Emerging roles of melanocortin receptor accessory proteins (MRAP and MRAP2) in physiology and pathophysiology.

Melanocortin-2 receptor accessory protein (MRAP) has an unusual dual topology and influences the expression, localisation, signalling and internalisation of the melanocortin receptor 2 (MC ); the adrenocorticotropic hormone (ACTH) receptor. Mutations in MRAP are associated with familial glucocorticoid deficiency type-2 and evidence is emerging of the importance of MRAP in adrenal development and ACTH signalling. Human MRAP has two functional splice variants: MRAP-α and MRAP-β, unlike MRAP-β, MRAP-α has little expression in brain but is highly expressed in ovary. MRAP2, identified through whole human genome sequence analysis, has approximately 40% sequence homology to MRAP. MRAP2 facilitates MC2 localisation to the cell surface but not ACTH signalling. MRAP and MRAP2 have been found to regulate the surface expression and signalling of all melanocortin receptors (MC ). Additionally, MRAP2 moderates the signalling of the G-protein coupled receptors (GCPRs): orexin, prokineticin and GHSR1a; the ghrelin receptor. Whilst MRAP appears to be mainly involved in glucocorticoid synthesis, an important role is emerging for MRAP2 in regulating appetite and energy homeostasis. Transgenic models indicate the importance of MRAP in adrenal gland formation. Like MC3R and MC4R knockout mice, MRAP2 knockout mice have an obese phenotype. In vitro studies indicate that MRAP2 enhances the MC3 and MC4 response to the agonist αMSH, which, like ACTH, is produced through precursor polypeptide proopiomelanocortin (POMC) cleavage. Analysis of cohorts of individuals with obesity have revealed several MRAP2 genetic variants with loss of function mutations which are causative of monogenic hyperphagic obesity with hyperglycaemia and hypertension. MRAP2 may also be associated with female infertility. This review summarises current knowledge of MRAP and MRAP2, their influence on GPCR signalling, and focusses on pathophysiology, particularly familial glucocorticoid deficiency type-2 and obesity. [Abstract copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Implementierung eines hybriden Lenksystems in einen Versuchs- Lkw, sowie die Überprüfung der Funktionsspezifikation anhand geeigneter Testmethoden

Inhalt dieser Diplomarbeit ist die Vorbereitung und Durchführung von Tests zur Funktionserprobung eines hybriden Lenksystems in einem Versuchs-Lkw. Das hybride Lenksystem besteht aus einer hydraulisch und elektrisch unterstützten Kugelumlauflenkung. Diese Lenkung bietet die Möglichkeit eines aktiven Lenkeingriffs und wurde für den Einsatz eines Fahrerassistenzsystems entwickelt. Eingangs werden das System an sich, das dahinterstehende Fahrerassistenzsystem und die Entwicklungswerkzeuge beschrieben. Im weiteren Verlauf werden der Aufbau und die Durchführung einzelner Versuchsreihen vorgestellt und ausgewertet. Das angewendete Testmanagement wird beschrieben und die Erstellung der Testspezifikation für weitere Tests vorgestellt und an Beispielen angewendet

MP16: Development, implementation and evaluation of a curriculum for healthcare students working at electronic dance music events

Introduction: Mass Gathering Medicine (MGM) is a growing field within emergency medicine (EM) and providing care at electronic dance music events (EDMEs) is an increasingly popular activity with MGM groups. Often, health care students are allowed to participate. However, there is a lack of documented curricula to train junior learners in providing medical care at these events. To address this, we developed and initiated an interprofessional, simulation-based workshop for University of Alberta health care students interested in working at EDMEs. Methods: We used Kerns six-step approach to develop the workshops. Our MGM Interest Group identified a need for educational sessions in toxicology case management at EDMEs. A subsequent literature review revealed a paucity of pre-existing curricula on this topic for MGM learners. We created goals and objectives for the workshops, reflecting the knowledge, skills and attitudinal competencies required to provide appropriate medical care at these events. The workshops were implemented and evaluated in November 2016 and 2017. Results: A total of 44 medical and nursing students attended the workshops. An EM resident and staff physician, both with prior experience working at EDMEs, led each session. Each workshop began with a short didactic lecture followed by two hours of case-based training using two standardized patients and a high fidelity simulator. Topics were chosen based on previously published articles describing medical cases seen at EDMEs. The simulation replicated the actual space, noise and equipment available at the medical tents at these events. Two interprofessional learner groups took turns managing a different set of 3 patients: Set 1-opioid overdose (OD), alcohol/vomiting, sympathomimetic OD; Set 2-opioid OD not responsive to naloxone, anticholinergic/seizure, OD with hyperthermia. Initial assessment, medical management and team communication skills were emphasized. Debriefing was provided to learners immediately after each set of cases. After each workshop, the learners completed evaluation forms utilizing both Likert scale and open-ended responses. Overall, students were extremely complimentary about the workshop structure, content and communication skills teaching. They were especially appreciative of the opportunity to participate in their first interprofessional team experience. Conclusion: To address local needs, a well-received simulation-based workshop was created to train students in toxicology case management at EDMEs. Future work will include using this workshop in a just-in-time fashion before upcoming EDMEs and documenting students actual use of skills taught (Kirkpatrick level 3). The workshop will also be further modified to implement more detailed interprofessional objectives and can provide a venue for EM residents to practice teaching interprofessional education competencies as part of their CanMEDS Scholar role.</jats:p

P117: Procedural skills training in emergency medicine physicians within the Edmonton zone: a needs assessment

Introduction: Procedural skills are a key component of an emergency physician's practice. The Edmonton Zone is a health region that comprises eleven tertiary, urban community and rural community emergency departments (EDs) that represents over three hundred emergency physicians. We report the initial stakeholder and site leadership needs assessment used to inform the development of a comprehensive continuing professional development (CPD) procedural skills curriculum for the Edmonton Zone. Methods: A list of procedural skills was distributed to the two Edmonton Zone Clinical Department Heads of Emergency Medicine (EM). This list was based on a previous Canadian study that utilized procedures from the Objectives of Training in EM. Based on perceived needs, twenty-five procedures were chosen by consensus from zone leadership and study authors as the initial focus for a skills curriculum. This list was sent via survey to the physician site leads of all EDs in the zone. Each site lead was asked to indicate the fifteen procedure curriculum they felt would most benefit their respective physician groups. Responses were collated to look at all departments as a group and stratified by the type of ED (tertiary, urban and rural community). Results: Every site chief of Edmonton Zone EDs completed the survey (100% response rate). Cricothyrotomy and pediatric intubation were the two procedures prioritized by every site. One procedure (ultrasound guided central lines) was prioritized by 10/11 sites while three procedures (ultrasound guided central lines, adult intubation and chest tube insertion) were specified by 9/11 sites as needs. Two procedures (pericardiocentesis and thoracotomy) were named as priorities only by tertiary centers. Conversely, three procedures (extensor tendon repair, anterior and posterior nasal packing) were highlighted by all rural sites, but not consistently by any urban sites. Conclusion: Over the next few years, competency-based CPD will emerge for physicians in practice. Our preliminary needs assessment showed that while a common zone-wide curriculum will be possible, targeted curricula tailored to the unique needs of the various types of EDs will also be necessary. This has implications for the resources and teaching requirements needed to deliver effective and recurring CPD courses to an entire health region. A targeted needs assessment to all Edmonton Zone physicians will be the next step to verify and further elaborate on these preliminary results.</jats:p