Management of Ventricular Arrhythmias in Heart Failure: Can Less Be More?

Purpose Of Review: Ventricular arrhythmias (VAs) affect many patients with heart failure and underlying structural heart disease and are associated with significant morbidity and mortality. Antiarrhythmic drugs are often the initial treatment, but medication alone often fails to sufficiently suppress VAs. While catheter ablation (CA) remains the gold standard for treatment of VAs, CA is an invasive procedure and can be associated with periprocedural complications including acute clinical decompensation.

Ablation Versus Antiarrhythmic Drugs as First-Line Therapy for Treatment-Naive Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Evidence on the relative safety and efficacy of atrial fibrillation catheter ablation and antiarrhythmic drugs (AADs) as the first-line therapy for patients with treatment-naive atrial fibrillation (AF) remains disputed. Digital databases were queried to identify relevant randomized controlled trials. The incidence of recurrent AF, major adverse cardiovascular events, and its components (all-cause death, nonfatal stroke, and bleeding) were compared using the DerSimonian and Laird method under the random-effects model to calculate pooled unadjusted risk ratio (RR) with 95% confidence intervals (CIs).

Protein-lipid interactions drive presynaptic assembly upstream of cell adhesion molecules.

Textbook models of synaptogenesis position cell adhesion molecules such as neurexin as initiators of synapse assembly. Here we discover a mechanism for presynaptic assembly that occurs prior to neurexin recruitment, while supporting a role for neurexin in synapse maintenance. We find that the cytosolic active zone scaffold SYD-1 interacts with membrane phospholipids to promote active zone protein clustering at the plasma membrane, and subsequently recruits neurexin to stabilize those clusters.

Clarinet/CLA-1 recruits RIMB-1/RIM-binding protein and UNC-13 to orchestrate presynaptic neurotransmitter release.

Synaptic transmission requires the coordinated activity of multiple synaptic proteins that are localized at the active zone (AZ). We previously identified a protein named Clarinet (CLA-1) based on homology to the AZ proteins Piccolo, Rab3-interactingmolecule (RIM)/UNC-10 and Fife. At the neuromuscular junction (NMJ), mutants exhibit release defects that are greatly exacerbated in mutants.

Bridging the gap with bacterial art.

Living art made with bacteria is gaining global attention, spreading from laboratories into the public domain: from school STEAM (Science, Technology, Engineering, the Arts, and Mathematics) events to art galleries, museums, community labs, and ultimately to the studios of microbial artists. Bacterial art is a synthesis of science and art that can lead to developments in both fields. Through the 'universal language of art', many social and preconceived ideas-including abstract scientific concepts-can be challenged and brought to the public attention in a unique way.

Obstetric and perioperative management of patients with factor XI deficiency: a retrospective observational study.

Factor XI (FXI) deficiency is an autosomal inherited, milder bleeding disorder that may predispose to a potential risk of life-threatening bleeding during childbirth or surgery. Unfortunately, data regarding obstetric and perioperative management of this condition are scarce, with limited cases reviewed in the last decade. Therefore, the present study aimed to expand this database and identify factors associated with increased bleeding risk.

The ESCRT machinery directs quality control over inner nuclear membrane architecture.

The late-acting endosomal sorting complex required for transport (ESCRT) machinery has been implicated in facilitating the resealing of the nuclear envelope (NE) after mitosis, enabling compartmentalization of the genome away from the cytoplasm. Here, we leverage the stereotypic first division of the C. elegans embryo to identify additional functions of the ESCRT machinery in maintaining the structure of the inner nuclear membrane.

JRDB: A Dataset and Benchmark of Egocentric Robot Visual Perception of Humans in Built Environments.

We present JRDB, a novel egocentric dataset collected from our social mobile manipulator JackRabbot. The dataset includes 64 minutes of annotated multimodal sensor data including stereo cylindrical 360 RGB video at 15 fps, 3D point clouds from two 16 planar rays Velodyne LiDARs, line 3D point clouds from two Sick Lidars, audio signal, RGB-D video at 30 fps, 360 spherical image from a fisheye camera and encoder values from the robot's wheels. Our dataset incorporates data from traditionally underrepresented scenes such as indoor environments and pedestrian areas, all from the ego-perspective of the robot, both stationary and navigating.

Initial Experience in Monitoring QT Intervals Using a Six-lead Contactless Mobile Electrocardiogram in an Inpatient Setting.

Mobile electrocardiograms (ECGs) (mECGs) using smartphone applications are an emerging technology. In the coronavirus disease 2019 (COVID-19) era, minimizing patient contact has gained increasing importance. Additionally, increased QT/corrected QT (QTc) monitoring has concurrently been required.

Algorithm for cavo-tricuspid isthmus flutter on surface ECGs: the ACTIONS study.

Objective: Cavo-tricuspid isthmus atrial flutter (CTI-AFL) is an important arrhythmia to recognise because there is a highly effective and relatively low-risk ablation strategy. However, clinical experience has demonstrated that providers often have difficulty distinguishing AFL from atrial fibrillation.

Methods: We developed a novel ECG-based three-step algorithm to identify CTI-AFL based on established CTI flutter characteristics and verified on consecutive ablation cases of typical flutter, atypical flutter and atrial fibrillation.

One Patient, Three Variants, Four Episodes of Takotsubo Cardiomyopathy.

• TCM is an increasingly recognized clinical entity. • Variants include apical, midventricular, basal, and focal. • The authors present a unique case in which one patient developed three variants.

All Talk, No Assembly: Voltage-Gated Calcium Channels Do Not Mediate Active Zone Formation.

How synapses assemble remains unknown. In this issue of Neuron, Held et al. (2020) demonstrate that Ca2-type voltage-gated calcium channels do not mediate presynaptic assembly.

Growth factor stimulation promotes multivesicular endosome biogenesis by prolonging recruitment of the late-acting ESCRT machinery.

The formation of multivesicular endosomes (MVEs) mediates the turnover of numerous integral membrane proteins and has been implicated in the down-regulation of growth factor signaling, thereby exhibiting properties of a tumor suppressor. The endosomal sorting complex required for transport (ESCRT) machinery plays a key role in MVE biogenesis, enabling cargo selection and intralumenal vesicle (ILV) budding. However, the spatiotemporal pattern of endogenous ESCRT complex assembly and disassembly in mammalian cells remains poorly defined.

Template-directed RNA polymerization and enhanced ribozyme catalysis inside membraneless compartments formed by coacervates.

Membraneless compartments, such as complex coacervates, have been hypothesized as plausible prebiotic micro-compartments due to their ability to sequester RNA; however, their compatibility with essential RNA World chemistries is unclear. We show that such compartments can enhance key prebiotically-relevant RNA chemistries. We demonstrate that template-directed RNA polymerization is sensitive to polycation identity, with polydiallyldimethylammonium chloride (PDAC) outperforming poly(allylamine), poly(lysine), and poly(arginine) in polycation/RNA coacervates.

Driving Safety and Real-Time Glucose Monitoring in Insulin-Dependent Diabetes.

Our goal is to address the need for driver-state detection using wearable and in-vehicle sensor measurements of driver physiology and health. To address this goal, we deployed in-vehicle systems, wearable sensors, and procedures capable of quantifying real-world driving behavior and performance in at-risk drivers with insulin-dependent type 1 diabetes mellitus (DM). We applied these methodologies over 4 weeks of continuous observation to quantify differences in real-world driver behavior profiles associated with physiologic changes in drivers with DM (N=19) and without DM (N=14).

Pathogenic TFG Mutations Underlying Hereditary Spastic Paraplegia Impair Secretory Protein Trafficking and Axon Fasciculation.

Length-dependent axonopathy of the corticospinal tract causes lower limb spasticity and is characteristic of several neurological disorders, including hereditary spastic paraplegia (HSP) and amyotrophic lateral sclerosis. Mutations in Trk-fused gene (TFG) have been implicated in both diseases, but the pathomechanisms by which these alterations cause neuropathy remain unclear. Here, we biochemically and genetically define the impact of a mutation within the TFG coiled-coil domain, which underlies early-onset forms of HSP.

Efficacy and Safety of Toreforant, a Selective Histamine H4 Receptor Antagonist, for the Treatment of Moderate-to-Severe Plaque Psoriasis: Results from a Phase 2 Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

Background: Toreforant is a selective histamine H4 receptor antagonist. H4 receptor activation may play a role in immune-mediated inflammation in psoriasis.

Objective: To evaluate Toreforant efficacy and safety in patients with moderate-to-severe psoriasis.

Cellular conditions of weakly chelated magnesium ions strongly promote RNA stability and catalysis.

Most RNA folding studies have been performed under non-physiological conditions of high concentrations (≥10 mM) of Mg, while actual cellular concentrations of Mg are only ~1 mM in a background of greater than 50 mM Mg. To uncover cellular behavior of RNA, we devised cytoplasm mimic systems that include biological concentrations of amino acids, which weakly chelate Mg. Amino acid-chelated Mg (aaCM) of ~15 mM dramatically increases RNA folding and prevents RNA degradation.

Membrane Transport at an Organelle Interface in the Early Secretory Pathway: Take Your Coat Off and Stay a While: Evolution of the metazoan early secretory pathway.

Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum-Golgi intermediate compartment (ERGIC). These membranous vesicular-tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII-coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI-dependent transport on to the cis-Golgi.

Complexity in pH-Dependent Ribozyme Kinetics: Dark pK Shifts and Wavy Rate-pH Profiles.

Charged bases occur in RNA enzymes, or ribozymes, where they play key roles in catalysis. Cationic bases donate protons and perform electrostatic catalysis, while anionic bases accept protons. We previously published simulations of rate-pH profiles for ribozymes in terms of species plots for the general acid and general base that have been useful for understanding how ribozymes respond to pH.

Efficacy of Secukinumab in the Treatment of Moderate to Severe Plaque Psoriasis in the North American Subgroup of Patients: Pooled Analysis of Four Phase 3 Studies.

Introduction: Demographic and disease characteristics may impact response to psoriasis therapies. The objective of this study is to explore the safety and efficacy profile of secukinumab in North American (NA) versus non-NA patients with moderate to severe psoriasis.

Methods: Data were pooled from four phase 3 studies of secukinumab.

Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos.

Degradation of most integral membrane proteins is directed by the endosomal sorting complex required for transport (ESCRT) machinery, which selectively targets ubiquitin-modified cargoes into intralumenal vesicles (ILVs) within multivesicular endosomes (MVEs). To better understand the mechanisms underlying ESCRT-mediated formation of ILVs, we exploited the rapid, de novo biogenesis of MVEs during the oocyte-to-embryo transition in C. elegans.