System Diseases 1

The System Diseases 1 course takes the students into clinical medicine with the study of the "Diseases of the Kidney and Urinary System" (Nephrology) and the "Diseases of the Heart and Vessels" (Cardiology). Such studies will be dealt on a comprehensive basis, i.e. including Diagnostic Imaging, Pathology, Clinical Biochemistry and Microbiology, in relation to the diseases of the organ.
CARDIOVASCULAR DISEASES
This module will focus on some relevant aspects of cardiology, which shall be discussed with a predominantly pathophysiological approach. A more clinical and therapy oriented approach will be in place at 5th year, in the exam of Translational Cariovascular Medicine and Surgery.
NEPHROLOGY
The purpose of this module is to provide essential knowledge of the kidney role in maintaining the body homeostasis, both in patients with renal diseases and in patients with other conditions, such as arterial hypertension and diabetes mellitus, in which kidneys play a pivotal role in the genesis and the response of the organism to the disease process. The module offers the unique opportunity to systematically explore specific renal disorders, like the glomerulopathies, and an introduction to very relevant clinical syndromes, such as acute and chronic kidney disease.
Course Relevance: The knowledge of signs and symptoms (semeiotics) in nephrology and the ability to identify the clinical presentation of renal diseases represent an essential part of the medical heritage and practice. It is of utmost importance in the everyday clinical and surgical practice, if we consider the high incidence of both acute (mostly in surgical setting) and chronic kidney injury (mostly in internal medicine). Also, the ability to detect the first signs and symptoms of a specific renal disease is crucial for an early nephrology referral. Despite the intended field of specialization in medicine, we believe that this module is very important both for the future physician and the future surgeon.
MICROBIOLOGY
The main purpose of the module is the understanding of the role of microorganisms, as etiological agents or cofactors, in the pathogenesis of myocardial/cardiac (cardiology module) and urinary tract diseases (nephrology module).
Every lecture will focus on four main aspects: the epidemiology of the involved microorganisms, the mechanisms of pathogenesis employed by the microorganisms, the diagnostic approaches for the detection of the microorganisms, and, when available, the antimicrobial therapies.
PATHOLOGY
The first part of the course will focus on the definition of Anatomic Pathology and on its contribution in modern medicine. The organization of the work flow at a Pathology Department, with particular focus on its three major sections (histology, cytology and autopsy) will be described, together with the structure and the contents of a modern pathological report. Principles, applications and clinical implications of some ancillary techniques of the anatomic pathology such as immunohistochemistry and molecular pathology will also be considered in detail.
The second part of the course will deal with the anatomic pathology of the heart. In particular, lectures will be focused on the pathogenetic mechanisms, morphologic changes, evolution and complications of the diseases involving the most important structures of the heart (myocardium, endocardium and valves, pericardium) and the blood vessels.
DIAGNOSTIC IMAGING
The module is focused on explaining the different interactions between iodizing and non iodizing radiation and matter in order to obtain diagnostic images (i.e. x rays, sonography and magnetic resonance imaging) and the use of radiopharmaceuticals in Nuclear Medicine. The course is also designed to highlight the different diagnostic capabilities of imaging techniques in detecting and characterizing pathologic conditions in the cardiovascular and urinary systems.
In particular, the course will focus on conditions such as ischemic heart disease, valvular heart disease, urinary tract stones, infections and tumors.

1) Adaptation of cellular growth and differentiation Mechanisms of cellular injury and cell death (necrosis, apoptosis, autophagy, pyroptosis, necroptosis) Reactive oxygen species (ROS): types, source, effects Balance between ROS and antioxidants in human health and unbalance in human disease Intracellular accumulations of endogenous and exogenous substances Molecular and cellular aspects of protein misfolding and mechanisms of protein-folding diseases The stem cell and the concept of pluripotency Main properties of embryonic and adult stem cells The hematopoietic stem cell as a paradigm of adult stem cells Reprogrammed cells and induced pluripotency Somatic cell reprogramming by nuclear transfer ("therapeutic cloning") Hallmarks of aging Genetic and biochemical changes in aging Cellular senescence Stem cell exhaustion Altered intercellular communication Sources, biochemical functions, and health benefits of energy-releasing and energy-converting vitamins (B1, B2, B3, B5, B6, B7), and deficiency-related diseases Sources, biochemical functions, and health benefits of hematopoietic vitamins (B9, B12), vitamin C, and deficiency-related diseases Lipid-soluble vitamins (A, D, E, K), and deficiency/excess-related diseases
2) Effect of mutations on protein function Mechanism linking mutations to disease Same gene, different phenotypes; different genes, same phenotype Mutation not affecting coding gene sequences Molecular basis of reduced penetrance in human inherited diseases Identification of genetic risk factors in complex diseases Common versus rare variant hypothesis in neurodegenerative disorders Lessons from studying monogenic disease for common disease: the genetics of Alzheimer disease and mellitus diabetes Epigenetic mechanisms Epigenetic modifications and environment Role of epigenetics in human diseases Mechanisms of action of miRNA and lncRNA Role of miRNA and lncRNA in human diseases Genetic variation and drug response Genetic variation and personalized medicine
3) Microbiota in health and disease Basics of bacterial cell structure Properties of bacterial cell walls (Gram staining, structure of peptidoglycan, LPS structure and role in human pathogenesis, target sites for antibiotics) The genetic makeup of bacteria Mechanisms of bacterial virulence: secretory, membrane-associated, and cytosolic factors. Structure, regulation, expression and their contribution to pathogenesis and immune evasion. The eukaryotic nature of fungi and their classification The fungal relationships with humans: basic pathogenic mechanisms for opportunistic and invasive infections. Structure, morphology, genome organization and virulence factors of parasites Pathogenesis of Giardia, Trichomonas, Plasmodii, and intestinal nematodes Structure, morphology, genome organization and evolution theories of viruses Classification of the viruses infecting humans Replication's strategies Mechanisms of viral pathogenesis Determinants of communicable diseases
4) Structures, genome organization, replication properties and pathogenesis of clinical relevant human picornaviruses. Structures, genome organization, replication properties and pathogenesis of clinical relevant human flaviviruses. Structures, genome organization, replication properties and pathogenesis of the human viruses belonging to the viral families: togaviridae, coronaviridae, rhabdoviridae Structures, genome organization, replication properties and pathogenesis of the viruses belonging to the viral families: orthomixoviridae, paramixoviridae, and pneumoviridae. Structures, genome organization, replication properties and pathogenesis of the viruses belonging to the viral families: filoviridae, arenaviridae, bunyaviridae. Structures, genome organization, replication and pathogenesis of the major viruses causing hepatitis. Structures, genome organization, replication and pathogenesis of the major viruses causing hepatitis (II). Structures, genome organization, replication properties and pathogenesis of the human herpesviruses. Structures, genome organization, replication properties and pathogenesis of the viruses belonging to the viral families: parvoviridae, adenoviridae, papillomaviridae. Structures, genome organization, replication properties and pathogenesis of the human polyomaviruses. Structures, genome organization, and replication properties of HIV. Pathogenesis of HIV. Structures, genome organization, replication properties and pathogenesis of the human delta retroviruses (HTLV-I and II). Structures and pathogenesis of the prions.
5) Classification, pathogenetic mechanisms and diagnostic aspects of most clinically relevant bacteria. Staphylococcus, Streptococcus, Enterococcus. Corynebacterium diphtheriae. Listeria monocytogenes, Legionella pneumophila, Chlamydiae, Neisseriae. Haemophilus influenzae. Bordetella pertussis. Campylobacter, Helicobacter pylori, Vibrio cholerae, Pseudomonas aeruginosa, Acinetobacter. Clostridia and bacilli Mycobacteria Fungi (Candida, Cryptococcus, Aspergillus, dermatophytes, Blastomyces, Coccidioides, Histoplasma, Pneumocystis). The burden of nosocomial infections Anti-microbial resistance Superbugs (MRSA, VRE, KPC)
6) The hematopoietic niche and hematopoietic stem cells Hematopoietic lineages and cytokines The normal and altered blood counts Biological and physical barriers of innate immunity Cardinal signs of acute inflammation Blood flow alterations and vascular permeability The endothelium as a reactive biological structure Mast cells, phagocytes and NK cells Molecular mediators active on vessels Molecular mediators active on leukocytes Primary inflammatory cytokines Eicosanoids Cell adhesion: adhesion molecules and cell migration, the chemokine system Pathogen-Associated Molecular Patterns (PAMPs) and Pathogen Recognition Receptors (PRRs) Danger-Associated Molecular Patterns (DAMPs) and their receptors The TLR system Intracellular PRR Opsonic receptors Genetic defects in pathogen recognition Complement system: Activation pathways, functions, regulatory mechanisms, genetic defects in the complement system Mechanisms of cell-mediated cytotoxicity: phagocytosis and degranulation Oxygen-dependent mechanisms, oxygen independent mechanisms, opsonic agents Genetic defects in pathogen killing mechanisms Energy for immunity Metabolic signatures and profiles of key immune cells Metabolic control of immune responses Neutrophils metabolism and bioenergetics of anti-microbial action Metabolism of macrophages Metabolic shifts in macrophage activation and polarization Negative regulators of the inflammatory response The hypothalamic-pituitary-adrenal axis Anti-inflammatory cytokines and eicosanoids Stem cells and growth factors in tissue renewal Multistep process of tissue repair, fibrosis, anomalies in wound healing Distinct types of chronic inflammation Cellular and molecular effectors of chronic inflammation Macrophage polarization in chronic inflammatory responses Systemic inflammation: Fever, leukocytosis, acute phase proteins
7) Key features of acquired immunity: specificity, memory, tolerance The lymphoid system Primary and secondary lymphoid tissues, lymphatic vessels The antigen: source, structure, processing Thymus-dependent and thymus-independent antigens Structure and function of Major Histocompatibility Complex I and II MHC-I and MHC-II loci organization Superantigens Professional and non-professional antigen presenting cells Dendritic cells origin and subsets Dendritic cells maturation and migration Costimulatory molecules Intrathymic development Positive and negative selection of T lymphocytes TCR structure and repertoire generation Central and peripheral tolerance The TCR/CD3 signalling complex and transduction pathways Helper and cytotoxic T lymphocytes BCR signalling and B cell activation Antibody classes: structure and functions Isotype switch Antibody classes in primary and secondary immune responses Affinity maturation T helper subsets and polarized immune responses Differentiation and signalling in T helper cells Immune response polarization in pathology T cell / macrophage crosstalk in chronic inflammatory responses Impact on effector cells Immune granulomata: an immune perspective Regulatory T cells Myeloid regulatory cells Metabolic differences between innate and adaptive immunity Metabolism of specific T cell lineages T cell metabolism changes during immune response Vaccines and their development
8) Recognition of viral infection by the immune system Effector mechanisms against viral infections Viral strategies for evading antiviral immune responses Recognition of intracellular infection by the immune system Microbial strategies for evading immune responses The mucosal immune system Mucosal immunity and commensal microorganisms Mucosal immunity to pathogenic microbes General issues on hypersensitivity reactions Type I hypersensitivity Type II hypersensitivity Type III hypersensitivity Type IV hypersensitivity The multifactorial pathogenesis of autoimmune diseases Failure mechanisms of the central and peripheral tolerance Effector mechanisms of autoimmune reactions Immune mechanisms of the most common autoimmune diseases Differential features of autoimmune vs autoinflammatory diseases Immune deficiency caused by defects in innate immunity Immune deficiency caused by defects in B and T maturation Iatrogenic immunodeficiencies HIV infection and immune response Acquired immune deficiency syndrome (AIDS) pathogenesis Animal models to assess HIV-1 infection and AIDS pathogenesis Immunological basis of allograft rejection Major and minor histocompatibility antigens Molecular basis of direct and indirect allorecognition Mechanisms of hyperacute, acute and chronic rejection graft-versus-host disease Age-related changes in the innate immune system Age-related changes in the adaptive immune system Impact of immunosenescence on diseases and vaccination Tissue immunometabolism: relationships in the gastrointestinal tract, liver, and adipose tissue Relationships between systemic metabolism and immunity Vitamins in the control of immunity Obesity as a multifactorial disease Immunological implications of obesity
9) Definition of cancer and epidemiology Tumor nomenclature, TNM classification Differentiation and cell grading, rate of growth Local invasion Metastasis, pathways of spread Oncogenic signaling and tumor microenvironment as drivers of cancer metabolism Tumor sensing and metabolic adaptations to hypoxia and nutrient deprivation Signals and targets of metabolic reprogramming in cancer cells Advantages and liabilities of tumor cell metabolism Genes in which mutations cause cancer: oncogenes, tumor suppressor genes (gatekeepers and caretakers genes) Type of genetic alterations responsible for initiating cancer Activating or gain of function mutations Ectopic or heterochronic mutations Chromosome translocations Loss of function mutations Genomic instability and tumor progression Activated oncogenes in hereditary cancer syndrome: MEN2 Gatekeeper tumor suppressor genes in AD cancer syndromes The two-hit origin of cancer: the hereditary and sporadic forms of retinoblastoma The Li-Fraumeni syndrome Caretaker gene in autosomal dominant cancer syndromes BRCA1 and BRCA2 mutations in familial breast cancer Familial colon cancer Counselling and germline mutation testing The hallmarks of cancer The cancer-associated genes involved in the hallmarks of cancer Genomic instability and multistep carcinogenesis Cancer stem cells UV and ionizing radiations Chemical carcinogenesis: initiation, promotion and progression Metabolic activation of chemical compounds in vivo Factors that control chemical carcinogenesis Genotoxic and non-genotoxic effects of carcinogens Oncogenic DNA and RNA viruses Genetic mechanisms underlying the oncogenic process Host interaction with oncogenic viruses Pathogenic role of viruses into the oncogenic process Role of bacteria into the oncogenic process: the H. pylori case The immunosurveillance hypothesis Determinants of tumor antigenicity Defensive mechanisms against tumors Mechanisms of cancer immune evasion Cancer immunoediting Principles of cancer immunotherapy Epidemiologic evidence Myeloid-derived suppressor cells Tumor-associated macrophages and neutrophils Mechanisms of angiogenesis and vasculogenesis Endothelial progenitors and other pro-angiogenetic bone marrow-derived cells Angiogenetic cytokines and their receptors Common and distinctive features of blood and lymphatic vessels Role of angiogenesis to tumor survival and growth The role of the tumor microenvironment Cancer-related anorexia and cachexia Metabolic mechanisms of neoplastic cachexia Molecular mediators of neoplastic cachexia Tumor factors contributing to cancer cachexia Clinical characteristics of neoplastic cachexia Paraneoplastic syndromes
10) Platelets Primary and secondary hemostasis and coagulation cascade Fibrinolytic system Mechanisms of atherosclerotic plaque generation: risk factors, clinical manifestations and complications Thrombus formation and evolution Thromboembolism and immunothrombosis Pathogenesis and stages of shock Disseminated intravascular coagulopathy Biology of the red blood cell and classification of anemias BLOCK 11 iPCs-technology as a tool to investigate pathogenesis and therapy of human diseases Modern translational approaches in immunologic disorders Bio-informatics approaches in the diagnosis of a new primary immune deficiencies Regulatory agencies and policies of physicians facing new challenges and technologies Flow cytometry in diagnosis and therapy of hematologic malignancies Bone marrow reconstitution.