The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.

An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human "protective" proteins, e.

Testing the Effectiveness of a Mobile Smartphone App Designed to Improve the Mental Health of Junior Physicians: Protocol for a Randomized Controlled Trial.

Background: Shift (Black Dog Institute) is the first mobile health smartphone app created to support the mental health of junior physicians. Junior physicians experience demanding work conditions, leading to high levels of psychological distress and burnout. However, they are often concerned about the potential career impacts of seeking mental health support.

A mentally healthy framework to guide employers and policy makers.

Mental health problems among the working population represent a growing concern with huge impacts on individuals, organizations, compensation authorities, and social welfare systems. The workplace presents both psychosocial risks and unique opportunities for intervention. Although there has been rapid expansion of workplace mental health interventions over recent decades, clear direction around appropriate, evidence-based action remains limited.

Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression.

Background: Xenotransplantation has made significant advances recently using pigs genetically engineered to remove carbohydrate antigens, either alone or with addition of various human complement, coagulation, and anti-inflammatory ''transgenes''. Here we evaluated results associated with gene-edited (GE) pig hearts transplanted in baboons using an established costimulation-based immunosuppressive regimen and a cold-perfused graft preservation technique.

Methods: Eight baboons received heterotopic abdominal heart transplants from 3-GE (GalKO.

Systematic Search and Scoping Review of Physicians' Intolerance of Uncertainty and Medical Decision-Making Uncertainties During the COVID-19 Pandemic: A Summary of the Literature and Directions for Future Research.

Pandemic-related uncertainties and intolerance of uncertainty (IU) could negatively affect physicians' well-being and functioning, being associated with experiences of distress and problematic decision-making processes. To summarize the available quantitative and qualitative evidence of physicians' IU and decisional uncertainty during COVID-19 and problems associated with it, a systematic search was conducted to identify all relevant articles describing physician uncertainty with regard to medical decision making and well-being in COVID-19 pandemic conditions. Medical, psychological, and preprint databases were searched.