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.

Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing

Abstract: Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. Common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K–epoxide reductase complex (VKORC1) enzymes, in addition to known nongenetic factors, account for ~50% of warfarin dose variability. The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for estimating therapeutic warfarin dose to achieve an INR of 2–3, should genotype results be available to the clinician. The Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer-reviewed gene–drug guidelines that are published and updated periodically on http://www.pharmgkb.org based on new developments in the field. 1 Focused Literature review The Supplementary Notes online include a systematic literature review of CYP2C9 and VKORC1 genotype and warfarin dosing, which forms the basis for this guideline. drug: w arF arin Warfarin (Coumadin and others) is the most commonly used oral anticoagulant worldwide, with annual prescriptions typically equaling 0.5–1.5% of the population. It is prescribed for treatment and prevention of thrombotic disorders. 2 Although highly efficacious, warfarin’s narrow therapeutic index and wide interindividual variability make its dosing notoriously challenging. 3–5 Complications from inappropriate warfarin dosing are among the adverse events most frequently reported to the US Food and Drug Administration (FDA) and one of the most common reasons for emergency room visits. 6 Warfarin is often dosed empirically: an initial dose is prescribed, typically followed by at least weekly measurement of the INR and subsequent dose adjustment. The initial dose is often based on population averages (e.g., 3–5 mg/day), but stable doses to achieve an INR of 2–3 can range from 1–20 mg/ day. The iterative process to define the appropriate dose can take weeks to months, and during this period patients are at increased risk of over- or under-anticoagulation and thus at risk of thromboembolism or bleeding.

Fibromuscular dysplasia

Abstract: The most common clinical manifestations of fibromuscular dysplasia (FMD) are hypertension due to renal artery involvement and transient ischemic attack or stroke due to carotid or vertebral artery involvement. Patients with renal artery FMD and hypertension should undergo primary angioplasty with the goal of curing the hypertension. If the blood pressure fails to normalize following angioplasty, the physician should institute antihypertensive medications according to the recommendations of the Joint National Committee on the Prevention, Detection, and Treatment of High Blood Pressure VII. In patients with cerebrovascular FMD, antiplatelet agents represent the cornerstone of therapy. Percutaneous angioplasty has emerged as the preferred treatment for symptomatic cerebrovascular FMD.

Antidepressant Effect of Optogenetic Stimulation of the Medial Prefrontal Cortex

Abstract: Brain stimulation and imaging studies in humans have highlighted a key role for the prefrontal cortex in clinical depression; however, it remains unknown whether excitation or inhibition of prefrontal cortical neuronal activity is associated with antidepressant responses. Here, we examined cellular indicators of functional activity, including the immediate early genes (IEGs) zif268 (egr1), c-fos, and arc, in the prefrontal cortex of clinically depressed humans obtained postmortem. We also examined these genes in the ventral portion of the medial prefrontal cortex (mPFC) of mice after chronic social defeat stress, a mouse model of depression. In addition, we used viral vectors to overexpress channel rhodopsin 2 (a light-activated cation channel) in mouse mPFC to optogenetically drive "burst" patterns of cortical firing in vivo and examine the behavioral consequences. Prefrontal cortical tissue derived from clinically depressed humans displayed significant reductions in IEG expression, consistent with a deficit in neuronal activity within this brain region. Mice subjected to chronic social defeat stress exhibited similar reductions in levels of IEG expression in mPFC. Interestingly, some of these changes were not observed in defeated mice that escape the deleterious consequences of the stress, i.e., resilient animals. In those mice that expressed a strong depressive-like phenotype, i.e., susceptible animals, optogenetic stimulation of mPFC exerted potent antidepressant-like effects, without affecting general locomotor activity, anxiety-like behaviors, or social memory. These results indicate that the activity of the mPFC is a key determinant of depression-like behavior, as well as antidepressant responses.

Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution

Abstract: Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.