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Background Constraint induced movement therapy (CIMT) is effective at improving upper limb outcomes after stroke. Aim The aim of this study was to carry out a systematic review and meta-analysis of the effects of lower limb CIMT studies of any design in people with stroke. Materials/ Method PubMED, PEDro, OTSeeker, CENTRAL, and Web of Science were searched from their earliest dates to February 2021. Lower limbs CIMT studies that measured outcomes at baseline and post-intervention were selected. Sample size, mean, and standard deviation on the outcomes of interest and the protocols of both the experimental and control groups were extracted. McMaster Critical Review Form was used to assess the methodological quality of the studies. Result Sixteen studies with different designs were included in this review. The result showed that lower limb CIMT improves functional, physiological and person's reported outcomes including motor function, balance, mobility, gait speed, oxygen uptake, exertion before and after commencement of activities, knee extensor spasticity, weight bearing, lower limb kinematics and quality of life in people with stroke post intervention. However, there were only significant differences in quality of life in favor of CIMT post-intervention [mean difference (MD) = 16.20, 95% CI = 3.30-29.10, p = 0.01]; and at follow-up [mean difference (MD) = 14.10, 95% CI = 2.07-26.13, p = 0.02] between CIMT and the control group. Even for the quality of life, there was significant heterogeneity in the studies post intervention (I 2 = 84%, p = 0.01). Conclusion Lower limb CIMT improves motor function, balance, functional mobility, gait speed, oxygen uptake, weigh bearing, lower limb kinematics, and quality of life. However, it is only superior to the control at improving quality of life after stroke based on the current literature.Introduction Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program. Methods PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes. Results Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention (d values ranging from -0.26 to 0.42). Conclusions Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. RTA-408 in vivo The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM.Background Patient and public involvement (PPI) is an active partnership between the public and researchers in the research process. In dementia research, PPI ensures that the perspectives of the person with "lived experience" of dementia are considered. To date, in many lower- and middle-income countries (LMIC), where dementia research is still developing, PPI is not well-known nor regularly undertaken. Thus, here, we describe PPI activities undertaken in seven research sites across South Asia as exemplars of introducing PPI into dementia research for the first time. Objective Through a range of PPI exemplar activities, our objectives were to (1) inform the feasibility of a dementia-related study; and (2) develop capacity and capability for PPI for dementia research in South Asia. Methods Our approach had two parts. Part 1 involved co-developing new PPI groups at seven clinical research sites in India, Pakistan and Bangladesh to undertake different PPI activities. Mapping onto different "rings" of the Wellcoand (4) adaptations to the study protocol through co-production. Conclusions Introducing PPI for dementia research in LMIC settings, using a range of activity types is important for meaningful and impactful dementia research. To our knowledge, this is the first example of PPI for dementia research in South Asia.Purpose To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging. Methods Sixty-four healthy adults (28 men) aged 23-79 years (mean 45.0, SD = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL). Results Adjusted for depreion symptoms, which also increased with age.This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.