Seminars: Critical Analysis of Research Projects Developed in the Program – II

The concept of translational science has as principles the practical implementation of knowledge acquired through research for citizens and society. The student should understand, upon his admission into the graduate program, all stages of preparation of a project, from the formulation of the hypothesis, to structuring, raising of funds, achievement of the goals and practical application of knowledge. – We will encourage students to present their project structured as a paper in English. -The teachers will evaluate the content and form of presentation, developing an objective set of guidelines in partnership with students to guide the development of research. Contribute to the consolidation of the researchers’ training, improving their critical capacity to question the results of a study and its potential application; -To understand the concepts and implementation of the dissemination of knowledge; -Preparation of the paper, from the choice of the journal to the review of article; -Understand, discuss, analyze and develop research projects in various fields. Medical School (FM) São Paulo, Pinheiros campus Roberto Kalil Filho, Ludhmila Abrah_o Hajjar 45 MCP5868 4 Frequency, performance and participation during lectures and discussions (the responsible teachers are present in all classes). The course will be offered every semester. Students will present, in the form of a seminar structured as a paper, which will have a duration of 15 minutes. -There will be in-depth examination of the content and form of presentation of the project with the preparation of a plan that should contemplate the graduate program�fs period.

Critical Analysis of Clinical Studies in Cardio-Oncology

In the last decades, the cancer treatment has advanced significantly and improved patients’ survival. As a result, cardiovascular complications related to chemotherapy have had a higher impact in their overall survival and quality of. Thus, understanding cardiotoxicity related to cancer treatment, the main medications involved, the potential for reversibility and the management of patients at risk of toxicity has become part of the daily practice of clinical cardiology. Additionally, the potential cardiotoxicity of newer cancer treatment drug is yet to be defined. The collaboration of the Cancer Institute of the State of S_o Paulo and the Heart Institute of the Hospital das Cl_nicas of the Medical School of the University of S_o Paulo, with extensive interaction between cardiologists and oncologists, provides a unique setting for the development of research in the field. The present course aims to bring the discussion on the development of the science related to the field to postgraduate students. Discipline aimed at postdoctoral physicians and other health professionals with scientific interest in the area of Cardio-Oncology. The main objective is to enable students to apply the key fundamental Cardio-oncology concepts in research and clinical practice. Medical School (FM) São Paulo, Pinheiros campus Topics to be addressed: 1. Critical analysis of the studies on cardiotoxicity by Anthracyclines, Trastuzumab and tyrosine kinase inhibitors; 2. Radiotherapy and cardiovascular system; 3. Effects of endocrine therapy for breast and prostate cancer and cardiovascular complications; 4. Peculiarities in the treatment of heart failure and coronary disease in cancer patients, evidence gaps and opportunities for research; 5. Pericardium diseases in cancer patients. Roberto Kalil Filho, Ludhmila Abrah_o Hajjar, M_rcio Sommer Bittencourt 42 MCP5872 2 Frequency, performance and participation during lectures and discussions (the responsible teachers are present in all classes) – On-line questionnaires

Inovations on the Diagnosis and Treatment of Arrhythmias, Syncope and Prevention of Sudden Cardiac Death

The risk assessment and treatment of heart rhythm disorders have been modified and advanced substantially in recent years, as a consequence of the development of the technology and recognition of the anatomical and electrophysiological substrates, autonomic modulation and, more recently, molecular origins of cardiac arrhythmias. These instruments provided earlier and more accurate diagnoses, as well as deepened pathophysiological knowledge at the functional, macroscopic and even at the ultra structural level. In this context, there has been constant progresses and accelerated development of new therapeutic options, pharmacological and non-pharmacological, for patients suffering from heart rhythm disorders. Therefore, the understanding of the methods used for its investigation, as well as the development of adequate critical analysis in the decision making to treat them are fundamental for the improvement of researchers in this broad area of __cardiology. To update and motivate a critical analysis of the diagnosis approaches and management (both clinical and interventionists) of cardiac arrhythmias and syncope, as well as of prevention of sudden cardiac death. At the end, the student is expected to achieve a critical sense on the interpretation of the methods, recognizing its potentialities and limitations. Core Question How to diagnose and manage a patient with arrhythmia or syncope, recognizing the risk of sudden cardiac death and achieving the better therapeutic option, considering cost-effectiveness and the influence on the patient’s quality of life. Medical School (FM) São Paulo, Pinheiros campus The course will be divided into 4 modules. The teachers will give classes on the state of the art of the selected topics and the students will be requested to prepare specific seminars. At the end, there will be an evaluation based on their performance in the seminars (content and didactics) and their participation in the discussions. Denise Tessariol Hachul, Mauricio Ibrahim Scanavacca, Francisco Carlos da Costa Darrieux 12 MCP5875 2 Performance in the presentation and the content of seminars Assiduity Participation in discussions.

Difficult to Control Asthma: Differential Diagnosis, Associated Co-Morbidities, Treatment Adhrence, Indoor and Outdoor Pollution

Rhinosinusitis, gastro-gastro esophageal reflux disease, vocal fold dyskinesia, anxiety / depression, obesity, sleep apnea, as well as, heart failure or presence of foreign body in the airways, among others, may aggravate or undermine asthma. The high percentage of these co-morbidities in asthmatics has led to an intense debate reflected in the literature on the cause-consequence relationship between both. However, even in relation to rhinitis – allergic disease present in 80% of asthmatics – the pathophysiological connection is inferred, due to the absence of conclusive evidence. The challenge of treating the uncontrolled asthmatic patient with associated morbidities, measuring the impact of the latter, and the need to address them determine the characterization of difficult-to-control asthma. Likewise, symptomatic patients treated as asthmatics and with a low response to treatment, not clinically controlled, may not have asthma. Or they may have adherence to treatment of less than 50%, as well as being exposed to environmental factors, also leading to difficult asthma control. At the request of the World Health Organization, a group of global experts has developed a classification that defines severe asthma in 3 types: 1) untreated or poorly treated asthma related to lack of adequate treatment due to lack of inputs or health infrastructure; 2) difficult to control asthma in patients who are poorly or partially controlled by the presence of comorbidities and / or continuous exposure to triggers and / or low adherence to treatment; and 3) severe asthma dependent on high doses of continuous corticosteroids with High risk of known adverse events or severe asthma refractory to treatment, even at high doses. This discipline aims to clarify the differences between these types of asthma, but focuses on the second type where the aforementioned factors confuse it with the other two types. To present and discuss the current concept of difficult-to-control asthma – called “problematic” – considering the particularities that classify it in some studies as severe asthma. The definition of asthma as morbidity characterized by symptoms such as dyspnea, dry cough and wheezing, commonly leads to the axiom “all that wheeze is asthma.” Morbidities from other systems are often present in asthmatics or mimic asthma. Similarly, low adherence to treatment and continuous exposure to triggers lead to uncontrolled asthma. To clarify the relationships between asthma and these morbidities, as well as to identify and treat these factors, it is essential to differentiate an uncontrolled asthma from severe (or both at the same time), including with regard to care and research outcomes. At the end of the course the student will master the concepts necessary for critical analysis of the evidences and plan research projects in the area of __physiopathology, management and treatment of difficult to control asthma Medical School (FM) São Paulo, Pinheiros campus Lecture 1: 1 hour – Definition of severe asthma vs. difficult to control asthma: is it possible to separate them? Lesson 2: 1 hour – How to measure control objectively and evaluate it after treatment of co-morbidities associated with difficult-to-control asthma. Seminars: 5 hours (presentation of articles by students, followed by group discussion) A) Is it asthma or not? Morbidities that mimic asthma B) Is severe asthmatic adherent to treatment? Causes and consequences C) Atopy, rhinitis, sinusitis and asthma control D) Obesity, gastro-esophageal reflux,sleep apnea and asthma control E) Anxiety, depression, vocal cord dyskinesia and asthma F) Asthma and COPD overlap Practical Class: 4 hours Pulmonology oupatient clinic Study Hours: 4 hours Alberto Cukier, Rafael Stelmach 13 MCP5881 2 This discipline has didactic continuity with the Discipline “Severe Asthma: Phenotypes and their Implications”. It is suggested the student be enrolled in both. Minimum number of students: 6 Maximum number of students: 12 Presence, participation in seminars and practical activities

Scientific Method Applied to Clinical Research

The discipline is justified in the post-graduate context that aims at the production of high level scientific knowledge, which recognizes the importance of choosing a suitable research method in front of the research question previously formulated, be it of a basic or applied nature, with observational or experimental design, considering their bias and control powers, in the planning, execution and analysis phases. The course aims to provide a basic training on the nature of scientific knowledge, studying the fundamentals of methodology; Preparing students for the identification of problems, concepts and arguments that influence the theoretical, technical and operational strategies of health research with a special focus on those applied to clinical practice. Medical School (FM) São Paulo, Pinheiros campus Basic principles of the scientific method in health. Ethics in research. Planning and control of biases that promote the internal and external validity of the studies. Causal and statistical inference. Clinical relevance and statistical significance. Main types of designs for clinical studies, in view of clinical epidemiology. Descriptive measures of frequency and association between study variables. Common mistakes and biases in the development of research projects. Critical analysis of scientific articles. Application of basic statistical knowledge for the interpretation of association measures and random bias. Moacyr Roberto Cuce Nobre 61 MCP5884 2 The evaluation will be done through participation in lessons and seminars where research projects, literature papers and conceitual material are presented and discussed.

Host-Bacterial Interactions in Women’s Health

Studies of the female genital tract in health and disease are being reported at a very rapid rate. New findings that enhance our understanding of the mechanisms leading to disorders in this area are published almost daily. Whereas previously the predominant focus in infections affecting women was on identification of the causative microorganism and finding the most effective drug for treatment, there is now a much greater appreciation of the role of host-microorganism interactions that promote well being or, conversely, that lead to disease. This has led to a concomitant increased understanding that all women are not identical nor will benefit from the same standard prevention or treatment protocol. There is a great need, currently not effectively met in a many cases, to appreciate genetic, immune, hormonal, microbiological and biochemical differences between women and to modify how we define disease and provide the most effective treatment on an individual basis. Development of increasingly sensitive methods to define the composition of the genital tract microbiome by gene amplification technology, coupled with a greater appreciation of host-microbe interactions, has led to a fundamental change in our understanding of the mechanisms that promote a healthy local environment. This is paralleled by a concomitant increase in our knowledge of how specific alterations promote genital tract pathology. The objective of this course is to provide the most up-to-date information on bacterial, immunological, genetic, and biochemical factors operative in the female genital tract and how their interactions influence health and disease. Medical School (FM) São Paulo, Pinheiros campus The course will focus on the following topics: 1. What is a normal vaginal microbiome? The latest findings on the composition of the vaginal microbiota in girls, adolescents and pre- and post-menopausal women will be presented. The role of individual components of the vaginal microbiota in maintaining a physiological environment also will be addressed. 2. How does the composition of the microbiome influences female reproductive tract health? Alterations in the microbiome in women with vulvovaginal candidiasis, bacterial vaginosis, trichomoniasis, chlamydial, human papillomavirus and human immunodeficiency virus infections and how they influence disease will be detailed. 3. How does a womans genetic make-up influence her likelihood to develop specific alterations leading to genital tract disease. Specifically, recent studies on the role of variations (polymorphisms) in genes involved in anti-microbial defense or in the magnitude and direction of immune responses will be discussed and their influence on susceptibility to various infectious and non-infectious disorders affecting women. 4. What is the contribution of epithelial cells in the female genital tract to local immunity? It is now apparent that vaginal and cervical epithelial cells contribute to immune defense by the spontaneous or induced release of many compounds that are toxic for different groups of microorganisms or that activate a productive immune response. The range of compounds released by epithelial cells, the specific conditions under which they are produced and how they contribute to genital tract health will be discussed. 5. What is the current state of knowledge of genetic, immune, microbiological and environmental factors that contribute to development of female genital tract malignancies  ovarian, fallopian tube, endometrial, cervical and vaginal cancer? Is it possible to predict the occurrence or relapse of these malignancies? 6. What is the current state of knowledge of the causes, diagnosis and treatment of endometriosis? 7. What is the current state of knowledge of the causes and treatment of polycystic ovarian syndrome? Is there any relationship with microbiome? 8. Metabolic syndrome and microbiome: what is the link? 9. What are heat shock proteins and how do they influence health or disease? What is their role in womens health? Classes 1) The human microbioma and the vaginal microbioma. 2) Microbioma and reproductive health infections. 3) Genetic polymorphism and womens health. 4) Autophagy. 5) Malignant genital neoplasias. 6) Endometriosis: the state of the art . 7) Polycistic ovarian syndrome: what is new? 8) Heat shock proteins . 9) Enviromental and sexual factors influencing HIV transmission . 10) Reproductive genital infections during pregnancy: mother and baby consequences. 11) Immunization: where are we today? 12) Society, women, heath and disease. 13) Metabolic syndrome and microbiome. Seminars 1) Gender and Immunity: hormonal influences on local and systemic immunity 2) Infection, immunity and cancer 3) The human microbiome in health and disease: does gender differences matter? 4) Women empowerment , immunity and reproductive health infections: where do we stand ? Iara Moreno Linhares, Edmund Chada Baracat, Jos_ Maria Soares J_nior 20 MGO5730 4 Minimum attendance of 75%, interest and participation in discussions at lectures and seminars. Monograph delivery and evaluation will be mandatory

Evidence-Basead Medicine: Scientific Principles and Applicability in Research

The current discipline is organized in order to provide information for the researcher and the future professor for the establishment of the frontier of medical knowledge and substantiate questions, which if answered within the appropriate methodology, will motivate the scientific progress. With the easy access to the medical literature through the internet and the profusion of medical journals, update in medicine had become increasingly difficult, especially regarding the selection of the most reliable and papers with greatest impact in the clinical and surgical management of patients with gastroenterological conditions. Using epidemiology and the concepts of evidence-based medicine, it is possible to evaluate the methodological quality of the research, the cynical relevance, and the applicability of its conclusions in clinical-surgical practice. It is also possible to search for the research that provides the best answer(s) to the formulated question. On the other hand, applying “best evidence” in daily medical practice requires the comparison with the practical experience obtained over the years. Thus, the ideal is the development of concepts in evidence-based medicine in gastroenterology and the comparison with the clinical experience acquired in the Discipline of Digestive Surgery – FMUSP. To define evidence-based medicine, its functions and limitations. – To access the medical literature and how to look for the best evidence in the medical literature, in clinical and surgical gastroenterology. – To evaluate the impact of scientific research in the management of patients with gastroenterological conditions. – To evaluate the minimum prerequisites to develop a clinical research project in clinical and surgical gastroenterology. – To evaluate Meta-analyzes on clinical and surgical gastroenterology topics. Medical School (FM) São Paulo, Pinheiros campus What is and what is not Evidence Based Medicine, history, fundamentals, methods and objectives. • Critical analysis on the limits of the contribution of evidence-based medicine method. • Types of Epidemiological Studies • Basic Concepts in Biostatistics: Measures of Association: Odds Ratio, Relative Risk, Likelihood Ratio, etc … • Practical Application of Association Measures • Basic Concepts in Biostatistics: Confidence Interval. Type I error, Type II error. • Practical Application of Concepts: Confidence Interval, Type I error, Type II error. • How to access Medical Literature and How to look for the “best evidence” in Medical Literature • Systematic Reviews and Meta-Analysis • Main statistical tests used. How to select the test? What are the most common mistakes? • Use of Evidence Based Medicine in the adoption of new health technologies. The accreditation of new technologies in the public health system (SUS). Fauze Maluf Filho, Paulo Herman, Moacyr Roberto Cuce Nobre 34 MGT5736 4 The evaluation will be done by each professor´s criteria: participation grade and/or a written essay to evaluate the understanding of the content immediately after the end of each module. The average of these assessments will be the final mark awarded by the Discipline. Updated articles from the international medical literature will be provided.

Cardiology Didactics

This course is justified by the main objective of the “Strito-Sensu” Graduate Program, which is to train teachers and researchers, responsible for promoting and developing scientific advances, but also know how to transmit them and carry the basic tools for a continuous learning. The didactics must be inserted within the principle of the integral formation of the students that will be trained in the current techniques of transmission of the knowledge. Therefore, didactics is a fundamental foundation in the training of these PG students. On the other hand, it can be observed that there is an intimate relationship between didactics and research, since its dissemination and communication to the scientific community and, even to the laity, must be clear, exact and follow ethical principles within established standards. ournals have specific, internationally established rules and, both publications and presentations, must adhere to the basic principles: ethics, accuracy, clarity, exemption, synthesis and conclusion with no other interests. For all these reasons the Discipline of Didactics in the formation of new PGs is justified. Provide postgraduate students with the basic principles of Didactics fundamentals and techniques, based on efficiency, propriety, precision and clarity in scientific expositions, whether oral or written. The form and content of the presentations are analyzed according to the theoretical bases and practical training. Medical School (FM) São Paulo, Pinheiros campus 1.Objectives and forms of scientific communication 2.Principles and methods of oral communication 3. How to prepare a lesson or scientific communication 4. Principles and methods of audio-visual scientific communication 5.Principles and methods of written scientific communication 6.Principles and methods of distance scientific communication 7.Use of projections: computation 8.Exhibition of themes in Poster 9. How to identify or highlight highlights in an oral presentation 10.Criteria for programming courses for: Undergraduate, Residency and Postgraduate Jose Antonio Franchini Ramires, Paulo Cury Rezende 16 MCP5823 3 1. Presentation of two seminars: 1) free themes with oral presentation and 2) data of the thesis project with presentation in the English language. 2. Elaboration of the program of a course for undergraduate students and / or specialization applying the acquired knowledge and evaluation of the discipline._

Factors Associated with Cancer Development in Young Patients

Most studies in Oncology, including tumor molecular biology and therapeutic clinical trials, have focused on cancers that occur in children and older adults. Recently, the interest in characterizing cancers affecting young adults has increased. Estimates in our state indicate that 4.8-5.0% of cancer cases occur in young adults aged 20-34 years ( Between 2000 and 2009, the Cancer Hospital Registry Bulletin of the Oncocentro Foundation of S_o Paulo (RHC / FOSP Bulletin, 2011) reported 13,373 cancer cases in adolescents and young adults, 40% in males and 60% in females. In general, germline mutation carriers in cancer predisposing genes develop the disease at an early age, however, only 10-20% of young patients have mutations in these genes, and the development of cancer remains largely unexplained. Habits and environmental factors, which may be involved in the processes of genetic damage or epigenetic events that control gene expression, may also influence the development of cancer. This course intends to explore the role of gene mutations and environmental factors in the development of cancer in young patients To investigate hereditary and environmental factors involved in the development of cancer in young adults, including family history, habits, gene mutations. Medical School (FM) São Paulo, Pinheiros campus Cancer in young adults and: 1. Germline mutations in cancer predisposing genes; 2. Environmental factors modifying the risk of cancer; 3. Gene polymorphisms; 4. Somatic mutations; 4. Prognosis Maria Aparecida Azevedo Koike Folgueira, Geertruida Hendrika de Bock 19 MCM5912 6 Presentation of seminars and / or written examination

Scientific Publication in Medical Journals: A Survival Guide for Future Authors

1. To disseminate the knowledge of policies and processes related to the publication of scientific papers in medicine. 2. To organize and clarify the steps by which a scientific work passes from completion to publication in a medical journal. 3. To enable students to the publication of data from a research in the best possible way. Medical School (FM) São Paulo, Pinheiros campus 1. Writing and scientific literature _ historical and philosophical principles, the role of the editor, reviewer and author. 2. The choice of the jornal in which to publish. Classes 1 and 2 are classical lectures followed by Q&A delivered in day 1 3. Bibliometric indicators (number of citations, impact factor, , altmetrics): what are, how they are calculated and what is the hierarchy? Class 3 is more practical (tutorial) and to be delivered in day 2. 4. Authorship, title, language, grammar, clarity, formatting, organization of concepts and information, structured abstract, the IMRAD model, the ethics committee, mandatory registration of clinical trials, figures and tables. Class 4 is a classical lecture to be delivered in day 3 (45 min) + Q&A 5. Important details: cover letter, statement of reviewers, contraindication of reviewers, key words, inclusion, choice and formatting references. Class 5 is also practical (tutorial) and to be delivered in day 3 as well. 6. Rejection and frustration, the Editor will do anything to reject; the opinion of the reviewer; the preparation of the response to the reviewer; how many rejections a work resists? 7. The post-sale marketing: quote, impact factor of the article and the author’s h-index. Class 6 and 7 are classical lectures to be delivered in day 4 (2 X 45 min) + Q&A Day 5 _ Paper Clinic. This day is reserved to practicing examples of preparing a manuscript for submission: a deep and practical look into class number 4 (students are encouraged to bring their own research manuscript) Bruno Caramelli, Ana Marusic 28 MCM5917 2

Mechanisms of Action of Immunomodulatory Agents

We aim at exposing Brazilian students to discussions on the state-of-the- art concepts of immunology and their application to the understanding of chronic diseases, either infectious or noncommunicable diseases, and in the implementation of prophylactic and therapeutic interventions. The course is divided into 4 one-week courses, that could be attended independently and will be delivered simultaneously to Paris and New York, via videoconference. All students and the responsible for the course will meet and attend to the course (so it is a presential course) which will be transmitted online simultaneously to S_o Paulo, Paris and New York. The responsible for the course will mediate discussions with the students at the end of every videoconference session. The discussion will serve as evaluation of active participation of the students by the responsible for the course. This course is an initiative from USP International Office and is part of an active strategy to foster international collaborations between USP and the Sorbonne University (Universit_ Pierre et Marie Curie). This is a pilot project; the course may be repeated in the future, depending on the results achieved. Medical School (FM) São Paulo, Pinheiros campus Principles and definitions of immunotherapies; legal and ethical issues; antibodies cytokines and chemokines; cell-based therapy; genetic vaccines. Roger Chammas 20 MCM5918 2 Participation in seminars

Cancer Immunotherapy

We aim at exposing Brazilian students to discussions on the state-of-the- art concepts of immunology and their application to the understanding of chronic diseases, either infectious or noncommunicable diseases, and in the implementation of prophylactic and therapeutic interventions. The course is divided into 4 one-week courses, that could be attended independently and will be delivered simultaneously to Paris and New York, via videoconference. All students and the responsible for the course will meet and attend to the course (so it is a presential course) which will be transmitted online simultaneously to S_o Paulo, Paris and New York. The responsible for the course will mediate discussions with the students at the end of every videoconference session.The discussion will serve as evaluation of active participation of the students by the responsible for the course. This course is an initiative from USP International Office and is part of an active strategy to foster international collaborations between USP and the Sorbonne University (Universit_ Pierre et Marie Curie). This is a pilot project; the course may be repeated in the future, depending on the results achieved. Medical School (FM) São Paulo, Pinheiros campus Immunotherapies enhancing anti-tumor immunity or targeting T-cell inhibitory molecules; Chimeric Antigen receptors (CARs); Vaccines/cytokines; allogeneic stem cell transplantation for haematological malignancies. Roger Chammas 20 MCM5919 2 Participation in seminars