20 research outputs found

    Implementing (and evaluating) peer support with people living with noncommunicable diseases in humanitarian settings.

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    In line with the peer reviewers comments, the authors have added highlights in stead of an abstract. It was felt that it was better able to capture the findings and is more in line with the paper's target audience

    Heart Failure-Inducible Gene Therapy Targeting Protein Phosphatase 1 Prevents Progressive Left Ventricular Remodeling

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    BACKGROUND: The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice. METHODS: We created an adeno-associated virus 9 (AAV9) vector encoding PP1β short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months. RESULTS: In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1β by 25% in the myocardium. Inducible PP1βshRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1βshRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months. CONCLUSION: Heart failure-inducible molecular targeting of PP1β has potential as a novel therapeutic strategy for heart failure

    Complexity in Graduate Medical Education: A Collaborative Education Agenda for Internal Medicine and Geriatric Medicine

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    Internal medicine residents today face significant challenges in caring for an increasingly complex patient population within ever-changing education and health care environments. As a result, medical educators, health care system leaders, payers, and patients are demanding change and accountability in graduate medical education (GME). A 2012 Society of General Internal Medicine (SGIM) retreat identified medical education as an area for collaboration between internal medicine and geriatric medicine. The authors first determined a short-term research agenda for resident education by mapping selected internal medicine reporting milestones to geriatrics competencies, and listing available sample learner assessment tools. Next, the authors proposed a strategy for long-term collaboration in three priority areas in clinical medicine that are challenging for residents today: (1) team-based care, (2) transitions and readmissions, and (3) multi-morbidity. The short-term agenda focuses on learner assessment, while the long-term agenda allows for program evaluation and improvement. This model of collaboration in medical education combines the resources and expertise of internal medicine and geriatric medicine educators with the goal of increasing innovation and improving outcomes in GME targeting the needs of our residents and their patients
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