Locomotor training improves function after a spinal cord injury both in experimental and clinical settings. The activity-dependent mechanisms underlying such improvement, however, are sparsely understood. Adult rats received a complete spinal cord transection (T9), and epidural stimulation (ES) electrodes were secured to the dura matter at L2. EMG electrodes were implanted bilaterally in selected muscles. Using a servo-controlled body weight support system for bipedal stepping, five rats were trained 7 d/week for 6 weeks (30 min/d) under quipazine (0.3 mg/kg) and ES (L2; 40 Hz). Nontrained rats were handled as trained rats but did not receive quipazine or ES. At the end of the experiment, a subset of rats was used for c-fos immunohistochemistry. Three trained and three nontrained rats stepped for 1 h (ES; no quipazine) and were returned to their cages for 1 h before intracardiac perfusion. All rats could step with ES and quipazine administration. The trained rats had higher and longer steps, narrower base of support at stance, and lower variability in EMG parameters than nontrained rats, and these properties approached that of noninjured controls. After 1 h of stepping, the number of FOSϩ neurons was significantly lower in trained than nontrained rats throughout the extent of the lumbosacral segments. These results suggest that training reinforces the efficacy of specific sensorimotor pathways, resulting in a more selective and stable network of neurons that controls locomotion.

Background: In-person counselling programs promote self-care behaviour and health-related quality of life (HRQoL). ODYSSEE Kidney Health (ODYSSEE-KH) is an automated, scalable, digital counselling program for patients with CKD. This open-label, single-arm pilot study tested the efficacy potential of ODYSSEE-KH to improve HRQoL in patients with CKD. Methods: Adults with categories G3b to 5D CKD were recruited from nephrology clinics in Toronto, Canada. Patients (n=29) received access to ODYSSEE-KH in conjunction with usual care. Generalized linear models and pairwise comparisons of mean change scores were conducted to assess the primary outcome: Mental Component Score (MCS) of the Kidney Disease Quality of Life – Short Form (KDQoL-SF) instrument. Secondary outcomes included: MCS mental health scale, 36-item KDQoL-SF, Generalized Anxiety Disorder scale (GAD-7), Patient Health Questionnaire for depression (PHQ-9), Enhancing Recovery in Coronary Heart Disease Social Support Instrument (ESSI), and 3-item Revised UCLA Loneliness (RULS-3) scale. Results: Mean age was 53.5 years (SD=18.3); 35% women; 56% White; 93% completed ≥ post-secondary education; patients came from the Multi-Care Kidney Clinic (n=9), the Home Peritoneal Dialysis Unit (n=12), and the Home Hemodialysis Unit (n=8); and 24 participants completed the 4-month end of study questionnaires. Outcomes were assessed according to tertiles of program logon minutes: median (range) = 67 (62-108), 212 (119-355), and 500 (359-1573) minutes. Patients in the highest tertile of engagement showed significant improvements on the MCS vs. the moderate tertile group (p = 0.01). Significant dose-response associations were observed for MCS Mental Health (p<0.05), KDQoL Burden on Kidney Disease (p<0.01), KDQoL Effect of Kidney Disease on Everyday Life (p<0.01), aggregated KDQoL summary (p<0.05), GAD-7 (p<0.01), PHQ-9 (p<0.05), ENRICHD-SSI (p<0.01), and RULS-3 (p<0.01). Conclusion: ODYSSEE-KH demonstrated feasibility as an automated, scalable, digital self-care program for patients with CKD. There is evidence of efficacy potential to improve HRQoL. Further evaluation with a larger sample is warranted.

Background Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low‐grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains largely unexplored. Methods and Results EGFP + (Enchanced green fluorescent protein) mice were subjected to coronary artery ligation, and BM was collected 8 weeks after myocardial infarction. Transplantation of EGFP + BM into wild‐type mice revealed reduced reconstitution potential of BM from mice subjected to myocardial infarction versus BM from sham mice. To study the effects HF has on human BM function, 71 patients, HF (n=20) and controls (n=51), who were scheduled for elective cardiac surgery were consented and enrolled in this study. Patients with HF exhibited more circulating blood myeloid cells, and analysis of patient BM revealed significant differences in cell composition and colony formation potential. Human CD34 + cell reconstitution potential was also assessed using the NOD‐SCID‐IL2rγ null mouse xenotransplant model. NOD‐SCID‐IL2rγ null mice reconstituted with BM from patients with HF had significantly fewer engrafted human CD34 + cells as well as reduced lymphoid cell production. Analysis of tissue repair responses using permanent left anteriordescending coronary artery ligation demonstrated reduced survival of HF‐BM reconstituted mice as well as significant differences in human (donor) and mouse (host) cellular responses after MI. Conclusions HF alters the BM composition, adversely affects cell reconstitution potential, and alters cellular responses to injury. Further studies are needed to determine whether restoring BM function can impact disease progression or improve cellular responses to injury.