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Background: This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models. Methods: Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated. Results: The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten–eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups. Conclusions: The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered. [ABSTRACT FROM AUTHOR]

Echocardiography is a widely used modality for the assessment of right ventricular (RV) function; however, few studies have comprehensively compared the accuracy of echocardiographic parameters using invasively obtained reference values. Therefore, this exploratory study aimed to compare the accuracy of echocardiographic parameters of RV function and RV–pulmonary artery (PA) coupling. We calculated four indices of RV function (end‐systolic elastance [Ees] for systolic function [contractility], τ for relaxation, and β and end‐diastolic elastance [Eed] for stiffness), and an index of RV–PA coupling (Ees/arterial elastance [Ea]), using pressure catheterization, cardiac magnetic resonance imaging, and a single‐beat method. We then compared the correlations of RV indices with echocardiographic parameters. In 63 participants (54 with pulmonary hypertension (PH) and nine without PH), Ees and τ correlated with several echocardiographic parameters, such as RV diameter and area, but the correlations were moderate (|correlation coefficients (ρ)| < 0.5 for all parameters). The correlations of β and Eed with echocardiographic parameters were weak, with |ρ| < 0.4. In contrast, Ees/Ea closely correlated with RV free wall longitudinal strain (RVFW‐LS)/estimated systolic PA pressure (eSPAP) (ρ = −0.72). Ees/Ea also correlated with tricuspid annular plane systolic excursion/eSPAP, RV diameter, and RV end‐systolic area, with |ρ | >0.65. In addition, RVFW‐LS/eSPAP yielded high sensitivity (0.84) and specificity (0.75) for detecting reduced Ees/Ea. The present study indicated a limited accuracy of echocardiographic parameters in assessing RV systolic and diastolic function. In contrast to RV function, they showed high accuracy for assessing RV–PA coupling, with RVFW‐LS/eSPAP exhibiting the highest accuracy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic polyarthritis. It is well-established that helper T cells play crucial roles in the development and deterioration of RA. Recent studies also revealed the significant roles of regulatory T (Treg) cells in this context. Although Treg cells distributed in peripheral tissues exhibit various functions, the characteristics of synovial Treg cells remain unknown. In this study, we demonstrate that synovial Treg cells exacerbate synovial inflammation by reducing the number of immunoregulatory eosinophils through competitive consumption of IL-33. Synovial Treg cells expressed ST2 in a murine arthritis model, and surprisingly, Treg-specific ST2 knockout (ST2 ΔTreg ) mice exhibited attenuated arthritis. In ST2 ΔTreg mice, an increase in immunoregulatory synovial eosinophils was observed. Additionally, immunoregulatory eosinophils were found to express ST2, and ST2-expressing Treg cells controlled the abundance of immunoregulatory eosinophils, possibly by consuming IL-33. Our results highlight that a subset of synovial Treg cells possesses the machinery to worsen arthritis by suppressing eosinophils. In the future landscape where Treg cell-based therapies are employed for autoimmune diseases, it is important to comprehend the characteristics of disease-related Treg cells. Understanding these aspects is crucial for ensuring safer treatment modalities that do not inadvertently worsen the diseases., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Precapillary pulmonary hypertension (PH) is characterized by a sustained increase in right ventricular (RV) afterload, impairing systolic function. Two-dimensional (2D) echocardiography is the most performed cardiac imaging tool to assess RV systolic function; however, an accurate evaluation requires expertise. We aimed to develop a fully automated deep learning (DL)-based tool to estimate the RV ejection fraction (RVEF) from 2D echocardiographic videos of apical four-chamber views in patients with precapillary PH., Methods: We identified 85 patients with suspected precapillary PH who underwent cardiac magnetic resonance imaging (MRI) and echocardiography. The data was divided into training (80%) and testing (20%) datasets, and a regression model was constructed using 3D-ResNet50. Accuracy was assessed using five-fold cross validation., Results: The DL model predicted the cardiac MRI-derived RVEF with a mean absolute error of 7.67%. The DL model identified severe RV systolic dysfunction (defined as cardiac MRI-derived RVEF < 37%) with an area under the curve (AUC) of .84, which was comparable to the AUC of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) measured by experienced sonographers (.87 and .72, respectively). To detect mild RV systolic dysfunction (defined as RVEF ≤ 45%), the AUC from the DL-predicted RVEF also demonstrated a high discriminatory power of .87, comparable to that of FAC (.90), and significantly higher than that of TAPSE (.67)., Conclusion: The fully automated DL-based tool using 2D echocardiography could accurately estimate RVEF and exhibited a diagnostic performance for RV systolic dysfunction comparable to that of human readers., (© 2024 Wiley Periodicals LLC.)

Background and study aims Balloon dilation and plastic stent deployment have been performed as hepaticojejunostomy stricture (HJS) treatment techniques under endoscopic ultrasound guidance (EUS). Although these techniques have shown favorable clinical results, the treatment period can be long because stent deployment is required. In addition, HJS may recur even after treatment because the scar tissue itself remains. To overcome these challenges, we developed an EUS-guided antegrade drill dilation technique for treating HJS. The aim of this study was to evaluate the technical feasibility and safety of this technique in terms of the pre- and post-cholangioscopic findings. Patients and methods This retrospective study included consecutive patients whose conditions were complicated with symptomatic HJS between November 2022 and February 2023. Transluminal antegrade drill dilation (TAD) using a novel drill dilator was attempted within 14 days after EUS-guided hepaticogastrostomy (HGS). HJS was diagnosed with cholangioscopy before TAD, and resolution was evaluated after TAD using cholangioscopy. Results TAD was attempted at approximately 11 days after EUS-HGS. The cholangioscope was inserted successfully in all patients after this procedure. Cholangioscopy revealed stricture without evidence of malignancy in 19 patients. In the remaining three patients, stricture was not observed and these patients underwent stent exchange rather than TAD. Among the 19 patients, passage of the guidewire across the HJS into the intestine was unsuccessful in four patients, and the technical success rate for this procedure was 78.9%. TAD was successful in all 15 patients in whom passage of the guidewire was achieved. Conclusions In conclusion, TAD appears to be technically feasible and safe., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)