Evolution and Functional Diversification of Serine Racemase Homologs in Bacteria.

Amino acid racemases catalyze the interconversion of L- and D-amino acids, maintaining intracellular levels of both D- and L-amino acids. While alanine and glutamate racemases are widespread in bacteria, serine racemase (SerR) is predominantly found in animals. Recently, homologs of animal SerR were reported in some bacterial genomes, but their evolutionary distribution and functional roles remain poorly understood.

Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study.

Background/aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response.

Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled.

Results: Persistence with vedolizumab was 64.

Association between ventricular arrhythmia (premature ventricular contractions burden and nonsustained ventricular tachycardia) and cardiovascular events in patients without structural heart disease.

Background: Premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) are common arrhythmias in cardiovascular clinical settings. However, the clinical significance of PVCs and NSVT in the absence of structural heart disease has not yet been fully elucidated. This study aimed to evaluate the association between PVCs, NSVT, and clinical outcomes.

Differential response to right ventricular extrastimuli from the base and apex during long RP' supraventricular tachycardia.

We report a case of long RP' tachycardia diagnosed as fast-slow atrioventricular nodal reentrant tachycardia (AVNRT) with a bystander nodoventricular pathway (NVP). Differential responses to right ventricular extrastimuli from the base and apex highlighted the anatomical proximity of the NVP attachment, contributing to the diagnosis.

High-density mapping in catheter ablation for atrial fibrillation in Asia Pacific region: An observational study.

Background: Few clinical studies of atrial fibrillation (AF) have focused on Asian patients; data are lacking on current mapping and ablation strategies in the Asia Pacific region (APAC).

Objective: The HD Mapping Observational Study (NCT04022954) was designed to characterize electroanatomic mapping (EAM) with market-released high-density mapping (HDM) catheters in subjects with AF in APAC.

Methods: Subjects undergoing HDM and indicated for radiofrequency ablation (RFA) to treat AF were prospectively enrolled in APAC.

Different effects of catheter ablation on exercise tolerance, leg strength, and quality of life in paroxysmal versus persistent atrial fibrillation.

Background: Catheter ablation (CA) can improve exercise tolerance and quality of life (QOL) in patients with atrial fibrillation (AF). However, its differential effects on muscle strength between paroxysmal AF (PAF) and nonparoxysmal AF (Non-PAF) remain unclear.

Methods: We evaluated 94 patients (67.

Streptococcus pyogenes M1UK Variant-Associated Sartorius Muscle Necrotizing Soft Tissue Infection: A Case Report and Literature Review.

Necrotizing soft tissue infections (NTSIs) represent a concept of necrotizing infections involving the skin, subcutaneous tissue, fascia, and muscle, and it is a potentially fatal disease. Early exploratory incision is strongly recommended for both the diagnosis and treatment of necrotizing soft tissue infections. Treatment of necrotizing soft tissue infections requires the administration of appropriate antimicrobial agents and adequate surgical debridement.

Diversity of TCR repertoire predicts recurrence after CRT followed by durvalumab in patients with NSCLC.

Chemoradiotherapy (CRT) followed by durvalumab is standard for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study assesses how CRT alters the T-cell receptor (TCR) repertoire in CD8 + PD-1 + T-cells and its impact on clinical outcomes. This prospective study, conducted from November 2019 to May 2021 at three institutions in Japan, evaluated the diversity of TCR repertoire (DE50) in PD-1 + CD8 + T-cells and CD8 + T-cell phenotypes in peripheral blood before and after CRT.

Anti-inflammatory effects of water-dispersible hesperetin on endotoxin-induced uveitis in rats involving the nuclear factor κB and Wnt/β-catenin signaling pathways.

This study investigated the anti-inflammatory effects of water-dispersible hesperetin (WD-Hpt) in an endotoxin-induced uveitis (EIU) rat model. The rats were orally administered 10, 25, or 50 mg/kg WD-Hpt immediately after lipopolysaccharide (LPS) injection at the concentration of 200 μg. Clinical scores, cellular inflammation, the aqueous humor (ApH) protein concentration, as well as the levels of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) in AqH, and histopathological grades were assessed.

Expanding the Chemical Space of Reverse Fosmidomycin Analogs.

Multidrug-resistant pathogens pose a major threat to human health, necessitating the identification of new drug targets and lead compounds that are not susceptible to cross-resistance. This study demonstrates that novel reverse thia analogs of the phosphonohydroxamic acid antibiotic fosmidomycin inhibit 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme for , , and that is absent in humans. Some novel analogs with large α-phenyl substituents exhibited strong inhibition across these three DXR orthologues, surpassing the inhibitory activity of fosmidomycin.

Scoping review of initiation criteria for inhaled nitric oxide in preterm infants (born <34 weeks) after 7 days of age.

Objectives: Inhaled nitric oxide (iNO) is a known treatment for pulmonary hypertension (PH) associated with bronchopulmonary dysplasia in preterm infants after 7 days of age (postacute phase). However, a consensus regarding the optimal criteria for initiating iNO therapy in this population in the postacute phase is currently lacking. This study, therefore, aimed to identify the criteria for initiating iNO therapy, alongside the associated clinical and echocardiographic findings, in this population.

A Descriptive Comparative Analysis of Safety Concerns Outlaid in the Risk Management Plans of the European Union and Japan.

Purpose: This study aimed to obtain a better understanding of the characteristics of the risk management plans (RMP) and the background regulatory policies governing them, in the European Union (EU) and Japan. This was done by descriptively comparing the safety concerns (SCs) listed in the RMP and examining their relationships with product labeling.

Methods: Information regarding SCs was collected from the published RMP of both the EU and Japan for the targeted products-all of which were commonly approved in both regions.

Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval.

Drug lag is a serious issue for patients with life-threatening diseases such as cancer. Japan and Korea have been facing a large drug lag, despite having a large market and a good clinical trial environment. We analyzed drug lags for anticancer drugs between these countries, using the information on 82 anticancer drugs approved in the United States between 2017 and 2022.

Induction of phospholipase A2 group 4C by HCV infection regulates lipid droplet formation.

Background & Aims: Hepatic steatosis, characterized by lipid accumulation in hepatocytes, is a key diagnostic feature in patients with chronic hepatitis C virus (HCV) infection. This study aimed to clarify the involvement of phospholipid metabolic pathways in the pathogenesis of HCV-induced steatosis.

Methods: The expression and distribution of lipid species in the livers of human liver chimeric mice were analyzed using imaging mass spectrometry.

LysR-Type Transcriptional Regulator VirR Responds to Temperature and pH and Directly Activates the Transcription of -Containing Operon in .

-a facultative intracellular pathogen of macrophages-causes bronchopneumonia in foals and patients who are immunocompromised. Virulent strains of possess a virulence-associated plasmid, which encodes a 15- to 17-kDa surface protein called virulence-associated protein A (VapA). VapA expression is regulated by temperature and pH.

Corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis stratified by left ventricular ejection fraction.

Aims: This study aimed to investigate the relationship between corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis, stratified by left ventricular ejection fraction (LVEF) at diagnosis.

Methods And Results: This study conducted a analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis, a retrospective multicentre registry. Cardiac sarcoidosis was diagnosed based on the 2016 Japanese Circulation Society and 2014 Heart Rhythm Society criteria.

Approaches for difficult-to-induce-seizures electroconvulsive therapy cases (DEC): a Japanese expert consensus.

Background: Seizure threshold increases with age and the frequency of electroconvulsive therapy (ECT). Therefore, therapeutic seizures can be difficult to induce, even at maximum stimulus charge with available ECT devices. Such cases are known as difficult-to-induce-seizures electroconvulsive therapy cases (DECs).

The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying -Substituents.

It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.

Clinical effect of ventricular entry during resection of IDH-wildtype glioblastoma: A multi-institutional analysis.

Purpose: Glioblastomas contacting the subventricular zone (SVZ) are associated with poor prognosis and the impact of ventricular entry (VE) during resection remains controversial. Since glioblastomas with SVZ involvement often require VE, both SVZ involvement and VE are confounding factors. This study aimed to evaluate the effect of VE during glioblastoma resection by comparing patients with and without SVZ involvement.

Three Cases of Amblyopia With Fusion Maldevelopment Nystagmus Successfully Treated With Dichoptic Treatment.

We present three cases where traditional occlusion therapy with an eye patch proved ineffective for treating amblyopia associated with fusion maldevelopment nystagmus. In these cases, we transitioned to dichoptic therapy using the Occlu-pad, achieving successful outcomes. Eye patch occlusion of the sound eye consistently exacerbated nystagmus, whereas dichoptic treatment did not.

Radiologic Parameters Predicting the Histologic Invasiveness of Pure Ground-Glass Nodules.

Background: This study aimed to investigate the diagnostic performance of combined computed tomography (CT) and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for predicting histologic invasiveness of pure ground-glass nodules (pGGNs).

Methods: The study analyzed 91 patients who underwent resection of pGGNs and examined the correlation of pathologic invasiveness with preoperative CT and FDG PET findings.

Results: Overall, 24, 36, and 31 patients had adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAD), respectively.

Detection of Eimeria oocysts in chicken feces using flotation recovery with sucrose or saturated saline solution.

Purpose: Flotation methods are widely used to detect oocysts/cysts of protozoans and eggs of helminths, except trematodes. However, details regarding the concentration and recovery rates of these parasites are poorly understood.

Methods: Using Eimeria tenella oocysts as a model parasite, the present study evaluated three check points: (1) the proportion of parasites that remain floating in flotation solution (sucrose or saturated saline) during centrifugation, (2) the proportion of oocysts that naturally float after addition of flotation solution after centrifugation, and (3) the rate of recovery on cover slips after completion of the flotation protocol.

Benefit of minimally invasive extracorporeal circulation on minimally invasive aortic valve replacement through right lateral mini-thoracotomy using femoral cannulation: a propensity-matched analysis.

Objectives: The objective of this study was to evaluate the impact of minimally invasive extracorporeal circulation on blood transfusion and asymptomatic brain injury in comparison to conventional extracorporeal circulation in the context of minimally invasive aortic valve replacement through right lateral mini-thoracotomy surgery.

Methods: This was a retrospective observational study. Patients who underwent isolated aortic valve replacement through right lateral mini-thoracotomy surgery were divided into two groups: the minimally invasive extracorporeal circulation group and the conventional extracorporeal circulation group.

Are Exposure Recommendations for QT Evaluation Being Fulfilled?

Pharmaceutical companies have several options to evaluate drug-induced QT prolongation, often referred to as QT pathways, during clinical development. Current regulatory practices recommend achieving high clinical exposure (HCE) for conventional thorough QT (TQT) studies. An alternative to the TQT study, commonly known as the Q&A 5.