Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle c...Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle cells, no contraction can take place. Therefore, calcium homeostasis is one of the critical regulatory mechanisms in all muscle cells, including skeletal muscle and heart [1,2]. Ca2+ adenosine triphosphatase the relaxation of muscle cells Sarco-endoplasmic reticulum (SERCA) is responsible for by pumping Ca2+ into the sarcoplasmic reticulum (SR) .展开更多
Next-generation sequencing (NGS) is getting routinely used in the diagnosis of hereditary diseases, such as human cardiomyopathies. Hence. it is of utter importance to secure high quality sequencing data, enabling t...Next-generation sequencing (NGS) is getting routinely used in the diagnosis of hereditary diseases, such as human cardiomyopathies. Hence. it is of utter importance to secure high quality sequencing data, enabling the identification of disease-relevant mutations or the conclusion of negative test results. During the process of sample preparation, each protocol for target enrichment library preparation has its own requirements for quality control (QC); however, there is little evi- dence on the actual impact of these guidelines on resulting data quality. In this study, we analyzed the impact of QC during the diverse library preparation steps of Agilent SureSelect XT target enrichment and lllumina sequencing. We quantified the parameters for a cohort of around 600 samples, which include starting amount of DNA, amount of sheared DNA, smallest and largest fragment size of the starting DNA; amount of DNA after the pre-PCR, and smallest and largest fragment size of the resulting DNA; as well as the amount of the final library, the corresponding smallest and largest fragment size, and the number of detected variants. Intriguingly, there is a high tolerance for variations in all QC steps, meaning that within the boundaries proposed in the current study, a considerable variance at each step of QC can be well tolerated without compromising NGS quality.展开更多
The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a globa...The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau (τ). Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated significantly across the patient population with τ. This study shows that multi-modal cardiac models can successfully capture diastolic (dys) function, a prerequisite for future clinical trials on HF-pEF.展开更多
Over the past two decades, improved diagnosis, pharmaceutical therapies, and interventional strategies have impressively improved the armamentarium of modern cardiologists in the fight against the most incident and le...Over the past two decades, improved diagnosis, pharmaceutical therapies, and interventional strategies have impressively improved the armamentarium of modern cardiologists in the fight against the most incident and lethal diseases: heart failure, ischemic heart disease, and arrhythmia. The innovations in the field have mostly been enabled by inventions based on hypothesis-driven approaches. The invention and development of key cardiac biomarkers, such as natriuretic peptides and cardiac-specific troponins, may serve as examples.展开更多
基金supported by the German Centre for Cardiovascular Research (DZHK) and the German Ministry of Education and Research (BMBF)
文摘Calcium homeostasis is crucial for muscle contractilityMuscle cells are critically dependent on calcium homeostasis. Without having the right amount of calcium ions just on the spot and coordinated in between muscle cells, no contraction can take place. Therefore, calcium homeostasis is one of the critical regulatory mechanisms in all muscle cells, including skeletal muscle and heart [1,2]. Ca2+ adenosine triphosphatase the relaxation of muscle cells Sarco-endoplasmic reticulum (SERCA) is responsible for by pumping Ca2+ into the sarcoplasmic reticulum (SR) .
基金supported by the German Centre for Cardiovascular Research (DZHK), the European Union (FP7 Inheritance and FP7 Best Ageing), and the German Ministry of Education and Research (BMBF)
文摘Next-generation sequencing (NGS) is getting routinely used in the diagnosis of hereditary diseases, such as human cardiomyopathies. Hence. it is of utter importance to secure high quality sequencing data, enabling the identification of disease-relevant mutations or the conclusion of negative test results. During the process of sample preparation, each protocol for target enrichment library preparation has its own requirements for quality control (QC); however, there is little evi- dence on the actual impact of these guidelines on resulting data quality. In this study, we analyzed the impact of QC during the diverse library preparation steps of Agilent SureSelect XT target enrichment and lllumina sequencing. We quantified the parameters for a cohort of around 600 samples, which include starting amount of DNA, amount of sheared DNA, smallest and largest fragment size of the starting DNA; amount of DNA after the pre-PCR, and smallest and largest fragment size of the resulting DNA; as well as the amount of the final library, the corresponding smallest and largest fragment size, and the number of detected variants. Intriguingly, there is a high tolerance for variations in all QC steps, meaning that within the boundaries proposed in the current study, a considerable variance at each step of QC can be well tolerated without compromising NGS quality.
基金supported by grants from the German Ministry of Education and Research(BMBF)DZHK(“Deutsches Zentrum für Herz-Kreislauf-Forschung”–German Centre for Cardiovascular Research),the European Union(FP7 Best Ageing)and Siemens Healthcare(Siemens Healthcare/University Heidelberg Joint Research Project:Care4DCM)
文摘The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau (τ). Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated significantly across the patient population with τ. This study shows that multi-modal cardiac models can successfully capture diastolic (dys) function, a prerequisite for future clinical trials on HF-pEF.
基金supported by grants from the German Ministry of Education and Research (BMBF)Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK, German Centre for Cardiovascular Research), and Siemens Health Care Gmb H (Siemens/University Heidelberg Joint Research Project: Care4DCM) of Germany as well as the European Union (FP7 Best Ageing)supported by grants from Siemens Health Care Gmb H (Siemens/University Heidelberg Joint Research Project: Care4DCM) of Germany and the European Union (FP7 Best Ageing)
文摘Over the past two decades, improved diagnosis, pharmaceutical therapies, and interventional strategies have impressively improved the armamentarium of modern cardiologists in the fight against the most incident and lethal diseases: heart failure, ischemic heart disease, and arrhythmia. The innovations in the field have mostly been enabled by inventions based on hypothesis-driven approaches. The invention and development of key cardiac biomarkers, such as natriuretic peptides and cardiac-specific troponins, may serve as examples.