Association between estimated glucose disposal rate and subclinical coronary atherosclerosis.

BACKGROUND AND AIMS: The estimated glucose disposal rate (eGDR) is an easily accessible clinical parameter for assessing insulin resistance in patients with diabetes mellitus. In this study, we aimed to investigate the link between eGDR and subclinical coronary atherosclerosis in an asymptomatic middle-aged Korean population. METHODS AND RESULTS: This study involved 4004 subjects who underwent routine health checkups with coronary multidetector computed tomography (MDCT) at Asan Medical Center from 2007 to 2011, among whom 913 had a follow-up analysis through 2014. The eGDR was calculated using: 21.16 - (0.09 ∗ waist circumference [cm]) - (3.41 ∗ hypertension) - (0.55 ∗ glycated hemoglobin [%]). Patients were categorized into three groups according to the tertiles of eGDR. Subclinical coronary atherosclerosis was defined by significant coronary stenosis (≥50%), presence of plaques, coronary artery calcification (CAC) score, and its progression. As a result, a lower eGDR level was associated with higher prevalence of significant coronary stenosis, plaques, moderate to severe CAC, and CAC progression. Compared to other markers or risk scores, eGDR was superior to other biomarkers of insulin resistance but did not provide additional information beyond classic cardiovascular risk models like the Framingham Risk Score and Pooled Cohort Equations. CONCLUSION: Decreased eGDR values were significantly associated with higher subclinical coronary atherosclerosis burdens in an asymptomatic middle-aged Korean population. However, its clinical implications remain uncertain due to its weaker performance compared to established cardiovascular risk models.

Association between atherogenic dyslipidemia and muscle quality defined by myosteatosis.

Background: Myosteatosis, ectopic fat accumulation in skeletal muscle, is a crucial component of sarcopenia, linked to various cardiometabolic diseases. This study aimed to analyze the association between dyslipidemia and myosteatosis using abdominal computed tomography (CT) in a large population. Methods: This study included 11,823 patients not taking lipid-lowering medications with abdominal CT taken between 2012 and 2013. Total abdominal muscle area (TAMA), measured at the L3 level, was segmented into skeletal muscle area (SMA) and intramuscular adipose tissue. SMA was further classified into normal attenuation muscle area (NAMA: good quality muscle) and low attenuation muscle area (poor quality muscle). NAMA divided by TAMA (NAMA/TAMA) represents good quality muscle. Atherosclerotic dyslipidemia was defined as high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL in men and 50 mg/dL in women, low-density lipoprotein cholesterol (LDL-C) greater than 160 mg/dL, triglycerides (TG) greater than 150 mg/dL, small dense LDL-C (sdLDL-C) greater than 50.0 mg/dL, or apolipoprotein B/A1 (apoB/A1) greater than 0.08. Results: The adjusted odds ratios (ORs) of dyslipidemia according to the HDL-C and sdLDL definitions were greater in both sexes in the lower quartiles (Q1~3) of NAMA/TAMA compared with Q4. As per other definitions, the ORs were significantly increased in only women for LDL-C and only men for TG and ApoB/A1. In men, all lipid parameters were significantly associated with NAMA/TAMA, while TG and ApoB/A1 did not show significant association in women. Conclusion: Myosteatosis measured in abdominal CT was significantly associated with a higher risk of dyslipidemia. Myosteatosis may be an important risk factor for dyslipidemia and ensuing cardiometabolic diseases.

Apple Watch 6 vs. Galaxy Watch 4: A Validity Study of Step-Count Estimation in Daily Activities.

The purpose of this study was to examine the validity of two wearable smartwatches (the Apple Watch 6 (AW) and the Galaxy Watch 4 (GW)) and smartphone applications (Apple Health for iPhone mobiles and Samsung Health for Android mobiles) for estimating step counts in daily life. A total of 104 healthy adults (36 AW, 25 GW, and 43 smartphone application users) were engaged in daily activities for 24 h while wearing an ActivPAL accelerometer on the thigh and a smartwatch on the wrist. The validities of the smartwatch and smartphone estimates of step counts were evaluated relative to criterion values obtained from an ActivPAL accelerometer. The strongest relationship between the ActivPAL accelerometer and the devices was found for the AW (r = 0.99, p < 0.001), followed by the GW (r = 0.82, p < 0.001), and the smartphone applications (r = 0.93, p < 0.001). For overall group comparisons, the MAPE (Mean Absolute Percentage Error) values (computed as the average absolute value of the group-level errors) were 6.4%, 10.5%, and 29.6% for the AW, GW, and smartphone applications, respectively. The results of the present study indicate that the AW and GW showed strong validity in measuring steps, while the smartphone applications did not provide reliable step counts in free-living conditions.

Association between metabolic dysfunction-associated steatotic liver disease and myosteatosis measured by computed tomography.

BACKGROUND: In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. METHODS: This cross-sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score < -1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100. RESULTS: Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]). CONCLUSIONS: Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.

Correlation between environmental pollutant exposure and cardiopulmonary health by serum biomarker analysis in the Swedish elderly population.

Persistent organic pollutants (POPs) affect human health through the aryl hydrocarbon receptor (AhR) pathway and are implicated in mitochondrial dysfunction. Using data from the PIVUS study, we investigated the associations of serum AhR ligand (POP)-mediated luciferase activity (AhRL), mitochondrial ATP production inhibiting substances (MIS-ATP), and those affecting reactive oxygen species (MIS-ROS) with several metabolic syndrome (MetS) and cardiopulmonary function parameters. These include insulin resistance (HOMA-IR), inflammation, oxidative stress, and cardiopulmonary variables (FVC, FEV1, LV-EF, CCA distensibility). MIS-ATP showed significant correlations with HOMA-IR and pulmonary functions, indicating its direct impact of MIS-ATP on metabolic and pulmonary health. MIS-ROS correlated with oxidative stress markers and CCA distensibility, suggesting a role in systemic inflammatory responses. This study highlights the intricate relationships between environmental pollutant mixture and cardiopulmonary health in MetS as indicated by biomarkers of POP exposure in the elderly population, suggesting POP exposure may influence MetS onset and progression through mitochondrial dysfunction.

Survival After Contralateral Axillary Metastasis in Breast Cancer.

BACKGROUND: Despite stage IV categorization, survival outcomes for breast cancer patients who experience contralateral axillary lymph node metastasis (CAM) remain uncertain. This study aimed to investigate the clinical outcomes for patients with metachronous CAM to provide insights into its prognosis and treatment recommendations. METHODS: This study retrospectively reviewed medical records of patients who underwent curative surgery for breast cancer and experienced CAM as the first site of distant metastasis (DM) during the follow-up period between January 2001 and April 2023. Survival outcomes of the CAM patients were compared with those of breast cancer patients with other DM via propensity score-matching (PSM). RESULTS: The study identified 40 breast cancer patients with metachronous CAM. The estimated 5-year overall survival (OS) was 39.6%, and the progression-free survival was 39.4%. The patients with CAM exhibited marginally better OS than the patients with DM (p = 0.071), but survival similar to that of the patients with isolated supraclavicular node recurrence (SCN) (p = 0.509). Moreover, matching of CAM with DM using two PSM models showed a consistently insignificant survival difference (hazard ratio [HR], 1.47; p = 0.124 vs. HR, 1.19; p = 0.542). Ipsilateral breast tumor recurrences (IBTRs) were experienced by 12 patients before or concurrently with the CAM. These patients exhibited significantly better survival than the remaining patients (HR, 0.28; p = 0.024). CONCLUSION: The breast cancer patients with CAM showed survival similar to that for the patients with DM, supporting the current stage IV classification of the CAM. However, CAM associated with IBTR exhibited superior survival outcomes, suggesting that this subset of CAM may benefit from treatments with curative intent.

Secondary hematological malignancies in patients with sarcoma: A single­center retrospective study.

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

A Comparative Study of Micromechanical Analysis Models for Determining the Effective Properties of Out-of-Autoclave Carbon Fiber-Epoxy Composites.

This study aims to critically assess different micromechanical analysis models applied to carbon-fiber-reinforced plastic (CFRP) composites, employing micromechanics-based homogenization to accurately predict their effective properties. The paper begins with the simplest Voigt and Reuss models and progresses to more sophisticated micromechanics-based models, including the Mori-Tanaka and Method of Cells (MOC) models. It provides a critical review of the areas in which these micromechanics-based models are effective and analyses of their limitations. The numerical analysis results were confirmed through finite element simulations of the periodic representative volume element (RVE). Furthermore, the effective properties predicted by these micromechanics-based models were validated via experiments conducted on IM7/5320-1 composite material with a fiber volume fraction of 0.62.

Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease.

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transfer on PD in vitro and in vivo. The results showed that PN-101 mitochondria isolated from human mesenchymal stem cells exhibited a neuroprotective effect against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and rotenone in dopaminergic cells and ameliorated dopaminergic neuronal loss in the brains of C57BL/6J mice injected 30 â€‹mg/kg of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, PN-101 exhibited anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines in microglial cells and suppressing microglial activation in the striatum. Furthermore, intravenous mitochondrial treatment was associated with behavioral improvements during the pole test and rotarod test in the MPTP-induced PD mice. These dual effects of neuroprotection and anti-neuroinflammation support the potential for mitochondrial transplantation as a novel therapeutic strategy for PD.

The distance of insertion points from wound margins in interrupted and vertical mattress sutures influences the tensile load capacity: An in vitro experimental study.

AIM: To determine the tensile load capacity (TLC) and the tearing characteristics for interrupted and vertical mattress sutures with different insertion points from the wound margin, and the effect of the bite size when using vertical mattress sutures. MATERIALS AND METHODS: A total of 120 gingiva and lining mucosa samples obtained from pig jaws were divided into groups according to the suturing technique (interrupted and vertical mattress sutures), distance of the insertion points from the wound margin (margin, 1, 3, and 5 mm) and bite size (1, 3, and 5 mm). The TLC of the suture and the tearing characteristics were evaluated using a tensile tester device. RESULTS: The TLC was significantly higher for vertical mattress sutures than for interrupted sutures regardless of the distance of the insertion points from the wound margin (intergroup p < .001). This distance significantly influenced the TLC for vertical mattress sutures (p < .05) but not for interrupted sutures (p > .05). Testing the tearing characteristics revealed that no tissue tearing occurred in groups when the insertion points were more than 3 mm from the wound margin. CONCLUSION: The TLC is higher for vertical mattress sutures than for interrupted sutures, and it increases when the insertion points are farther from the wound margin.

Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy.

BACKGROUND: This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy. METHODS: Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12. MAIN OUTCOME MEASURE: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA). RESULTS: In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters. CONCLUSIONS: Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.

Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties.

Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

Comparison of long-term oncologic outcomes of central lumpectomy and conventional breast-conserving surgery for invasive breast cancer: propensity score matching analysis.

PURPOSE: Central lumpectomy (CL) is a breast-conserving surgical (BCS) technique that involves excision of the nipple-areolar complex with breast tumor in centrally located breast cancers. We aimed to investigate the long-term clinical outcomes of CL in comparison with conventional BCS (cBCS). METHODS: Patient records who underwent BCS with clear resection margins for invasive breast cancer between 2004 and 2018 were retrospectively reviewed. Of the total 6,533 patients, 106 (1.6%) underwent CL. Median follow-up duration was 73.4 months. 1:3 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize selection bias. RESULTS: The CL group showed a significantly higher ipsilateral breast tumor recurrence (IBTR) rate than the cBCS group (10-year IBTR rate: 5.8% vs. 3.1%, p = 0.004), even after adjusting for other variables (hazard ratio (HR), 2.65; 95% confidence interval (CI), 1.07-6.60, p = 0.048). However, there were no significant differences observed in regional recurrence, distant metastasis, or overall survival rates between the two groups. Both PSM and IPTW analyses showed significantly higher IBTR in the CL group (PSM HR, 3.27; 95% CI, 0.94-11.36; p = 0.048 and IPTW HR, 4.66; 95%CI, 1.85-11.77; p < 0.001). Lastly, when analyzing 2,213 patients whose tumors were located within 3 cm of the nipple, the CL group showed a significantly higher IBTR than the cBCS group before and after PSM. CONCLUSION: CL was associated with a higher rate of IBTR compared to cBCS, while other survival outcomes were comparable. For centrally located tumors, CL may be considered for patients preferring breast preservation. However, higher risk for IBTR should be informed and careful surveillance may be necessary during the early post-operative follow-up periods.

Dynamic insights into infection risk over time in two-stage implant-based breast reconstruction: a retrospective cohort study.

BACKGROUND: Infections following postmastectomy implant-based breast reconstruction (IBR) can compromise surgical outcomes and lead to significant morbidity. This study aimed to discern the timing of infections in two-stage IBR and associated risk factors. METHOD: A review of electronic health records was conducted on 1096 breasts in 1058 patients undergoing two-stage IBR at Seoul National University Hospital (2015-2020). Infections following the first-stage tissue expander (TE) insertion and second-stage TE exchange were analyzed separately, considering associated risk factors. RESULTS: Over a median follow-up of 53.5 months, infections occurred in 2.9% (32/1096) after the first stage and 4.1% (44/1070) after the second stage. Infections following the first-stage procedure exhibited a bimodal distribution across time, while those after the second-stage procedure showed a unimodal pattern. When analyzing risk factors for infection after the first-stage procedure, axillary lymph node dissection (ALND) was associated with early (≤7 weeks) infection, while both ALND and obesity were independent predictors of late (>7 weeks) infection. For infections following the second-stage procedure, obesity, postmastectomy radiotherapy, a history of expander infection, ALND, and the use of textured implants were identified as independent risk factors. Postmastectomy radiotherapy was related to non-salvaged outcomes after infection following both stages. CONCLUSION: Infections following first and second-stage IBR exhibit distinct timelines reflecting different pathophysiology. Understanding these timelines and associated risk factors will inform patient selection for IBR and aid in tailored postoperative surveillance planning. These findings contribute to refining patient suitability for IBR and optimizing personalized postoperative care strategies.

Genome-wide association analyses using machine learning-based phenotyping reveal genetic architecture of occupational creativity and overlap with psychiatric disorders.

Creativity is known to be heritable and exhibits familial aggregation with psychiatric disorders; however, the complex nature of their relationship has not been well-established. In the present study, we demonstrate that using an expanded and validated machine learning (ML)-based phenotyping of occupational creativity (OC) can allow us to further understand the trait of creativity, which was previously difficult to define and study. We conducted the largest genome-wide association study (GWAS) on OC with 241,736 participants from the UK Biobank and identified 25 lead variants that have not yet been reported and three candidate causal genes that were previously associated with educational attainment and psychiatric disorders. We found extensive genetic overlap between OC and psychiatric disorders with mixed effect direction through various post-GWAS analyses, including the bivariate causal mixture model. In addition, we discovered a strongly genetic correlation between our original GWAS and the GWAS adjusted for education years (rg = 0.95). Our GWAS analysis via ML-based phenotyping contributes to the understanding of the genetic architecture of creativity, which may inform genetic discovery and genetic prediction in human cognition and psychiatric disorders.

Fludioxonil induces cardiotoxicity via mitochondrial dysfunction and oxidative stress in two cardiomyocyte models.

Fludioxonil (Flu) is a phenylpyrrole fungicide and is currently used in over 900 agricultural products globally. Flu possesses endocrine-disrupting chemical-like properties and has been shown to mediate various physiological and pathological changes, such as apoptosis and differentiation, in diverse cell lines. However, the effects of Flu on cardiomyocytes have not been studied so far. The present study investigated the effects of Flu on mitochondria in AC16 human cardiomyocytes and H9c2 rat cardiomyoblasts. Flu decreased cell viability in a water-soluble tetrazolium assay and mediated morphological changes suggestive of apoptosis in AC16 and H9c2 cells. We confirmed that annexin V positive cells were increased by Flu through annexin V/propidium iodide staining. This suggests that the decrease in cell viability due to Flu may be associated with increased apoptotic changes. Flu consistently increased the expression of pro-apoptotic markers such as Bcl-2-associated X protein (Bax) and cleaved-caspase 3. Further, Flu reduced the oxygen consumption rate (OCR) in AC16 and H9c2 cells, which is associated with decreased mitochondrial membrane potential (MMP) as observed through JC-1 staining. In addition, Flu augmented the production of mitochondrial reactive oxygen species, which can trigger oxidative stress in cardiomyocytes. Taken together, these results indicate that Flu induces mitochondrial dysregulation in cardiomyocytes via the downregulation of the OCR and MMP and upregulation of the oxidative stress, consequently resulting in the apoptosis of cardiomyocytes. This study provides evidence of the risk of Flu toxicity on cardiomyocytes leading to the development of cardiovascular diseases and suggests that the use of Flu in agriculture should be done with caution and awareness of the probable health consequences of exposure to Flu.

Overexpression of R2R3-MYB IbMYB1a induces anthocyanin pigmentation in soybean cotyledon.

KEY MESSAGE: This is the first report showing anthocyanin accumulation in the soybean cotyledon via genetic transformation of a single gene. Soybean [Glycine max (L.) Merrill] contains valuable components, including anthocyanins. To enhance anthocyanin production in Korean soybean Kwangankong, we utilized the R2R3-type MYB gene (IbMYB1a), known for inducing anthocyanin pigmentation in Arabidopsis. This gene was incorporated into constructs using two promoters: the CaMV 35S promoter (P35S) and the ß-conglycinin promoter (Pß-con). Kwangankong was transformed using Agrobacterium, and the presence of IbMYB1a and Bar transgenes in T0 plants was confirmed through polymerase chain reaction (PCR), followed by gene expression validation. Visual inspection revealed that one P35S:IbMYB1a and three Pß-con:IbMYB1a lines displayed seed color change. Pß-con:IbMYB1a T1 seeds accumulated anthocyanins in cotyledon outer layers, whereas P35S:IbMYB1a and non-transgenic black soybean (Cheongja 5 and Seum) accumulated anthocyanins in the seed coat. During the germination and growth phase, T1 seedlings from Pß-con:IbMYB1a lines exhibited anthocyanin pigmentation in cotyledons for up to 1 month without growth aberrations. High-performance liquid chromatography confirmed cyanidin-3-O-glucoside as the major anthocyanin in the Pß-con:IbMYB1a line (#3). We analyzed the expression patterns of anthocyanin biosynthesis genes, chalcone synthase 7,8, chalcone isomerase 1A, flavanone 3-hydroxylase, flavanone 3'-hydroxylase, dihydroflavanol reductase 1, dihydroflavanol reductase 2, anthocyanidin synthase 2, anthocyanidin synthase 3, and UDP glucose flavonoid 3-O-glucosyltransferase in transgenic and control Kwangankong and black soybean (Cheongja 5 and Seum) seeds using quantitative real-time PCR. We conclude that the induction of gene expression in transgenic plants in comparison with Kwangankong was attributable to IbMYB1a transformation. Notably, flavanone 3-hydroxylase, flavanone 3'-hydroxylase, and dihydroflavanol reductase 1 were abundantly expressed in black soybean seed coat, distinguishing them from transgenic cotyledons.

Gastrointestinal Bleeding in Extracorporeal Membrane Oxygenation Patients: A Comprehensive Analysis of Risk Factors and Clinical Outcomes.

Background: Extracorporeal membrane oxygenation (ECMO) is an intervention for severe heart and lung failure; however, it poses the risk of complications, including gastrointestinal bleeding (GIB). Comprehensive analyses of GIB in patients undergoing ECMO are limited, and its impact on clinical outcomes remains unclear. Methods: This retrospective study included 484 patients who received venovenous and venoarterial ECMO between January 2015 and December 2022. Data collected included patient characteristics, laboratory results, GIB details, and interventions. Statistical analyses were performed to identify risk factors and assess the outcomes. Results: GIB occurred in 44 of 484 patients (9.1%) who received ECMO. Multivariable analysis revealed that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06; p=0.0130) and need to change the ECMO mode (OR, 3.74; 95% CI, 1.75-7.96; p=0.0006) were significant risk factors for GIB, whereas no association was found with antiplatelet or systemic anticoagulation therapies during ECMO management. Half of the patients with GIB (22/44, 50%) underwent intervention, with endoscopy as the primary modality (19/22, 86.4%). Patients who underwent ECMO and developed GIB had higher rates of mortality (40/44 [90.9%] vs. 262/440 [59.5%]) and ECMO weaning failure (38/44 [86.4%] vs. 208/440 [47.3%]). Conclusion: GIB in patients undergoing ECMO is associated with adverse outcomes, including increased risks of mortality and weaning failure. Even in seemingly uncomplicated cases, it is crucial to avoid underestimating the significance of GIB.