Icahn School of Medicine at Mount Sinai

About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Abstract: Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.

Hematology: Basic Principles and Practice

Abstract: Part I: Mollecular and Cellular Basis of Hematology. Anatomy and Physiology of the Gene. Protein Synthesis and Intracellular Sorting. Protein Architecture: Relationship of Form and Function. Membrane Biology. Cell Adhesion. Cellular Regulatory and Control Mechanism. Part II: Immunologic Basis of Hematology. Overview of the Immune System (including Compartmentalization of the Immune Response). Generation of B-cells. T-cell Immunity. Regulation of Activation of B and T-cells. Tolerance and Autoimmunity. Part III: Biology of Stem Cells and Disorders of Hematopoiesis. Stem Cell Model of Hematopoiesis. Anatomy and Physiology of Hematopoiesis. Growth Factors and the Control of Hematopoiesis. Biology of Erythropoiesis, Erythroid Differentiation and Maturation. Granulopoiesis and Monocytopoiesis. Thrombocytopoiesis. Inherited Forms of Bone Marrow Failure. Aplastic Anemia. Paroxysmal Nocturnal Hemoglobinuria. Pure Red Blood Cell Aplasia. Part IV: Red Blood Cells. Pathobiology of the Red Cell. Approach to the Adult and Child with Anemia. Anemia of Chronic Diseases. Erythrocytosis. Disorders of Iron Metabolism: Iron Deficiency and Overload. Heme Biosynthesis and Its Disorders: Porphyrias and Sideroblastic Anemias. Megaloblastic Anemias. Thalassemia Syndromes. Sickle Cell Disease. Hemoglobin Variants Associated with Hemolytic Anemia, Altered Oxygen Affinity, and Methemoglobinemias. Enzymopathies. Red Cell Membrane Disorders. Autoimmune Hemolytic Anemias. Extrinsic Nonimmune Hemolytic Anemias. Part V: Host Defense and Its Disorders. Immunoglobulins: Structure, Function, and Uses. Complement Biology. Neutrophil Structure and Function. Monocyte and Macrophage Development and Function. Eosinophils and the Hypereosinophilic Syndrome. Disorders of the Phagocyte Function. Disorders of the Lymphocyte Function. Histiocytic Syndromes. Lysosomal Storage Disease. Infectious Mononucleosis and Other Epstein-Barr Virus-Associated Diseases. Spleen and Its Disorders. Systemic Mastocytosis. Part VI: Hemat

Levodopa and the progression of Parkinson's disease.

Abstract: background Despite the known benefit of levodopa in reducing the symptoms of Parkinson’s disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson’s disease. methods In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson’s disease who were assigned to receive carbidopa–levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123–labeled 2- b -carboxymethoxy3- b -(4-iodophenyl)tropane ([ 123 I] b -CIT) uptake. results The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and i1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [ 123 I] b -CIT uptake was significantly greater with levodopa than placebo (–6 percent among those receiving levodopa at 150 mg daily, –4 percent in those receiving it at 300 mg daily, and –7.2 percent among those receiving it at 600 mg daily, as compared with –1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. conclusions The clinical data suggest that levodopa either slows the progression of Parkinson’s disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson’s disease remain uncertain.