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Professional advisory groups, with patient and public involvement (PPI) representatives, can be used for co-production within research projects. This paper aims to document the benefits and challenges of undertaking stakeholder and participant engagement for an implementation research project within NHS (National Health Service) Wales. A patient focused research project, initiated by clinicians, on the use of patient empowerment tools within standard patient care, used a professional advisory group to identify appropriate tools to use within the research proposal. The professional advisory group was made up of therapists, NHS stakeholders, academics and PPI representatives. A hybrid-meeting style was employed to optimise participation for all members of the group. Benefits of the professional advisory group included increased engagement and ownership of the study due to co-creation, and obtaining important contextual information and lived experience. However, challenges included keeping the discussion on topic due to pre-conceived agendas, pleasing everyone in the room due to varied backgrounds, and technological issues. Future professional advisory groups should consider how to facilitate the full involvement of PPI representatives within the discussion and having a variety of resources to present the topic of discussion. Furthermore, clearly communicating what the purpose and direction of the research project is and how it fits into the wider system, should be carefully considered. Overall, it was recognised that the professional advisory group was of significant value to shape the research proposal. Due to the situational challenges faced by healthcare professional within the NHS and preconceived ideas for solutions, it is hoped that by involving stakeholders early in the process there will be greater acceptance and usability of the research findings. [ABSTRACT FROM AUTHOR]

The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have revealed that a further action of insulin is to mediate the dispersal of GLUT4 molecules away from the site of GLUT4 vesicle fusion with the plasma membrane. Although shown in adipocytes, whether insulin-stimulated dispersal occurs in other cells and/or is exhibited by other proteins remains a matter of debate. Here we show that insulin stimulates GLUT4 dispersal in the plasma membrane of adipocytes, induced pluripotent stem cell-derived cardiomyocytes and HeLa cells, suggesting that this phenomenon is specific to GLUT4 expressed in all cell types. By contrast, insulin-stimulated dispersal of TfR was not observed in HeLa cells, suggesting that the mechanism may be unique to GLUT4. Consistent with dispersal being an important physiological mechanism, we observed that insulin-stimulated GLUT4 dispersal is reduced under conditions of insulin resistance. Adipocytes of different sizes have been shown to exhibit distinct metabolic properties: larger adipocytes exhibit reduced insulin-stimulated glucose transport compared to smaller cells. Here we show that both GLUT4 delivery to the plasma membrane and GLUT4 dispersal are reduced in larger adipocytes, supporting the hypothesis that larger adipocytes are refractory to insulin challenge compared to their smaller counterparts, even within a supposedly homogeneous population of cells. [ABSTRACT FROM AUTHOR]

With 2.3 million individuals incarcerated in the United States, incarceration remains a pressing social influence on health. While risk factors for incarceration are known, research has been slow to identify protective factors. Characterizing adolescent protective and risk factors for incarceration outcomes can inform interventions to prevent incarceration. Using survey data from the National Longitudinal Study of Adolescent to Adult Health, we tested the influence of adolescent risk and protective factors for incarceration of young people. We used ordinal logistic regressions, investigating the relationship between adolescent characteristics (wave I, grades 7–12) with two outcomes: incarceration onset (no incarceration, onset of incarceration as a juvenile, and onset of incarceration as an adult) and incarceration frequency (never incarcerated, incarcerated once, incarcerated more than once) during adolescence and into adulthood (N = 12,136, wave IV, ages 24–32). Adolescent protective factors against incarceration onset and higher incarceration frequency centered on education, including a higher grade point average and a higher likelihood of having future plans to attend college. Risk factors included disruptive behavior, physical or sexual abuse in childhood, parental incarceration, and living with a stepfather figure. Stratified analyses suggested that Latinos may have unique risk profiles compared to African American and White youth. The educational system may be a locus for protective interventions promoting academic achievement and educational aspirations. Understanding both incarceration risk and protective factors may allow interventions to be tailored appropriately. Highlights: Nationally representative study examined risk factors and protective factors in adolescence associated with incarceration. Protective factors in adolescence centered on educational success and future educational plans. Latino youth appeared to have differences in incarceration risk factors as compared to youth from other racial groups that warrant further examination. Educational success may be a locus for the prevention of incarceration in adolescence and adulthood. [ABSTRACT FROM AUTHOR]

In muscle and fat cells, insulin stimulates the delivery of the glucose transporter GLUT4 from an intracellular location to the cell surface, where it facilitates the reduction of plasma glucose levels. Understanding the molecular mechanisms that mediate this translocation event involves integrating our knowledge of two fundamental processes ? the signal transduction pathways that are triggered when insulin binds to its receptor and the membrane transport events that need to be modified to divert GLUT4 from intracellular storage to an active plasma membrane shuttle service. [ABSTRACT FROM AUTHOR]

Key to whole body glucose homeostasis is the ability of fat and muscle cells to sequester the facilitative glucose transporter GLUT4 in an intracellular compartment from where it can be mobilized in response to insulin. We have previously demonstrated that this process requires ubiquitination of GLUT4 while numerous other studies have identified several molecules that are also required, including the insulin-responsive aminopeptidase IRAP and its binding partner, the scaffolding protein tankyrase. In addition to binding IRAP, Tankyrase has also been shown to bind the deubiquinating enzyme USP25. Here we demonstrate that USP25 and Tankyrase interact, and colocalise with GLUT4 in insulin-sensitive cells. Furthermore depletion of USP25 from adipocytes reduces cellular levels of GLUT4 and concomitantly blunts the ability of insulin to stimulate glucose transport. Collectively, these data support our model that sorting of GLUT4 into its insulin-sensitive store involves a cycle of ubiquitination and subsequent deubiquitination. [ABSTRACT FROM AUTHOR]