Targeting PAR-2 in atopic dermatitis: Preclinical evaluation of the novel inhibitor E6795.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions, intense itching, and compromised skin barrier function. Despite the advent of new therapeutics, many individuals still face insufficient disease control, high costs, and relapse. Protease-activated receptor 2 (PAR-2), overexpressed in AD lesions, plays a central role in promoting inflammation, itch, and alterations in epidermal homeostasis.

Restenosis After Pulmonary Vein Stenting Following Pulmonary Vein Isolation With Nonobstructive General Angioscopy.

A 33-year-old male developed pulmonary vein (PV) stenosis 3 months after PV isolation for atrial fibrillation. Stents were implanted in the left superior and inferior PVs, but 2 years later, in-stent restenosis occurred. Intravascular ultrasound and nonobstructive general angioscopy (NOGA) revealed severe ostial stenosis and neointimal hyperplasia.

Predictors of early progressive disease and antitumor effects by metastatic site in renal cell carcinoma treated with ipilimumab plus nivolumab.

Background: Despite durable benefits of ipilimumab and nivolumab in metastatic renal cell carcinoma (mRCC), early progressive disease (PD), defined as disease progression within 3 months, occurs, and its predictors remain unclear. We aimed to investigate the clinical factors associated with early PD in patients with mRCC treated with this regimen.

Methods: A retrospective analysis of a multi-institutional database identified 193 patients with mRCC treated with ipilimumab plus nivolumab.

Investigating the Effectiveness of an Enhanced Coin-Shaped Lithium Battery With Titanium Coating in Reducing Esophageal Damage From Accidental Ingestion in Living Piglets.

Background Accidental ingestion of coin-shaped lithium batteries (CSLBs) poses a serious health risk, leading to severe esophageal injuries and fatal complications. Conventional CSLBs cause rapid tissue damage due to electrochemical reactions, necessitating the development of safer battery designs. This study aimed to develop and evaluate an improved CSLB with a titanium-clad design to reduce electrochemical reactions and delay esophageal tissue damage in cases of accidental ingestion.

Immune checkpoint inhibitors in gynecologic oncology: Current status and perspectives.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by leveraging the immune system's capacity to fight gynecologic cancer. This review summarizes the current status and future perspectives of ICIs in the treatment of cervical, endometrial, and ovarian cancers and rare tumors. ICIs have demonstrated significant efficacy in tumors with high tumor mutational burden and immune markers such as PD-L1 expression and microsatellite instability.

Periplasmic serine protease Prc is responsible for amyloid subunit CsgA degradation and proteostasis in Escherichia coli.

Escherichia coli synthesizes curli amyloid fibers extracellularly during biofilm formation and host colonization. The proteostasis network regulates the major curli subunit, CsgA, to prevent intracellular amyloid aggregation, yet the degradation mechanism remains elusive. Here, through a comprehensive investigation employing genetically engineered E.

Psychotic-like experiences, sleep problems, and loneliness: A population-based study.

Research indicates that psychotic-like experiences (PLEs) are associated with sleep problems, which in turn may contribute to negative outcomes in individuals with PLEs. This study examined the association between sleep problems and PLEs in the Japanese general population, and whether sleep problems are linked to loneliness among individuals with PLEs. Data were analyzed from 3717 adults aged 18 and above who participated in an online survey in 2023.

Transgenic mice overexpressing Pitx2 in the atria develop tachycardia-bradycardia syndrome.

Sinoatrial node (SAN) dysfunction often accompanies supraventricular tachyarrhythmias such as atrial fibrillation (AF), which is referred to as tachycardia-bradycardia syndrome (TBS). Although there have been many studies on electrical remodeling in TBS, the regulatory mechanisms that cause electrical remodeling in the SAN and atrial muscles by chronic bradycardia or tachycardia have not yet been fully investigated. Here we hypothesized Pitx2c, a transcription factor that played a central role in the late aspects of left-right asymmetric morphogenesis, regulated an interrelationship between the SAN and the atrial muscles and was involved in TBS-like pathology.

Advances in malignant hyperthermia: novel insights into heat-induced Ca release as a thermal signaling.

Thermoregulation is essential for maintaining homeostasis in mammals under various environmental conditions. Impairment of this function can result in severe conditions, such as fever, heat stroke, and malignant hyperthermia (MH). In this review, we will focus on the role of the type 1 ryanodine receptor (RYR1), a Ca release channel that is crucial for excitation-contraction coupling in skeletal muscles.

Expanding diverse horizons in smooth muscle research: a symposium review of "Muscle and Pathology/Health: Frontiers of Translational Research" at the 66th Annual Meeting of Japan Society of Smooth Muscle Research.

Smooth muscle research is at the forefront of translational science, bridging the gap between basic molecular discoveries and clinical applications. The symposium "Muscle and Pathology/Health: Frontiers of Translational Research" at the 66th Annual Meeting of Japan Society of Smooth Muscle Research showcased recent advances in this field. The presentations highlighted diverse topics, including molecular targeting in malignant hyperthermia, the therapeutic potential of probiotics in inflammatory bowel disease, sex differences in pulmonary hypertension and the impact of dietary components on vascular health.

Light chain proximal tubulopathy in Sjögren syndrome: the critical role of tubular function tests in revealing a hidden threat.

A 65-year-old female patient with Sjögren syndrome (SJS) and tubulointerstitial nephritis (TIN) confirmed by kidney biopsy results 7 years previously presented to our department with progressive kidney function deterioration. Laboratory findings revealed increased serum creatinine level accompanied with deterioration of tubular function. Although she already had signs of proximal tubular dysfunction due to TIN from 7 years before, deterioration of the proximal tubule related parameters was particularly prominent.

Response predictors and long-term outcomes of preprandial single-daily cyclosporine in children with steroid-dependent nephrotic syndrome.

Background: Although single-daily cyclosporine may offer an effective therapeutic option with increased compliance and reduced nephrotoxicity, response predictors and long-term outcomes following this regimen remain unclear in children with steroid-dependent nephrotic syndrome.

Methods: A retrospective study was conducted between October 2005 and December 2021 on children with steroid-dependent nephrotic syndrome caused by minimal change disease (MCD) who were treated with preprandial single-daily cyclosporine to maintain 2-h post-dose levels of 500-700 ng/mL. The primary endpoint was the time to treatment failure after single-daily cyclosporine initiation.

Vaginal Laser Therapy as a Potential Treatment Option for Postmenopausal Women With Recurrent Cystitis: Initial Experience From a Single Institution.

Background: Recurrent cystitis is a prevalent condition, especially among postmenopausal women, significantly impairing their quality of life. Antibiotic therapy has historically been the primary treatment; however, concerns over antimicrobial resistance have highlighted the need for alternative therapies. Vaginal laser therapy, a noninvasive approach, has shown promise in improving vaginal health and may help prevent recurrent cystitis.

Treatment outcomes of squamous cell carcinoma of the external auditory canal and potential benefit of induction chemotherapy followed by chemoradiotherapy.

Introduction: Carcinoma of the external auditory canal (EAC) is rare, and squamous cell carcinoma (SCC) is the most common histological type. There are few reports on the treatment outcomes for a large number of cases at a single institution, and a standard treatment has not been established.

Methods: Treatment details and prognoses were retrospectively examined for patients who underwent primary treatment for SCC of the EAC at The Jikei University between April 2015 and May 2023.

Late Administration of Remdesivir, Guided by Antigen Test Results, in a Patient Experiencing Difficulty Weaning From the Ventilator Due to Severe COVID-19 Pneumonia.

A 70-year-old woman with a history of malignant lymphoma (in remission) and systemic sclerosis required mechanical ventilation because of severe coronavirus disease 2019 pneumonia. Despite the administration of broad-spectrum antibiotics, antifungal agents, and corticosteroids, respiratory failure persisted, and a tracheostomy was performed on hospital day 17. Ventilator weaning remained difficult up to hospital day 30 and persistent detection of the severe acute respiratory syndrome coronavirus 2 antigen prompted initiation of remdesivir.

An efficient approach for detecting atrial fibrillation in ischemic stroke patients using a wearable device: a prospective multicenter substudy of the STABLED trial.

Objective: Stroke caused by atrial fibrillation (AF) is associated with high mortality and severe morbidity. Screening patients for AF may facilitate early initiation of anticoagulant therapy and prevent recurrent stroke; therefore, strategies to effectively detect AF in stroke patients are important.

Methods: This prospective multicenter study was conducted between April 27, 2020 and March 31, 2021 at seven sites in Japan, as a substudy of the STABLED trial, a multicenter prospective randomized study to evaluate the efficacy and safety of catheter ablation with anticoagulant therapy using edoxaban in patients with ischemic stroke and AF.

Innovative Orbital Periosteum Suturing Technique for Endoscopic Medial Orbital Wall Reconstruction.

Background: Advances in endoscopic orbital surgery have sparked discussion regarding reconstructive procedures for medial orbital wall defects following tumor removal. This study describes an innovative orbital periosteal suturing technique that addresses the functional and aesthetic concerns created by orbital surgery.

Objective: Comprehensive clinical evaluation of a novel orbital periosteal suturing technique for endoscopic medial orbital wall reconstruction.

A novel synthetic bile acid derivative inhibits hepatitis B virus infection at entry step by interfering with the oligomerization of sodium taurocholate co-transporting polypeptide.

Hepatitis B virus (HBV) infection is a major global health burden worldwide despite the availability of an effective vaccine and effective anti-HBV drugs. The currently approved anti-HBV drugs-i.e.

Association between women's weight gain during their infancy and being overweight or underweight in adulthood: a retrospective cohort study.

This study aimed to explore the associations between weight gain during infancy with pre-pregnant body mass index (BMI) later in life, focusing on risks of being overweight or underweight. A retrospective cohort study was conducted using data from women ( = 1082) who visited the National Center for Child Health and Development between 2017 and 2021. The participants provided their Maternal and Child Health Handbook, which included records of their own birthweight and weight gain from birth to 1, 3, and 6 months.

Lubiprostone in chronic kidney disease: Insights into mitochondrial function and polyamines from a randomized phase 2 clinical trial.

Chronic kidney disease (CKD) is a life-threatening condition, and constipation is a progressive risk factor. We evaluated changes in uremic toxins, renal function, and the safety of lubiprostone, a selective chloride channel activator, in patients with CKD. In this phase 2, randomized, double-blind, placebo-controlled trial across nine centers in Japan, 150 patients with stage IIIb-IV CKD received lubiprostone (8 or 16 micrograms) or placebo for 24 weeks.

Defining statistical cure in patients with T1 high-grade non-muscle-invasive bladder carcinoma treated with BCG immunotherapy.

Objective: To assess cure fraction and conditional survival probabilities for oncological outcomes in patients with T1 high-grade (T1HG) non-muscle-invasive bladder carcinoma (NMIBC) treated with adequate Bacillus Calmette-Guérin (BCG) immunotherapy.

Patients And Methods: This multi-institutional retrospective cohort study included 1403 patients with T1HG NMIBC treated between 2007 and 2020, adhering to modern guidelines including mandatory second transurethral resection of bladder tumour and adequate BCG, defined as at least five of six induction doses and at least two of three maintenance doses. Cure fraction, defined as the proportion of patients who will never experience the event of interest, was calculated for recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using a mixture cure model.

Development of a Computationally Efficient CFD Method for Blood Flow Analysis Following Flow Diverter Stent Deployment and Its Application to Treatment Planning.

Intracranial aneurysms are a serious cerebrovascular condition with a risk of subarachnoid hemorrhage due to rupture, leading to high mortality and morbidity. Flow Diverter Stents (FDSs) have become an important endovascular treatment option for unruptured large or wide-neck aneurysms. Hemodynamic factors significantly influence treatment outcomes in aneurysms treated with FDSs, and Computational Fluid Dynamics (CFD) has been widely used to evaluate post-deployment flow characteristics.