FSP27 (fat-specific protein 27) is a member of the cell deathinducing DNA fragmentation factor-␣-like effector (CIDE) family. Although Cidea and Cideb were initially characterized as activators of apoptosis, recent studies have demonstrated important metabolic roles for these proteins. In this study, we investigated the function of another member of this family, FSP27 (Cidec), in apoptosis and adipocyte metabolism. Although overexpression of FSP27 is sufficient to increase apoptosis of 293T and 3T3-L1 cells, more physiological levels of expression stimulate spontaneous lipid accumulation in several cell types without induction of adipocyte genes. Increased triacylglycerol is likely due to decreased ␤-oxidation of nonesterified fatty acids. Altered flux of fatty acids into triacylglycerol may be a direct effect of FSP27 function, which is localized to lipid droplets in 293T cells and 3T3-L1 adipocytes. Stable knockdown of FSP27 during adipogenesis of 3T3-L1 cells substantially decreases lipid droplet size, increases mitochondrial and lipid droplet number, and modestly increases glucose uptake and lipolysis. Expression of FSP27 in subcutaneous adipose tissue of a human diabetes cohort decreases with total fat mass but is not associated with measures of insulin resistance (e.g. homeostasis model assessment). Together, these data indicate that FSP27 binds to lipid droplets and regulates their enlargement.The cell death-inducing DNA fragmentation factor-␣-like effector (CIDE) 5 family of proteins shares sequence similarity with DNA fragmentation factors and was initially characterized as mitochondrial activators of apoptosis (1, 2). However, strong metabolic phenotypes of mice lacking Cidea and Cideb indicate that this family plays critical roles in energy balance (3, 4). Cidea knock-out mice are lean and resistant to diet-induced obesity because of increased lipolysis and mitochondrial uncoupling in brown adipose tissue (3). Although expression of Cidea is limited to brown adipocytes in mice, humans express CIDE-A in white adipose tissue, where lower levels are observed with obesity and insulin resistance (5, 6). Although a coding variant of CIDE-A, V115F, is associated with human obesity (7), knockdown of CIDE-A in human adipocytes enhances lipolysis (5).Cideb knock-out mice are also lean and resistant to diet-induced obesity; however, this family member is expressed highly in liver, and the phenotype is because of decreased hepatic lipogenesis, increased fatty acid oxidation, and increased whole body energy expenditure (4). Thus, through a number of mechanisms, the CIDE family appears to have important roles in lipid metabolism. FSP27 (fat-specific protein of 27 kDa or Cidec) is the third member of the CIDE family. FSP27 was identified prior to the other family members based upon induction during adipogenesis (8). CIDE-3, the human version of FSP27, was characterized as 66% homologous to mouse and as an activator of apoptosis when expressed in 293T cells (9). However, the lack of function ascribed to FSP27 limit...

Background Older adults with multimorbidity and complex care needs (CCN) are among those most likely to experience frequent care transitions between settings, particularly from hospital to home. Transition periods mark vulnerable moments in care for individuals with CCN. Poor communication and incomplete information transfer between clinicians and organizations involved in the transition from hospital to home can impede access to needed support and resources. Establishing digitally supported communication that enables person-centered care and supported self-management may offer significant advantages as we support older adults with CCN transitioning from hospital to home. Objective This protocol outlines the plan for the development, implementation, and evaluation of a Digital Bridge co-designed to support person-centered health care transitions for older adults with CCN. The Digital Bridge builds on the foundation of two validated technologies: Care Connector, designed to improve interprofessional communication in hospital, and the electronic Patient-Reported Outcomes (ePRO) tool, designed to support goal-oriented care planning and self-management in primary care settings. This project poses three overarching research questions that focus on adapting the technology to local contexts, evaluating the impact of the Digital Bridge in relation to the quadruple aim, and exploring the potential to scale and spread the technology. Methods The study includes two phases: workflow co-design (phase 1), followed by implementation and evaluation (phase 2). Phase 1 will include iterative co-design working groups with patients, caregivers, hospital providers, and primary care providers to develop a transition workflow that will leverage the use of Care Connector and ePRO to support communication through the transition process. Phase 2 will include implementation and evaluation of the Digital Bridge within two hospital systems in Ontario in acute and rehab settings (600 patients: 300 baseline and 300 implementation). The primary outcome measure for this study is the Care Transitions Measure–3 to assess transition quality. An embedded ethnography will be included to capture context and process data to inform the implementation assessment and development of a scale and spread strategy. An Integrated Knowledge Translation approach is taken to inform the study. An advisory group will be established to provide insight and feedback regarding the project design and implementation, leading the development of the project knowledge translation strategy and associated outputs. Results This project is underway and expected to be complete by Spring 2024. Conclusions Given the real-world implementation of Digital Bridge, practice changes in the research sites and variable adherence to the implementation protocols are likely. Capturing and understanding these considerations through a mixed-methods approach will help identify the range of factors that may influence study results. Should a favorable evaluation suggest wide adoption of the proposed intervention, this project could lead to positive impact at patient, clinician, organizational, and health system levels. Trial Registration ClinicalTrials.gov NCT04287192; https://clinicaltrials.gov/ct2/show/NCT04287192 International Registered Report Identifier (IRRID) PRR1-10.2196/20220

Twelve principles to support caregiver engagement in health care systems and health research Cover Page Footnote Ethics approval and consent to participate: Not applicable Consent for publication: Not applicable Availability of data and material: Not applicable Competing interests: The authors declare that they have no competing interests Funding: This project was funded by a Planning Grant from the Canadian Institutes of Health Research [Fund number410008186] Authors' contributions: KK conceptualized the study and took the lead in writing the manuscript. KMK revised the manuscript versions. KK, AP and JG lead the acquisition of data and the data analysis. KMK, CAA and JP assisted with the interpretation of the data, the addition of concrete examples and insured that the text was readable for a range of audiences. All authors approved the final manuscript. Acknowledgements: The authors thank the participants of the two day stakeholder meeting. The 48 important perspectives that came together and the vast experiences shared, culminated into the insights shared in this paper. The authors are also grateful to the Change Foundation, a policy think tank in Toronto, Ontario, Canada who generously provided the space to hold the meeting that brought together so many individuals to discuss the important topics raised in this paper.

BACKGROUND Older adults with multi-morbidity and complex care needs (CCN) are among those most likely to experience frequent care transitions between settings, particularly from hospital to home. Transition periods mark vulnerable moments in care for individuals with CCN. Poor communication and incomplete information transfer between the various clinicians and organizations involved in the transition from hospital to home can impede access to needed support and resources. Establishing digitally supported communication that enables person-centred care and supported self-management may offer significant advantages as we support older adults with CCN transitioning from hospital to home. OBJECTIVE This protocol outlines the plan for the development, implementation and evaluation of a Digital Bridge co-designed to support person-centred health care transitions for older adults with CCN. The Digital Bridge builds on the foundation of two validated technologies; Care Connector, designed to improve inter-professional communication in hospital, and the electronic Patient Reported Outcomes (ePRO) tool, designed to support goal-oriented care planning and self-management in primary care settings. This project poses three overarching research questions that focus on adapting the technology to local contexts, evaluating the impact of the Digital Bridge in relation to the quadruple aim, and exploring the potential to scale and spread the technology. METHODS The study includes two phases: workflow co-design (PHASE 1), followed by implementation and evaluation (PHASE 2). PHASE 1 will include iterative co-design working groups with patients, caregivers, hospital providers and primary care providers to develop a transition workflow that will leverage the use of Care Connector and ePRO to support communication through the transition process. PHASE 2 will include implementation and evaluation of the Digital Bridge within one acute hospital system and one rehab hospital system in Ontario (n=600 patients; 300 baseline, 300 implementation). The primary outcome measure for this study is the Care Transitions Measure-3 to assess transition quality. An embedded ethnography will also be included to capture context and process data to inform the implementation assessment and the development of a scale and spread strategy. An Integrated Knowledge Translation approach is taken to inform the study. An Advisory Group will be established to provide insight and feedback regarding the project design and implementation, leading the development of the project KT strategy and associated outputs. RESULTS TBC CONCLUSIONS Given the ‘real world’ implementation of Digital Bridge, there will be several practice changes in the research sites and variable adherence to the implementation protocols. Capturing and understanding these considerations is essential in order to identity the range of factors that may influence study Adopting a pragmatic trial design with an embedded case study will provide insights into outcomes as well as the mechanisms that are likely driving those outcomes. This study has been funded by the Canadian Institute for Health Research through a Team Grant in Transitions in Care (FRN- 165733).