Clinical and Genetic Characterization of Adolescent-Onset Epilepsy: A Single-Center Experience in Republic of Korea.

Objectives: This study investigated the characteristics of adolescent-onset epilepsy (AOE) and conducted genetic tests on a cohort of 76 Korean patients to identify variants and expand the spectrum of mutations associated with AOE.

Methods: Clinical exome sequencing after routine karyotyping and chromosomal microarray was performed to identify causative variants and expand the spectrum of mutations associated with AOE.

Results: In cases of AOE without neurodevelopmental delay (NDD), this study identified four likely pathogenic variants (LPVs) or variants of uncertain significance (VUS) and two copy number variations (CNVs).

Surgical Treatment of Brachiocephalic Artery Aneurysm With Impending Rupture and Tracheal Communication.

Brachiocephalic artery aneurysm is uncommon but may require surgery because it tends to enlarge, rupture, or cause symptoms related to thrombosis or compression. This case report describes a brachiocephalic artery aneurysm in a 72-year-old man who presented at the hospital with dyspnea and hemoptysis resulting from impending rupture and tracheal communication.

The Aggravation of Neuropsychiatric Symptoms in the Offspring of a Korean Family with Intellectual Disability and Developmental Delay Caused by a Novel p.Lys385Ter Variant.

The mutations encompass a nearly continuous spectrum of neurodevelopmental disorders (NDDs), ranging from lissencephaly to Proud syndrome, as well as infantile spasms without brain malformations, and including both syndromic and non-syndromic intellectual disabilities (IDs). We describe worsening neuropsychiatric symptoms in the offspring of a Korean family with ID/developmental delay (DD) caused by a novel p.Lys385Ter variant.

Surgical Repair of Postinfarction Left Ventricular Pseudoaneurysm.

Left ventricular pseudoaneurysm is a serious and rare disorder that usually develops after acute myocardial infarction. It can lead to potentially lethal mechanical complications, such as acute left ventricular free wall rupture. This report presents the case of a 64-year-old man with a left ventricular pseudoaneurysm and myocardial rupture that was managed by left ventricular restoration with aneurysmectomy and coronary artery bypass with 2 grafts.

A Korean Family Presenting with Renal Cysts and Maturity-Onset Diabetes of the Young Caused by a Novel In-Frame Deletion of .

Maturity-onset diabetes of the young (MODY; OMIM # 606391) comprises a cluster of inherited disorders within non-autoimmune diabetes mellitus (DM), typically emerging during adolescence or young adulthood. We report a novel in-frame deletion of in a family with renal cysts and MODY, furthering our understanding of -related phenotypes. We conducted sequential genetic testing to investigate the glucose intolerance, renal cysts, hepatic cysts, and agenesis of the dorsal pancreas observed in the proband.

Transient pacing in pigs with complete heart block via myocardial injection of mRNA coding for the T-box transcription factor 18.

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses.

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI).

Evaluation of the Analytical Performance of Oncomine Lung cfDNA Assay for Detection of Plasma Mutations.

Background: The clinical utility of circulating tumor DNA (ctDNA) in the early detection of tumor mutations for targeted therapy and the monitoring of tumor recurrence has been reported. However, the analytical validation of ctDNA assays is required for clinical application.

Methods: This study evaluated the analytical performance of the Oncomine Lung cfDNA Assay compared with the cobas Mutation Test v2.

Myofibroblast senescence promotes arrhythmogenic remodeling in the aged infarcted rabbit heart.

Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases.

Five Years' Experience with Gene Panel Sequencing in Hereditary Hemolytic Anemia Screened by Routine Peripheral Blood Smear Examination.

Background: Hereditary hemolytic anemia (HHA) is defined as a group of heterogeneous and rare diseases caused by defects of red blood cell (RBC) metabolism and RBC membrane, which leads to lysis or premature clearance. The aim of this study was to investigate individuals with HHA for potential disease-causing variants in 33 genes reported to be associated with HHA.

Methods: A total of 14 independent individuals or families diagnosed with suspected HHA, and in particular, RBC membranopathy, RBC enzymopathy, and hemoglobinopathy, were collected after routine peripheral blood smear testing.

Action potential metrics and automated data analysis pipeline for cardiotoxicity testing using optically mapped hiPSC-derived 3D cardiac microtissues.

Recent advances in human induced pluripotent stem cell (hiPSC)-derived cardiac microtissues provide a unique opportunity for cardiotoxic assessment of pharmaceutical and environmental compounds. Here, we developed a series of automated data processing algorithms to assess changes in action potential (AP) properties for cardiotoxicity testing in 3D engineered cardiac microtissues generated from hiPSC-derived cardiomyocytes (hiPSC-CMs). Purified hiPSC-CMs were mixed with 5-25% human cardiac fibroblasts (hCFs) under scaffold-free conditions and allowed to self-assemble into 3D spherical microtissues in 35-microwell agarose gels.

Targeted Panel Sequencing Identifies an Intronic c.5225-3C>G Variant of the Gene Causing Sporadic Marfan Syndrome with Annuloaortic Ectasia.

Marfan syndrome (MFS) is a hereditary connective tissue disease whose clinical severity varies widely. Mutations of the gene encoding fibrillin-1 are the most common genetic cause of Marfanoid habitus; however, about 10% of MFS patients are unaware of their genetic defects. Herein, we report a Korean patient with MFS and annuloaortic ectasia caused by an intronic c.

Hyperglycemia and Hypoglycemia Are Associated with In-Hospital Mortality among Patients with Coronavirus Disease 2019 Supported with Extracorporeal Membrane Oxygenation.

Metabolic abnormalities, such as preexisting diabetes or hyperglycemia or hypoglycemia during hospitalization aggravated the severity of COVID-19. We evaluated whether diabetes history, hyperglycemia before and during extracorporeal membrane oxygenation (ECMO) support, and hypoglycemia were risk factors for mortality in patients with COVID-19. This study included data on 195 patients with COVID-19, who were aged ≥19 years and were treated with ECMO.

Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia.

Background: Oxidative stress in cardiac disease promotes proarrhythmic disturbances in Ca homeostasis, impairing luminal Ca regulation of the sarcoplasmic reticulum (SR) Ca release channel, the RyR2 (ryanodine receptor), and increasing channel activity. However, exact mechanisms underlying redox-mediated increase of RyR2 function in cardiac disease remain elusive. We tested whether the oxidoreductase family of proteins that dynamically regulate the oxidative environment within the SR are involved in this process.

Magnetic Anisotropy and Magnetic Ordering of Transition-Metal Phosphorus Trisulfides.

A magnetic model with an unprecedentedly large number of parameters was determined from first-principles calculations for transition-metal phosphorus trisulfides (TMPS's), reproducing the measured magnetic ground states of bulk TMPS's. Our Monte Carlo simulations for the critical temperature, magnetic susceptibility, and specific heat of bulk and few-layer TMPS's agree well with available experimental data and show that the antiferromagnetic order of TMPS's persists down to monolayers. Remarkably, the orbital polarization, neglected in recent first-principles studies, dramatically enhances the magnetic anisotropy of FePS by almost 2 orders of magnitude.

Human Atrial Cardiac Microtissues for Chamber-Specific Arrhythmic Risk Assessment.

Introduction: Although atrial fibrillation is the most prevalent disorder of electrical conduction, the mechanisms behind atrial arrhythmias remain elusive. To address this challenge, we developed a robust model of 3D atrial microtissue from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and evaluated chamber-specific chemical responses experimentally and computationally.

Methods: We differentiated atrial and ventricular cardiomyocytes (aCMs/vCMs) from GCaMP6f-expressing hiPSCs and assessed spontaneous AP activity using fluorescence imaging.

Self-rechargeable cardiac pacemaker system with triboelectric nanogenerators.

Self-powered implantable devices have the potential to extend device operation time inside the body and reduce the necessity for high-risk repeated surgery. Without the technological innovation of in vivo energy harvesters driven by biomechanical energy, energy harvesters are insufficient and inconvenient to power titanium-packaged implantable medical devices. Here, we report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator (I-TENG) based on body motion and gravity.

A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues.

Cardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation.

Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk.

Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1β and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM.

Highly efficient double plasma mirror producing ultrahigh-contrast multi-petawatt laser pulses.

We present a highly efficient double plasma mirror (DPM) that provides ultrahigh-contrast multi-petawatt (PW) laser pulses with a temporal contrast ratio reaching 10 up to 160 ps and 10 up to 2 ps before the main pulse. The high reflectivity of 70%, along with the high-contrast enhancement factor of 700,000, was achieved from the DPM installed after the final stage of a 4 PW Ti:sapphire laser. The 4 PW laser was equipped with cross-polarized wave generation and optical parametric chirped-pulse amplification stages for initial high-contrast operation.

IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.

Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes.