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Cynthia Wu Michael Sean McMurtry Roopinder K. Sandhu Erik Youngson Justin A. Ezekowitz Padma Kaul Finlay A. McAlister 《PloS one》2015,10(10)
Background and Purpose
We studied whether anticoagulant use and outcomes differed between rural versus urban Canadian non-valvular atrial fibrillation (NVAF) patients prior to the introduction of direct oral anticoagulant drugs.Methods
Retrospective cohort study of 25,284 adult Albertans with NVAF between April 1, 1999 and December 31, 2008.Results
Compared to urban patients, rural patients were older (p = 0.0009) and had more comorbidities but lower bleeding risk at baseline. In the first year after NVAF diagnosis, urban patients were less likely to be hospitalized (aOR 0.82, 95%CI 0.77–0.89) or have an emergency department visit for any reason (aOR 0.61, 95%CI 0.56–0.66) but warfarin dispensation rates (72.2% vs 71.8% at 365 days, p = 0.98) and clinical outcomes were similar: 7.8% died in both groups, 3.2% rural vs. 2.8% urban had a stroke or systemic embolism (SSE) (aOR 0.92, 95%CI 0.77–1.11), and 6.6% vs. 5.7% (aOR 0.93, 95%CI 0.81–1.06) had a bleed. Baseline SSE risk did not impact warfarin dispensation (73.0% in those with high vs. 72.8% in those with low CHADS2 score, p = 0.85) but patients at higher baseline bleeding risk were less likely to be using warfarin (69.2% high vs. 73.6% low HASBLED score, p<0.0001) in the first 365 days after diagnosis. In warfarin users, bleeding was more frequent (7.5% vs 6.2%, aHR 1.51 [95%CI 1.33–1.72]) but death or SSE was less frequent (7.0% vs 18.1%, aHR 0.60 [0.54–0.66]).Conclusion
Warfarin use and clinical event rates did not differ between rural and urban NVAF patients in a universal access publically-funded healthcare system. 相似文献23.
Das B Chowdhury C Kumar D Sen R Roy R Das P Chatterjee M 《Bioorganic & medicinal chemistry letters》2010,20(23):6947-6950
A series of analogues of andrographolide, prepared through chemo-selective functionalization at C14 hydroxy, have been evaluated for in vitro cytotoxicities against human leukemic cell lines. Two of the analogues (6a, 9b) exhibited significant potency. Preliminary studies on structure-activity relationship (SAR) revealed that the α-alkylidene-γ-butyrolactone moiety of andrographolide played a major role in the activity profile. The structures of the analogues were established through spectroscopic and analytical data. 相似文献
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Chien JR Aletti G Bell DA Keeney GL Shridhar V Hartmann LC 《Journal of cellular biochemistry》2007,102(5):1117-1129
Ovarian cancer, the most aggressive gynecologic cancer, is the foremost cause of death from gynecologic malignancies in the developed world. Two primary reasons explain its aggressive behavior: most patients present with advanced disease at diagnosis, and die of recurrences from disease that has become resistant to conventional chemotherapies. In this paper on epithelial ovarian cancer (EOC), we will review molecular alterations associated with the few precursor lesions identified to date, followed by the more commonly recognized processes of de novo carcinogenesis, metastasis, and the development of chemoresistance. We will propose a unifying model of ovarian epithelial tumorigenesis that takes into account various hypotheses. We will also review novel approaches to overcome the major problem of chemoresistance in ovarian cancer. Finally, we will discuss advances and new challenges in the development of mouse model systems to investigate EOC precursor lesions, progression, metastasis, and chemoresistance. 相似文献
27.
NFIL3 Suppresses Hypoxia‐induced Apoptotic Cell Death by Targeting the Insulin‐like Growth Factor 2 Receptor
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Josephine Anthony Vijaya Raghavan Rangamaran Dharani Gopal Kumar T. Shivasankarasubbiah Mary Leema J. Thilagam Magesh Peter Dhassiah Divya Shridhar M. Padinjattayil VinithKumar N. Valsalan Vijayakumaran Manambrakat Sivakumar Dakshinamurthy Sivaraman Thirunavukkarasu Kirubagaran Ramalingam 《Marine biotechnology (New York, N.Y.)》2015,17(1):66-80
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Dang Y Schneider-Poetsch T Eyler DE Jewett JC Bhat S Rawal VH Green R Liu JO 《RNA (New York, N.Y.)》2011,17(8):1578-1588
Mycalamide B (MycB) is a marine sponge-derived natural product with potent antitumor activity. Although it has been shown to inhibit protein synthesis, the molecular mechanism of action by MycB remains incompletely understood. We verified the inhibition of translation elongation by in vitro HCV IRES dual luciferase assays, ribosome assembly, and in vivo [(35)S]methinione labeling experiments. Similar to cycloheximide (CHX), MycB inhibits translation elongation through blockade of eEF2-mediated translocation without affecting the eEF1A-mediated loading of tRNA onto the ribosome, AUG recognition, or dipeptide synthesis. Using chemical footprinting, we identified the MycB binding site proximal to the C3993 28S rRNA residue on the large ribosomal subunit. However, there are also subtle, but significant differences in the detailed mechanisms of action of MycB and CHX. First, MycB arrests the ribosome on the mRNA one codon ahead of CHX. Second, MycB specifically blocked tRNA binding to the E-site of the large ribosomal subunit. Moreover, they display different polysome profiles in vivo. Together, these observations shed new light on the mechanism of inhibition of translation elongation by MycB. 相似文献