Background: Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells Methods: To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys in vivo and in TGF-β-treated renal cells in vitro. Results: Alantolactone (0.25 to 4 µM) did not affect the viability of renal cells. Mice orally administered 5 mg/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and α-smooth muscle actin (α-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-βstimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and α-SMA. In HK-2 cells, alantolactone inhibited TGF-β-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-β secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines. Conclusion Alantolactone improves renal fibrosis by inhibiting the TGF-β/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease.

OBJECTIVES: This study was conducted to investigate the effects of aircraft noise exposure on children's mental health problems such as depression and personality. METHODS: We obtained data from the health examinations of school children in the vicinity of Gunsan airport. This survey was conducted in the rural area, Gunsan during 2009. The study population included 195 children attending 4th to 6th grade from 6 elementary schools near the airport. Based on 60 Weighted Equivalent Continuous Perceived Noise Level (WECPNL) measures of aircraft noise, participants were divided into 2 groups; the exposure group consisted of 106 children from 4 schools, and the reference group included 89 children from the 2 schools in Gunsan. All children completed questions on general characteristics, the Korean Children's Depression Inventory (KCDI) for depression, and the Korea Human Nature Inspection (KHNI) for personality. RESULTS: Children in the exposure group were at higher risk of depression (5.62, 95% CI 1.12~28.25), and personality changes (2.08, 95% CI 1.07~4.05) than those of the reference group. In particular, children's diligence, cooperation, and concentration, subgroups of personality measure, were affected significantly and negatively, by aircraft noise level. CONCLUSIONS: Our results suggest that exposure to aircraft noise at school is associated with mental health problems in children. Requirements should be implemented to manage aircraft noise of its affect on children's health.
Aircraft ; Airports ; Child ; Depression ; Health Surveys ; Human Characteristics ; Humans ; Korea ; Mental Health ; Noise

Background: An activating mutation (c.617A>C/p.Lys206Arg, L206R) in protein kinase cAMP-activated catalytic subunit alpha (PRKACA) has been reported in 35% to 65% of cases of cortisol-producing adenomas (CPAs). We aimed to compare the clinical characteristics and transcriptome analysis between PRKACA L206R mutants and wild-type CPAs in Korea. Methods: We included 57 subjects with CPAs who underwent adrenalectomy at Seoul National University Hospital. Sanger sequencing for PRKACA was conducted in 57 CPA tumor tissues. RNA sequencing was performed in 13 fresh-frozen tumor tissues. Results: The prevalence of the PRKACA L206R mutation was 51% (29/57). The mean age of the study subjects was 42±12 years, and 87.7% (50/57) of the patients were female. Subjects with PRKACA L206R mutant CPAs showed smaller adenoma size (3.3±0.7 cm vs. 3.8±1.2 cm, P=0.059) and lower dehydroepiandrosterone sulfate levels (218±180 ng/mL vs. 1,511±3,307 ng/mL, P=0.001) than those with PRKACA wild-type CPAs. Transcriptome profiling identified 244 differentially expressed genes (DEGs) between PRKACA L206R mutant (n=8) and wild-type CPAs (n=5), including five upregulated and 239 downregulated genes in PRKACA L206R mutant CPAs (|fold change| ≥2, P<0.05). Among the upstream regulators of DEGs, CTNNB1 was the most significant transcription regulator. In several pathway analyses, the Wnt signaling pathway was downregulated and the steroid biosynthesis pathway was upregulated in PRKACA mutants. Protein-protein interaction analysis also showed that PRKACA downregulates Wnt signaling and upregulates steroid biosynthesis. Conclusion The PRKACA L206R mutation in CPAs causes high hormonal activity with a limited proliferative capacity, as supported by transcriptome profiling.

BACKGROUND AND OBJECTIVES: A risk prediction is needed even in the contemporary era of acute myocardial infarction (AMI). We sought to develop a risk scoring specific for patients with AMI being treated with guideline-adherent optimal therapies, including percutaneous coronary intervention and all 5 medications (aspirin, thienopyridine, β-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin). METHODS: From registries, 12,174 AMI patients were evaluated. The primary outcome was 1-year all-cause death or AMI. The Korea Working Group in Myocardial Infarction (KorMI) system was compared with the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), and Global Registry of Acute Coronary Events scores (GRACE) models. RESULTS: Ten predictors were identified: left ventricular dysfunction (hazard ratio [HR], 2.3), bare-metal stent (HR, 2.0), Killip class ≥II (HR, 1.9), renal insufficiency (HR, 1.8), previous stroke (HR, 1.6), regional wall-motion- score >20 on echocardiography (HR, 1.5), body mass index ≤24 kg/m2 (HR, 1.4), age ≥70 years (HR, 1.4), prior coronary heart disease (HR, 1.4), and diabetes (HR, 1.4). Compared with the previous models, the KorMI system had good discrimination (time-dependent C statistic, 0.759) and showed reasonable goodness-of-fit by Hosmer-Lemeshow test (p=0.84). Moreover, the continuous-net reclassification improvement varied from −27.3% to −19.1%, the integrated discrimination index varied from −2.1% to −0.9%, and the median improvement in risk score was from −1.0% to −0.4%. CONCLUSIONS The KorMI system would be a useful tool for predicting outcomes in survivors treated with guideline-adherent optimal therapies after AMI.

BACKGROUND AND OBJECTIVES: There are no data comparing clinical outcomes of complex percutaneous coronary intervention (PCI) between biodegradable polymer-biolimus-eluting stents (BP-BES) and durable polymer-everolimus-eluting stents (DP-EES). We sought to evaluate the safety and efficacy of BP-BES compared with DP-EES in patients undergoing complex PCI. METHODS: Patients enrolled in the SMART-DESK registry were stratified into 2 categories based on the complexity of PCI. Complex PCI was defined as having at least one of the following features: unprotected left main lesion, ≥2 lesions treated, total stent length >40 mm, minimal stent diameter ≤2.5 mm, or bifurcation as target lesion. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR) at 2 years of follow-up. RESULTS: Of 1,999 patients, 1,145 (57.3%) underwent complex PCI: 521 patients were treated with BP-BES and 624 with DP-EES. In propensity-score matching analysis (481 pairs), the risks of TLF (3.8% vs. 5.2%, adjusted hazard ratio [HR], 0.578; 95% confidence interval [CI], 0.246–1.359; p=0.209), cardiac death (2.5% vs. 2.5%, adjusted HR, 0.787; 95% CI, 0.244–2.539; p=0.689), TV-MI (0.5% vs. 0.4%, adjusted HR, 1.128; 95% CI, 0.157–8.093; p=0.905), and TLR (1.1% vs. 2.9%, adjusted HR, 0.390; 95% CI, 0.139–1.095; p=0.074) did not differ between 2 stent groups after complex PCI. CONCLUSIONS Clinical outcomes of BP-BES were comparable to those of DP-EES at 2 years after complex PCI. Our data suggest that use of BP-BES is acceptable, even for complex PCI.

BACKGROUND AND OBJECTIVES: A risk prediction is needed even in the contemporary era of acute myocardial infarction (AMI). We sought to develop a risk scoring specific for patients with AMI being treated with guideline-adherent optimal therapies, including percutaneous coronary intervention and all 5 medications (aspirin, thienopyridine, β-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin). METHODS: From registries, 12,174 AMI patients were evaluated. The primary outcome was 1-year all-cause death or AMI. The Korea Working Group in Myocardial Infarction (KorMI) system was compared with the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), and Global Registry of Acute Coronary Events scores (GRACE) models. RESULTS: Ten predictors were identified: left ventricular dysfunction (hazard ratio [HR], 2.3), bare-metal stent (HR, 2.0), Killip class ≥II (HR, 1.9), renal insufficiency (HR, 1.8), previous stroke (HR, 1.6), regional wall-motion- score >20 on echocardiography (HR, 1.5), body mass index ≤24 kg/m2 (HR, 1.4), age ≥70 years (HR, 1.4), prior coronary heart disease (HR, 1.4), and diabetes (HR, 1.4). Compared with the previous models, the KorMI system had good discrimination (time-dependent C statistic, 0.759) and showed reasonable goodness-of-fit by Hosmer-Lemeshow test (p=0.84). Moreover, the continuous-net reclassification improvement varied from −27.3% to −19.1%, the integrated discrimination index varied from −2.1% to −0.9%, and the median improvement in risk score was from −1.0% to −0.4%. CONCLUSIONS: The KorMI system would be a useful tool for predicting outcomes in survivors treated with guideline-adherent optimal therapies after AMI.
Angioplasty ; Angiotensins ; Body Mass Index ; Coronary Disease ; Discrimination (Psychology) ; Drug Therapy ; Echocardiography ; Humans ; Korea ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Registries ; Renal Insufficiency ; Stents ; Stroke ; Survivors ; Ventricular Dysfunction, Left

BACKGROUND AND OBJECTIVES: There are no data comparing clinical outcomes of complex percutaneous coronary intervention (PCI) between biodegradable polymer-biolimus-eluting stents (BP-BES) and durable polymer-everolimus-eluting stents (DP-EES). We sought to evaluate the safety and efficacy of BP-BES compared with DP-EES in patients undergoing complex PCI. METHODS: Patients enrolled in the SMART-DESK registry were stratified into 2 categories based on the complexity of PCI. Complex PCI was defined as having at least one of the following features: unprotected left main lesion, ≥2 lesions treated, total stent length >40 mm, minimal stent diameter ≤2.5 mm, or bifurcation as target lesion. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR) at 2 years of follow-up. RESULTS: Of 1,999 patients, 1,145 (57.3%) underwent complex PCI: 521 patients were treated with BP-BES and 624 with DP-EES. In propensity-score matching analysis (481 pairs), the risks of TLF (3.8% vs. 5.2%, adjusted hazard ratio [HR], 0.578; 95% confidence interval [CI], 0.246–1.359; p=0.209), cardiac death (2.5% vs. 2.5%, adjusted HR, 0.787; 95% CI, 0.244–2.539; p=0.689), TV-MI (0.5% vs. 0.4%, adjusted HR, 1.128; 95% CI, 0.157–8.093; p=0.905), and TLR (1.1% vs. 2.9%, adjusted HR, 0.390; 95% CI, 0.139–1.095; p=0.074) did not differ between 2 stent groups after complex PCI. CONCLUSIONS: Clinical outcomes of BP-BES were comparable to those of DP-EES at 2 years after complex PCI. Our data suggest that use of BP-BES is acceptable, even for complex PCI.
Coronary Artery Disease ; Death ; Drug-Eluting Stents ; Follow-Up Studies ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Stents