Background: All relevant authorities recommend an interval of 10 years between normal screening colonoscopies. We assessed the timing of repeated colonoscopies after a negative screening colonoscopy finding in a population-based sample of Medicare patients. Methods: A 5% national sample of Medicare enrollees from 2000 through 2008 was used to identify average-risk patients undergoing screening colonoscopy between 2001 and 2003. Colonoscopy was classified as a negative screening examination finding if no indication other than screening were in the claims and if no biopsy, fulguration, or polypectomy was performed. Time to repeated colonoscopy was calculated. Results: Among 24 071 Medicare patients who had a negative screening colonoscopy finding in 2001 through 2003, 46.2% underwent a repeated examination in fewer than 7 years. In 42.5% of these patients (23.5% of the overall sample), there was no clear indication for the early repeated examination. In patients aged 75 to 79 years or 80 years or older at the time of the initial negative screening colonoscopy result, 45.6% and 32.9%, respectively, received a repeated examination within 7 years. In multivariable analyses, male sex, more comorbidities, and colonoscopy by a high-volume colonoscopist or in an office setting were associated with higher rates of early repeated colonoscopy without clear indication, while those 80 years or older had a reduced risk. There were also marked geographic variations, from less than 5% in some health referral regions to greater than 50% in others. Conclusions: A large proportion of Medicare patients who undergo screening colonoscopy do so more frequently than recommended. Current Medicare regulations intending to limit reimbursement for screening colonoscopy to every 10 years would not appear to be effective.

OBJECTIVES To evaluate the extent to which preexisting mental disorders influence diagnosis, treatment, and survival in older adults with colon cancer. DESIGN Retrospective cohort study. SETTING The Surveillance, Epidemiology and End Results (SEER)–Medicare linked database. PARTICIPANTS Eighty thousand six hundred seventy participants, aged 67 and older with a diagnosis of colon cancer. MEASUREMENTS The association between the presence of a preexisting mental disorder and the stage of colon cancer at diagnosis, receipt of cancer treatment, and overall and colon cancer-specific mortality were assessed using Cox proportional hazards regression and logistic regression. RESULTS Participants with mental disorders were more likely to have been diagnosed with colon cancer at autopsy (4.4% vs 1.1%; P<.001) and at an unknown stage of cancer (14.6% vs 6.2%; P<.001); to have received no surgery, chemotherapy, or radiation therapy (adjusted risk ratio (ARR) =2.09, 95% confidence interval (CI) =1.86–2.35); and to have received no chemotherapy for Stage 3 cancer (ARR =1.63, 95% CI =1.49–1.79). The rate of overall mortality (hazard ratio (HR) =1.33, 95% CI =1.31–1.36) and colon cancer-specific mortality (HR =1.23, 95% CI =1.19–1.27) was substantially higher in participants with a preexisting mental disorder than in their counterparts. All of these associations were particularly pronounced in participants with psychotic disorders and those with dementia. CONCLUSION Public health initiatives are needed to improve colon cancer detection and treatment in older adults with mental disorders.

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The RE1 Silencing Transcription Factor (REST) is a repressor of neuronal differentiation and its elevated expression in neural cells blocks neuronal differentiation. In the present study, we demonstrate a role for REST in the control of proliferation of medulloblastoma cells. REST expression decreased the levels of CDKNIB/p27, a cyclin-dependent kinase inhibitor and a brake of cell proliferation in these cells. The reciprocal relationship between REST and p27 was validated in human tumor samples. REST knockdown in medulloblastoma cells derepessed a novel REST-target gene encoding the deubiquitylase ubiquitin-specific peptidase 37 (USP37). Ectopically expressed wild type USP37 formed a complex with p27, promoted its deubiquitination and stabilization and blocked cell proliferation. Knockdown of REST and USP37 prevented p27 stabilization and blocked the diminution in proliferative potential that normally accompanied REST loss. Unexpectedly, wild type USP37 expression also induced the expression of REST-target neuronal differentiation genes even though REST levels were unaffected. In contrast, a mutant of USP37 carrying a site-directed change in a conserved cysteine failed to rescue REST-mediated p27 destabilization, maintenance of cell proliferation and blockade to neuronal differentiation. Consistent with these findings, a significant correlation between USP37 and p27 was observed in patient tumors. Collectively, these findings provide a novel connection between REST and the proteasomal machinery in the control of p27 and cell proliferation in medulloblastoma cells.

Brassinosteroids (BRs) hormones are important for plant growth, development and immune responses. They are sensed by the transmembrane receptor kinase Brassinosteroid-Insensitive 1 (BRI1) when they bind to its extracellular Leu-rich repeat (LRR) domain. We cloned and characterized the TaBRI1 from T. aestivum and raised overexpression transgenics in Arabidopsis to decipher its functional role. TaBRI1 protein consists of a putative signal peptide followed by 25 leucine rich repeats (LRR), a transmembrane domain and a C-terminal kinase domain. The analysis determined the interaction of TaBRI1 with five members of the wheat Somatic Embryogenesis Receptor Kinase (TaSERKs) gene family (TaSERK1, TaSERK2, TaSERK3, TaSERK4 and TaSERK5), at the plasma membrane. Furthermore, overexpression of TaBRI1 in Arabidopsis leads to the early flowering, increased silique size and seed yield. Root growth analysis of TaBRI1 overexpressing transgenic plants showed hypersensitivity to epi-brassinolide (epi-BL) hormone in a dose-dependent manner. Interestingly, transgenic Arabidopsis plants show thermotolerance phenotype at the seedling stages as revealed by chlorophyll content, photosystem II activity and membrane stability. The transcriptome profiling on the basis of microarray analysis indicates up-regulation of several genes related to brassinosteroid signaling pathway, abiotic stress response, defense response and transcription factors. These studies predict the possible role of TaBRI1 gene in plant growth and development imparting tolerance to thermal stress.

BACKGROUND:The repressor element-1 silencing transcription factor (REST) is a repressor of neuronal genes. Its expression is associated with poor neuronal differentiation in many neuroblastoma patient samples and cell lines. Because retinoic acid promotes neuronal differentiation, the authors postulated that it involves modulation of REST expression.