The long-term effects of the fenestration in patients with extracardiac Fontan circulation-a multicenter Korean cohort study based on national Fontan registry.

Introduction: The long-term effects of fenestration in patients with Fontan circulation remain unclear. We aim to evaluate the fenestration impact on early and late outcomes in patients with extracardiac Fontan (ECF) using a propensity score matching analysis. Methods: We performed an extensive retrospective multicenter clinical data review of the Korean Fontan registry and included 1,233 patients with surgical ECF (779 fenestrated, 454 non-fenestrated). Demographics, baseline, and follow-up data were collected and comprehensively analyzed. Patients were divided into two groups according to the baseline presence or absence of surgical fenestration. Subsequently, patients were sub-divided according to the fenestration status at the last follow-up. Propensity-score matching was performed to account for collected data between the 2 groups using a multistep approach. The primary outcomes were survival and freedom from Fontan failure (FFF). We also looked at postoperative hemodynamics, cardiopulmonary exercise test results, oxygen saturations, and functional status. Results: After propensity-score matching (454 matched pairs), there was no difference in survival or FFF between the 2 groups. However, ECF patients with baseline fenestration had significantly lower oxygen saturation (p = 0.001) and lower functional status (p < 0.001). Patients with fenestration had significantly longer bypass times, higher postoperative central venous pressure, higher postoperative left atrial pressure, and less prolonged pleural effusion in the early postoperative period. The propensity score matching according to the fenestration status at the last follow-up (148 matched pairs) showed that patients with a persistent fenestration had significantly lower oxygen saturation levels (p < 0.001). However there were no intergroup differences in the functional status, survival and FFF. Conclusions: Our results showed no long-term benefits of the Fenestration in terms of survival and FFF. Patients with persistent fenestration showed oxygen desaturation but no difference in exercise intolerance was shown between the 2 groups.

People-Oriented Culture and its association with burnout, depressive symptoms, and sleep problems during COVID-19 pandemic among EMS providers in Korea.

OBJECTIVE: This study examined how perceived people-oriented culture (POC) was associated with burnout, depressive symptoms, and sleep problems during the COVID-19 pandemic among emergency medical service (EMS) providers in Korea. METHODS: We conducted a cross-sectional survey among 693 EMS providers in 2021. RESULTS: Overall, 60% reported burnout and around 25% had depressive symptoms. Prevalence of poor sleep quality, unrestful sleep, and sleep disturbance were 46.5%, 58.2%, and 52.2%, respectively. Compared to high POC group, higher prevalence of depressive symptoms was observed among medium (PR: 1.57, 95% CI: 1.06, 2.32) and low (PR: 2.70, 95% CI: 1.92, 3.79) POC group. Similar trends were observed in the analysis of burnout and sleep problems. CONCLUSIONS: Our findings underscore that low POC could play a critical role in worsening burnout, depressive symptoms, and sleep problems among EMS providers.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Novel germline JAK2R715T mutation causing PV-like erythrocytosis in 3 generations. Amelioration by Ropeg-Interferon.

Polycythemia vera (PV) is a clonal disorder arising from the acquired somatic mutations of the JAK2 gene, including JAK2V617F or several others in exon 12. A 38-year-old female had a stroke at age 32 and found to have elevated hemoglobin, normal leukocytes, normal platelets, and tested negative for JAK2V617F and exon 12 mutations. Next generation sequencing revealed a novel mutation: JAK2R715T in the pseudokinase domain (JH2) at 47.5%. Its presence in her nail DNA confirmed a germline origin. Her mother and her son similarly had erythrocytosis and a JAK2R715T mutation. Computer modeling indicated gain-of-function JAK2 activity. The propositus and her mother had polyclonal myelopoiesis, ruling out another somatic mutation-derived clonal hematopoiesis. Some erythroid progenitors of all three generations grew without erythropoietin, a hallmark of PV. The in vitro reporter assay confirmed increased activity of the JAK2R715T kinase. Similar to PV, the JAK2R715T native cells have increased STAT5 phosphorylation, augmented transcripts of prothrombotic and inflammatory genes, and decreased KLF2 transcripts. The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon-alfa-2b (Ropeg-IFN-α) induced a remission. Ropeg-IFN-α treatment also reduced JAK2 activity in the propositus, her mother and JAK2V617F PV subjects. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2R715T gain-of-function mutation with many but not all comparable molecular features to JAK2V617F PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg-IFN-α.

TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.

BACKGROUND: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells. RESULTS: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells. CONCLUSIONS: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells.

Hemodialysis Efficiency Predictor in End-Stage Kidney Disease Using Real-Time Heart Rate Variability.

BACKGROUND: Autonomic dysfunction as a long-term complication may occur in end-stage kidney disease (ESKD) patients and can be diagnosed using heart rate variability (HRV) analyzed from electrocardiogram (ECG) recordings. There is limited data about HRV using real-time ECG to predict hemodialysis (HD) efficiency in patients with ESKD who are routinely doing HD in the real world. METHODS: A total of 50 patients (62.1 ± 10.7 years) with ESKD underwent continuous real-time ECG monitoring (237.4 ± 15.3 min) during HD for HRV using remote monitoring system. Their electrolyte levels were checked before and after HD. We compared HRV according to electrolyte levels. RESULTS: During the monitor, we checked the ECG and electrolyte levels simultaneously a total of 2374 times for all of the patients. Both time and frequency domain HRV were higher when the patients had lower K+ level (<0.5 mEq/L) and P+ level change (<2 mEq/L) before and after HD as compared to those with a higher K+ level (≥0.5 mEq/L) and P+ level change (≥2 mEq/L). Additionally, patients with lower K+ and P+ level change groups had higher incidences of arrhythmic events including atrial/ventricular premature complexes, despite no difference of mean heart rate (p < 0.001). CONCLUSIONS: Higher HRV was independently associated with a poorly controlled K+ and P+ level during HD in patients with ESKD. This is consistently evidenced by the independent association between higher HRV, K+ and P+ levels in real time, suggesting that low electrolyte changes before and after HD alone may cause cardiac autonomic dysfunction.

Realizing Minimally Perturbed, Nonlocal Chiral Metasurfaces for Direct Stokes Parameter Detection.

Recent development in nonlocal resonance based chiral metasurfaces draws great attention due to their abilities to strongly interact with circularly polarized light at a relatively narrow spectral bandwidth. However, there still remain challenges in realizing effective nonlocal chiral metasurfaces in optical frequency due to demanding fabrications such as 3D-multilayered or nanoscaled chiral geometry, which, in particular, limit their applications to polarimetric detection with high-Q spectra. Here, we study the underlying working principles and reveal the important role of the interaction between high-Q nonlocal resonance and low-Q localized Mie resonance in realizing effective nonlocal chiral metasurfaces. Based on the working principles, we demonstrate one of the simplest types of nonlocal chiral metasurfaces which directly detects a set of Stokes parameters without the numerical combination of transmitted values presented from typical Stokes metasurfaces. This is achieved by minimally altering the geometry and filling ratio of every constituent nanostructure in a unit cell, facilitating consistent-sized nanolithography for all samples experimentally at a targeted wavelength with relatively high-Q spectra. This work provides an alternative design rule to realizing effective polarimetric metasurfaces and the potential applications of nonlocal Stokes parameters detection.

Draft genome sequence of multiple antibiotic-resistant Vibrio harveyi isolated from diseased olive flounder (Paralichthys olivaceus) farmed in South Korea.

Vibrio harveyi strain 22FBVib0145 was isolated from a diseased olive flounder farmed in Jeju, Korea. Here, we report the draft genome sequence of this strain. It is 6,238,277 bp in length with a G + C content of 44.8%.

From Homogeneity to Turing Pattern: Kinetically Controlled Self-Organization of Transmembrane Protein.

Understanding the spatial organization of membrane proteins is crucial for unraveling key principles in cell biology. The reaction-diffusion model is commonly used to understand biochemical patterning; however, applying reaction-diffusion models to subcellular phenomena is challenging because of the difficulty in measuring protein diffusivity and interaction kinetics in the living cell. In this work, we investigated the self-organization of the plasmalemma vesicle-associated protein (PLVAP), which creates regular arrangements of fenestrated ultrastructures, using single-molecule tracking. We demonstrated that the spatial organization of the ultrastructures is associated with a decrease in the association rate by actin destabilization. We also constructed a reaction-diffusion model that accurately generates a hexagonal array with the same 130 nm spacing as the actual scale and informs the stoichiometry of the ultrastructure, which can be discerned only through electron microscopy. Through this study, we integrated single-molecule experiments and reaction-diffusion modeling to surpass the limitations of static imaging tools and proposed emergent properties of the PLVAP ultrastructure.

CYB5R3 functions as a tumor suppressor by inducing ER stress-mediated apoptosis in lung cancer cells via the PERK-ATF4 and IRE1α-JNK pathways.

Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD+) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD+ activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer.

Overproduction of Xanthophyll Pigment in Flavobacterium sp. JSWR-1 under Optimized Culture Conditions.

Flavobacterium can synthesize xanthophyll, particularly the pigment zeaxanthin, which has significant economic value in nutrition and pharmaceuticals. Recently, the use of carotenoid biosynthesis by bacteria and yeast fermentation technology has shown to be very efficient and offers significant advantages in large-scale production, cost-effectiveness, and safety. In the present study, JSWR-1 strain capable of producing xanthophyll pigment was isolated from a freshwater reservoir in Wanju-gun, Republic of Korea. Based on the morphological, physiological, and molecular characteristics, JSWR-1 classified as belonging to the Flavobacterium species. The bacterium is strictly aerobic, Gram-negative, rod-shaped, and psychrophilic. The completed genome sequence of the strain Flavobacterium sp. JSWR-1 is predicted to be a single circular 3,425,829-bp chromosome with a G+C content of 35.2% and 2,941 protein-coding genes. The optimization of carotenoid production was achieved by small-scale cultivation, resulting in zeaxanthin being identified as the predominant carotenoid pigment. The enhancement of zeaxanthin biosynthesis by applying different light-irradiation, variations in pH and temperature, and adding carbon and nitrogen supplies to the growth medium. A significant increase in intracellular zeaxanthin concentrations was also recorded during fed-batch fermentation achieving a maximum of 16.69 ± 0.71 mg/l, corresponding to a product yield of 4.05 ± 0.15 mg zeaxanthin per gram cell dry weight. Batch and fed-batch culture extracts exhibit significant antioxidant activity. The results demonstrated that the JSWR-1 strain can potentially serve as a source for zeaxanthin biosynthesis.

Perovskite Lanthanum-Doped Barium Stannate: A Refractory Near-Zero-Index Material for High-Temperature Energy Harvesting Systems.

The recent interests in bridging intriguing optical phenomena and thermal energy management has led to the demonstration of controlling thermal radiation with epsilon-near-zero (ENZ) and the related near-zero-index (NZI) optical media. In particular, the manipulation of thermal emission using phononic ENZ and NZI materials has shown promise in mid-infrared radiative cooling systems operating under low-temperature environments (below 100 °C). However, the absence of NZI materials capable of withstanding high temperatures has limited the spectral extension of these advanced technologies to the near-infrared (NIR) regime. Herein, a perovskite conducting oxide, lanthanum-doped barium stannate (La:BaSnO3 [LBSO]), as a refractory NZI material well suited for engineering NIR thermal emission is proposed. This work focuses on the experimental demonstration of superior high-temperature stability (of at least 1000 °C) of LBSO films in air and its durability under intense UV-pulsed laser irradiation below peak power of 9 MW cm-2 . Based on the low optical-loss in LBSO, a selective narrow-band thermal emission utilizing a metal-insulator-metal (MIM) Fabry-Pérot nanocavity consisting of LBSO films as metallic component is demonstrated. This study shows that LBSO is an ideal candidate as a refractory NZI component for thermal energy conversion operating at high temperatures in air and under strong light irradiations.

Abnormalities in red blood cell production and pathogenesis of anemia in the progression of rock bream iridovirus (RBIV).

Rock bream iridovirus (RBIV), belonging to Megalocytivirus, causes severe mortality in rock bream. Almost all deaths associated with RBIV are accompanied by splenic enlargement and anemia. Although red blood cells (RBCs) are involved in the immune response against viral infections, their involvement in rock bream has not yet been studied in terms of the immune response against RBIV. In this study, the viral replication patterns, blood characteristics and anemia-related factors were evaluated in rock bream post RBIV infection. The virus-infected RBCs of rock bream demonstrated similarities in the expression levels of hemoglobins (HGB) (α and ß), cytokine-dependent hematopoietic cell linker (CLNK) and hematopoietic transcription factor GATA (GATA), with significantly decreasing levels from 4 days post infection (dpi) to 17 (dpi), when the viral replication was at its peak. This suggests that the expression of blood-related genes is inadequate for HGB synthesis and RBC production, thereby causing anemia leading to death. Moreover, the levels of complete blood cell count (CBC) indicators, such as RBCs, HGB and hematocrit (HCT), significantly decreased from 10 to 17 dpi. This phenomenon suggests that blood-related gene expression and/or RBC-, HGB- and HCT-related levels are critical factors in RBIV-induced anemia and disease progression. These results highlight the significance of blood-mediated immune responses against RBIV infection in rock bream. Understanding blood-related gene levels to identify blood-related immune response interactions in rock bream will be useful for development of future strategies in controlling RBIV diseases in rock bream.

Determination of the minimum infective dose of viral hemorrhagic septicemia virus (VHSV) in juvenile olive flounder, Paralichthys olivaceus using an immersion challenge model.

Viral hemorrhagic septicemia virus (VHSV) affects over 80 fish species, leading to viral hemorrhagic septicemia (VHS). Horizontal VHSV transmission is widely studied, with researchers utilizing various doses to establish infection models. Infected hosts shed the virus into the environment, elevating the risk of transmission to naïve fish within the same system. This study aimed to ascertain the minimum infective dose of VHSV in olive flounder (Paralichthys olivaceus). In olive flounder, the detection of VHSV within the kidney exhibited the highest infection rate on the third day among days 1, 3 and 5. Doses of 103.0 to 104.7 TCID50/ml were administered to juvenile olive flounder across three farms. Results showed resistance to infection below 103.4 TCID50/ml at 15 °C. While infection frequency varied by concentration, higher concentrations correlated with more infections. Nonetheless, viral copy numbers did not differ significantly among infected fish at varying concentrations. This study underscores the need for early VHSV management and contributes essential data for pathogenicity assessment and foundational knowledge.

Transcriptional Response of Pectobacterium carotovorum to Cinnamaldehyde Treatment.

Cinnamaldehyde is a natural compound extracted from cinnamon bark essential oil, acclaimed for its versatile properties in both pharmaceutical and agricultural fields, including antimicrobial, antioxidant, and anticancer activities. Although potential of cinnamaldehyde against plant pathogenic bacteria like Agrobacterium tumefaciens and Pseudomonas syringae pv. actinidiae causative agents of crown gall and bacterial canker diseases, respectively has been documented, indepth studies into cinnamaldehyde's broader influence on plant pathogenic bacteria are relatively unexplored. Particularly, Pectobacterium spp., gram-negative soil-borne pathogens, notoriously cause soft rot damage across a spectrum of plant families, emphasizing the urgency for effective treatments. Our investigation established that the Minimum Inhibitory Concentrations (MICs) of cinnamaldehyde against strains P. odoriferum JK2, P. carotovorum BP201601, and P. versatile MYP201603 were 250 µg/ml, 125 µg/ml, and 125 µg/ml, respectively. Concurrently, their Minimum Bactericidal Concentrations (MBCs) were found to be 500 µg/ml, 250 µg/ml, and 500 µg/ml, respectively. Using RNA-sequencing analysis, we identified 1,907 differentially expressed genes in P. carotovorum BP201601 treated with 500 µg/ml cinnamaldehyde. Notably, our results indicate that cinnamaldehyde upregulated nitrate reductase pathways while downregulating the citrate cycle, suggesting a potential disruption in the aerobic respiration system of P. carotovorum during cinnamaldehyde exposure. This study serves as a pioneering exploration of the transcriptional response of P. carotovorum to cinnamaldehyde, providing insights into the bactericidal mechanisms employed by cinnamaldehyde against this bacterium.

Real-time heart rate variability according to ambulatory glucose profile in patients with diabetes mellitus.

Background: Autonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM. Methods: A total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR). Results: There were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR < 70%) compared with well controlled glucose levels (TIR > 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P < 0.001). Conclusions: Poorly controlled glucose levels were independently associated with lower HRV in patients with DM. This was further substantiated by the independent continuous association between real-time measurements of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is caused by elevated blood sugar levels.

Maternal Strangulated Diaphragmatic Hernia with Gangrene of the Entire Stomach During Pregnancy: A Case Report and Review of the Recent Literature.

Background: Bochdalek hernia (BH) of congenital diaphragm hernia is infrequently seen in adults. Strangulation of the diaphragm hernia has been recognized as a severe complication. Among several factors, pregnancy is an important cause of diaphragm hernia's deterioration. However, nausea, vomiting, and upper abdominal pain are often considered non-specific pregnancy-related symptoms. Case Presentation: We report a case of a 39-year-old (gravida II, para I) multigravida woman with a delayed diagnosis of strangulated herniated viscera complicating total gastric gangrene at 26+1 weeks' gestation. The preoperative diagnosis was confirmed by an X-ray examination and magnetic resonance imaging (MRI). After identifying the size and severity of the herniated contents through video-assisted thoracoscopy (VAT), we immediately converted to abdominal laparotomy. Antenatal corticosteroids were administered simultaneously with diagnosis to promote fetal maturity. The fetal condition was maintained well in the maternal uterus during the operation. Careful monitoring of the fetus and the mother's clinical conditions should be performed during expectant management to achieve delayed delivery after maternal surgical correction. Delivery was completed through cesarean delivery at 27+1 weeks of gestation. Conclusion: Despite the rarity of maternal Bochdalek hernias during pregnancy, early diagnosis and appropriate treatment via multidisciplinary care are essential for maternal and fetal outcomes.

Are Primary Outcomes Really Primary? An Exploratory Cross-Sectional Nationwide Web-Based Survey Study for Outcomes Reflecting Real Symptoms and Needs of Patients with Lumbar Disc Herniation.

As primary outcomes differ among clinical lumbar disc herniation (LDH) studies, this study aimed to explore outcomes reflecting real-world patient experiences through an exploratory questionnaire survey. Those diagnosed with LDH having radiating leg pain in South Korea in November of 2022 (N = 500) were administered a questionnaire including basic characteristics, disease onset, symptoms and severity, priority symptoms for improvement, and important treatment factors. Outcome measures included the identification of priority symptoms and disabilities. Most common symptoms were numbness in the leg (N = 435, 87.0%) and back pain (N = 406, 81.2%); most common disabilities were discomfort in sitting (N = 323, 64.6%) and lifting (N = 318, 63.6%). The highest priority symptom was back pain (N = 242, 48.4%). A satisfactory degree of symptom improvement was a decrease of at least 3 points on the numeric rating scale. The majority of respondents preferred improvement in disability over pain (N = 270, 55.8%), a stable effect over a rapid effect (N = 391, 78.2%), and safety over treatment efficacy (N = 282, 56.4%). Safety (N = 129, 25.8%) and cost (N = 111, 22.2%) were the most important treatment factors. Improvements in back pain, leg pain, sitting, and sleeping were prioritized, and safety, stable treatment effect, and functional recovery were desired. Clinical trials for LDH should be designed to reflect this real-world patient need. Further study to examine the patients' symptoms and needs in details is needed.

Effects of the beta-blocker carvedilol on arrhythmia and long-term clinical outcomes in benign prostate hypertrophy patients.

Benign prostatic hypertrophy (BPH) is associated with autonomic dysfunction and sympathetic nervous system mediated by the alpha receptor. However, limited data exist regarding the effects of the beta-blocker (BB) carvedilol on arrhythmia and urologic outcomes in BPH patients. Our database of patients diagnosed with BPH from 2015 to 2020 was used to obtain echocardiography and electrocardiogram data. Inclusion criteria were BPH patients taking BBs. International Prostate Symptom Score questionnaire were used to evaluate the urinary symptoms and quality of life. Among 448 patients with BPH (69.2 ± 10.9 years) taking BBs, 219 patients took carvedilol (48.9%) and 229 patients took a non-carvedilol BB (51.1%; bisoprolol, 184 patients, 80% or nebivolol, 45 patients, 20%). Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P = .029), total urologic events (P < .001), and less use of additive alpha-blocker was observed in the carvedilol group (P = .022). In multivariate analysis, less carvedilol use (P = .019), heart failure (P < .001), stroke (P < .001), and cardiomyopathy (P = .046) were independent risk factors for arrhythmic events. In addition, less carvedilol use (P = .009) and older age (P = .005) were independent risk factors for urologic events based on BB type at the median 36-month follow-up. The use of carvedilol was associated with less arrhythmic events in BPH patients with palpitation and decreased the incidence of urologic events in BPH compared with the use of non-carvedilol BBs in long-term follow-up.

Exosomal miR-184 in the aqueous humor of patients with central serous chorioretinopathy: a potential diagnostic and prognostic biomarker.

BACKGROUND: Central serous chorioretinopathy (CSC) is the fourth most prevalent retinal disease leading to age-related macular degeneration (AMD) and retinal atrophy. However, CSC's pathogenesis and therapeutic target need to be better understood. RESULTS: We investigated exosomal microRNA in the aqueous humor of CSC patients using next-generation sequencing (NGS) to identify potential biomarkers associated with CSC pathogenesis. Bioinformatic evaluations and NGS were performed on exosomal miRNAs obtained from AH samples of 62 eyes (42 CSC and 20 controls). For subgroup analysis, patients were divided into treatment responders (CSC-R, 17 eyes) and non-responders (CSC-NR, 25 eyes). To validate the functions of miRNA in CECs, primary cultured-human choroidal endothelial cells (hCEC) of the donor eyes were utilized for in vitro assays. NGS detected 376 miRNAs. Our results showed that patients with CSC had 12 significantly upregulated and 17 downregulated miRNAs compared to controls. miR-184 was significantly upregulated in CSC-R and CSC-NR patients compared to controls and higher in CSC-NR than CSC-R. In vitro assays using primary cultured-human choroidal endothelial cells (hCEC) demonstrated that miR-184 suppressed the proliferation and migration of hCECs. STC2 was identified as a strong candidate for the posttranscriptional down-regulated target gene of miR-184. CONCLUSION: Our findings suggest that exosomal miR-184 may serve as a biomarker reflecting the angiostatic capacity of CEC in patients with CSC.