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2.
Geriatr Orthop Surg Rehabil ; 11: 2151459320943165, 2020.
Article in English | MEDLINE | ID: mdl-32782850

ABSTRACT

Falls affect more than 29 million American adults ages ≥65 years annually. Many older adults experience recurrent falls requiring medical attention. These recurrent falls may be prevented through screening and intervention. In 2014 to 2015, records for 199 older adult patients admitted from a major urban teaching hospital's emergency department were queried. Open-ended variables from clinicians' notes were coded to supplement existing closed-ended variables. Of the 199 patients, 52 (26.1%) experienced one or more recurrent falls within 365 days after their initial fall. Half (50.0%) of all recurrent falls occurred within the first 90 days following discharge. A large proportion of recurrent falls among older adults appear to occur within a few months and are statistically related to identifiable risk factors. Prevention and intervention strategies, delivered either during treatment for an initial fall or upon discharge from an inpatient admission, may reduce the incidence of recurrent falls among this population.

3.
Sci Transl Med ; 12(539)2020 04 15.
Article in English | MEDLINE | ID: mdl-32295898

ABSTRACT

Osteoarthritis (OA) is a degenerative disease of the joint, which results in pain, loss of mobility, and, eventually, joint replacement. Currently, no disease-modifying drugs exist, partly because of the multiple levels at which cartilage homeostasis is disrupted. Recent studies have highlighted the importance of epigenetic dysregulation in OA, sparking interest in the epigenetic modulation for this disease. In our previous work, we characterized a fivefold increase in cytosine hydroxymethylation (5hmC), an oxidized derivative of cytosine methylation (5mC) associated with gene activation, accumulating at OA-associated genes. To test the role of 5hmC in OA, here, we used a mouse model of surgically induced OA and found that OA onset was accompanied by a gain of ~40,000 differentially hydroxymethylated sites before the notable histological appearance of disease. We demonstrated that ten-eleven-translocation enzyme 1 (TET1) mediates the 5hmC deposition because 98% of sites enriched for 5hmC in OA were lost in Tet1-/- mice. Loss of TET1-mediated 5hmC protected the Tet1-/- mice from OA development, including degeneration of the cartilage surface and osteophyte formation, by directly preventing the activation of multiple OA pathways. Loss of TET1 in human OA chondrocytes reduced the expression of the matrix metalloproteinases MMP3 and MMP13 and multiple inflammatory cytokines. Intra-articular injections of a dioxygenases inhibitor, 2-hydroxyglutarate, on mice after surgical induction of OA stalled disease progression. Treatment of human OA chondrocytes with the same inhibitor also phenocopied TET1 loss. Collectively, these data demonstrate that TET1-mediated 5hmC deposition regulates multiple OA pathways and can be modulated for therapeutic intervention.


Subject(s)
DNA-Binding Proteins , Mixed Function Oxygenases , Osteoarthritis , Pharmaceutical Preparations , Proto-Oncogene Proteins , 5-Methylcytosine , Animals , DNA-Binding Proteins/genetics , Mice , Osteoarthritis/genetics , Proto-Oncogene Proteins/genetics
4.
AJR Am J Roentgenol ; 213(6): 1267-1273, 2019 12.
Article in English | MEDLINE | ID: mdl-31532256

ABSTRACT

OBJECTIVE. The purpose of this study was to evaluate the utility of T1- and T2-weighted MRI signal-intensity ratios and signal-intensity SDs of renal lesions to determine the feasibility of distinguishing between simple cysts, hemorrhagic renal cysts, clear cell renal cell carcinoma (RCC), and papillary RCC. MATERIALS AND METHODS. Pathology records of 53 cases of papillary RCCs between 1 and 5 cm in size were included. Thirty-eight pathology-proven clear cell RCCs, 54 simple renal cysts seen on abdominal MRI, and 59 hemorrhagic renal cysts seen on abdominal MRI were identified. Lesion location and size, T1- and T2-weighted signal intensity, and corresponding SD values for each renal lesion and psoas muscle (from which lesion-to-muscle ratios were calculated) were collected. RESULTS. Analysis revealed a statistically significant difference (p < 0.001) in T1-weighted lesion-to-muscle signal-intensity ratios between simple cysts (mean ± standard error, 0.54 ± 0.05), clear cell RCCs (0.86 ± 0.06), papillary RCCs (1.17 ± 0.05), and hemorrhagic renal cysts (1.95 ± 0.04). The T2-weighted lesion-to-muscle signal-intensity ratios showed a statistically significant difference between all lesion types (p < 0.02) except between hemorrhagic renal cysts and papillary RCCs, where the difference approached significance (p = 0.075). ROC analysis showed an optimal cutoff of T1-weighted lesion-to-muscle signal-intensity ratio of 1.39 to differentiate hemorrhagic cysts (above this value) from RCCs (below this value). Corresponding sensitivity and specificity were 91.2% and 74.6%, respectively. CONCLUSION. T1-weighted lesion-to-muscle signal-intensity ratio is a useful measure to discriminate mildly hyperintense RCCs from more hyperintense hemorrhagic cysts when contrast enhancement is unavailable.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Hemorrhage/diagnostic imaging , Kidney Diseases, Cystic/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
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