Best practice exercise for emerging depression in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: To examine the effects of instructor-led exercise on depression symptoms in adults with multiple sclerosis, with a focus on moderating factors to treatment response. DATA SOURCES: Cochrane Library, Embase, PEDro, PsycINFO and PubMed databases were searched until 21 April 2024. REVIEW METHODS: The reporting quality of included studies assessed (PEDro and TESTEX scales). Hedges' g effect sizes were calculated and pooled using random and mixed-effects modelling. RESULTS: Twenty-two independent studies (k), representing 785 participants with relapsing remitting or progressive MS, were included. Individual studies varied in their reporting quality (PEDro range: 3-8) and did not routinely detail exercise parameters (TESTEX range: 5-13). Nonetheless, exercise reduced core symptoms of depression (gw = .52, CI: .30-.73, P < .01). Treatment effects were, however, not maintained once training had ceased (gw = -.53, CI: -.80 to .24, P ≤ .01, k = 5). Both aerobic and non-aerobic exercise groups experienced a significant (P < .01) reduction in depression scores. Larger gains were noted by those with better ambulation at baseline (P = .03). CONCLUSION: Regular exercise can help to stabilise mood for people living with multiple sclerosis, regardless of session frequency or duration. Treatment efficacy could be maximised by addressing potential barriers for those with limited mobility, including exercise type, delivery and intensity. Protocol registered on Open Science Framework [https://osf.io/zfymq/].

Towards a Clinical Decision-Making Algorithm Guiding Locomotor Therapy Modality in Subacute Stroke: An Exploratory Study.

OBJECTIVES: To propose a clinical decision-making algorithm guiding modality choice and transition from the Lokomat® robotic to body-weight supported treadmill training in subacute stroke, due to current evidence being limited, making clinical decisions difficult. MATERIALS AND METHODS: For 10 adult patients with subacute stroke completing Lokomat® therapy, physiotherapist clinical judgement regarding body-weight supported treadmill training readiness and the following objective measurements were collected; Functional Ambulation Category; sit to stand/standing ability; Lokomat® settings; maximal active hip and knee flexion in standing; and gait biomechanics during body-weight supported treadmill training. Based on observed patterns a proposed clinical decision-making algorithm was developed. RESULTS: Clinical judgement deemed four of 10 participants ready to transition to body-weight supported treadmill training. Unlike participants judged not ready, these participants had: a) a Functional Ambulation Category of 1; b) independence with sit to stand and standing with even weight bearing; c) Lokomat®: Body-Weight Support <30%, Guidance Force <30-35%, speed >2.0kph; d) >45° standing active hip and knee flexion; e) no significant issues with physiological stepping in treadmill training or only requiring assistance from one therapist to achieve this. CONCLUSION: Participants judged ready for transition from the Lokomat® to body-weight supported treadmill training presented with increased independent functional ability, more challenging Lokomat® settings, greater active volitional lower-limb control, and less issues with physiological stepping in treadmill training, than those participants judged not ready. Results were translated into a proposed clinical decision-making algorithm guiding transition from the Lokomat® to body-weight supported treadmill training, to be further tested in clinical trials.

Augmented Performance Feedback during Robotic Gait Therapy Results in Moderate Intensity Cardiovascular Exercise in Subacute Stroke.

BACKGROUND: Low cardiovascular fitness is common poststroke. Conventional subacute stroke rehabilitation does not meet Australian National Stroke Guidelines for cardiovascular exercise, particularly in mobility-dependent patients. Walking robotics can potentially achieve recommended cardiovascular exercise with these patients. AIM: The primary aim was to determine whether sustained moderate intensity cardiovascular exercise can be achieved using 3 Lokomat Augmented Performance Feedback activities in mobility-dependent adults with subacute stroke. Secondary aims were to assess if cardiovascular workload was influenced by the activity completed, participants motivation or enjoyment, or changes in Lokomat settings. METHODS: Ten patients with subacute stroke (mean (SD) age: 63.4 (13) years) participated in 6x20-minute Lokomat study sessions. Each study session involved a warm-up and 3x5-minute APF activities presented in a random order. Metabolic data were collected using the COSMED-K5. Participants rated their perceived exertion on the BORG CR10 scale and Lokomat settings of body-weight support, guidance force, and speed were recorded. RESULTS: Moderate intensity cardiovascular exercise was achieved and maintained over the 15 minutes of exercise, objectively demonstrated by a mean (SD) Metabolic Equivalent Task of 3.1 (1.3), and mean (SD) oxygen consumption of 8.0 (3.8) ml/kg/min, estimated as 52% VO2max. This was subjectively confirmed by exertion scores between 3 and 5. The cardiovascular workload was not affected by which activity was completed, participant motivation or enjoyment, or significant progression of Lokomat settings between study sessions. CONCLUSIONS: Mobility-dependent patients with subacute stroke can achieve sustained moderate intensity cardiovascular exercise on the Lokomat when using APF activities.

The signaling protein CD38 is essential for early embryonic development.

CD38 is a multifunctional protein possessing ADP-ribosyl cyclase activity responsible for both the synthesis and the degradation of several Ca(2+)-mobilizing second messengers. Although a variety of functions have been ascribed to CD38, such as immune responses, insulin secretion, and social behavior in adults, nothing is known of its role during embryonic development when Ca(2+) signals feature prominently. Here, we report the identification and functional expression of CD38 from Xenopus laevis, a key model organism for the study of vertebrate development. We show that CD38 expression and endogenous ADP-ribosyl cyclase activity are developmentally regulated during cellular differentiation. Chemical or molecular inhibition of CD38 abolished ADP-ribosyl cyclase activity and disrupted elongation of the anterior-posterior axis and differentiation of skeletal muscle, culminating in embryonic death. Our data uncover a previously unknown role for CD38 as an essential regulator of embryonic development.