Validation of an international prediction model including the Oxford classification in Korean patients with IgA nephropathy.

BACKGROUND: Recently, a new international risk prediction model including the Oxford classification was published which was validated in a large multi-ethnic cohort. Therefore, we aimed to validate this risk prediction model in Korean patients with IgA nephropathy. METHODS: This retrospective cohort study was conducted with 545 patients who diagnosed IgA nephropathy with renal biopsy in three medical centers. The primary outcome was defined as a reduction in estimated glomerular filtration rate (eGFR) of >50% or incident end-stage renal disease (ESRD). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were used to validate models. RESULTS: During the median 3.6 years of follow-up period, 53 (9.7%) renal events occurred. In multivariable Cox regression model, M1 (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.02-4.82; p = .043), T1 (HR, 2.98; 95% CI, 1.39-6.39; p = .005) and T2 (HR, 4.80; 95% CI, 2.06-11.18; p < .001) lesions were associated with increased risk of renal outcome. When applied the international prediction model, the area under curve (AUC) for 5-year risk of renal outcome was 0.69, which was lower than previous validation and internally derived models. Moreover, cNRI and IDI analyses showed that discrimination and reclassification performance of the international model was inferior to the internally derived models. CONCLUSION: The international risk prediction model for IgA nephropathy showed not as good performance in Korean patients as previous validation in other ethnic group. Further validation of risk prediction model is needed for Korean patients with IgA nephropathy.

Flexibility of Semitransparent Perovskite Light-Emitting Diodes Investigated by Tensile Properties of the Perovskite Layer.

Organic-inorganic hybrid perovskites have been investigated extensively for use in perovskite-based solar cells and light-emitting diodes (LEDs) because of their excellent electrical and optical properties. Although the flexibility of perovskite LEDs has been studied through empirical methods such as cyclic bending tests, the flexibility of the perovskite layer has not been investigated systemically. Here, flexible and semitransparent perovskite LEDs are fabricated: a PEDOT:PSS anode and Ag nanowire cathode allow for flexible and semitransparent devices, while the use of a conjugated polyelectrolyte as an interfacial layer reduces the electron injection barrier between the cathode and the electron transport layer (SPW-111), resulting in enhanced device efficiency. Cyclic bending tests performed on the electrodes and in situ hole-nanoindentation tests performed on the constituent materials suggest that mechanical failure occurs in the perovskite MAPbBr3 layer during cyclic bending, leading to a decrease in the luminance. Tensile properties of the MAPbBr3 layer explain the critical bending radius ( rb) of the perovskite LEDs on the order of 1 mm.

Protective effects of carbenoxolone, an 11ß-HSD1 inhibitor, against chemical induced dry eye syndrome.

Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11ß-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11ß-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11ß-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11ß-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11ß-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11ß-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.

Carbenoxolone prevents chemical eye ischemia-reperfusion-induced cell death via 11ß-hydroxysteroid dehydrogenase type 1 inhibition.

Glaucoma is one of the leading causes of preventable blindness diseases, affecting more than 2 million people in the United States. Recently, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors were found to exert preventive effects against glaucoma. Therefore, we investigated whether carbenoxolone (CBX), an 11ß-HSD1 inhibitor, prevents chemical ischemia-reperfusion-induced cell death in human trabecular meshwork (HTM) cells. The present study demonstrated that CBX inhibited cell death caused by iodoacetic acid (IAA)-induced ischemia-reperfusion, and its effect was associated with the inhibition of 11ß-HSD1 expression and activity. Furthermore, CBX reversed the IAA-induced structural damage on filamentous actin in HTM cells. In IAA-treated cells, the levels of 11ß-HSD1 and the apoptosis-related factors Bax and FASL were increased throughout the reperfusion period, and CBX was able to attenuate the expression of 11ß-HSD1 and the apoptosis-related factors. CBX also effectively suppressed IAA-induced intracellular ROS formation and cytochrome c release, which are involved in the mitochondrial apoptosis pathway. In addition, IAA-induced chemical ischemia-reperfusion stimulated TNF-α expression and NF-κB p65 phosphorylation, and these effects were attenuated by CBX. 11ß-HSD1 RNAi also suppressed IAA-induced cell apoptosis via reduction of oxidative stress and inhibition of the pro-inflammatory pathway. Taken together, the present study demonstrated that the inhibition of 11ß-HSD1 protected the TM against chemical ischemia-reperfusion injury, suggesting that the use of 11ß-HSD1 inhibitors could be a useful strategy for glaucoma therapy.

Anti-inflammatory effect of a selective 11ß-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts inactive cortisone to the active cortisol. 11ß-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a selective 11ß-HSD1 inhibitor, in lipopolysaccharide (LPS)-activated C57BL/6J mice and macrophages. LPS increased 11ß-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11ß-HSD1 activity. Thus, we concluded that the selective 11ß-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.

Clinical usefulness of capnographic monitoring when inserting a feeding tube in critically ill patients: retrospective cohort study.

BACKGROUND: It is not rare for a small-bore feeding tube to be inserted incorrectly into the respiratory system in critically ill patients. Thus, monitoring is necessary to prevent respiratory malplacement of the tube. We investigated the utility of capnographic monitoring to prevent respiratory complications due to feeding tube mispositioning in critically ill patients. METHODS: This study was a pre and post-interventional study, including 445 feeding tube placements events studied retrospectively in the medical and surgical intensive care units of the Samsung Medical Center. We compared outcomes between time periods before and after capnographic monitoring and documented any respiratory complications. RESULTS: Feeding tubes were inserted in 275 cases without capnographic monitoring. Capnographic monitoring was performed in 170 cases. Sixteen patients (4%) had respiratory complications of all tube placements. Feeding tube was inserted into the trachea in 11 (2%) patients and for a pneumothorax in five (1%) patients. Fourteen cases of respiratory complications were detected in the control group (14/275, 5%, 10 tracheal insertions and four pneumothoraxes). Two respiratory complications were detected in the capnographic monitoring group (2/170, 1%, one tracheal insertion and one pneumothorax). Respiratory complications were detected less frequently in the capnographic monitoring group than that in the control group (P = 0.035). CONCLUSIONS: Capnographic monitoring is simple, easy to learn, and may be useful to prevent respiratory complications when placing a feeding tube in a critically ill patient.

Superaerophobic/Superhydrophilic Multidimensional Electrode System for High-Current-Density Water Electrolysis.

Water electrolysis is emerging as a promising renewable-energy technology for the green production of hydrogen, which is a representative and reliable clean energy source. From economical and industrial perspectives, the development of earth-abundant non-noble metal-based and bifunctional catalysts, which can simultaneously exhibit high catalytic activities and stabilities for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), is critical; however, to date, these types of catalysts have not been constructed, particularly, for high-current-density water electrolysis at the industrial level. This study developed a heterostructured zero-dimensional (0D)-one-dimensional (1D) PrBa0.5Sr0.5Co1.5Fe0.5O5+δ (PBSCF)-Ni3S2 as a self-supported catalytic electrode via interface and morphology engineering. This unique heterodimensional nanostructure of the PBSCF-Ni3S2 system demonstrates superaerophobic/superhydrophilic features and maximizes the exposure of the highly active heterointerface, endowing the PBSCF-Ni3S2 electrode with outstanding electrocatalytic performances in both HER and OER and exceptional operational stability during the overall water electrolysis at high current densities (500 h at 500 mA cm-2). This study provides important insights into the development of catalytic electrodes for efficient and stable large-scale hydrogen production systems.

Clinical significance of acute care surgery system as a part of hospital medical emergency team for hospitalized patients.

Purpose: Acute care surgery (ACS) has been practiced in several tertiary hospitals in South Korea since the late 2000s. The medical emergency team (MET) has improved the management of patients with clinical deterioration during hospitalization. This study aimed to identify the clinical effectiveness of collaboration between ACS and MET in hospitalized patients. Methods: This was an observational before-and-after study. Emergency surgical cases of hospitalized patients were included in this study. Patients hospitalized in the Department of Emergency Medicine or Department of Surgery, directly comanaged by ACS were excluded. The primary outcome was in-hospital mortality rate. The secondary outcome was the alarm-to-operation interval, as recorded by a Modified Early Warning Score (MEWS) of >4. Results: In total, 240 patients were included in the analysis (131 in the pre-ACS group and 109 in the post-ACS group). The in-hospital mortality rates in the pre- and post-ACS groups were 17.6% and 22.9%, respectively (P = 0.300). MEWS of >4 within 72 hours was recorded in 62 cases (31 in each group), and the median alarm-to-operation intervals of each group were 11 hours 16 minutes and 6 hours 41 minutes, respectively (P = 0.040). Conclusion: Implementation of the ACS system resulted in faster surgical intervention in hospitalized patients, the need for which was detected early by the MET. The in-hospital mortality rates before and after ACS implementation were not significantly different.

Non-occlusive mesenteric ischemia in critically ill patients.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) is a life-threatening acute condition that has an overall in-hospital mortality rate of up to 75%. Critically ill patients are often admitted to intensive care units (ICUs) due to shock, and these patients are frequently at risk of developing NOMI. The objective of this study was to determine the clinical features of critically ill patients with NOMI and evaluate the risk factors for in-hospital mortality among these patients. METHODS: We reviewed the electronic medical records of 7,346 patients who underwent abdominal contrast-enhanced computed tomography during their ICU stay at Samsung Medical Center (Seoul, Korea) between January 1, 2010 and December 31, 2019. After reviewing each patient's computed tomography (CT) scans, 60 patients were diagnosed with NOMI and included in this analysis. The patients were divided into survivor (n = 23) and non-survivor (n = 37) groups according to the in-hospital mortality. RESULTS: The overall sequential organ failure assessment (SOFA) score for the included patients upon admission to the ICU was 8.6 ± 3.1, and medical ICU admissions were most common (66.7%) among the patients. The SOFA score upon admission to the ICU was higher for the non-survivors than for the survivors (9.4 vs. 7.4; p = 0.017). Non-survivors were more often observed in the medical ICU admissions (39.1% vs. 83.8%) than in the surgical ICU admissions (47.8% vs. 10.8%) or the cardiac ICU admissions (13.0% vs. 5.4%). Laboratory test results, abdominal CT findings, and the use of vasopressors and inotropes did not differ between the two groups. In a multivariable analysis, SOFA scores >8 upon admission to the ICU (odds ratio [OR] 4.51; 95% 1.12-18.13; p = 0.034), patients admitted to the ICU with medical problems (OR 7.99; 95% 1.73-36.94; p = 0.008), and abdominal pain (OR 4.26; 95% 1.05-17.35; p = 0.043) were significant prognostic predictors for in-hospital mortality. CONCLUSIONS: The SOFA score >8 upon admission to the ICU, admission to the ICU for medical problems, and abdominal pain at diagnosis are associated with increased mortality among patients with NOMI.

Epicardial adipose tissue radiodensity is associated with all-cause mortality in patients undergoing hemodialysis.

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm3) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range 16.67-44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR] 1.055; 95% confidence interval [CI] 1.015-1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis.

Multiplex PCR detection of waterborne intestinal protozoa: microsporidia, Cyclospora, and Cryptosporidium.

Recently, emerging waterborne protozoa, such as microsporidia, Cyclospora, and Cryptosporidium, have become a challenge to human health worldwide. Rapid, simple, and economical detection methods for these major waterborne protozoa in environmental and clinical samples are necessary to control infection and improve public health. In the present study, we developed a multiplex PCR test that is able to detect all these 3 major waterborne protozoa at the same time. Detection limits of the multiplex PCR method ranged from 10(1) to 10(2) oocysts or spores. The primers for microsporidia or Cryptosporidium used in this study can detect both Enterocytozoon bieneusi and Encephalitozoon intestinalis, or both Cryptosporidium hominis and Cryptosporidium parvum, respectively. Restriction enzyme digestion of PCR products with BsaBI or BsiEI makes it possible to distinguish the 2 species of microsporidia or Cryptosporidium, respectively. This simple, rapid, and cost-effective multiplex PCR method will be useful for detecting outbreaks or sporadic cases of waterborne protozoa infections.

iTRAQ-Based Quantitative Proteomic Comparison of 2D and 3D Adipocyte Cell Models Co-cultured with Macrophages Using Online 2D-nanoLC-ESI-MS/MS.

The demand for novel three-dimensional (3D) cell culture models of adipose tissue has been increasing, and proteomic investigations are important for determining the underlying causes of obesity, type II diabetes, and metabolic disorders. In this study, we performed global quantitative proteomic profiling of three 3D-cultured 3T3-L1 cells (preadipocytes, adipocytes and co-cultured adipocytes with macrophages) and their 2D-cultured counterparts using 2D-nanoLC-ESI-MS/MS with iTRAQ labelling. A total of 2,885 shared proteins from six types of adipose cells were identified and quantified in four replicates. Among them, 48 proteins involved in carbohydrate metabolism (e.g., PDHα, MDH1/2, FH) and the mitochondrial fatty acid beta oxidation pathway (e.g., VLCAD, ACADM, ECHDC1, ALDH6A1) were relatively up-regulated in the 3D co-culture model compared to those in 2D and 3D mono-cultured cells. Conversely, 12 proteins implicated in cellular component organisation (e.g., ANXA1, ANXA2) and the cell cycle (e.g., MCM family proteins) were down-regulated. These quantitative assessments showed that the 3D co-culture system of adipocytes and macrophages led to the development of insulin resistance, thereby providing a promising in vitro obesity model that is more equivalent to the in vivo conditions with respect to the mechanisms underpinning metabolic syndromes and the effect of new medical treatments for metabolic disorders.

Structural, optical, and electrical properties of semiconducting ZnO nanosheets.

ZnO nanosheets were fabricated by an oxygen-assisted carbothermal reduction process and their properties were evaluated. In particular, the FET characteristics and photoluminescence properties of ZnO nanosheets were evaluated. The conduction type of ZnO nanosheets was determined as an n-type and the mobility was 20-40 cm2/ V-s, which is fairly high compared to ZnO nanowires. This might be attributed to the wide conduction area of ZnO nanosheet compared to nanowire structures and their better crystallinity.

Highly conductive coaxial SnO(2)-In(2)O(3) heterostructured nanowires for Li ion battery electrodes.

Novel SnO(2)-In(2)O(3) heterostructured nanowires were produced via a thermal evaporation method, and their possible nucleation/growth mechanism is proposed. We found that the electronic conductivity of the individual SnO(2)-In(2)O(3) nanowires was 2 orders of magnitude better than that of the pure SnO(2) nanowires, due to the formation of Sn-doped In(2)O(3) caused by the incorporation of Sn into the In(2)O(3) lattice during the nucleation and growth of the In(2)O(3) shell nanostructures. This provides the SnO(2)-In(2)O(3) nanowires with an outstanding lithium storage capacity, making them suitable for promising Li ion battery electrodes.

Xylocydine, a novel inhibitor of cyclin-dependent kinases, prevents the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptotic cell death of SK-HEP-1 cells.

Xylocydine (4-amino-6-bromo-7-(beta-l-xylofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide) blocks cyclin-dependent kinase CDK1 and CDK2/cyclin A activity in vitro (IC(50) 1.4 and 61 nM, respectively) while minimally inhibiting the three other Ser/Thr protein kinases tested (IC(50) 21-86 microM). Reduced phosphorylated nucleolin and retinoblastoma protein levels showed it also efficiently inhibited cellular CDK1 and CDK2 activity (IC(50) 50-100 and 200-500 nM, respectively). Moreover, it blocked the functional activity of CDKs in tumor necrosis factor-related apoptosis-inducing ligand-induced SK-HEP-1 cell apoptosis 20 to 1000-fold more potently than olomoucine and roscovitine. Xylocydine is thus a novel and potent CDK inhibitor that could be used to interfere with cell cycle- and apoptosis-related CDK activity in various diseases.