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.

Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults

Abstract: Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults Eoin O’Brien,Thomas Pickering, Roland Asmar, Martin Myers, Gianfranco Parati, Jan Staessen, Thomas Mengden, Yutaka Imai, Bernard Waeber and Paolo Palatini and with the statistical assistance of Neil Atkins and William Gerin, on behalf of the Working Group on Blood Pressure Monitoring of the European Society of Hypertension

Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche

Abstract: Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1(hi) monocytes (MOs), Gr-1(lo) MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin(+) niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169(+) MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin(+) niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.

Detection of Abnormal Memory Decline in Mild Cases of Alzheimer's Disease Using CERAD Neuropsychological Measures

Abstract: • The present study was designed to determine which of the memory tasks included in the CERAD ( C onsortium to E stablish a R egistry for A lzheimer's D isease) neuropsychological battery best differentiate patients with early Alzheimer's disease from cognitively normal elderly control subjects and also best distinguish between the various levels of severity of the dementia process. A sample of CERAD patients with Alzheimer's disease was stratified by disease severity into those with mild, moderate, or severe dementia and matched with control subjects for sex, age, and education. Using multivariate procedures and cutting scores, the efficacy of each memory measure in distinguishing between these groups and control subjects was determined. The test for delayed recall was found to be the best overall discriminatory measure. The other tests of memory, ie, immediate recall, intrusion errors, and recognition memory, had poor overall discriminability. None of the CERAD memory measures were found to be particularly powerful in staging the severity of dementia. These findings suggest that tests for delayed recall may be particularly useful in the early detection of Alzheimer's disease and should be considered in screening batteries for dementia in community surveys.

Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy

Abstract: CD8 + T cell–dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (“A,” “B,” and “C”) improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8 + T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.