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.

An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines.

Abstract: Parkinson’s disease (PD) is named in honor of James Parkinson, whose classic monograph, “An Essay on the Shaking Palsy,” written in 1817, has provided an enduring description of the clinical features of this disorder.1 PD is an age-related neurodegenerative disorder with an average age at onset of 60 years. An estimated 1 million persons in the United States suffer from PD,2 and there are approximately 60,000 new cases each year. United States Census Bureau projections indicate that there will be a substantial increase in the number of at-risk individuals 60 years of age and older, and therefore the prevalence of PD is likely to increase in the coming decades. The introduction of levodopa in the late 1960s represented a major therapeutic advance in the management of PD,3 providing clinical benefit to virtually all patients and reduced mortality. However, it soon became apparent that long-term treatment with levodopa is complicated by the development of adverse events that include motor fluctuations, dyskinesias, and neuropsychiatric complications.4-6⇓⇓ In addition, with disease progression, patients develop features that do not respond well to levodopa therapy, such as freezing episodes, autonomic dysfunction, falling, and dementia. As a consequence, despite levodopa treatment, most PD patients eventually suffer disabilities that cannot be satisfactorily controlled with existing medical therapies. Therefore, there has been an intensive effort to develop new treatments that reverse disabilities in patients with advanced disease, that provide enhanced clinical benefits with a reduced risk for adverse events, and that slow the rate of disease progression. This has led to an explosion of new laboratory and clinical information and to a variety of new treatment strategies for the management of PD. Physicians who treat PD patients must now assimilate a considerable body of data to optimally manage patients with this complex disorder. …

Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which numerous mouse models have been generated. In both AD patients and mouse models, there is increasing evidence that neuronal dysfunction occurs before the accumulation of β-amyloid (Aβ)-containing plaques and neurodegeneration. Characterization of the timing and nature of preplaque dysfunction is important for understanding the progression of this disease and to identify pathways and molecular targets for therapeutic intervention. Hence, we have examined the progression of dysfunction at the morphological, functional, and behavioral levels in the Tg2576 mouse model of AD. Our data show that decreased dendritic spine density, impaired long-term potentiation (LTP), and behavioral deficits occurred months before plaque deposition, which was first detectable at 18 months of age. We detected a decrease in spine density in the outer molecular layer of the dentate gyrus (DG) beginning as early as 4 months of age. Furthermore, by 5 months, there was a decline in LTP in the DG after perforant path stimulation and impairment in contextual fear conditioning. Moreover, an increase in the Aβ42/Aβ40 ratio was first observed at these early ages. However, total amyloid levels did not significantly increase until ≈18 months of age, at which time significant increases in reactive astrocytes and microglia could be observed. Overall, these data show that the perforant path input from the entorhinal cortex to the DG is compromised both structurally and functionally, and this pathology is manifested in memory defects long before significant plaque deposition.

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Abstract: Summary paragraph The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and disease biology of heart, lung, blood, and sleep disorders, with the ultimate goal of improving diagnosis, treatment, and prevention. The initial phases of the program focus on whole genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here, we describe TOPMed goals and design as well as resources and early insights from the sequence data. The resources include a variant browser, a genotype imputation panel, and sharing of genomic and phenotypic data via dbGaP. In 53,581 TOPMed samples, >400 million single-nucleotide and insertion/deletion variants were detected by alignment with the reference genome. Additional novel variants are detectable through assembly of unmapped reads and customized analysis in highly variable loci. Among the >400 million variants detected, 97% have frequency

HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

Abstract: In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies--treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism--are needed to reverse or improve HAND-related neurological dysfunction.

Tetracyclines: Nonantibiotic properties and their clinical implications

Abstract: Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.