Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction

Published online: 11 September 2023Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1-/-) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3-6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.Lucy A. Murtha, Sean A. Hardy, Nishani S. Mabotuwana, Mark J. Bigland, Taleah Bailey, Kalyan Raguram, Saifei Liu, Doan T. Ngo, Aaron L. Sverdlov, Tamara Tomin, Ruth Birner, Gruenberger, Robert D. Hume, Siiri E. Iismaa, David T. Humphreys, Ralph Patrick, James J. H. Chong, Randall J. Lee, Richard P. Harvey, Robert M. Graham, Peter P. Rainer and Andrew J. Boyl

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The effects of governments on management and organization

We review and integrate existing research from organization theory, strategy, organizational behavior, economics, sociology and political science on the effects of governments on organization and management, with a focus on how governing ideology and government capability influence independent organizations’ forms, strategies, and their participants’ behavior. When brought together these works suggest significant research opportunities in the fields of management and organization, as well as new perspectives on public policy challenges. Several avenues of potentially profitable empirical research include more attention to the influence of government on corporate strategies, more research on the strategies of pursuing corruption and government capture for competitive advantage, the role of government in fostering innovation and the growth of entrepreneurial organizations, and extra‐organizational contextual effects on managerial and employee organizational behavior. Possible public policy implications are illustrated with an application to the role of organizations in national wealth generation and dispersion

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar