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In the context of normal cell turnover, apoptosis is a natural phenomenon involved in making essential life and death decisions. Apoptotic pathways balance signals which promote cell death (pro-apoptotic pathways) or counteract these signals (anti-apoptotic pathways). We proposed that changes in anti-apoptotic proteins would occur during mammalian hibernation to aid cell preservation during prolonged torpor under cellular conditions that are highly injurious to most mammals (e.g. low body temperatures, ischemia). Immunoblotting was used to analyze the expression of proteins associated with pro-survival in six tissues of thirteen-lined ground squirrels, Ictidomys tridecemlineatus. The brain showed a concerted response to torpor with significant increases in the levels of all anti-apoptotic targets analyzed (Bcl-2, Bcl-xL, BI-1, Mcl-1, cIAP1/2, xIAP) as well as enhanced phosphorylation of Bcl-2 at S70 and T56. Heart responded similarly with most anti-apoptotic proteins elevated significantly during torpor except for Bcl-xL and xIAP that decreased and Mcl-1 that was unaltered. In liver, BI-1 increased whereas cIAP1/2 decreased. In kidney, there was an increase in BI-1, cIAP and xIAP but decreases in Bcl-xL and p-Bcl-2(T56) content. In brown adipose tissue, protein levels of BI-1, cIAP1/2, and xIAP decreased significantly during torpor (compared with euthermia) whereas Bcl-2, Bcl-xL, Mcl-1 were unaltered; however, Bcl-2 showed enhanced phosphorylation at Thr56 but not at Ser70. In skeletal muscle, only xIAP levels changed significantly during torpor (an increase). The data show that anti-apoptotic pathways have organ-specific responses in hibernators with a prominent potential role in heart and brain where coordinated enhancement of anti-apoptotic proteins occurred in response to torpor.

In this study, RSL had lower costs than WGL, allowed for more efficient use of radiology scheduling and resources, and had shorter wait times for patients on their day of surgery. In addition, RSL led to fewer vasovagal reactions at insertion. Therefore, RSL should be used instead of WGL given the reduced cost, decreased need of human resources, improved efficiency, and potential benefits to the patient experience.

ObjectivesThe purpose of this literature review was to identify potential ways in which undergraduate medical anatomy education may be relevant to the CanMEDS Roles, a competency-based framework used throughout Canadian medical training. MethodsA scoping review of medical education literature was conducted in March 2017 for English language publications that included key words related to anatomy education and to key competencies formally described for each of the Roles in the CanMEDS 2015 framework. Indicated benefits were then collated, characterized, and synthesized for each CanMEDS Role. ResultsThere were 71 studies identified describing original findings. Perceived benefits of anatomy education were most often identified for competencies related to the Medical Expert Role. Multiple studies also cited benefits related to the Scholar, Professional and Collaborator Roles. There was a lack of literature related to the Health Advocate, Communicator, and Leader Roles. The majority of benefits defined in the literature were limited to student perceptions rather than objectively measured outcomes. ConclusionsThere is some evidence to suggest that anatomy education can facilitate the development of core competencies related to several CanMEDS Roles, outside of simply developing medical knowledge in the Medical Expert Role. Future studies need to develop methods to objectively assess outcomes related to these competencies.

Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in transplantation. Islet transplantation provides a unique opportunity to study the critical immunological crossroads between auto and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that cellular transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet transplantation.

Extracorporeal circulation (ECC) systems, including cardiopulmonary bypass, and extracorporeal membrane oxygenation have been an irreplaceable part of the cardiothoracic surgeries, and treatment of critically ill patients with respiratory and/or cardiac failure for more than half a century. During the recent decades, the concept of extracorporeal circulation has been extended to isolated machine perfusion of the donor organ including thoracic organs (ex-situ organ perfusion, ESOP) as a method for dynamic, semi-physiologic preservation, and potential improvement of the donor organs. The extracorporeal life support systems (ECLS) have been lifesaving and facilitating complex cardiothoracic surgeries, and the ESOP technology has the potential to increase the number of the transplantable donor organs, and to improve the outcomes of transplantation. However, these artificial circulation systems in general have been associated with activation of the inflammatory and oxidative stress responses in patients and/or in the exposed tissues and organs. The activation of these responses can negatively affect patient outcomes in ECLS, and may as well jeopardize the reliability of the organ viability assessment, and the outcomes of thoracic organ preservation and transplantation in ESOP. Both ECLS and ESOP consist of artificial circuit materials and components, which play a key role in the induction of these responses. However, while ECLS can lead to systemic inflammatory and oxidative stress responses negatively affecting various organs/systems of the body, in ESOP, the absence of the organs that play an important role in oxidant scavenging/antioxidative replenishment of the body, such as liver, may make the perfused organ more susceptible to inflammation and oxidative stress during extracorporeal circulation. In the present manuscript, we will review the activation of the inflammatory and oxidative stress responses during ECLP and ESOP, mechanisms involved, clinical implications, and the interventions for attenuating these responses in ECC.

Machine perfusion (MP) is at the forefront of innovation in modern liver transplantation. Several approaches, mainly varying the temperature at which the graft is perfused, have shown benefit in preclinical models and nonrandomized clinical trials. Given the recent randomized controlled trial by Nasralla et al demonstrating the efficacy of normothermic MP over static cold storage, MP is likely here to stay for the foreseeable future. We are only beginning to explore the possibilities of this technology, including the prediction of graft function and modification of suboptimal livers. This has the potential to both increase the donor pool and improve the quality of grafts provided to recipients. Beyond transplantation, there may be a role for MP in extracorporeal liver support, cancer research and therapeutics, and pharmaceutical testing. In this review, we provide the rationale and explore the relevant preclinical studies that support the use of ex situ liver perfusion for these extended applications.

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