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.

The impact of post-operative pain on outcomes following hip fracture.

Abstract: Untreated pain is a major health care issue and very little is known about the treatment of pain and the effect of pain on post-operative outcomes in older adults. This study was performed to identify the impact of pain on outcomes following hip fracture in older adults. Four hundred and eleven consecutive cognitively intact patients admitted with hip fracture to four New York hospitals were enrolled in a prospective cohort study. Patients were interviewed daily using standardized pain assessments. We used multiple logistic regression and ordinary least squares linear regression to examine the association of post-operative pain on immediate post-operative outcomes (duration of stay, physical therapy sessions missed or shortened, ambulation following surgery, and post-operative complications) and outcomes 6 months following fracture (locomotion, mortality, return to the community, residual pain). Patients with higher pain scores at rest had significantly longer hospital lengths of stay (P=0.03), were significantly more likely to have physical therapy sessions missed or shortened (P=0.002), were significantly less likely to be ambulating by post-operative day 3 (P<0.001), took significantly longer to ambulate past a bedside chair (P=0.01), and had significantly lower locomotion scores at 6 months (P=0.02). Pain at rest was not significantly associated with post-operative complications, nursing home placement, survival at 6 months, or residual pain at 6 months. Post-operative pain is associated with increased hospital length of stay, delayed ambulation, and long-term functional impairment. Whereas appropriate caution is warranted in administering opioid analgesics to older adults, these data suggest that improved pain control may decrease length of stay, enhance functional recovery, and improve long-term functional outcomes.

Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease.

Abstract: Environmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin-proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD-inducing toxins. Here, we systemically injected six doses of naturally occurring (epoxomicin) or synthetic (Z-lle-Glu(OtBu)-Ala-Leu-al [PSI]) proteasome inhibitors into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture, which improved with apomorphine treatment. Positron emission tomography demonstrated reduced carbon-11-labeled 2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) binding to dopaminergic nerve terminals in the striatum, indicative of degeneration of the nigrostriatal pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic cell death with apoptosis and inflammation in the substantia nigra pars compacta. In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative sites, intracytoplasmic, eosinophilic, α-synuclein/ubiquitin–containing, inclusions resembling Lewy bodies were present in some of the remaining neurons. This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness. Ann Neurol 2004

Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel

Abstract: Metastasis, the cardinal feature of malignant tumors, is an important clinical variable in patient prognosis. To understand the basis for metastasis, we systematically selected for highly invasive cells from breast cancer cell lines, MCF7 and MDA-MB-453, with moderate to low invasive ability using Boyden chamber invasion assay. The four-cycle selected invasive lines, named MCF7-I4 and MDA-MB-453-I4, respectively, displayed epithelial-mesenchymal transition (EMT) and dramatically enhanced invasive ability. EMT changes were corroborated with decreased level of E-cadherin and increased vimentin, fibronectin, and beta(1) integrin. Twist, a basic helix-loop-helix transcription factor, and AKT2, a known proto-oncogene, were found to be elevated in the invasive cells compared with the parental. Ectopic expression and knockdown of Twist by short interference RNA resulted in significant increase and reduction, respectively, of AKT2 protein and mRNA expression. Twist bound to E-box elements on AKT2 promoter and enhanced its transcriptional activity. Moreover, silencing AKT2 decreased Twist-promoted migration, invasion, and paclitaxel resistance. Reintroducing AKT2 largely rescued the phenotype resulted from knockdown of Twist in I4 cells, suggesting that AKT2 is a downstream target and functional mediator of Twist. Finally, we observed a 68.8% correlation of elevated Twist and AKT2 expression in late-stage breast cancers as oppose to 13% in early-stage breast cancers. Our study identifies Twist as a positive transcriptional regulator of AKT2 expression, and Twist-AKT2 signaling is involved in promoting invasive ability and survival of breast cancer cells.