抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Nancy M. Albert, PhD, RN, FAHA

Biykem Bozkurt, MD, PhD, FACC, FAHA

Ralph G. Brindis, MD, MPH, MACC

Mark A. Creager, MD, FACC, FAHA[#][1]

Lesley H. Curtis, PhD, FAHA

David DeMets, PhD[#][1]

Robert A

/pdf/2014-aha-acc-hrs-guideline-for-the-management-of-patients-1v8ficsqox.pdf

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)  

Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC  

Endorsed by the European Stroke Organisation (ESO)

/pdf/2016-esc-guidelines-for-the-management-of-atrial-ba0601yb9m.pdf

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

/pdf/2016-esc-guidelines-for-the-management-of-atrial-36b2cidm1x.pdf

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO)

Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

/pdf/2020-esc-guidelines-for-the-diagnosis-and-management-of-38dpic1xu8.pdf

2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Background: Systemic defects in intestinal iron absorption, circulation, and retention cause iron deficiency in 50% of patients with heart failure. Defective subcellular iron uptake mechanisms that are independent of systemic absorption are incompletely understood. The main intracellular route for iron uptake in cardiomyocytes is clathrin-mediated endocytosis. Methods: We investigated subcellular iron uptake mechanisms in patient-derived and CRISPR/Cas–edited induced pluripotent stem cell–derived cardiomyocytes as well as patient-derived heart tissue. We used an integrated platform of DIA-MA (mass spectrometry data-independent acquisition)–based proteomics and signaling pathway interrogation. We employed a genetic induced pluripotent stem cell model of 2 inherited mutations (TnT [troponin T]-R141W and TPM1 [tropomyosin 1]-L185F) that lead to dilated cardiomyopathy (DCM), a frequent cause of heart failure, to study the underlying molecular dysfunctions of DCM mutations. Results: We identified a druggable molecular pathomechanism of impaired subcellular iron deficiency that is independent of systemic iron metabolism. Clathrin-mediated endocytosis defects as well as impaired endosome distribution and cargo transfer were identified as a basis for subcellular iron deficiency in DCM-induced pluripotent stem cell–derived cardiomyocytes. The clathrin-mediated endocytosis defects were also confirmed in the hearts of patients with DCM with end-stage heart failure. Correction of the TPM1-L185F mutation in DCM patient–derived induced pluripotent stem cells, treatment with a peptide, Rho activator II, or iron supplementation rescued the molecular disease pathway and recovered contractility. Phenocopying the effects of the TPM1-L185F mutation into WT induced pluripotent stem cell–derived cardiomyocytes could be ameliorated by iron supplementation. Conclusions: Our findings suggest that impaired endocytosis and cargo transport resulting in subcellular iron deficiency could be a relevant pathomechanism for patients with DCM carrying inherited mutations. Insight into this molecular mechanism may contribute to the development of treatment strategies and risk management in heart failure.

An Alternative Mechanism of Subcellular Iron Uptake Deficiency in Cardiomyocytes

/pdf/insights-into-cardiovascular-research-in-gottingen-and-28c4hos1gn.pdf

Insights into cardiovascular research in Göttingen and Heidelberg: a report by the ESC Scientists of Tomorrow

Arzneimittelinteraktionen (AMI) sind ein haufig unterschatztes Problem der modernen Medizin. Die Zahl alterer, multimorbider Patienten, die mehrere Wirkstoffe gleichzeitig einnehmen, nimmt stetig zu – der damit verbundene exponentielle Anstieg moglicher AMI ist fast unuberschaubar. Diese Ubersicht stellt haufige, relevante AMI anhand von Beispielen dar und zeigt Strategien auf, wie sie in der Praxis fruhzeitig erkannt und vermieden werden konnen.

Arzneimittelinteraktionen, die man kennen muss!

Heart Research Center Göttingen, Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany; Heart Research Center Göttingen, Department of Cardiology & Pneumology, University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research) site Göttingen, Germany; and BioMET, Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, USA

Niels Voigt

Papers

An Alternative Mechanism of Subcellular Iron Uptake Deficiency in Cardiomyocytes

Insights into cardiovascular research in Göttingen and Heidelberg: a report by the ESC Scientists of Tomorrow

Arzneimittelinteraktionen, die man kennen muss!

Ryanodine receptor dysfunction and the resolution revolution: how Nobel Prize-winning techniques transform cardiovascular research.

DNA damage in cytoskeletal protein variant-induced atrial fibrillation: A guide to novel treatment and screening targets (DnAFiX)