Value of Regular Defibrillation Threshold Testing After Extracardiac Implantable Cardioverter Defibrillator Placement in Small Children During Mid-Term Follow-Up.

Objectives: The purpose of this study was to analyze course of defibrillation threshold (DFT) with growth.

Background: Data on regular DFT testing after extracardiac implantable cardioverter-defibrillator (ICD) placement in infants and small children is still limited.

Methods: An extracardiac ICD was placed in 23 pediatric patients (median age 6.

Arrhythmias in congenital heart disease: a position paper of the European Heart Rhythm Association (EHRA), Association for European Paediatric and Congenital Cardiology (AEPC), and the European Society of Cardiology (ESC) Working Group on Grown-up Congenital heart disease, endorsed by HRS, PACES, APHRS, and SOLAECE.

The population of patients with congenital heart disease (CHD) is continuously increasing with more and more patients reaching adulthood. A significant portion of these young adults will suffer from arrhythmias due to the underlying congenital heart defect itself or as a sequela of interventional or surgical treatment. The medical community will encounter an increasing challenge as even most of the individuals with complex congenital heart defects nowadays become young adults.

Atropine augments cardiac contractility by inhibiting cAMP-specific phosphodiesterase type 4.

Atropine is a clinically relevant anticholinergic drug, which blocks inhibitory effects of the parasympathetic neurotransmitter acetylcholine on heart rate leading to tachycardia. However, many cardiac effects of atropine cannot be adequately explained solely by its antagonism at muscarinic receptors. In isolated mouse ventricular cardiomyocytes expressing a Förster resonance energy transfer (FRET)-based cAMP biosensor, we confirmed that atropine inhibited acetylcholine-induced decreases in cAMP.

Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease.

Background: Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress.

Diverging effects of nicotine on motor learning performance: Improvement in deprived smokers and attenuation in non-smokers.

Nicotine modulates cognition and neuroplasticity in smokers and non-smokers. A possible mechanism for its effect on learning and memory performance is its impact on long-term potentiation (LTP) and long-term depression (LTD). As neuroplasticity is closely connected to learning processes, we aimed to explore the effect of nicotine in healthy, young smokers and non-smokers on performance of the serial reaction time task (SRTT), a sequential motor learning paradigm.

Long-Term Follow-Up After Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia in Children.

Background: Catheter ablation of the slow conducting pathway (SP) is treatment of choice for atrioventricular nodal reentrant tachycardia (AVNRT). Although there are abundant data on AVNRT ablation in adult patients, little is known about the long-term results ≥3 years after AVNRT ablation in pediatric patients.

Methods And Results: Follow-up data from 241 patients aged ≤18 years who had undergone successful AVNRT ablation were analyzed.

The Antiproliferative Effect of Bevacizumab on Human Tenon Fibroblasts Is Not Mediated by Vascular Endothelial Growth Factor Inhibition.

Purpose: Vascular endothelial growth factor-signaling in human tenon fibroblasts (hTFs) has recently become a target for antifibrotic treatment in glaucoma filtration surgery. The anti-VEGF antibody bevacizumab (BVC) has been shown to increase filtration bleb size. Given the relatively high concentration of BVC needed to obtain an effect, we investigated whether BVC acts through VEGF inhibition or via non-antigen-dependent ways.

Structure of smAKAP and its regulation by PKA-mediated phosphorylation.

Unlabelled: The A-kinase anchoring protein (AKAP) smAKAP has three extraordinary features; it is very small, it is anchored directly to membranes by acyl motifs, and it interacts almost exclusively with the type I regulatory subunits (RI) of cAMP-dependent kinase (PKA). Here, we determined the crystal structure of smAKAP's A-kinase binding domain (smAKAP-AKB) in complex with the dimerization/docking (D/D) domain of RIα which reveals an extended hydrophobic interface with unique interaction pockets that drive smAKAP's high specificity for RI subunits. We also identify a conserved PKA phosphorylation site at Ser66 in the AKB domain which we predict would cause steric clashes and disrupt binding.

Baseline CSF/Serum-Ratio of Apolipoprotein E and Rate of Differential Decline in Alzheimer's Disease.

Background/objective: Apolipoprotein E (ApoE) has an active part in the pathogenesis of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations have been reported in AD patients. In search of a biomarker potentially predictive of cognitive, functional, or motor decline, we analyzed the CSF to serum ratios of ApoE levels (CSF/serum ApoE) in AD patients in this regard.

Imaging alterations of cardiomyocyte cAMP microdomains in disease.

3',5'-cyclic adenosine monophosphate (cAMP) is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques.

Catheter ablation of pediatric AV nodal reentrant tachycardia: results in small children.

Background: AV nodal reentrant tachycardia (AVNRT) is commonly encountered in pediatric patients. Definite treatment can be achieved by catheter ablation. The purpose of the study was to evaluate the efficacy and safety of AVNRT ablation focusing on children with a body weight ≤25 kg.

Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine.

Nicotine has been shown to affect cortical excitability measured using transcranial magnetic stimulation in smoking and non-smoking subjects in different ways. In tobacco-deprived smokers, administration of nicotine restores compromised cortical facilitation while in non-smokers, it enhances cortical inhibition. As cortical excitability and activity are closely linked to cognitive processes, we aimed to explore whether nicotine-induced physiological alterations in non-smokers and smokers are associated with cognitive changes.

Microdomain switch of cGMP-regulated phosphodiesterases leads to ANP-induced augmentation of β-adrenoceptor-stimulated contractility in early cardiac hypertrophy.

Rationale: Cyclic nucleotides are second messengers that regulate cardiomyocyte function through compartmentalized signaling in discrete subcellular microdomains. However, the role of different microdomains and their changes in cardiac disease are not well understood.

Objective: To directly visualize alterations in β-adrenergic receptor-associated cAMP and cGMP microdomain signaling in early cardiac disease.

Cerebrospinal fluid apolipoprotein E concentration and progression of Alzheimer's disease.

Background/objective: Apolipoprotein E plays a role in the pathogenesis of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations have been reported in AD patients. In search of a potential biomarker, which would be predictive of cognitive, functional, or motor decline, we analyzed CSF apolipoprotein E (ApoE) levels of AD patients in this regard.

Understanding spatial relationships in US: a computer-based training tool that utilizes inexpensive off-the-shelf game controllers.

The authors present a simulation-based ultrasonographic (US) training tool that can help improve the understanding of spatial relationships in US. Use of a game controller to simulate a US probe allows examination of different virtual three-dimensional (3D) objects. These 3D objects are either completely artificial simple geometric objects (eg, spheres, tubes, and ellipsoids, or more complex combinations thereof) or derived from photographed gross anatomic data (eg, the Visible Human dataset [U.

CR1 is potentially associated with rate of decline in sporadic Alzheimer's disease.

The objective of this study was to investigate potential associations of Alzheimer's disease risk single nucleotide polymorphisms (SNP) with disease progression. SNP in ACE, ApoE, BIN1, CLU, CR1, CST3, EXOC3L2, GWA14q32.13, IL8, LDLR, PICALM, and TNK1 were determined in 40 Alzheimer's disease patients who were observed for 2 to 3 years.

Transgenic mice for real-time visualization of cGMP in intact adult cardiomyocytes.

Rationale: 3',5'-Cyclic guanosine monophosphate (cGMP) is an important second messenger that regulates cardiac contractility and protects the heart from hypertrophy. However, because of the lack of real-time imaging techniques, specific subcellular mechanisms and spatiotemporal dynamics of cGMP in adult cardiomyocytes are not well understood.

Objective: Our aim was to generate and characterize a novel cGMP sensor model to measure cGMP with nanomolar sensitivity in adult cardiomyocytes.

Plasma prion protein concentration and progression of Alzheimer disease.

Background/objective: Recently, PrP(c) has been linked to AD pathogenesis. Second, a relation of PrP(c) plasma levels with cognitive status and decline of healthy elderly subjects has been reported. Therefore, we hypothesized baseline plasma levels of PrP(c) to be associated with AD progression in cognitive and functional domains.

Biophysical techniques for detection of cAMP and cGMP in living cells.

Cyclic nucleotides cAMP and cGMP are ubiquitous second messengers which regulate myriads of functions in virtually all eukaryotic cells. Their intracellular effects are often mediated via discrete subcellular signaling microdomains. In this review, we will discuss state-of-the-art techniques to measure cAMP and cGMP in biological samples with a particular focus on live cell imaging approaches, which allow their detection with high temporal and spatial resolution in living cells and tissues.

Compartmentation of cAMP signalling in cardiomyocytes in health and disease.

3',5'-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger critically involved in the regulation of heart function. It has been shown to act in discrete subcellular signalling compartments formed by differentially localized receptors, phosphodiesterases and protein kinases. Cardiac diseases such as hypertrophy or heart failure are associated with structural and functional remodelling of these microdomains which leads to changes in cAMP compartmentation.

FRET microscopy for real-time monitoring of signaling events in live cells using unimolecular biosensors.

Förster resonance energy transfer (FRET) microscopy continues to gain increasing interest as a technique for real-time monitoring of biochemical and signaling events in live cells and tissues. Compared to classical biochemical methods, this novel technology is characterized by high temporal and spatial resolution. FRET experiments use various genetically-encoded biosensors which can be expressed and imaged over time in situ or in vivo.

The role of FGF-2 in renal fibrogenesis.

Basic fibroblast growth factor (FGF-2) is a pleiotropic cytokine which exerts its effects via four different high affinity receptors (FGFR-1 to -4) which function as protein tyrosine kinases. In the kidney, FGF-2 is expressed in epithelial cells already during fetal development. During later stages, expression of the cytokine can be found in distal tubular epithelial cells, glomerular cells and few interstitial cells.

EMT and proteinuria as progression factors.

Tubulointerstitial fibrosis is an integral part of the structural changes of the kidney in chronic progressive renal failure. The accumulation of the extracellular matrix in the tubulointerstitial space is mediated mainly by myofibroblasts. These are derived from resident interstitial fibroblasts, tubular epithelial cells, periadventitial cells, and possibly also mesenchymal stem cells and endothelial cells.