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Background: Interest in how stroke survivors might be better supported to manage life after stroke has grown rapidly in recent years, with a particular emphasis on enabling 'self-management'. Post-stroke communication difficulties may pose a unique barrier to longer term adaptation and adjustment. It is important to understand how stroke survivors with communication difficulties manage life after stroke and what support may be needed to facilitate this process. Aims: To explore how stroke survivors with communication difficulties manage life after stroke in the first year. Methods & Procedures: A cross-sectional qualitative study involving in-depth semi-structured interviews with stroke survivors with communication difficulties (aphasia, dysarthria or apraxia of speech) and/or their family members at single time points during the first year post-stroke. A total of 21 participants (14 stroke survivors and seven family members) took part in interviews for the study. Interview data were analysed using thematic analysis. Outcome & Results: A total of six themes were identified: (1) strategies to manage changes to communication; (2) testing communication outside of the home; (3) balancing support and independence; (4) hope for recovery; (5) obtaining support from healthcare professionals; and (6) adapting activities and keeping busy. Stroke survivors with communication difficulties and their family members undertook significant work (practical, relational, emotional) to manage their condition. Adaptation and adjustment was often facilitated by 'doing'; testing out which activities could be managed independently and which required additional support. Some stroke survivors and their family members demonstrated considerable resourcefulness and creativity in developing strategies to manage their communication difficulties. Despite the work undertaken, many expressed a lack of confidence in their ability and feelings of powerlessness and abandonment at the point of discharge from community services. Conclusions & Implications: Stroke survivors and their family members develop personally meaningful and context-specific strategies to adjust to and manage life after stroke. Future interventions should recognize, support and build upon the active work already undertaken by stroke survivors with communication difficulties and their families. Further support before and around the point of discharge from community services may be needed to help build confidence and skills to manage in the longer term. The benefit of a supported self-management approach for stroke survivors with communication difficulties should be further investigated.

Introduction Community-based services to sustain independence for older people have varying configurations. A typology of these interventions would improve service provision and research by providing conceptual clarity and enabling the identification of effective configurations. We aimed to produce such a typology. Method We developed our typology by qualitatively synthesising community-based complex interventions to sustain independence in older people, evaluated in randomised controlled trials (RCTs), in four stages: (i) systematically identifying relevant RCTs; (ii) extracting descriptions of interventions (including control) using the Template for Intervention Description and Replication; (iii) generating categories of key intervention features and (iv) grouping the interventions based on these categories. PROSPERO registration: CRD42019162195. Results Our search identified 129 RCTs involving 266 intervention arms. The Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology comprises 14 action components and 5 tailoring components. Action components include procedures for treating patients or otherwise intended to directly improve their outcomes; regular examples include formal homecare; physical exercise; health education; activities of daily living training; providing aids and adaptations and nutritional support. Tailoring components involve a process that may result in care planning, with multiple action components being planned, recommended or prescribed. Multifactorial action from care planning was the most common tailoring component. It involves individualised, multidomain assessment and management, as in comprehensive geriatric assessment. Sixty-three different intervention types (combinations) were identified. Conclusions Our typology provides an empirical basis for service planning and evidence synthesis. We recommend better reporting about organisational aspects of interventions and usual care. [ABSTRACT FROM AUTHOR]

WebStructural details of how oncogenic human papilloma viruses induce cancer by targeting the tumour suppressor p53 for ubiquitin-mediated degradation. Viral hijack of p53 tumour suppressor Oncogenic human papillomaviruses induce cancer by targeting the tumour suppressor p53 for ubiquitin-mediated degradation. Katia Zanier and colleagues now reveal structural details of how this viral hijacking occurs. They solve the structure of a ternary complex revealing the interaction between the HPV16 oncoprotein E6, the LxxLL motif of the cellular ubiquitin ligase E6AP, and the core domain of p53. The p53 pro-apoptotic tumour suppressor is mutated or functionally altered in most cancers. In epithelial tumours induced by 'high-risk' mucosal human papilloma viruses, including human cervical carcinoma and a growing number of head-and-neck cancers.sup.1, p53 is degraded by the viral oncoprotein E6 (ref. 2). In this process, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP.sup.3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (ref. 4). Neither E6 nor E6AP are separately able to recruit p53 (refs 3, 5), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumour suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against oncogenesis mediated by human papilloma virus., Author(s): Denise Martinez-Zapien [sup.1] , Francesc Xavier Ruiz [sup.2] , Juline Poirson [sup.1] , André Mitschler [sup.2] , Juan Ramirez [sup.1] , Anne Forster [sup.1] , Alexandra Cousido-Siah [sup.2] , [...]

Aim: The aim of the study was to reach consensus on modifiable risk factors for a novel system of care to address Manifestations of Frailty in hospitalized older adults. Design: Consensus study. Method: A modified nominal group technique, incorporating expert group face‐to‐face interaction, review of existing evidence and pre/post‐meeting questionnaire completion was undertaken November 2019–February 2020. Results: Seventy‐one risk factors, within seven risk factor domains (pain, medication, fluid and nutrition intake, mobility, elimination, infection, additional patient factors) were considered. It was agreed that 44 risk factors incorporating patient, organizational and environmental risk factors were modifiable and should be included in a novel system of care. [ABSTRACT FROM AUTHOR]