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Benyam Kinde Harrison W. Gabel Caitlin S. Gilbert Eric C. Griffith Michael E. Greenberg 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(22):6800-6806
DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system. 相似文献
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Background
The purpose of this study was to compare the outcomes of trauma patients who were injured in a motor vehicle crash and tested positive for alcohol upon hospital arrival versus those who tested negative.Methods
Study data came from the US National Trauma Data Bank (2007–2010). Any blood alcohol concentration (BAC) found at or above the legal limit (≥0.08?g/dL) was considered “alcohol positive”, and if no alcohol was identified through testing, the patient was considered “alcohol negative”. Patients’ demographics including age >?=?14, race, gender, drug test results, systolic blood pressure, heart rate, injury severity score (ISS), and Glasgow Coma Scale (GCS) were included in the study. Propensity score and exact pair matching were performed between the groups using baseline characteristics.Results
From a total of 88,794 patients, 30.9% tested positive and 69.1% tested negative for alcohol. There were significant differences found between the groups regarding age, gender, race, and GCS (all p?<?0.001) as well as a significantly higher in-hospital mortality rate (3.5% vs. 2.7%, p?<?0.001) and median time to patient expiration (4 vs. 3 days, p?<?0.001) in the alcohol negative group. After running both matching scenarios, there was no evidence of a significant difference seen in the rates of in-hospital mortality or the median time to patient expiration between the alcohol groups in either matched comparison.Conclusion
Patients who tested positive for alcohol following a traumatic motor vehicle crash showed no significant increase in in-hospital mortality or time to expiration when compared to propensity score and exact matched patients who tested negative for alcohol. 相似文献6.
Yinong Young-Xu Julia Thornton Snider Robertus van Aalst Salaheddin M. Mahmud Edward W. Thommes Jason K.H. Lee David P. Greenberg Ayman Chit 《Vaccine》2019,37(11):1484-1490
Background
Observational studies of the relative effectiveness of influenza vaccines are essential for public health decision making. Their estimates, however, are subject to bias due to unmeasured confounders. Instrumental variable (IV) methods can control for observed and unobserved confounders.Methods
We used linked electronic medical record databases in the Veterans Health Administration (VHA) as well as Medicare administrative files to examine the relative vaccine effectiveness (rVE) of high-dose influenza vaccine (HD) versus standard-dose influenza vaccines (SD) in preventing hospitalizations among VHA-enrolled Veterans ≥65?years of age during 5 influenza seasons (2010–2011 through 2014–2015). Using multivariable IV Poisson regression modeling to address unmeasured confounding and bias, we analyzed the data by each season and through longitudinal analysis of all five seasons.Findings
We included 3,638,924 person–influenza seasons of observation where 158,636 (4%) were among HD vaccine recipients and 3,480,288 (96%) were among SD vaccine recipients. Of the 1,728,562 Veterans, 1,702,824 (98.5%) were male and 1,299,412 (75%) were non-Hispanic white. Based on the longitudinal analysis of all five seasons, the IV-adjusted rVE estimate of HD vs. SD was 10% (95% CI, 8–12%) against all-cause hospitalization; 18% (95% CI, 15–21%) against cardiorespiratory-associated hospitalization; and 14% (95% CI, 6–22%) against influenza/pneumonia-associated hospitalization. The findings by season were similar.Interpretation
Our analysis of VHA clinical data collected from approximately 1.7 million Veterans 65?years and older during five seasons demonstrates that high-dose influenza vaccine is more effective than standard-dose influenza vaccines in preventing influenza- or pneumonia-associated hospitalizations, cardiorespiratory hospitalizations, and all-cause hospitalizations. 相似文献7.
Diabetes mellitus(DM) negatively affects the development and progression of chronic liver diseases(CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma(HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed. 相似文献
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