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NOVEL FUNCTION OF SGOL1 IN CARDIOVASCULAR AND GASTROINTESTINAL DEVELOPMENT: UNRAVELING THE MECHANISMS OF CAID SYNDROME
Abstracts
maternal treatment with methimazole, right cardiomyopathy improved and tricuspid regurgitation resolved. CONCLUSION: Fetal thyrotoxicosis diagnosis needs a high index of suspicion as classic sinus tachycardia may not be present. Hypervascularisation of the goitre leads to redirection of aortic isthmic flow to the head, mimicking a cerebral vasodilatation with diastolic retrograde aortic isthmic flow and increased systemic venous return. Cardiac findings associate right ventricular cardiomyopathy with significative tricuspid regurgitation which resolves after maternal treatment. 116 NOVEL FUNCTION OF SGOL1 IN CARDIOVASCULAR AND GASTROINTESTINAL DEVELOPMENT: UNRAVELING THE MECHANISMS OF CAID SYNDROME A Song, G Andelfinger, S Leclerc Montréal, Québec BACKGROUND:
Generation of a spontaneous rhythm is an important property of cardiac and intestinal tissue. CAID syndrome (chronic atrial and intestinal dysrhythmia) leads to a loss of heart and intestinal pacemakers. It is caused by K23E mutation of SGOL1 gene, which is known to regulate the cell cycle. The specific role of this gene in the heart and the intestine is yet unknown. METHODS: The primary objective of this study is to examine the role of Sgol1 in the heart by determining when and where Sgol1 is expressed in embryogenesis with particular attention to the development of the heart utilizing Sgol1-lacz-Knockin mice and immunostaining methods. RESULTS: We inserted a LacZ reporter gene in the locus of Sgol1 in mouse to mark the expression of the gene. We also utilized immunohistochemistry in wild type mouse tissues. Sgol1 shows a very dynamic expression pattern with a significant increase in expression in the heart during early embryonic development from E10.5 onwards. Expression analysis also showed Sgol1 is expressed in compact area more strongly than the trabecular area. Beyond E12.5, Sgol1 expression becomes contiguous with area of primary heart field lineage. High level of Sgol1 was also observed in the intestinal villi epithelium in developing mouse from E15.5 but absent in E12.5 embryonic intestinal epithelium and both stages showed intermittent Sgol1 expression in the muscular layer of the intestines suggesting Sgol1 may be involved with normal development/maintenance of intestinal epithelium. Additionally, we have also found that homozygous Sgol1 K23E mutation is embryonic lethal in Sv129 strain. CONCLUSION: The pattern and timing of expression of Sgol1 in mice suggest a role in the expansion of the heart tissue, rather than their initial formation. The subsequent study of distinct role in meiosis and / or early embryonic formation will be carried out with a conditional expression of Sgol1.
S133
Canadian Cardiovascular Society (CCS) ePoster INNOVATION IN MEDICAL EDUCATION: INSIGHTS FROM ACROSS THE COUNTRY Saturday, October 22, 2016 117 FELLOW-INITIATED RESEARCH: A TEACHING MODEL FOR TRAINEES TO BOLSTER INTEREST AND INCREASE PROFICIENCY IN CLINICAL RESEARCH M Tremblay-Gravel, G Marquis-Gravel, R Avram, O Desplantie, A Ducharme, H Ly, M Jolicoeur Montréal, Québec BACKGROUND:
Research is embedded in the practice of modern cardiologists and therefore should be a core aspect of postgraduate training. The eagerness of fellows to perform meaningful clinical research is hindered by demanding clinical duties, restricted network and limited contact with clinicianscientist role models. Collectively-Operated Fellow-Initiated Research (COFIR) aims to bring together a cohort of fellows to create a multi-faceted research project that can be sustainably integrated in their postgraduate training program. METHODS AND RESULTS: Eleven fellows in Cardiology and Internal Medicine from the Université de Montréal, McGill, Sherbrooke, and Laval developed a COFIR project on peripartum cardiomyopathy (PPCM). The project is based on self-directed learning and autonomy, forecasts maximization of research exposure, skills acquisition and scientific proficiency. As opposed to classical teaching and research projects performed in silos, our work was sustained by a group of trainees that worked communally under one chief research topic and under a group of mentors. The underpinnings of our approach can be outlined in 3 dictates: 1- Fellows must formulate the research hypothesis; 2- Fellows must be actively involved in all aspects of the research process, under the mentorship of clinician-scientists; 3- Fellows must document and disseminate the newly acquired research knowledge. Core principles of medical education acknowledge that focusing on one’s strengths yields better results than trying to compensate for weaknesses. Considering our versatile skill-sets as a group, fellows expanded their skills in communication, statistics, trial design, ethics, and even pedagogy based on their interests. Fellows assigned to specific tasks developed expertises of their own and were responsible to teach back what they learned to the group of fellows, so that they become collectively familiar with the steps required to develop and operate a clinical trial. Once the research question was decided upon, the background literature was systematically reviewed, a nation-wide multicentric retrospective PPCM cohort was created and used to design a prospective randomized controlled trial. CONCLUSION: Adequate scientific literacy has become a distinctive element of the best postgraduate training programs. A structured and supervised research platform in which fellows take leadership and express autonomy in the
maternal treatment with methimazole, right cardiomyopathy improved and tricuspid regurgitation resolved. CONCLUSION: Fetal thyrotoxicosis diagnosis needs a high index of suspicion as classic sinus tachycardia may not be present. Hypervascularisation of the goitre leads to redirection of aortic isthmic flow to the head, mimicking a cerebral vasodilatation with diastolic retrograde aortic isthmic flow and increased systemic venous return. Cardiac findings associate right ventricular cardiomyopathy with significative tricuspid regurgitation which resolves after maternal treatment. 116 NOVEL FUNCTION OF SGOL1 IN CARDIOVASCULAR AND GASTROINTESTINAL DEVELOPMENT: UNRAVELING THE MECHANISMS OF CAID SYNDROME A Song, G Andelfinger, S Leclerc Montréal, Québec BACKGROUND:
Generation of a spontaneous rhythm is an important property of cardiac and intestinal tissue. CAID syndrome (chronic atrial and intestinal dysrhythmia) leads to a loss of heart and intestinal pacemakers. It is caused by K23E mutation of SGOL1 gene, which is known to regulate the cell cycle. The specific role of this gene in the heart and the intestine is yet unknown. METHODS: The primary objective of this study is to examine the role of Sgol1 in the heart by determining when and where Sgol1 is expressed in embryogenesis with particular attention to the development of the heart utilizing Sgol1-lacz-Knockin mice and immunostaining methods. RESULTS: We inserted a LacZ reporter gene in the locus of Sgol1 in mouse to mark the expression of the gene. We also utilized immunohistochemistry in wild type mouse tissues. Sgol1 shows a very dynamic expression pattern with a significant increase in expression in the heart during early embryonic development from E10.5 onwards. Expression analysis also showed Sgol1 is expressed in compact area more strongly than the trabecular area. Beyond E12.5, Sgol1 expression becomes contiguous with area of primary heart field lineage. High level of Sgol1 was also observed in the intestinal villi epithelium in developing mouse from E15.5 but absent in E12.5 embryonic intestinal epithelium and both stages showed intermittent Sgol1 expression in the muscular layer of the intestines suggesting Sgol1 may be involved with normal development/maintenance of intestinal epithelium. Additionally, we have also found that homozygous Sgol1 K23E mutation is embryonic lethal in Sv129 strain. CONCLUSION: The pattern and timing of expression of Sgol1 in mice suggest a role in the expansion of the heart tissue, rather than their initial formation. The subsequent study of distinct role in meiosis and / or early embryonic formation will be carried out with a conditional expression of Sgol1.
S133
Canadian Cardiovascular Society (CCS) ePoster INNOVATION IN MEDICAL EDUCATION: INSIGHTS FROM ACROSS THE COUNTRY Saturday, October 22, 2016 117 FELLOW-INITIATED RESEARCH: A TEACHING MODEL FOR TRAINEES TO BOLSTER INTEREST AND INCREASE PROFICIENCY IN CLINICAL RESEARCH M Tremblay-Gravel, G Marquis-Gravel, R Avram, O Desplantie, A Ducharme, H Ly, M Jolicoeur Montréal, Québec BACKGROUND:
Research is embedded in the practice of modern cardiologists and therefore should be a core aspect of postgraduate training. The eagerness of fellows to perform meaningful clinical research is hindered by demanding clinical duties, restricted network and limited contact with clinicianscientist role models. Collectively-Operated Fellow-Initiated Research (COFIR) aims to bring together a cohort of fellows to create a multi-faceted research project that can be sustainably integrated in their postgraduate training program. METHODS AND RESULTS: Eleven fellows in Cardiology and Internal Medicine from the Université de Montréal, McGill, Sherbrooke, and Laval developed a COFIR project on peripartum cardiomyopathy (PPCM). The project is based on self-directed learning and autonomy, forecasts maximization of research exposure, skills acquisition and scientific proficiency. As opposed to classical teaching and research projects performed in silos, our work was sustained by a group of trainees that worked communally under one chief research topic and under a group of mentors. The underpinnings of our approach can be outlined in 3 dictates: 1- Fellows must formulate the research hypothesis; 2- Fellows must be actively involved in all aspects of the research process, under the mentorship of clinician-scientists; 3- Fellows must document and disseminate the newly acquired research knowledge. Core principles of medical education acknowledge that focusing on one’s strengths yields better results than trying to compensate for weaknesses. Considering our versatile skill-sets as a group, fellows expanded their skills in communication, statistics, trial design, ethics, and even pedagogy based on their interests. Fellows assigned to specific tasks developed expertises of their own and were responsible to teach back what they learned to the group of fellows, so that they become collectively familiar with the steps required to develop and operate a clinical trial. Once the research question was decided upon, the background literature was systematically reviewed, a nation-wide multicentric retrospective PPCM cohort was created and used to design a prospective randomized controlled trial. CONCLUSION: Adequate scientific literacy has become a distinctive element of the best postgraduate training programs. A structured and supervised research platform in which fellows take leadership and express autonomy in the