Education vs TFP: Empirical evidence from the Sub-Saharan Countries

This single-case, mixed-method study explored the feasibility of self-administered, home-based SMART (sensorimotor active rehabilitation training) Arm training for a 57-yr-old man with severe upper-limb disability after a right frontoparietal hemorrhagic stroke 9 mo earlier. Over 4 wk of self-administered, home-based SMART Arm training, the participant completed 2,100 repetitions unassisted. His wife provided support for equipment set-up and training progressions. Clinically meaningful improvements in arm impairment (strength), activity (arm and hand tasks), and participation (use of arm in everyday tasks) occurred after training (at 4 wk) and at follow-up (at 16 wk). Areas for refinement of SMART Arm training derived from thematic analysis of the participant's and researchers' journals focused on enabling independence, ensuring home and user friendliness, maintaining the motivation to persevere, progressing toward everyday tasks, and integrating practice into daily routine. These findings suggest that further investigation of self-administered, home-based SMART Arm training is warranted for people with stroke who have severe upper-limb disability

Perseverance with home-based upper limb practice after stroke: perspectives of stroke survivors and their significant others

Purpose: The aim of this study was to explore factors that influence stroke survivors’ ability to persevere with home-based upper limb practice. Methods: A qualitative descriptive study embedded within a theoretical framework was conducted. Data were collected through semi-structured focus group, dyadic, and individual interviews. The Theoretical Domains Framework and Capability, Opportunity, Motivation – Behaviour (COM-B) model guided data collection and directed content analysis. Findings: Participants were 31 adult stroke survivors with upper limb impairment, with 13 significant other/s, who were living at home in Queensland, Australia. Three central tenants aligned with the COM-B and six themes were identified. Stroke survivors’ capability to persevere was influenced by being physically able to practice and being able to understand, monitor and modify practice, their opportunity to persevere was influenced by accessing therapy and equipment required for practice and fitting practice into everyday life, and their motivation to persevere was influenced by having goals and experiencing meaningful outcomes and having support and being accountable. Conclusion: Persevering with practice is multifaceted for stroke survivors. All facets need to be addressed in the design of strategies to enhance stroke survivors’ ability to persevere and in turn, enhance their potential for continued upper limb recovery

Perseverance with technology-facilitated home-based upper limb practice after stroke: a systematic mixed studies review

Background: Technology is being increasingly investigated as an option to allow stroke survivors to exploit their full potential for recovery by facilitating home-based upper limb practice. This review seeks to explore the factors that influence perseverance with technology-facilitated home-based upper limb practice after stroke. Methods: A systematic mixed studies review with sequential exploratory synthesis was undertaken. Studies investigating adult stroke survivors with upper limb disability undertaking technology-facilitated home-based upper limb practice administered ≥ 3 times/week over a period of ≥ 4 weeks were included. Qualitative outcomes were stroke survivors’ and family members’ perceptions of their experience utilising technology to facilitate home-based upper limb practice. Quantitative outcomes were adherence and dropouts, as surrogate measures of perseverance. The Mixed Methods Appraisal Tool was used to assess quality of included studies. Results: Forty-two studies were included. Six studies were qualitative and of high quality; 28 studies were quantitative and eight were mixed methods studies, all moderate to low quality. A conceptual framework of perseverance with three stages was formed: (1) getting in the game; (2) sticking with it, and; (3) continuing or moving on. Conditions perceived to influence perseverance, and factors mediating these conditions were identified at each stage. Adherence with prescribed dose ranged from 13 to 140%. Participants were found to be less likely to adhere when prescribed sessions were more frequent (6–7 days/week) or of longer duration (≥ 12 weeks). Conclusion: From the mixed methods findings, we propose a framework for perseverance with technology-facilitated home-based upper limb practice. The framework offers opportunities for clinicians and researchers to design strategies targeting factors that influence perseverance with practice, in both the clinical prescription of practice and technology design. To confirm the clinical utility of this framework, further research is required to explore perseverance and the factors influencing perseverance

SMART arm with outcome-triggered electrical stimulation: a pilot randomized clinical trial

Background: The SMART (SensoriMotor Active Rehabilitation Training) Arm is a nonrobotic device designed to allow stroke survivors with severe paresis to practice reaching. It can be used with or without outcome-triggered electrical stimulation (OT-stim) to augment movement. The aim of this study was to evaluate the efficacy of SMART Arm training when used with or without OT-stim, in addition to usual care, as compared with usual care alone during inpatient rehabilitation. Methods: Eight stroke survivors received 20 hours of SMART Arm training over 4 weeks; they were randomly assigned to either (1) SMART Arm training with OT-stim or (2) SMART Arm training alone. Usual therapy was also provided. A historical cohort of 20 stroke survivors formed the control group and received only usual therapy. The primary outcome was Motor Assessment Scale Item 6, Upper Arm Function. Results: Findings for all participants were comparable at baseline. SMART Arm training, with or without OT-stim, led to a significantly greater improvement in upper arm function than usual therapy alone (P=.024). There was no difference in improvement between training with or without OT-stim. Initial motor severity and presence of OT-stim influenced the number of repetitions performed and the progression of SMART Arm training practice conditions. Conclusion: Usual therapy in combination with SMART Arm training, with or without OT-stim, appears to be more effective than usual therapy alone for stroke survivors with severe paresis. These findings warrant further investigation into the benefits of SMART Arm training for stroke survivors with severe paresis undergoing inpatient rehabilitation during the subacute phase of recovery

Is Environmental Enrichment Ready for Clinical Application in Human Post-stroke Rehabilitation?

Environmental enrichment (EE) has been widely used as a means to enhance brain plasticity mechanisms (e.g., increased dendritic branching, synaptogenesis, etc.) and improve behavioral function in both normal and brain-damaged animals. In spite of the demonstrated efficacy of EE for enhancing brain plasticity, it has largely remained a laboratory phenomenon with little translation to the clinical setting. Impediments to the implementation of enrichment as an intervention for human stroke rehabilitation and a lack of clinical translation can be attributed to a number of factors not limited to: (i) concerns that EE is actually the “normal state” for animals, whereas standard housing is a form of impoverishment; (ii) difficulty in standardizing EE conditions across clinical sites; (iii) the exact mechanisms underlying the beneficial actions of enrichment are largely correlative in nature; (iv) a lack of knowledge concerning what aspects of enrichment (e.g., exercise, socialization, cognitive stimulation) represent the critical or active ingredients for enhancing brain plasticity; and (v) the required “dose” of enrichment is unknown, since most laboratory studies employ continuous periods of enrichment, a condition that most clinicians view as impractical. In this review article, we summarize preclinical stroke recovery studies that have successfully utilized EE to promote functional recovery and highlight the potential underlying mechanisms. Subsequently, we discuss how EE is being applied in a clinical setting and address differences in preclinical and clinical EE work to date. It is argued that the best way forward is through the careful alignment of preclinical and clinical rehabilitation research. A combination of both approaches will allow research to fully address gaps in knowledge and facilitate the implementation of EE to the clinical setting

Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce.

The first Stroke Recovery and Rehabilitation Roundtable established a game changing set of new standards for stroke recovery research. Common language and definitions were required to develop an agreed framework spanning the four working groups: translation of basic science, biomarkers of stroke recovery, measurement in clinical trials and intervention development and reporting. This paper outlines the working definitions established by our group and an agreed vision for accelerating progress in stroke recovery research

A draft map of the mouse pluripotent stem cell spatial proteome.

Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data.The authors thank Andreas Hühmer, Philip Remes, Jesse Canterbury and Graeme McAlister of Thermo Fisher Scientific, San Jose, CA, USA, for their advice regarding operation of the Orbitrap Fusion. We also thank Mike Deery for assistance with checking sample integrity on the mass spectrometers in the Cambridge Centre for Proteomics on equipment purchased via a Wellcome Trust grant (099135/Z/12/Z ), and Brian Hendrich of the Wellcome Trust-MRC Stem Cell Institute in Cambridge and Sean Munro of the MRC Laboratory of Molecular Biology in Cambridge for insightful comments about the data. AC was supported by BBSRC grant (BB/D526088/1). C.M.M. and L.G. were supported by European Union 7th Framework Program (PRIMEXS project, grant agreement number 262067), L.M.B was supported by a BBSRC Tools and Resources Development Fund (Award BB/K00137X/1), and P.C.H. was supported by an ERC Advanced Investigator grant to A.M.A. A.G. was funded through the Alexander S. Onassis Public Benefit Foundation, the Foundation for Education and European Culture (IPEP) and the Embiricos Trust Scholarship of Jesus College Cambridge. T.H. was supported by Commonwealth Split Site PhD Scholarship. T.N. was supported by an ERASMUS Placement scholarshipThis is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/ncomms999

Control intervention design for preclinical and clinical trials: consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders.</p

Lifestyle and Genetic Factors Modify Parent-of-Origin Effects on the Human Methylome

BACKGROUND: parent-of-origin effects (POE) play important roles in complex disease and thus understanding their regulation and associated molecular and phenotypic variation are warranted. Previous studies mainly focused on the detection of genomic regions or phenotypes regulated by POE. Understanding whether POE may be modified by environmental or genetic exposures is important for understanding of the source of POE-associated variation, but only a few case studies addressing modifiable POE exist. METHODS: in order to understand this high order of POE regulation, we screened 101 genetic and environmental factors such as ‘predicted mRNA expression levels’ of DNA methylation/imprinting machinery genes and environmental exposures. POE-mQTL-modifier interaction models were proposed to test the potential of these factors to modify POE at DNA methylation using data from Generation Scotland: The Scottish Family Health Study(N=2315). FINDINGS: a set of vulnerable/modifiable POE-CpGs were identified (modifiable-POE-regulated CpGs, N=3). Four factors, ‘lifetime smoking status’ and ‘predicted mRNA expression levels’ of TET2, SIRT1 and KDM1A, were found to significantly modify the POE on the three CpGs in both discovery and replication datasets. We further identified plasma protein and health-related phenotypes associated with the methylation level of one of the identified CpGs. INTERPRETATION: the modifiable POE identified here revealed an important yet indirect path through which genetic background and environmental exposures introduce their effect on DNA methylation, motivating future comprehensive evaluation of the role of these modifiers in complex diseases. FUNDING: NSFC (81971270),H2020-MSCA-ITN(721815), Wellcome (204979/Z/16/Z,104036/Z/14/Z), MRC (MC_UU_00007/10, MC_PC_U127592696), CSO (CZD/16/6,CZB/4/276, CZB/4/710), SFC (HR03006), EUROSPAN (LSHG-CT-2006-018947), BBSRC (BBS/E/D/30002276), SYSU, Arthritis Research UK, NHLBI, NIH