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41.
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
42.
《Journal of vascular surgery》2020,71(1):149-157
ObjectiveVascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015.MethodsThis is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation.ResultsEleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts.ConclusionsThis study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members. 相似文献
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Alessandro Vatrella Angelantonio Maglio Corrado Pelaia Girolamo Pelaia Carolina Vitale 《Expert opinion on pharmacotherapy》2020,21(12):1505-1515
ABSTRACT
Introduction
‘Critical Asthma Syndrome’ (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes. 相似文献48.
Paul J. Devlin Brian W. McCrindle James K. Kirklin Eugene H. Blackstone William M. DeCampli Christopher A. Caldarone Ali Dodge-Khatami Pirooz Eghtesady James M. Meza Peter J. Gruber Kristine J. Guleserian Bahaaladin Alsoufi Linda M. Lambert James E. OBrien Erle H. Austin Jeffrey P. Jacobs Tara Karamlou 《The Journal of thoracic and cardiovascular surgery》2019,157(2):684-695.e8
Objective
Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.Methods
From 2005 to 2017, 593 neonates in the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort underwent a Norwood procedure. Median follow-up was 3.7 years. Multivariable parametric models, including a modulated renewal analysis, were performed.Results
Of the 593 neonates, 146 (25%) underwent 218 reinterventions for arch obstruction after the Norwood procedure: catheter-based (n = 168) or surgical (n = 50) at a median age of 4.3 months (quartile 1-quartile 3, 2.6-5.7). Interdigitation of the distal aortic anastomosis was protective against arch reintervention. Development of ≥ moderate tricuspid valve regurgitation and right ventricular dysfunction at any point was associated with arch reintervention. Nonsignificant variables for arch reintervention included shunt type and preoperative aortic measurements. Surgical arch reintervention was protective against arch reintervention, but transcatheter reintervention was associated with increased reintervention. Arch reintervention was not associated with increased mortality. There was wide institutional variation in incidence of arch reintervention (range, 0-40 reinterventions per 100 years patient follow-up) and in preintervention gradient (range, 0-64 mm Hg).Conclusions
Interdigitation of the distal aortic anastomosis during the Norwood procedure decreased the risk of arch reintervention. Surgical arch reintervention is more definitive than transcatheter. Arch reintervention after the Norwood procedure is not associated with increased mortality. Serial surveillance for arch obstruction, integrated with changes in right ventricular function and tricuspid valve regurgitation, is recommended after the Norwood procedure to improve outcomes. 相似文献49.
Rosario Gulias-Cañizo Anell Lagunes-Guillén Arturo González-Robles Erika Sánchez-Guzmán Federico Castro-Muñozledo 《Burns : journal of the International Society for Burn Injuries》2019,45(2):398-412
Background
Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.Materials and methods
Initially, EGCG was assayed on the rabbit corneal epithelial cell line RCE1(5T5) to establish the best testing conditions, and to avoid unwanted outcomes in the experimental animals. Then, we studied its effects on cell proliferation, cell cycle progression and cell differentiation. Afterwards, we instilled EGCG in experimental grade II corneal alkali burns in mice, three times a day up to 21 days, and evaluated by slit lamp examination and histological sections of corneal epithelial, corneal endothelial and stromal edema, as well as the presence of inflammatory cells and neovascularization.Results
EGCG reduced cell growth and led to a decline in the proportion of proliferative cells in a concentration dependent manner. At 10 μM, EGCG promoted cell differentiation, an effect not related with apoptosis or cytotoxicity. When 10 μM EGCG was instilled in corneal alkali burns in mice three times a day up to 21 days, EGCG significantly reduced corneal opacity and neovascularization. The improved clinical appearance of the cornea was associated to a controlled epithelial growth; epithelial morphology was similar to that observed in normal epithelium and contrasted with the hyperproliferative, desquamating epithelium observed in control burn wounds. EGCG reduced corneal, stromal and endothelial edema, and wound inflammation.Conclusion
This work constitutes the first evidence for the use of EGCG in the acute phase of a corneal alkali burn, representing a possible novel alternative to improve patient outcomes as an add-on therapy. 相似文献50.
Mark Verrill 《Surgery (Oxford)》2019,37(3):181-185
Multimodality primary therapies for breast cancer combined with earlier detection have led to a sharp decline in the death rate from breast cancer in the UK over the last 40 years in the face of a rising incidence. The latest UK statistics from Cancer Research UK report 55,122 new cases of breast cancer in 2015 with 11,563 deaths from breast cancer recorded in 2016. Crudely, this equates to a cure rate of around 80% for all comers and demonstrates a clear improvement in outcome with 50,285 new cases in 2011 and 11,716 deaths in 2012. Despite this good news, there are still significant numbers of women (and men) who suffer from either a local recurrence or metastatic disease following apparently successful treatment for early breast cancer (Stage I to III). Only a minority of individuals, 6.6% with the stage recorded at diagnosis, present with stage IV disease. This review considers the treatment options available to individuals with locally recurrent and advanced breast cancer (ABC). 相似文献