Clinical Outcomes of Solid Organ Transplant Recipients Hospitalized with COVID-19: A Propensity Score-Matched Cohort Study.

BACKGROUND: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. MATERIALS AND METHODS: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. RESULTS: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization (P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12-4.11) and male gender (OR, 2.62; 95% CI, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24-0.79) was associated with better outcomes. CONCLUSION: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Autophagy caused by oxidative stress promotes TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Diabetes Disparities in the United States: Trends by Educational Attainment from 2001 to 2020.

INTRODUCTION: Tracking changes in socioeconomic disparities in diabetes in the U.S. is important to evaluate progress in health equity and guide prevention efforts. Disparities in diabetes prevalence by educational attainment from 2001 to 2020 were investigated. METHODS: Using a serial cross-sectional design, data from 33,220 adults aged 30-79 assessed in nine rounds of the National Health and Nutrition Examination Surveys between 2001 and 2020 were analyzed in 2023-2024. Diabetes was defined as self-reported prior diagnosis, elevated glycated hemoglobin (HbA1c≥6.5%), or use of diabetes medications. Marginalized age- and covariate-adjusted prevalence differences (PD) and prevalence ratios (PR) of diabetes by educational attainment (less than high school graduation, high school graduation, some college education or associate degree, or college graduation [reference]) by calendar period (2001-2004, 2005-2008, 2009-2012, 2013-2016, 2017-2020) were derived from logistic regression models. RESULTS: From 2001 to 2020, age-adjusted diabetes prevalence was consistently higher among adults without a college degree. Adults without a high school diploma exhibited the largest disparities in both 2001-2004 (PD 8.0%; 95%CI 5.6-10.5 and PR 2.1; 95%CI 1.5-2.6) and 2017-20 (PD 11.0%; 95%CI 6.7-15.2 and PR 2.1; 95%CI 1.5-2.7). Between 2001-2004 and 2017-2020, the absolute disparity in diabetes changed only among adults with a high school diploma (increase from PD 1.7%; 95%CI -0.5- 3.9 to PD 8.8% 95%CI 4.1-13.4, respectively), while the PR did not change in any group. Education-related disparities in diabetes were attenuated after accounting for socio-demographic factors and BMI. CONCLUSIONS: From 2001 to 2020, national education-related disparities in diabetes prevalence have shown no signs of narrowing.

Self-harm in sexually abused adolescents: The role of posttraumatic symptoms, emotional impulsivity, and negative cognition.

OBJECTIVE: Posttraumatic symptoms, emotional impulsivity, and negative cognition have been proposed as pathways in explaining why individuals have experienced trauma are at increased risk for self-harm. The present study examined whether emotional impulsivity (i.e., negative and positive urgency) and negative cognition (i.e., personal attribution and feeling different from peers) mediate the path from posttraumatic symptoms to self-harm in sexually abused adolescents, a population at the highest risk for self-harm. METHOD: One hundred and thirty-one sexually abused youths aged 10-18 years in South Korea completed the Self-Harm Inventory, UPPS-P (urgency-premeditation-perseverance-sensation seeking-positive urgency) Impulsive Behaviors Scales for use with children, and Children's Attribution and Perception Scale, and their parents completed the Korean version of the parent report of posttraumatic symptoms. RESULTS: Among the adolescent participants, 77.1% (n = 101) reported engaging in at least one self-harm behavior, and 61.8% (n = 81) reported engaging in deliberate self-injury. Mediation model analyses showed that parent-reported posttraumatic symptoms predicted more self-harm behaviors among sexually abused adolescents. The indirect effect of parent-reported posttraumatic symptoms on self-harm through adolescents' negative cognition was significant, but the indirect effect through emotional impulsivity was not. CONCLUSION: The results indicate that, at least among sexually abused adolescents, posttraumatic symptoms lead to self-harm via negative cognition rather than increased emotional impulsivity. These findings suggest that sexually abused adolescents suffering from posttraumatic symptoms are more likely to engage in self-harm in response to negative cognition of themselves and the world rather than as an impulsive response to intense emotions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Healthy and Unhealthy Dietary Patterns of Depressive Symptoms in Middle-Aged Women.

Depressive symptoms are a common menopausal feature in middle-aged women and are associated with dietary factors. This study aimed to determine the association between dietary patterns and depressive symptoms in 2190 Korean women aged 45-69 years. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and food intake was examined using a food frequency questionnaire. Dietary patterns were derived from principal components analysis and identified two dietary patterns: a "healthy" dietary pattern (high intake of whole-grain rice, legumes, vegetables, fruits, and fish) and an "unhealthy" dietary pattern (high intake of noodles, dumplings, sweets, red meat, soda, and coffee). After adjusting for all confounding factors, those with the highest healthy dietary pattern scores had a 0.56-fold lower risk of depressive symptoms than those with the lowest score (Odds Ratio (OR) = 0.56, 95% confidence interval (CI): 0.37-0.84, p for trend = 0.006). Conversely, those with the highest unhealthy pattern scores had a 1.85-fold higher risk of depressive symptoms than that of those in the lowest quartile (OR = 1.85, 95% CI: 1.30-2.63, p for trend = 0.002). In middle-aged women, a dietary pattern of high intake of fiber-rich whole-grain rice, fruits, vegetables, and legumes may help prevent and manage depressive symptoms.

Validation of a Korean Version of the Short UPPS-P Impulsive Behavior Scale for Children.

OBJECTIVE: Impulsivity is a multifaceted construct that plays an important role in various problem behaviors in children and adolescents. The purpose of this study was to validate a Korean version of the short UPPS-P Impulsive Behavior Scale for Children. METHODS: Participants were 330 children (166 female) from 2 elementary schools in Korea and 94 attention deficit hyperactivity disorder (ADHD) children (23 female) from two major hospitals. The Korean short UPPS-P Impulsive Behavior Scale for Children (UPPS-P-C) (20 items), Child Behavior Checklist for Ages 6-18 (CBCL 6-18), and Barratt Impulsiveness Scale-11 (BIS-11) were administered. 107 children from the control group were retested 6 months later. RESULTS: Confirmatory factor analysis (CFA) conducted in the control group supported a 5-factor hierarchical model in which 1) positive and negative urgency factors are loaded on a higher-order factor of general urgency; 2) lack of perseveration and lack of premeditation factors are loaded on a higher-order factor of lack of conscientiousness; and 3) sensation seeking remained as a separate dimension. Reliability analysis demonstrated that the 5 factors of the Korean short UPPS-P-C had acceptable internal consistency and test-retest reliability. Lack of premeditation and lack of perseveration subscales showed significant correlations with measures of problem behaviors in CBCL and all the subscales were correlated with the BIS-11. The ADHD group showed significantly higher scores in lack of premeditation, lack of perseveration, positive urgency, and negative urgency subscales. CONCLUSION: This study indicates that the Korean version of short UPPS-P-C has adequate reliability and validity. It may be a valid tool to assess impulsivity of healthy children as well as ADHD.

Measuring social-emotional development in schoolchildren: A national-level analysis of ECLS-B cohort data.

The present study examined the social-emotional development items assessed by kindergarten teachers in the Early Childhood Longitudinal Study-Birth Cohort to determine the optimal factor structure underlying the items as well as the reliability and validity of the resulting factors. This study identified an empirically derived factor structure for teacher-reported social development, investigated whether there was evidence of bias in teacher assessments of social-emotional constructs, examined factor invariance across demographic characteristics (i.e., race and ethnicity, sex, and poverty status), and examined the external validity of the derived factors by determining the extent to which they were associated with well-established measures of early childhood competencies. Findings suggested a 4-factor solution was optimal, consisting of (a) Interpersonal Skills, (b) Externalizing Behavior, (c) Approaches to Learning, and (d) Perspective Taking. Findings offer suggestive evidence of teacher biases in assessments and some, although not conclusive, support for the invariance of social-emotional dimension across demographic characteristics. Results provide a useful next step toward documenting reliable and valid social-emotional measures for use in early childhood research and challenges users of national datasets to think critically about the use of "scales" without a priori attention to important psychometric properties.

Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Rapid discrimination of Panax ginseng powder adulterated with various root plants by FT-IR spectroscopy coupled with multivariate analysis.

Panax ginseng powder adulterated with other root plants (arrowroot, bellflower, and lance asiabell) was discriminated using Fourier transform infrared (FT-IR) spectroscopy, combined with multivariate analysis. Principal component analysis visually diagnosed the adulteration by showing two distinct clusters based on presence of adulteration. Wavenumber regions (1000 cm-1 and 3300 cm-1) selected from the loading plot associated with the vibration of OH and CH bond in ginsenoside and aromatic compounds. A quantitative model for the content of ginsenosides and specific aromatic compounds as indicators of pure ginseng powder, was developed based on partial least square regression analysis. The performance of the prediction model preprocessed with the Savizky-Golay 1st derivative was improved to R2 of 0.9650, 0.9635, and 0.9591 for Rb1, Rc, and ß-Panasinsene, respectively. Therefore, FT-IR technology makes it possible to rapidly authenticate pure ginseng product based on the ginsenoside contents and aroma compound.

Severe Acute Kidney Injury Associated with Transformation of Chronic Myelomonocytic Leukemia into Acute Myeloid Leukemia: A Case Report.

Chronic myelomonocytic leukemia (CMML) is a rare hematologic disorder that infrequently causes acute kidney injury (AKI). CMML can transform into acute myeloid leukemia (AML), which can be accompanied by a deterioration in kidney function. However, severe AKI due to extramedullary manifestations of AML is rare. Herein, we present the case of a 67-year-old male patient with CMML that transformed into AML with severe AKI necessitating hemodialysis. The cause of the AKI was the AML transformation. The patient, with stable kidney function after chemotherapy for CMML, presented with a sudden decline in kidney function. Hemodialysis was initiated because of severe AKI, and histopathologic evaluation of the kidney biopsy specimen revealed severe, diffuse mixed inflammatory cell infiltrates in the interstitium and c-kit-immunopositive myeloblast-like cells. A bone marrow biopsy was performed because of the kidney biopsy findings suggesting that leukemic infiltration led to the diagnosis of AML. The patient received chemotherapy for AML, and his kidney function recovered. As illustrated in this case, severe AKI can develop as an early extramedullary manifestation during transformation from CMML to AML. Therefore, in patients with CMML and rapidly declining renal function, transformation into AML should be considered and histopathologically confirmed by kidney biopsy.

Changes in bacterial composition and metabolite profiles during kimchi fermentation with different garlic varieties.

Garlic, a key ingredient in kimchi, is an indispensable source of lactic acid bacteria, which are essential for fermentation. This study explored the effects of various garlic varieties on kimchi fermentation, focusing on changes in microbial communities and metabolite profiles. We observed that the type of garlic used did not significantly alter the microbial community. However, the presence of garlic itself made a significant difference. Specifically, kimchi with garlic showed higher abundance of Leuconostoc and Weissella, which are bacteria primarily responsible for kimchi fermentation. Additionally, kimchi containing garlic had increased levels of mannitol and fructose, which significantly influence taste; however, lactic acid and putrescine levels were decreased. Therefore, the addition of garlic directly contributes to the flavor profile of kimchi. Sixty-two metabolites were identified using gas chromatography and mass spectrometry. The variety of garlic added influenced the metabolite profiles of kimchi, particularly in the later stages of fermentation. These profiles were categorized based on the garlic's origin, whether from southern or northern ecotypes (R2X = 0.933, R2Y = 0.986, Q2 = 0.878). These findings confirm that both the presence and the variety of garlic significantly impact the microbial ecology and metabolites during kimchi fermentation, underscoring its essential role in the process.

Factors Related to General Sexual Behavior of Children Under 10 Years Old in Korea.

The risk factors for intrusive or problematic sexual behavior in a specific population, including abused or clinically referred children, have been occasionally explored. However, sexual behaviors broadly in the general population have not been investigated. This study aimed to determine whether child characteristics, exposure to trauma, family factors, and exposure to sexuality, which were proposed as predictors of sexual behavior problems in previous studies, significantly affected the general sexual behaviors of children under 10 years in the Korean population. The parents of 652 children aged 3-9 years in a Korean community completed questionnaires, including the Child Sexual Behavior Inventory, the Korean version of the Child Behavior Checklist, Trauma Symptom for Young Children, the Korean version of the Family Inventory of Life and Change, the Dysfunctional Parenting Scale, and exposure to trauma and sexuality. Regression analysis indicated that children's age, externalizing behavior problems, post-traumatic symptoms, exposure to trauma, and exposure to sexuality were significant predictors of overall sexual behaviors. Therefore, it may be helpful to explore trauma and exposure to sexuality even to understand a child's general sexual behavior. In addition, psychoeducation can help parents monitor and reset family boundaries and sexual exposure that can affect children's sexual behavior.

Investigation of Metabolite Differences in Salted Shrimp Varieties during Fermentation.

Fermentation of salted shrimp involves the interaction of multiple factors. However, studies of the effects of shrimp variety and fermentation temperature on metabolites generated during fermentation are limited. Therefore, we investigated the effects of the shrimp variety, fermentation temperature, and fermentation period on the composition of fermented salted shrimp. Four different varieties of salted shrimp, namely, Detteugijeot (SSA), Red shrimp jeot (SSB), Chujeot (SSC), and Yukjeot (SSD), were prepared and stored at 5 and 10 °C for 5 months. The pH values ranged from 6.71 to 6.99, with SSD showing the lowest pH at both temperatures. Although total nitrogen content remained relatively constant, amino nitrogen exhibited an upward trend after 2 months and was particularly increased at 10 °C. This increase was attributed to variations in microorganisms and enzymes in the salted shrimp. Except for proline, citrulline, and ornithine, amino acid levels increased during fermentation with the highest amounts detected in SSA. Additionally, the levels of glutamic acid and branched-chain amino acids were found to be sensitive to fermentation temperature. Amino acid levels were apparently affected by species-specific metabolic pathways of the microorganisms present in each salted shrimp. Compared to the other varieties, SSB had significantly higher contents of adenosine triphosphate and hypoxanthine. A high hypoxanthine content could contribute to increased bitterness and an umami taste profile. Furthermore, the correlation between salted shrimp and metabolites was unique in SSB, whereas partial clustering was observed between the SSA and SSC.

Does threshold growth benefit imaging criteria when used as a major diagnostic imaging feature for hepatocellular carcinoma?

PURPOSE: To evaluate the added value of threshold growth (TG) for imaging criteria for diagnosing hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI. METHODS: Patients who underwent preoperative gadoxetic acid-enhanced MRI because of absence of 'definite HCC' (Liver Imaging Reporting and Data System category 5) on prior CT or MRI between January 2016 and December 2020 were retrospectively analyzed. The sensitivity and specificity for 'definite HCC' according to the criteria of the European Association for the Study of the Liver [EASL], Asian Pacific Association for the Study of the Liver [APASL], and Korean Liver Cancer Association-National Cancer Center [KLCA-NCC] were separately calculated with and without TG as a major imaging feature. The results were compared using generalized estimating equations. RESULTS: Of 202 nodules in 154 patients, 19 % showed TG. When TG was used as a major imaging feature, the sensitivity of EASL were significantly higher than when it was not used (59.2 % vs. 51.4 %, p = 0.001), whereas the sensitivities of APASL and KLCA-NCC did not significantly differ. No significant difference was found in the specificities of the three imaging criteria when TG was used or not (p ≥ 0.16). Of 11 HCCs additionally detected when TG was added to EASL criteria, 9 showed transitional-phase or hepatobiliary-phase hypointensity without portal venous-phase washout. CONCLUSION: TG had added value for improving the sensitivity of EASL criteria for gadoxetic acid-enhanced MRI without extending washout to transitional-phase or hepatobiliary-phase images.

Mentha canadensis attenuates adiposity and hepatic steatosis in high-fat diet-induced obese mice.

BACKGROUND/OBJECTIVES: Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. MATERIALS/METHODS: Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. RESULTS: The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. CONCLUSIONS: These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.

Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy.

Background: Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Methods: Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Results: Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients from the total population who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). Conclusion: The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.

Microenvironmental network of clonal CXCL13+CD4+ T cells and Tregs in pemphigus chronic blisters.

BACKGROUNDPemphigus, a rare autoimmune bullous disease mediated by antidesmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area and require long-term maintenance systemic therapy.METHODSSkin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-Seq using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed.RESULTSWe demonstrated the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from patients with pemphigus. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T cell receptor-mediated signaling. Tregs are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-ß stimulation. Finally, intralesional corticosteroid injection improved chronic blisters and reduced skin TLSs in patients with pemphigus.CONCLUSIONThrough this study we conclude that skin TLSs are associated with the persistence of chronically recurrent blisters in patients with pemphigus, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.TRIAL REGISTRATIONClinicalTrials.gov NCT04509570.FUNDINGThis work was supported by National Research Foundation of South Korea (NRF-2021R1C1C1007179) and Korea Drug Development Fund, which is funded by Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (grant RS-2022-00165917).

Liver Imaging Reporting and Data System version 2018 for diagnosing hepatocellular carcinoma in alcoholic liver cirrhosis and virus-related cirrhosis.

PURPOSE: We aimed to evaluate and compare the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 for hepatocellular carcinoma (HCC) ≤ 3.0 cm on gadoxetic acid-enhanced MRI according to the etiology of cirrhosis. METHODS: Thirty-eight patients with alcoholic liver cirrhosis (ALC) and 37 with hepatitis C virus-related cirrhosis (HCV) who underwent preoperative MRI and subsequent surgical resection or transplantation were included. For comparison groups, patients with hepatitis B virus-related cirrhosis (HBV) were included by 1:1 matching with HCV and ALC groups according to age, lesion size, and Child-Pugh classification. The imaging characteristics of background liver and focal lesions were analyzed. The diagnostic performance of LI-RADS was compared between HCV and HBV groups, and between ALC and HBV groups. RESULTS: ALC group showed significantly higher frequency of hepatic steatosis (25.8 % vs. 6.1 %, p =.04) and lower frequency of nonperipheral washout on portal venous-phase in HCC (63.2 % vs. 97.1 %, p <.001) compared with HBV group. ALC group showed significantly lower sensitivity than HBV group (52.6 % vs. 88.6 %, p<.001). No significant differences in diagnostic performance were found between HCV and HBV groups. In ALC group, hepatobiliary-phase hypointensity provided significantly higher sensitivity (76.3 % vs. 52.6 %, p =.008). CONCLUSION: The sensitivity of LI-RADS for diagnosing HCC ≤ 3.0 cm was significantly lower in the ALC group than in the HBV group.