Background and Purpose-Limited data exist concerning obesity and survival in patients after acute stroke. The objective of this study was to investigate the association between obesity and survival in patients with acute first-ever stroke. Methods-Patients were prospectively investigated based on a standard diagnostic protocol over a period of 16 years.Evaluation was performed on admission, at 7 days, at 1, 3, and 6 months after discharge, and yearly thereafter for up to 10 years after stroke. The study patients were divided into 3 groups according to body mass index (BMI): normal weight (Ͻ25 kg/m 2 ), overweight (25-29.9 kg/m 2 ), and obese (Ն30 kg/m 2 ). Overall survival during follow-up was the primary end point. The secondary end point was the overall composite cardiovascular events over the study period.Results-Based on our inclusion criteria, 2785 patients were recruited. According to BMI, 1138 (40.9%)
LINE-1 and Alu elements are non-LTR retrotransposons, constituting together over 30% of the human genome and they are frequently hypomethylated in human tumors. A relationship between global hypomethylation and genomic instability has been shown, however, there is little evidence to suggest active role for hypomethylation-mediated reactivation of retroelements in human cancer. In our study, we examined by Pyrosequencing the methylation levels of LINE-1 and Alu sequences in 48 primary nonsmall cell carcinomas and their paired adjacent tissues. We demonstrate a significant reduction of the methylation levels of both elements (p 5 7.7 3 10 214 and 9.6 3 10 27 , respectively). The methylation indices of the 2 elements correlated (p 5 0.006), suggesting a possible common mechanism for their methylation maintenance. Genomic instability was measured utilizing 11 fluorescent microsatellite markers located on lung cancer hot-spot regions such as 3p, 5q 9p, 13q and 17p. Hypomethylation of both transposable elements was associated with increased genomic instability (LINE, p 5 7.1 3 10 25 ; Alu, p 5 0.008). The reduction of the methylation index of LINE-1 and Alu following treatment of 3 lung cell lines with 5-aza-2 0 -deoxycitidine, consistently resulted in increased expression of both elements. Our study demonstrates the strong link between hypomethylation of transposable elements with genomic instability in non-small cell lung cancer and provides early evidence for a potential active role of these elements in lung neoplasia. As demethylating agents are now entering lung cancer trials, it is imperative to gain a greater insight into the potential reactivation of silent retrotransposons in order to advance for the clinical utilization of epigenetics in cancer therapy. ' 2008 Wiley-Liss, Inc.Key words: LINE-1; Alu; hypomethylation; genomic instability; lung cancer LINE-1 elements are autonomous non-LTR retrotransposons comprising almost 21% of the human genome. 1 Although most of these elements are inactive, mostly due to 5 0 truncations, there are a number of 80-100 intact LINE-1 elements that remain capable of retrotransposition. 2,3 The full length human LINE-1 retrotransposon is about 6 kb consisting of a 5 0 UTR, two open reading frames (ORF 1 and ORF2), and a 3 0 UTR with a functional polyadenylation signal and a variable length poly-A tail. 1 The bicistronic mRNA of LINE-1 is generated by an internal promoter at the 5 0 UTR region. ORF1 encodes for p40, a 40 kDa RNA-binding protein with cis preference for LINE-1 RNA, while ORF2 encodes for a 150 kDa protein with 3 conserved domains. 4 LINE-1 retrotransposition is undertaken with the help of both ORF1 and ORF2 proteins through a target-primed reverse transcription mechanism (TPRT). 2 In normal human cells, transcription and retrotransposition of LINE-1 is suppressed by a variety of control mechanisms including methylation, siRNAs and transcription regulators. [4][5][6] As a result, cells manage to protect themselves from a number of adverse effects exerted by LINE-1 ...
Prestroke CHADS2 and CHA2DS2-VASc scores predict long-term stroke outcomes in non-AF patients with acute ischemic stroke. These scores may provide a simple way of stroke prognostic risk stratification among non-AF stroke patients.
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