G protein coupled receptor transcripts in human immune cells and platelets.

G-protein coupled receptors (GPCRs) are encoded by nonabundant mRNAs, and it is difficult to detect them reliably with the highly parallel methods that are in general use. Because of this, we developed and validated a sensitive, specific, semi-quantitative method for detecting these transcripts. We have used the method to profile GPCR transcripts in white blood cells (WBCs)-B, CD4, CD8, NK, and dendritic cells; monocytes, and macrophage-like monocytes treated with granulocyte-macrophage colony-stimulating factor-as well as platelets.

Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy.

Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury.

Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling.

Background: Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican.

Impairment of the ER/mitochondria compartment in human cardiomyocytes with PLN p.Arg14del mutation.

The phospholamban (PLN) p.Arg14del mutation causes dilated cardiomyopathy, with the molecular disease mechanisms incompletely understood. Patient dermal fibroblasts were reprogrammed to hiPSC, isogenic controls were established by CRISPR/Cas9, and cardiomyocytes were differentiated.

Regulation of I and force by PDEs in human-induced pluripotent stem cell-derived cardiomyocytes.

Background And Purpose: Phosphodiesterases (PDEs) are important regulators of β-adrenoceptor signalling in the heart. While PDE4 is the most important isoform that regulates I and force in rodent cardiomyocytes, the dominant isoform in adult human cardiomyocytes is PDE3.

Experimental Approach: Given the potential of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for biomedical research, this study characterized the contribution of PDE3 and PDE4 isoforms to the regulation of I and force in hiPSC-CMs in an engineered heart tissue (EHT) model.

Clinical Frailty Scale (CFS) reliably stratifies octogenarians in German ICUs: a multicentre prospective cohort study.

Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction.

Contractile Work Contributes to Maturation of Energy Metabolism in hiPSC-Derived Cardiomyocytes.

Energy metabolism is a key aspect of cardiomyocyte biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising tool for biomedical application, but they are immature and have not undergone metabolic maturation related to early postnatal development. To assess whether cultivation of hiPSC-CMs in 3D engineered heart tissue format leads to maturation of energy metabolism, we analyzed the mitochondrial and metabolic state of 3D hiPSC-CMs and compared it with 2D culture.

Atrio-ventricular deformation and heart failure in Ebstein's Anomaly - A cardiovascular magnetic resonance study.

Purpose: We aimed to quantify atrial and ventricular myocardial deformation in Ebstein's Anomaly (EA) in a case-control study with cardiovascular magnetic resonance (CMR) feature tracking and to correlate changes in cardiac performance with the severity of disease and clinical heart failure parameters.

Materials And Methods: Atrial and ventricular deformation was measured using CMR feature tracking in 30 EA and 20 healthy control subjects. Atrial performance was characterized using longitudinal strain and strain rate parameters for reservoir function, conduit function and booster pump function.

BNP and haematological parameters are markers of severity of Ebstein's anomaly: correlation with CMR and cardiopulmonary exercise testing.

Aims: Ebstein's anomaly (EA) involves a displaced and dysplastic tricuspid valve resulting in an atrialized portion of the right ventricle and an enlargement of the functional right ventricle and right atrium. Biomarkers targeting heart failure such as brain natriuretic peptide (BNP) or haematological parameters [haemoglobin (Hb) and haematocrit (Hct)] are upregulated in states of pulmonary hypoperfusion. We hypothesized that decreased pulmonary perfusion dependent on the stage of right heart failure is a possible mechanism in EA, and that it can be correlated with cardiac magnetic resonance (CMR) parameters.

Accelerometer and gyroscope based gait analysis using spectral analysis of patients with osteoarthritis of the knee.

[Purpose] A wide variety of accelerometer tools are used to estimate human movement, but there are no adequate data relating to gait symmetry parameters in the context of knee osteoarthritis. This study's purpose was to evaluate a 3D-kinematic system using body-mounted sensors (gyroscopes and accelerometers) on the trunk and limbs. This is the first study to use spectral analysis for data post processing.

Prevalence of noncardiac findings in computed tomography angiography before transcatheter aortic valve replacement.

Objective: This study sought to determine the prevalence of significant and nonsignificant noncardiac findings in patients undergoing preprocedural dual-source CT (DSCT) before transcatheter aortic valve implantation (TAVI).

Methods: Patients (n = 204; aged, 80.5 ± 5.