Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Background: CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear.

The Anti-Inflammatory Effects and Clinical Potential of Dexmedetomidine in Pulmonary Arterial Hypertension.

A pathogenic aspect of pulmonary arterial hypertension (PAH) is the aberrant pulmonary arterial smooth muscle cell (PASMC) proliferation. PASMC proliferation is significantly affected by inflammation. A selective -2 adrenergic receptor agonist called dexmedetomidine (DEX) modulates specific inflammatory reactions.

Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin.

 Disseminated intravascular coagulation (DIC) is not a homogeneous condition, but rather includes heterogeneous conditions, and its pathophysiology and outcome vary considerably depending on the background. Although anticoagulant therapy is expected to be of benefit in the treatment of DIC, previous studies have suggested that the benefits are limited only to a specific subtype.  The purpose of this study was to identify the group that would benefit from combination therapy using thrombomodulin/antithrombin.

Effect of the COVID-19 Pandemic on Surgical Outcomes for Rhegmatogenous Retinal Detachments.

We reviewed the medical records of 438 eyes in 431 patients who had undergone surgeries for rhegmatogenous retinal detachments (RRD) or proliferative vitreoretinopathy (PVR ≥ Grade C) to determine whether the COVID-19 pandemic had affected outcomes. The patients were divided into 203 eyes in Group A that had undergone surgery from April to September 2020, during the pandemic, and 235 eyes in Group B that had undergone surgery from April to September 2019, before the pandemic. The pre- and postoperative visual acuity, macular detachment, type of retinal breaks, size of the RRD, and surgical outcomes were compared.

Significance of Basal Membrane Permeability of Epithelial Cells in Predicting Intestinal Drug Absorption.

Drug absorption from the gastrointestinal tract is often restricted by efflux transport by P-glycoprotein (P-gp) and metabolism by CYP3A4. Both localize in the epithelial cells, and thus, their activities are directly affected by the intracellular drug concentration, which should be regulated by the ratio of permeability between apical (A) and basal (B) membranes. In this study, using Caco-2 cells with forced expression of CYP3A4, we assessed the transcellular permeation of A-to-B and B-to-A directions and the efflux from the preloaded cells to both sides of 12 representative P-gp or CYP3A4 substrate drugs and obtained the parameters for permeabilities, transport, metabolism, and unbound fraction in the enterocytes (f) using simultaneous and dynamic model analysis.

First measurements of pB fusion in a magnetically confined plasma.

Proton-boron (pB) fusion is an attractive potential energy source but technically challenging to implement. Developing techniques to realize its potential requires first developing the experimental capability to produce pB fusion in the magnetically-confined, thermonuclear plasma environment. Here we report clear experimental measurements supported by simulation of pB fusion with high-energy neutral beams and boron powder injection in a high-temperature fusion plasma (the Large Helical Device) that have resulted in diagnostically significant levels of alpha particle emission.

Effect of Lianhua Qingwen capsules on the positive rate of COVID-19 close contacts: A retrospective analysis of a large-scale population-based cohort study.

Objective: Coronavirus disease 2019 (COVID-19) is still spreading worldwide. COVID-19 close contact is a key point of this epidemic. However, no medication is now available for close contact.

Clinical phenotypes of older adults with non-valvular atrial fibrillation not treated with oral anticoagulants by hierarchical cluster analysis in the ANAFIE Registry.

Background: Although anticoagulants are indicated for many elderly patients with non-valvular atrial fibrillation (NVAF), some patients do not receive anticoagulant therapy, whose characteristics and outcomes are diverse.

Methods And Results: In this sub-analysis of the All Nippon AF In the Elderly (ANAFIE) Registry, the phenotypes of patients who were not receiving anticoagulants at baseline were evaluated by cluster analysis using Ward's linkage hierarchical algorithm. Of 32,275 enrolled patients, 2445 (7.

Outcome measures for Alzheimer's disease: A global inter-societal Delphi consensus.

Introduction: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome.

Methods: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria.

Results: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains.

Health and Work Performance Consequences of Working From Home Environment: A Nationwide Prospective Cohort Study in Japan.

Objectives: The physical work environment while working from home (WFH) is a key component of WFH, which, if inadequate, can impair workers' health and work functioning. We investigated environmental factors in WFH and worsening of work functioning.

Methods: A 1-year prospective cohort study was conducted involving 2530 Japanese workers who worked from home.

Communication from the Scientific Standardization Committees of the International Society on Thrombosis and Haemostasis on vascular endothelium-related biomarkers in disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is not a disease criterion but a pathomechanistic process that accompanies various underlying diseases. According to the International Society on Thrombosis and Haemostasis definition, endothelial injury is an essential component in addition to systemic coagulation activation. Despite this definition, current diagnostic criteria for DIC do not include biomarkers for vascular endothelial injury.

Impact of a Novel Digital Therapeutics System on Nonalcoholic Steatohepatitis: The NASH App Clinical Trial.

Introduction: Management of nonalcoholic steatohepatitis (NASH) is a currently unmet clinical need. Digital therapeutics (DTx) is an emerging class of medicine that delivers evidence-based therapeutic interventions. This study was aimed at investigating the efficacy of DTx in patients with NASH.

Systemic Opioids for Dyspnea in Cancer Patients: A Real-world Observational Study.

Context: Although Systemic opioids are recommended as a pharmacological treatment for cancer-related dyspnea, their effectiveness and safety needs to be investigated in a real-world context OBJECTIVES: To evaluate the effectiveness and safety of systemic regular opioids for dyspnea in cancer patients, in the real-world palliative care practice.

Methods: This was a multicenter prospective observational study. We consecutively enrolled adult cancer patients starting regular opioids (morphine, oxycodone, hydromorphone, or fentanyl) for dyspnea from 12 palliative care services across Japan.

Anti-LGI4 Antibody Is a Novel Juxtaparanodal Autoantibody for Chronic Inflammatory Demyelinating Polyneuropathy.

Background And Objectives: The objective of this study was to discover novel nodal autoantibodies in chronic inflammatory demyelinating polyneuropathy (CIDP).

Methods: We screened for autoantibodies that bind to mouse sciatic nerves and dorsal root ganglia (DRG) using indirect immunofluorescence (IFA) assays with sera from 113 patients with CIDP seronegative for anti-neurofascin 155 and anticontactin-1 antibodies and 127 controls. Western blotting, IFA assays using HEK293T cells transfected with relevant antigen expression plasmids, and cell-based RNA interference assays were used to identify target antigens.

Effect of Lycopene Intake on the Fasting Blood Glucose Level: A Systematic Review with Meta-Analysis.

Lycopene is a lipophilic unsaturated carotenoid exhibiting a strong singlet oxygen-quenching ability. Herein, we investigated the effect of lycopene intake on the fasting blood glucose (FBG) level by conducting a systematic review and meta-analyses. We searched 15 databases (from the earliest date to June 2022 for PubMed or to August or September 2018 for the other databases) and included human interventional studies that assessed the effects of oral lycopene intake on FBG levels of participants ≥ 18 years of age.

Effect of 4-Week Consumption of Soy Kori-tofu on Cardiometabolic Health Markers: A Double-Blind Randomized Controlled Cross-Over Trial in Adults with Mildly Elevated Cholesterol Levels.

Kori-tofu is a frozen soy tofu, and soy consumption is associated with positive effects on cardiometabolic health markers. We aimed to assess the potential of Kori-tofu to improve cardiometabolic health outcomes in humans by repetitive daily consumption. In a double-blind randomized controlled cross-over trial, 45 subjects aged 40-70 years with (mildly) elevated cholesterol levels, received a four week Kori-tofu intervention or whey protein control intervention with a four week wash-out period in between.

Evaluating the Differences Between Fluorescein Tear Break-up Time and Noninvasive Measurement Techniques.

Objectives: To compare fluorescein tear break-up time (BUT) and noninvasive BUT measured using interferometry and corneal topography.

Methods: We investigated 34 eyes of 34 patients with dry eye (mean age 39.2±8.

Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved.

The EMPEROR-Preserved trial showed that the sodium-glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF)  > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41-49%).

NLRP3 Inflammasome Activation Through Heart-Brain Interaction Initiates Cardiac Inflammation and Hypertrophy During Pressure Overload.

Background: Mechanical stress on the heart, such as high blood pressure, initiates inflammation and causes hypertrophic heart disease. However, the regulatory mechanism of inflammation and its role in the stressed heart remain unclear. IL-1β (interleukin-1β) is a proinflammatory cytokine that causes cardiac hypertrophy and heart failure.

Construction of a Versatile, Programmable RNA-Binding Protein Using Designer PPR Proteins and Its Application for Splicing Control in Mammalian Cells.

RNAs play many essential roles in gene expression and are involved in various human diseases. Although genome editing technologies have been established, the engineering of sequence-specific RNA-binding proteins that manipulate particular cellular RNA molecules is immature, in contrast to nucleotide-based RNA manipulation technology, such as siRNA- and RNA-targeting CRISPR/Cas. Here, we demonstrate a versatile RNA manipulation technology using pentatricopeptide-repeat (PPR)-motif-containing proteins.