DCM

DCM
  • 文章类型: Journal Article
    扩张型心肌病(DCM)是最常见的原发性心肌病之一。然而,直到今天,它仍然是一种神秘的心血管疾病(CVD),其特征是心室扩张,导致心肌收缩功能障碍.它是慢性充血性心力衰竭的最常见原因,也是年轻人进行心脏移植的最常见指征。遗传学和各种其他因素在扩张型心肌病的进展中起着重要作用,超过50个基因的变异与该疾病相关。然而,大量病例的病因仍然难以捉摸。已经对扩张型心肌病的遗传原因进行了许多研究。这些基因研究表明,纤连蛋白基因的突变,细胞骨架蛋白,心肌细胞中的肌球蛋白在DCM的发生发展中起关键作用。在这次审查中,我们提供了遗传基础的全面描述,机制,以及基于循证医学的与DCM密切相关的基因的研究进展。我们还强调了基因测序在潜在的早期诊断和改善DCM临床治疗中的重要作用。
    Dilated cardiomyopathy (DCM) is one of the most common primary myocardial diseases. However, to this day, it remains an enigmatic cardiovascular disease (CVD) characterized by ventricular dilatation, which leads to myocardial contractile dysfunction. It is the most common cause of chronic congestive heart failure and the most frequent indication for heart transplantation in young individuals. Genetics and various other factors play significant roles in the progression of dilated cardiomyopathy, and variants in more than 50 genes have been associated with the disease. However, the etiology of a large number of cases remains elusive. Numerous studies have been conducted on the genetic causes of dilated cardiomyopathy. These genetic studies suggest that mutations in genes for fibronectin, cytoskeletal proteins, and myosin in cardiomyocytes play a key role in the development of DCM. In this review, we provide a comprehensive description of the genetic basis, mechanisms, and research advances in genes that have been strongly associated with DCM based on evidence-based medicine. We also emphasize the important role of gene sequencing in therapy for potential early diagnosis and improved clinical management of DCM.
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  • 文章类型: Systematic Review
    Background: Taurine, 2-aminoethanesulfonic acid, is an amino acid found in animal products. Taurine is produced for human consumption as a supplement and ingredient in beverages. Supplementation is a safe, inexpensive, and effective treatment for dilated cardiomyopathy (DCM) in domestic mammals, however it is currently unlicensed in Europe and the United States for human medical treatment. Recent genome-wide association studies of DCM have identified the locus of the taurine transporter ( SLC6A6). To assess whether taurine supplementation may be a novel therapeutic option for DCM, we undertook a systematic review. Methods: Four electronic databases (PubMed, Cochrane Central Register, Web of Science, Biomed Central) were searched until 11/03/21. Included studies of human participants reported measured phenotypes or symptoms for cardiomyopathy, heart failure (HF), or altered left ventricle structure or function, administering taurine in any formulation, by any method. Non-English articles were excluded. Meta-analysis was completed in R software (version 3.6.0). The Newcastle-Ottawa Scale quality assessment score (NOQAS) tool was used to assess bias. Results: 285 articles were identified, of which eleven met our criteria for inclusion. Only one paper was deemed \"high quality\" using the NOQAS tool. Taurine supplementation varied across studies; by dose (500 mg to 6g per day), frequency (once to thrice daily), delivery method (tablet, capsule, drink, powder), and duration (2 to 48 weeks). Patient inclusion was all-cause HF patients with ejection fraction (EF) <50% and no study was specific to DCM. While improvements in diastolic and systolic function, exercise capacity, and haemodynamic parameters were described, only EF and stroke volume were measured in enough studies to complete a meta-analysis; the association was not significant with all-cause HF (P<0.05). No significant safety concerns were reported. Conclusions: A formal clinical trial is needed to address whether taurine supplementation is beneficial to the approximately 1/250 individuals with DCM in the population.
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  • 文章类型: Journal Article
    BACKGROUND: The potential association between Parvovirus B19 and heart disease has been controversial. The aim of the present study was to report the prevalence of B19 in myocarditis and dilated cardiomyopathy (DCM) as well as measure the statistical association between them.
    METHODS: Our systematic search was carried out to retrieve published articles between January 2000 and March 2021 using three major databases: PubMed, Scopus, and Web of Science, as well as the Google Scholar search engine. The overall prevalence of HAV, pooled odds ratio, and heterogeneity were estimated by comprehensive meta-analysis (V2.2, Biostat) software.
    RESULTS: The overall prevalence results in myocarditis and DCM were 23.7% (95% CI: 18.7%-29.5%) and 34.1% (95% CI: 23.8%-46.1%) respectively; in addition, the overall OR for B19 and myocarditis was 4.317 (95% CI, 1.831-10.180) versus 1.163 (95% CI: 0.706-1.916) for B19 and DCM.
    CONCLUSIONS: Our findings have shown a significant association between Parvovirus B19 and myocarditis with a high prevalence. In the case of DCM, no significant association was found while the prevalence of the virus was relatively high.
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  • 文章类型: Journal Article
    动态因果模型(DCM)-从大脑活动测量中推断隐藏神经元状态的框架(例如g.,fMRI)及其上下文相关调制是为人类神经成像开发的,并且尚未针对非人灵长类动物(NHP)研究进行优化,通常在麻醉下进行。动物神经成像研究通过将功能成像与侵入性程序(例如体内光遗传学或电刺激)相结合,提供了使用DCM改善有效连接建模的潜力。采用贝叶斯方法,基于可能与神经和BOLD动力学相关的条件的先验知识来估计模型参数(例如,需要关于合理参数值范围的经验知识)。因此,Weaddressthefollowingquestionsinthisreview:WhatfactorsneedstobeconsideredwhenapplyDCMtoNHPdata?Whatdifferencesinfunctionalnetworks,与DCM应用相关的人和NHP之间存在脑血管结构和生理学?麻醉药如何影响血管生理学,BOLD对比,和神经动力学——特别是,内部有效沟通,以及网络之间?考虑到DCM应用于NHP神经成像的相关因素,我们提出了一种使用综合生理-随机DCM(IPS-DCM)对麻醉下的有效连通性进行建模的策略.
    Dynamic causal modeling (DCM)-a framework for inferring hidden neuronal states from brain activity measurements (e. g., fMRI) and their context-dependent modulation-was developed for human neuroimaging, and has not been optimized for non-human primate (NHP) studies, which are usually done under anesthesia. Animal neuroimaging studies offer the potential to improve effective connectivity modeling using DCM through combining functional imaging with invasive procedures such as in vivo optogenetic or electrical stimulation. Employing a Bayesian approach, model parameters are estimated based on prior knowledge of conditions that might be related to neural and BOLD dynamics (e.g., requires empirical knowledge about the range of plausible parameter values). As such, we address the following questions in this review: What factors need to be considered when applying DCM to NHP data? What differences in functional networks, cerebrovascular architecture and physiology exist between human and NHPs that are relevant for DCM application? How do anesthetics affect vascular physiology, BOLD contrast, and neural dynamics-particularly, effective communication within, and between networks? Considering the factors that are relevant for DCM application to NHP neuroimaging, we propose a strategy for modeling effective connectivity under anesthesia using an integrated physiologic-stochastic DCM (IPS-DCM).
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  • 文章类型: Journal Article
    The history of stem cell therapies is one of a limited number of clinical applications despite a vast therapeutic potential. Major breakthroughs in stem cell research have not yet enjoyed clinical success-all stem cell therapies bar hematopoietic stem cell transplantations remain experimental. With the increased risk of organ failure and neurodegenerative disease associated with our ability to push the boundaries of life expectancy comes an increased pressure to pioneer novel stem cell-based therapeutic approaches. We conclude that the failure of such therapies to achieve clinical translation stems from the polarising effect of the ethical debate around their use. The intractability of the ethical debate is double edged: legislators not only have placed tighter restrictions on certain stem cell therapies, but do so in favour of less controversial cells which will have worse outcomes for patients. It is by considering this relationship between the politics, ethics and science of stem cells that the reasons for the currently limited clinical significance of stem cell therapies be realised.
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  • 文章类型: Journal Article
    背景:最近由国际脊柱研究信托基金(ISRT)和生命之翼基金会赞助的国际成像专家会议确定了5种最先进的MRI技术,这些技术有可能通过阐明微观结构和功能的元素来改变脊髓成像领域:扩散张量成像(DTI),磁化转移(MT),髓鞘水组分(MWF),MR波谱(MRS),和功能磁共振成像(fMRI)。然而,这些技术的临床转化进展尚未确定。
    方法:使用MEDLINE对英语文献进行了系统回顾,MEDLINE正在进行中,Embase,和Cochrane数据库来识别所有调查效用的人类研究,在诊断方面,与残疾的相关性,以及对结果的预测,这些有前途的技术在影响脊髓的病理。有关研究设计的数据,主题特征,MRI方法,损害的临床措施,和分析技术进行了提取和制表,以确定趋势和共性。这些研究评估了偏倚的风险,并使用建议分级评估对每个具体发现的总体证据质量进行评估,发展和评价(等级)框架。
    结果:在数据库搜索中总共发现了6597篇独特的引文,在对274篇文章进行全文审查后,共有104项相关研究被确定为最终纳入研究(97%来自初始数据库搜索).其中,69项研究使用了DTI,25项使用了MT,这两种技术显示近年来出版物数量增加。审查还确定了1MWF研究,11MRS研究,和8个fMRI研究。大多数研究都是探索性的,缺乏先验假设,并显示出高(72%)或中等高(20%)的偏见风险,由于研究设计的问题,采集技术,和分析方法。每种技术的收购在不同的研究中差异很大,呈现度量的直接比较无效。DTI度量分数各向异性(FA)具有最强的效用证据,具有中等质量的证据,证明其用作生物标志物,表明在几种临床病理中与残疾相关,和低水平的证据表明,与健康对照组相比,它识别组织损伤(在组差异方面)。然而,没有足够的证据来确定其作为敏感和特异性的诊断测试或作为预测临床结果的工具的效用.非常低的质量证据表明,与对照组相比,其他指标也显示出群体差异,包括DTI指标平均扩散系数(MD)和径向扩散系数(RD),扩散峰度成像(DKI)度量平均峰度(MK),MT指标MT比率(MTR)和MT脑脊液比率(MTCSF),和N-乙酰天冬氨酸(NAA)浓度的MRS度量,尽管这些结果有些不一致。
    结论:最先进的脊髓MRI技术正在兴起,在改善各种脊柱病变的诊断和治疗方面具有巨大潜力,但是到目前为止,目前的证据仅显示出有限的临床实用性。在这些成像工具中,DTI是最成熟的,但是在临床领域采用之前,还需要进一步的工作来标准化和验证其使用。大,精心设计的具有先验假设的研究,标准化的获取方法,详细的临床数据收集,和强大的自动分析技术需要充分展示这些快速发展的技术的潜力。
    BACKGROUND: A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI). However, the progress toward clinical translation of these techniques has not been established.
    METHODS: A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
    RESULTS: A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were identified for final inclusion (97% from the initial database search). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing an increased number of publications in recent years. The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls. However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent.
    CONCLUSIONS: State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.
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  • 文章类型: Journal Article
    持久性有机污染物(POPs)由于其持久性而成为主要的环境问题。远程运输,生物积累和对生物体的潜在不利影响。分析化学在持久性有机污染物的测量中起着至关重要的作用,并提供了有关其分布和环境变化的重要信息。在过去的二十年中,人们付出了很多努力来开发更快,更安全,这些污染物的更可靠、更灵敏的分析技术。自12年前通过关于持久性有机污染物的斯德哥尔摩公约以来,分析方法得到了广泛的发展。这篇综述文章介绍了环境和生物群样品中持久性有机污染物测定的最新分析技术和应用,并总结了提取,卤化持久性有机污染物的分离和仪器分析。此外,这项审查涵盖了SCPOPs分析的重要方面(例如脂质测定和质量保证/质量控制(QA/QC)),最后讨论了改进持久性有机污染物分析和潜在新持久性有机污染物的未来趋势。
    Persistent organic pollutants (POPs) are major environmental concern due to their persistence, long-range transportability, bio-accumulation and potentially adverse effects on living organisms. Analytical chemistry plays an essential role in the measurement of POPs and provides important information on their distribution and environmental transformations. Much effort has been devoted during the last two decades to the development of faster, safer, more reliable and more sensitive analytical techniques for these pollutants. Since the Stockholm Convention (SC) on POPs was adopted 12 years ago, analytical methods have been extensively developed. This review article introduces recent analytical techniques and applications for the determination of POPs in environmental and biota samples, and summarizes the extraction, separation and instrumental analyses of the halogenated POPs. Also, this review covers important aspects for the analyses of SC POPs (e.g. lipid determination and quality assurance/quality control (QA/QC)), and finally discusses future trends for improving the POPs analyses and for potential new POPs.
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  • 文章类型: Journal Article
    BACKGROUND: Dilated cardiomyopathy (DCM) is the most common form of nonischemic cardiomyopathy worldwide and can lead to sudden cardiac death and heart failure. Despite ongoing advances made in the treatment of DCM, improvement of outcome remains problematic. Stem cell therapy has been extensively studied in preclinical and clinical models of ischemic heart disease, showing potential benefit. DCM is associated with a major health burden, and few studies have been performed on cell therapy for DCM. In this systematic review we aimed to provide an overview of preclinical and clinical studies performed on cell therapy for DCM.
    RESULTS: A systematic search, critical appraisal, and summarized outcomes are presented. In total, 29 preclinical and 15 clinical studies were included. Methodologic quality of reported studies in general was low based on the Centre for Evidence Based Medicine, Oxford University, criteria. A large heterogeneity in inclusion criteria, procedural characteristics, and outcome measures was noted. The majority of studies showed a significant increase in left ventricular ejection fraction after cell therapy during follow-up.
    CONCLUSIONS: Stem cell therapy has shown moderate but significant effects in clinical trials for ischemic heart disease, but it remains to be determined if we can extrapolate these results to DCM patients. There is a need for methodologically sound studies to elucidate underlying mechanisms and translate those into improved therapy for clinical practice. To validate safety and efficacy of cell therapy for DCM, adequate randomized (placebo) controlled trials using different strategies are mandatory.
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