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Genetic and epigenetic alterations are involved in pituitary adenoma pathogenesis, however the molecular basis of proliferative nonfunctioning pituitary adenomas (NFPAs) remains unclear. Here, we analyzed integrated multi-omics profiling including copy number variation (CNV), DNA methylation and gene expression of 8 NFPAs. We collected 4 highly proliferative (hpNFPA, Ki-67 ≥ 3) and 4 lowly proliferative (Ki-67 ≤ 1) NFPAs, and comprehensively assessed CNV, DNA methylation, and gene expression by Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip PrimeView Human Gene Expression Array. We performed Ingenuity Pathway Analysis (IPA) for differentially expressed genes to illustrate aberrant pathways and delineated protein-protein networks of selected key genes in dysregulated pathways. Aberrant arm level CNV, dysregulated DNA methylation, and associated impacts on gene expressions were observed in 2 early occurring hpNFPAs. Chromosomal losses were associated with attenuated expression of DNA methyls of hpNFPA. Spindle cell oncocytoma (SCO) is an extremely rare sellar neoplasm. No observational studies have been reported so far to investigate the prognostic factors of this tumor entity. This systematic review aimed to elucidate the risk factors for tumor recurrence/progression of SCO. We searched for relevant articles in PubMed and Web of Science. https://www.selleckchem.com/products/repsox.html Studies providing individual patient data with follow-up information of SCO cases were included. Pearson's Chi square and Fisher's exact test were used for categorical variables while t test or Mann-Whitney tests were applied for continuous variables, if applicable. We used the Cox regression model to assess the effects of suspected variables on progression-free survival (PFS). A total of 38 case reports and case series comprising of 67 SCOs were included for final analyses. Recurrent/progressive tumors were noted in 38.8% of cases. Among the clinicopathological factors, only the extent of surgery was a significant risk factor for tumor recurrence/progression. SCO patients with a subtotal resection had a significantly higher risk for tumor relapse in comparison with complete removal (HR 7.51; 95% CI 1.75-32.31; p = 0.007). Our study demonstrated the characteristic clinicopathological features of SCOs with a high recurrence/progression rate and outlined the predictor for tumor relapse. Failure to achieve gross total resection is the only risk factor for tumor recurrence/progression. Our study demonstrated the characteristic clinicopathological features of SCOs with a high recurrence/progression rate and outlined the predictor for tumor relapse. Failure to achieve gross total resection is the only risk factor for tumor recurrence/progression. Potentially inappropriate medications (PIMs) often lead to sub-optimal or poor health outcomes in older adults. The objective of this study was to determine the prevalence and predictors of PIM prescription among older adults in Qatar. This was a cross-sectional, retrospective study using data from the electronic medical records of Qatari patients (age ≥ 65 years) attending the 23 primary healthcare (PHC) centers in Qatar from April 1, 2017 to September 30, 2017. PIMs were identified based on the Beers 2015 criteria (1) medications to avoid for many or most older adults, and (2) medications to be used with caution in older adults. Descriptive statistics were used to estimate the prevalence of PIM prescription; multivariable logistic regression analysis was performed to identify predictors of PIM prescription among the study population. 5639 older adults were included with a mean age of 72.8 (± 6.5) years; 53.8% were females. The prevalence of PIMs that should be avoided was 60.7%, with the most prevalent ones being gastrointestinal (84.2%), pain (49.9%), and central nervous system (10.4%) drugs. Most patients (61.1%) were prescribed one PIM, 26.9% two PIMs, and 12.0% three or more PIMs. The prevalence of PIMs that should be used with caution was 40.6%, with diuretics (83.1%), antidepressants (25.7%), and antiplatelets (18.3%) as the most prevalent drug classes. Multivariable logistic regression showed female gender, polypharmacy, and certain comorbidities to be significant predictors of PIM prescription. Older adults attending Qatar's 23 PHC centers are prescribed a high number of PIMs. Because of the high risk of PIM prescription, the practice of medication reconciliation should be strengthened and reinforced. Older adults attending Qatar's 23 PHC centers are prescribed a high number of PIMs. Because of the high risk of PIM prescription, the practice of medication reconciliation should be strengthened and reinforced.DNA methylation is an essential epigenetic mark that regulates normal mammalian embryonic development. DNA methylation profiles are not always static, especially during germline development. In zygotes, DNA is typically highly methylated but, during preimplantation, DNA methylation is erased globally. Then, at the start of post-implantation development in mouse embryos, DNA again becomes dramatically hypermethylated. Chromatin structure regulates the accessibility of DNA-modifying enzymes to target DNA. Beyond that, however, our understanding of the pathway by which chromatin regulation initiates changes in global DNA methylation during mouse embryonic development remains incomplete. To analyse the relationship between global regulation of DNA methylation and chromatin status, we examined 5-methylcytosine (5mC), modified by the DNA methyltransferase DNMT, and the oxidative derivative 5-hydroxymethylation (5hmC), converted from 5mC by TET-family enzymes, by means of immunofluorescence staining of mitotic chromosomes in mouse embryonic stem cells (ESCs). Our comparison of immunostaining patterns for those epigenetic modifications in wild-type, DNMT-deficient, and TET-deficient ESCs allowed us to visualise cell cycle-mediated DNA methylation changes, especially in euchromatic regions. Our findings suggest that DNA methylation patterns in undifferentiated mouse ESCs are stochastically balanced by the opposing effects of two activities demethylation by TET and subsequent remethylation by DNMT.
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