than in healthy controls. However, there was no considerable difference of IL-17 measured in CSF between the groups. In conclusion, a high activity and consequent consumption of IL-17-producing Th17-cells is suspected in acute IVDH. These findings may indicate an involvement of Th17-cells in the pathogenesis of IVDH and emphasize that these cells might be involved in the interaction of pain, stress and immune reaction. However, based on the findings of this study the development of Th17-cells as a biomarker cannot be recommended, yet. [ABSTRACT FROM AUTHOR]

Background: Social relationships are powerful determinants of health and inequalities in social relationships across socioeconomic status (SES) groups may contribute to social inequalities in health. This study investigates inequalities in social relationships in an international sample of persons with spinal cord injury and explores whether social gradients in relationships are moderated by the countries' socioeconomic development (SED). Methods: Data from 12,330 participants of the International SCI Community Survey (InSCI) performed in 22 countries were used. We regressed social relationships (belongingness, relationship satisfaction, social interactions) on individual SES (education, income, employment, financial hardship, subjective status) and countries' SED (Human Development Index) using multi-level models (main effects). To test potential moderation of the SED, interaction terms between individual SES and countries' SED were entered into multi-level models. Results: Paid work, absence of financial hardship and higher subjective status were related to higher belongingness (OR, 95% CI: 1.50, 1.34–1.67; 1.76, 1.53–2.03; 1.16, 1.12–1.19, respectively), higher relationship satisfaction (OR, 95% CI: 1.28, 1.15–1.42; 1.97, 1.72–2.27; 1.20, 1.17–1.24, respectively) and fewer problems with social interactions (Coeff, 95% CI: 0.96, 0.82–1.10; 1.93, 1.74–2.12; 0.26, 0.22–0.29, respectively), whereas associations with education and income were less consistent. Main effects for countries' SED showed that persons from lower SED countries reported somewhat higher relationship satisfaction (OR, 95% CI: 0.97, 0.94–0.99) and less problems with social interactions (Coeff, 95% CI: -0.04, -0.09- -0.003). Results from moderation analysis revealed that having paid work was more important for relationships in lower SED countries, while education and subjective status were more important for relationships in higher SED countries (interaction terms p<0.05). Conclusion: Social relationships in persons with spinal cord injury are patterned according to individual SES and the countries' SED and larger socioeconomic structures partly moderate associations between individual SES and social relationships. [ABSTRACT FROM AUTHOR]

Neurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI). Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such that a search for new treatments is warranted. Inosine is a naturally occurring purine nucleoside with neuroprotective, neurotrophic and antioxidant effects that is known to improve motor function in preclinical models of SCI. However, its effect on lower urinary tract function has not been determined. The objectives of this study were to determine the effect of systemic administration of inosine on voiding function following SCI and to delineate potential mechanisms of action. Sprague-Dawley rats underwent complete spinal cord transection, or cord compression by application of an aneurysm clip at T8 for 30 sec. Inosine (225 mg/kg) or vehicle was administered daily via intraperitoneal injection either immediately after injury or after a delay of 8 wk. At the end of treatment, voiding behavior was assessed by cystometry. Levels of synaptophysin (SYP), neurofilament 200 (NF200) and TRPV1 in bladder tissues were measured by immunofluorescence imaging. Inosine administration decreased overactivity in both SCI models, with a significant decrease in the frequency of spontaneous non-voiding contractions during filling, compared to vehicle-treated SCI rats (p

Background: The environment where people live, work or play can influence health and disability outcomes. People with spinal cord injury are at risk for secondary health conditions, with this increasing readmission rates and decreasing quality of life. Studies on preventative care for secondary health conditions and factors influencing the prevention of secondary health conditions are scarce in low to middle-income countries. Aim: To explore environmental factors influencing the prevention of secondary health conditions in people with spinal cord injury. Setting: This study was based at a public rehabilitation hospital, South Africa. Methods: Explorative qualitative design was used. Semi-structured interviews were conducted with 21 therapists, 17 people with a spinal cord injury and six caregivers. The interviews were transcribed verbatim. Analysis was conducted using content analysis. Results: The categories that emerged included the impact of social support, inaccessible built environment and transport system, and an inefficient health care system. Sub-categories for the inefficient health care systems were: Shortage of resources, health workers lack of knowledge on prevention of secondary health conditions and inadequate patient care approach. Conclusion: Environmental factors influencing the prevention of secondary health conditions are complex and multifactorial. When developing rehabilitation and prevention programmes, environmental factors must be considered. [ABSTRACT FROM AUTHOR]