Building a potent TREM2 agonistic, biparatopic, common light chain antibody.

Triggering Receptor Expressed on Myeloid cells 2 (TREM2) plays an important role in microglial function and has been genetically linked to Alzheimer's disease. Activation of TREM2 signaling may contribute to protection against neurotoxic effects of amyloid. Numerous TREM2 activating antibodies have been shown to modulate downstream microglial functions to different degrees, with mixed results in preclinical models and in the clinic.

Electrophysiological Characterization of Subclinical and Overt Hypertrophic Cardiomyopathy by Magnetic Resonance Imaging-Guided Electrocardiography.

Background: Ventricular arrhythmia in hypertrophic cardiomyopathy (HCM) relates to adverse structural change and genetic status. Cardiovascular magnetic resonance (CMR)-guided electrocardiographic imaging (ECGI) noninvasively maps cardiac structural and electrophysiological (EP) properties.

Objectives: The purpose of this study was to establish whether in subclinical HCM (genotype [G]+ left ventricular hypertrophy [LVH]-), ECGI detects early EP abnormality, and in overt HCM, whether the EP substrate relates to genetic status (G+/G-LVH+) and structural phenotype.

Delayed-enhancement cardiac magnetic resonance imaging detects disease progression in patients with mitral valve disease and atrial fibrillation.

Objectives: The mechanism by which mitral valve (MV) disease leads to atrial fibrillation (AF) remains poorly understood. Delayed-enhancement cardiac magnetic resonance imaging (DE-MRI) has been used to assess left atrial (LA) fibrosis in patients with lone AF before catheter ablation; however, few studies have used DE-MRI to assess MV-induced LA fibrosis in patients with or without AF undergoing MV surgery.

Methods: Between March 2018 and September 2022, 38 subjects were enrolled; 15 age-matched controls, 14 patients with lone mitral regurgitation (MR), and 9 patients with MR and AF (MR + AF).

Reference for Electrocardiographic Imaging-Based T-Wave Alternans Estimation.

Sudden cardiac death causes multiple deaths annually, and T-wave alternans are a reliable predictor of this fatal event. Detecting alternans is crucial for reducing disease incidence, and electrocardiographic imaging is a promising tool, providing spatial-temporal insights. The absence of references and segmentation methods specific to these data may complicate progress in the field.

Technical development and feasibility of a reusable vest to integrate cardiovascular magnetic resonance with electrocardiographic imaging.

Background: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo.

Mechanisms of persistent atrial fibrillation and recurrences within 12 months post-ablation: Non-invasive mapping with electrocardiographic imaging.

Introduction: Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient.

Methods: Seventeen persistent AF patients underwent ECGI before their first catheter ablation.

ZnT2 Is Critical for TLR4-Mediated Cytokine Expression in Colonocytes and Modulates Mucosal Inflammation in Mice.

A wide range of microbial pathogens can enter the gastrointestinal tract, causing mucosal inflammation and infectious colitis and accounting for most cases of acute diarrhea. Severe cases of infectious colitis can persist for weeks, and if untreated, may lead to major complications and death. While the molecular pathogenesis of microbial infections is often well-characterized, host-associated epithelial factors that affect risk and severity of infectious colitis are less well-understood.

Stock structure analysis of the endemic fish, Barbodes carnaticus (Jerdon 1849), for conservation in a biodiversity hotspot.

The population structure of Barbodes carnaticus species was studied using conventional (based on body morphometrics and meristic) and image-based analysis (truss network system) methods. The study was carried out with four stocks, namely Karnataka (KA) and Tamil Nadu (TN) stocks from the River Cauvery, Kerala (KE) stock from the River Chalakudy and farm-reared stock (CI) from Central Institute of Freshwater Aquaculture, Bangalore. A total of 27 morphometric, 9 meristic and 30 truss measurements were used in the study for the stock structure.

The Arrhythmic Substrate for Atrial Fibrillation in Patients with Mitral Regurgitation.

Objective: Patients with severe mitral regurgitation commonly develop atrial fibrillation. The precise mechanisms of this relationship remain unknown. The objective of this study was to apply noninvasive electrocardiographic imaging of the atria during sinus rhythm to identify changes in atrial electrophysiology that may contribute to development of atrial fibrillation in patients with severe mitral regurgitation referred for mitral valve surgery.

Exploring the Potential Use of Peels as a Source of Cosmeceutical Sunscreen Agent for Its Antioxidant and Photoprotective Properties.

Currently, consumers' demand for sunscreens derived from natural sources that provide photoprotection from ultraviolet (UV) radiation is pushing the cosmetic industry to develop breakthrough formulations of sun protection products by incorporating plant antioxidants as their active ingredients. In this context, the present study was initiated to evaluate the antioxidant and photoprotective properties of the underutilized peel extract (HPPE) using spectrophotometric techniques. The phytochemical screenings of HPPE conducted via high-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) revealed the presence of phenolic acids and flavonoids as the major secondary metabolites in HPPE.

The Polyphyletic Origins of Primase-Helicase Bifunctional Proteins.

We studied the evolutionary relationships of different primase-helicase bifunctional proteins, found mostly in viruses, virophages, plasmids, and organellar genomes, by phylogeny and correlation analysis. Our study suggests independent origins of primase-helicase bifunctional proteins resulting from multiple fusion events between genes encoding primase and helicase domains of different families. The correlation analysis further indicated strong functional dependencies of domains in the bifunctional proteins that are part of smaller genomes and plasmids.

Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias.

Background: Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping.

Electrophysiologic substrate in congenital Long QT syndrome: noninvasive mapping with electrocardiographic imaging (ECGI).

Background: Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis.

The electrophysiological cardiac ventricular substrate in patients after myocardial infarction: noninvasive characterization with electrocardiographic imaging.

Objectives: The aim of this study was to noninvasively image the electrophysiological (EP) substrate of human ventricles after myocardial infarction and define its characteristics.

Background: Ventricular infarct border zone is characterized by abnormal cellular electrophysiology and altered structural architecture and is a key contributor to arrhythmogenesis. The ability to noninvasively image its electrical characteristics could contribute to understanding of mechanisms and to risk-stratification for ventricular arrhythmia.

Noninvasive electroanatomic mapping of human ventricular arrhythmias with electrocardiographic imaging.

The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI).