Development of a psychological intervention for fatigue after stroke

Post-stroke fatigue (PSF) is common and distressing, but there is insufficient evidence to recommend any effective treatment for it. Psychological interventions are effective in treating fatigue in other conditions. This paper describes the development and evaluation of the feasibility of a psychological intervention for PSF.Based on psychological correlates of PSF and evidence-based psychological interventions for fatigue in other medical conditions, we developed a manualised psychological intervention for PSF, with input from stroke clinicians, psychological therapists, and stroke survivors. The intervention was delivered by a clinical psychologist to 12 participants with PSF to test its acceptability and feasibility. According to the feedback from participants and therapists, the intervention was refined for future use.The intervention consisted of six individual, face-to-face treatment sessions, and one follow-up, telephone-delivered booster session. It included psycho-education and discussion of strategies to promote physical and social activities and to challenge unhelpful thoughts. Four participants dropped out and the remaining eight participants completed the intervention. These eight participants also completed all assessments and feedback and reported fatigue levels as lower at the end of the study than at the baseline. All participants reported favourable opinions on the intervention and suggested that the last two treatment sessions be combined and the booster session be delivered in person as opposed to telephone.This psychological intervention was acceptable to stroke patients and was feasible in the local health service. These findings suggest that a randomised controlled trial to test efficacy is warranted

Revealing Higher Order Protein Structure Using Mass Spectrometry

International audienceThe development of rapid, sensitive, and accurate mass spectrometric methods for measuring peptides, proteins, and even intact protein assemblies has made mass spectrometry (MS) an extraordinarily enabling tool for structural biology. Here, we provide a personal perspective of the increasingly useful role that mass spectrometric techniques are exerting during the elucidation of higher order protein structures. Areas covered in this brief perspective include MS as an enabling tool for the high resolution structural biologist, for compositional analysis of endogenous protein complexes, for stoichiometry determination, as well as for integrated approaches for the structural elucidation of protein complexes. We conclude with a vision for the future role of MS-based techniques in the development of a multi-scale molecular microscope

Effect of Exercise Interventions on Health-Related Quality of Life After Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis

Exercise interventions have been shown to help physical fitness, walking and balance after stroke, but data is lacking on whether such interventions lead to improvements in health-related quality of life (HRQoL). In this systematic review and meta-analysis, thirty randomised controlled trials (n=1,836 patients) were found from PubMed, OVID MEDLINE, Web of Science, CINAHL, SCOPUS, The Cochrane Library and TRIP databases when searched from 1966 to Feb 2020, that examine the effects of exercise interventions on HRQoL after strokem or transient ischaemic attack (TIA). Exercise interventions resulted in small to moderate beneficial effects on HRQoL at intervention end (standardised mean difference (SMD) -0.23; 95% CI -0.40 to -0.07) that appeared to diminish at longer term follow up (SMD -0.11; 95%CI -0.26 to 0.04). Exercise was associated with moderate improvements in physical health (SMD -0.33; 95% CI -0.61 to -0.04) and mental health (SMD -0.29; 95% CI -0.49 to -0.09) domains of HRQoL while effects on social or cognitive composites showed little difference. Interventions that were initiated within 6 months, lasted at least 12 weeks in duration, involved at least 150 minutes per week, and included resistance training appeared most effective. Exercise can lead to moderate beneficial effects on HRQoL and should be considered an integral part of stroke rehabilitatio

Protocol 'Omgaan met beperkte belastbaarheid: Behandelprotocol voor ambulante hersenletselpatiënten met (ernstige) vermoeidheid'

Helft van patiënten met NAH last van vermoeidheid: Vermoeidheid is een van de meest voorkomende verschijnselen bij niet-aangeboren hersenletsel (NAH): ongeveer de helft van alle patiënten krijgt ermee te maken. Vermoeidheid heeft grote impact op alle terreinen van het leven, zoals werk, sociale relaties en hobby's. Hiernaast beïnvloedt vermoeidheid vaak ook de concentratie, het geheugen en de stemming. Hoe besteed je de beschikbare energie efficiënter? Het uitgangspunt van dit behandelprotocol is dat de vermoeidheid primair door het hersenletsel zelf wordt veroorzaakt. Het doel van de behandeling is dan ook niet om het energieniveau te herstellen tot het premorbide niveau, maar om de beschikbare energie efficiënter te besteden en patiënten te leren omgaan met de bestaande vermoeidheid. Meer energie door een betere lichamelijke conditie: De behandeling 'Omgaan met beperkte belastbaarheid' bestaat uit twee behandelsporen: een cognitieve behandeling en een Graded Activity Training. De Graded Activity Training richt zich op het vergroten van de lichamelijke conditie van de cliënt. Hierdoor hebben de deelnemers meer energie voor hun dagelijkse bezigheden, waardoor de vermoeidheid structureel vermindert. Opbouw van de behandeling: De behandeling duurt twaalf weken en wordt in kleine groepen (maximaal vier deelnemers) gegeven. De cognitieve behandeling vindt eenmaal per week plaats, gedurende twee uur. Deze kan worden gegeven door een psycholoog met neuropsychologische en cognitief gedragstherapeutische kennis en ervaring. De Graded Activity Training vindt tweemaal per week gedurende anderhalf uur plaats. Deze wordt gegeven door een fysiotherapeut met kennis van NAH. Beide behandelsporen omvatten een nauwgezet behandelprotocol en wekelijkse huiswerkopdrachten

GPCR endocytosis confers uniformity in responses to chemically distinct ligands

The ability of chemically distinct ligands to produce different effects on the same G protein-coupled receptor (GPCR) has interesting therapeutic implications, but, if excessively propagated downstream, would introduce biologic noise compromising cognate ligand detection. We asked whether cells have the ability to limit the degree to which chemical diversity imposed at the ligand-GPCR interface is propagated to the downstream signal. We carried out an unbiased analysis of the integrated cellular response elicited by two chemically and pharmacodynamically diverse β-adrenoceptor agonists, isoproterenol and salmeterol. We show that both ligands generate an identical integrated response, and that this stereotyped output requires endocytosis. We further demonstrate that the endosomal β2-adrenergic receptor signal confers uniformity on the downstream response because it is highly sensitive and saturable. Based on these findings, we propose that GPCR signaling from endosomes functions as a biologic noise filter to enhance reliability of cognate ligand detection