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Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome has been reported in diabetic complications including diabetic kidney disease (DKD). However, it remains unknown if NLRP3 inhibition is renoprotective in a clinically relevant interventional approach with established DKD. We therefore examined the effect of the NLRP3-specific inhibitor MCC950 in streptozotocin-induced diabetic mice to measure the impact of NLRP3 inhibition on renal inflammation and associated pathology in DKD. We identified an adverse effect of MCC950 on renal pathology in diabetic animals. Indeed, MCC950-treated diabetic animals showed increased renal inflammation and macrophage infiltration in association with enhanced oxidative stress as well as increased mesangial expansion and glomerulosclerosis when compared with vehicle-treated diabetic animals. Inhibition of the inflammasome by MCC950 in diabetic mice led to renal up-regulation of markers of inflammation (Il1β, Il18 and Mcp1), fibrosis (Col1, Col4, Fn1, α-SMA, Ctgf and Tgfβ1) and oxidative stress (Nox2, Nox4 and nitrotyrosine). In addition, enhanced glomerular accumulation of pro-inflammatory CD68 positive cells and pro-oxidant factor nitrotyrosine was identified in the MCC950-treated diabetic compared with vehicle-treated diabetic animals. Collectively, in this interventional model of established DKD, NLRP3 inhibition with MCC950 did not show renoprotective effects in diabetic mice. On the contrary, diabetic mice treated with MCC950 exhibited adverse renal effects particularly enhanced renal inflammation and injury including mesangial expansion and glomerulosclerosis.

Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2-3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2-3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.

AIM To examine the type of vesicular glutamate transporter (VGLUT)-immunopositive (+) axons that coexpress neuropeptides in the rat and human dental pulp, which may help understand peripheral mechanism of pulpal inflammatory pain in rats and humans. METHODOLOGY The trigeminal ganglia (TG) and the dental pulp of the maxillary molar teeth from three male Sprague-Dawley rats weighing 300-330 g and dental pulps of three healthy human (male) maxillary premolar teeth from three 16 to 28-year-old patients extracted for orthodontic treatment were used. The type of VGLUT + axons that coexpress substance P (SP)- and/or calcitonin gene-related peptide (CGRP) and parvalbumin in the rat TG and in the axons of the rat and the human dental pulp was examined by double fluorescence immunohistochemistry and quantitative analysis. Results were analyzed using one-way anova and the Kruskal-Wallis test. RESULTS SP and CGRP were expressed in many human VGLUT1 + pulpal axons but not in the rat VGLUT1 + TG neurons and pulpal axons (P

In April 2020, manufacturing of the ITER vacuum vessel (VV) first sector has been completed by the Korean domestic agency, manufacturing having started in February 2012. The ITER VV sector is the largest fusion VV structure in the world. Each step of the manufacturing was a challenge as a first-of-a-kind, and a French nuclear pressure vessel. The paper provides an overview of the major challenges which were overcome over the last 10 years.

Low-grade persistent inflammation is a feature of diabetes-driven vascular complications, in particular activation of the NLRP3-inflammasome to trigger the maturation and release of the inflammatory cytokine interleukin-1β (IL-1β). We investigated whether inhibiting the NLRP3-inflammasome, through the use of the specific small-molecule NLRP3 inhibitor, MCC950, could reduce inflammation, improve vascular function and protect against diabetes-associated atherosclerosis in the streptozotocin (STZ)-induced diabetic Apolipoprotein knockout (ApoE-/-) mouse. Diabetes led to a ~4-fold increase in atherosclerotic lesions throughout the aorta, which were significantly attenuated with MCC950 (PPP

During Phase-2 of the LHC, known as the High Luminosity LHC (HL-LHC), the accelerator will increase its instantaneous luminosity to 5 $\times$ 10$^{34}$ cm$^{-2}$ s$^{-1}$, delivering an integrated luminosity of 3000 fb$^{-1}$ over 10 years of operation starting from 2027. In view of the HL-LHC, the CMS muon system will be upgraded to sustain efficient muon triggering and reconstruction performance. Resistive Plate Chambers (RPCs) serve as dedicated detectors for muon triggering due to their excellent timing resolution, and will extend $|\eta|$ (pseudorapidity) up to a region of 2.4. Before Long Shutdown 3 (LS3), the RE3/1 and RE4/1 stations of the endcap will be equipped with new improved Resistive Plate Chambers (iRPCs) having different design and geometry than the present RPC system. The iRPC geometry configuration improves the detector's rate capability and its ability to survive the harsh background conditions of the HL-LHC. Also, new electronics equipped with excellent timing precision measurements with a resolution of less than 150 ps are developed to readout the RPC detectors from both sides of the strips to allow for good spatial resolution along them. The performance of the iRPC has been studied with gamma radiation at the Gamma Irradiation Facility (GIF++) at CERN. Ongoing longevity studies will help to certify the iRPCs for the HL-LHC running period. The main detector parameters such as the currents, rate and resistivity are regularly monitored as a function of the integrated charge. Preliminary results of the detector performance will be presented.

The relationship between reproductive breast risk factors and breast cancer survival in patients with different breast cancer subtypes is not well known.We examined a large-sized, retrospective study of 23,882 subjects from the Korean Breast Cancer Registry. The breast cancer subtype was determined by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Information regarding reproductive factors, including breastfeeding, age at first birth (AFB), and parity, was gathered. Multivariate Cox regression analysis was used to estimate the association among breast cancer subtypes, such as luminal A, luminal B, Her-2/neu overexpressing, and triple negative breast cancer (TNBC), and breast cancer survival as dependent variables and adjusting for age and stage.High parity (≥ 5) increased the recurrence risk of luminal A and B breast cancer (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.96-3.97; P = .0055 and HR, 1.12; 95% CI, 0.42-3.02, respectively; P = .0073) in breast cancer-specific survival (BCSS), but 1 to 3 child births decreased the recurrence risk of luminal A breast cancer (HR, 0.56; 95% CI, 0.34-0.91; P = .0055) and luminal B breast cancer (HR, 0.32; 95% CI, 0.17-0.61; P = .0073) in BCSS. Early AFB (20 years) increased the recurrence risk of luminal A breast cancers (HR, 1.61; 95% CI, 0.62-4.26; P = .039) in BCSS and of TNBC (HR, 1.31; 95% CI, 0.78-2.21; P = .0006) in overall survival. Her-2/neu overexpressing breast cancer had no correlation with parity and AFB in breast cancer survival.High parity (≥ 5) and early AFB (20 years) were correlated with worse clinical outcomes in patients with luminal breast cancer, but not with other subtyped breast cancers.

Background The transplantation of isolated islets is thought to be an attractive approach for curative treatment of diabetes mellitus. Panax ginseng has been used in oriental countries for its pharmacologic effects, such as antidiabetic and antiinflammatory activities. 20(S)-ginsenoside Rg3 (Rg3), an active ingredient of ginseng saponins, has been reported to enhance insulin secretion–stimulating and antiapoptotic activities in pancreatic beta cells. We performed this study to examine the hypothesis that preoperative Rg3 administration can enhance islet cell function and antiapoptosis before islet transplantation. Methods Balb/c mice were randomly divided into 2 groups according to the administration of Rg3 after islet isolation. Mouse islets were cultured in medium supplemented with or without Rg3. In vitro, islet viability and function were assessed. After treatment of islets with a cytokine cocktail (tumor necrosis factor α, interferon-γ, and interleukin-1β), cell viability, function, and apoptosis were assessed. Results Cell viability was similar between the 2 groups. Islets cultured in medium supplemented with Rg3 showed 2.3-fold higher glucose-induced insulin secretion than islets cultured in medium without Rg3. After treatment with a cytokine cocktail, glucose-induced insulin release, total insulin content of islets, and apoptosis were significantly improved in Rg3-treated islets compared with cytokine-treated islets. Cytokine-treated islets produced significantly higher levels of nitric oxide (NO) than islets treated with Rg3. Conclusions These results suggest that preoperative Rg3 administration enhanced islet function before islet transplantation and attenuated both cytokine-induced damage associated with NO production and apoptosis. Rg3 administration might be a prospective management to enhanced islet function and ameliorate early inflammation after transplantation.

BACKGROUND In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. PATIENTS AND METHODS Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. RESULTS Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. CONCLUSIONS The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.

As a participant of ITER project, ITER Korea has to supply two ITER vacuum vessel sectors (Sector #6, #1) of total nine ITER VV sectors. After the procurement arrangement with ITER Organization, ITER Korea made the contract with Hyundai Heavy Industries (HHI) for fabrication of two sectors. Then the start of the manufacturing design was initiated from January 2010. HHI made three real scale R&D mock-ups to verify the critical fabrication feasibility issues on electron beam welding, 3D forming, welding distortion and achievable tolerances. The documentation according to IO and the French nuclear safety regulation requirement, the qualification of welding and nondestructive examination procedures conform to RCC-MR 2007 were proceed in parallel. The mass production of raw material was done after receiving ANB (agreed notified body) verification of product/parts and shop qualification. The manufacturing drawing, manufacturing and inspection plan of VV sector with supporting fabrication procedures are also verified by ANB, accordingly the first cutting and forming of plates for VV sector fabrication started from February 2012. This paper reports the latest fabrication progress of ITER vacuum vessel Sector #6 that will be assembled as the first sector in the ITER pit. The overall fabrication route, R&D mock-up fabrication results with forming and welding distortion analysis, qualification status of welding and nondestructive examination (NDE) are also presented.

Background Melasma is associated with epidermal hyperpigmentation, weak basement membrane, vascular proliferation and increased numbers of mast cell. Tranexamic acid (TXA), a plasmin inhibitor, is reported to improve melasma when injected locally. However, the effects of oral and topical TXA on melasma have not been well studied and the underlying mechanism remains unclear. Objectives To elucidate the effects of oral and topical TXA on melasma. Methods A clinical study was conducted with 25 women for 8 weeks from March to July 2010. Volunteers were instructed to take two TXA tablets three times a day and apply a TXA topical agent twice a day for 8 weeks. Skin pigmentation and erythema was measured using a Mexameter® during each visit and skin biopsies were collected from eight subjects before and 8 weeks after treatment. Fontana-Masson, anti-CD31, antitryptase and antitype IV collagen staining was performed. Results Twenty-two subjects completed the study and no serious adverse events occurred during the study period. The mean lesional melanin index (MI) scores decreased significantly. Interestingly, the MI scores for the perilesional skin increased. The erythema index scores of lesional and perilesional skin also showed a similar pattern. Histological analysis showed significant reduction of epidermal pigmentation, vessel numbers and mast cell counts. Type IV collagen staining was not observed in all specimens. Conclusion TXA decreased epidermal pigmentation associated with melasma and also reversed melasma-related dermal changes, such as vessel number and increased numbers of mast cells.

Background Intense pulsed light (IPL) has been widely used for photorejuvenation. Although previous literature has shown clinical effectiveness of IPL treatments on cutaneous photoaging, the associated changes in the biophysical properties of the skin following IPL treatments have not been fully elucidated. Objective The aim of this study was to evaluate changes in skin biophysical properties in patients with photoaging after IPL treatments, using non-invasive, objective skin measuring devices. Patients and methods A total of 26 Korean women with facial dyschromias underwent three sessions of IPL treatment at 4-week intervals. Outcome assessments included standardized photography, global evaluation by blinded investigators, patients’ self-assessment and objective measurements of colour (Mexameter MX18, Chromatometer), elasticity (Cutometer), roughness (Visiometer), sebum (Sebumeter) and skin hydration (Corneometer). Results Intense pulsed light treatments produced a 15% decrease in the size of representative pigmented lesions (P

Cement concrete pavement provides durable service life and remarkable applicability for heavy traffic. Its purchase being easier than asphalt, cement concrete pavement offers excellent advantages in terms of durability and economic efficiency. However, adequate repair of this pavement is harder than asphalt concrete in case of degradation or damage. Cracking in the concrete pavement is the major cause of such disadvantages and the demand of repair on road sites is growing every day. This emphasizes the urgency to secure technologies for the control of early and longterm cracking. Accordingly, this study evaluates the drying and autogenous shrinkage strains regard to fiber reinforcement in order to reduce cracking of the concrete pavement mix so as to control the damage of the pavement by means of fiber reinforcement. The results show that the drying shrinkage strain can be significantly reduced to about 1/4 through the admixing of 0.2% volume ratio of NY fiber compared to the non-reinforced plain concrete, and that the hybrid fiber reinforcement mix H-N1-ST1 can realize remarkable reduction of the autogenous shrinkage.

Non-clustered protocadherins (PCDHs) are calcium-dependent adhesion molecules which have attracted attention for their possible roles in the neuronal circuit formation during development and their implications in the neurological disorders such as autism and mental retardation. Previously, we found that a subset of the non-clustered PCDHs exhibited circuit-dependent expression patterns in thalamo-cortical connections in early postnatal rat brain, but such patterns disappeared in adulthood. In this study, we identified that the non-clustered PCDHs showed differential expression patterns along the septotemporal axis in the subregions of adult hippocampus and dentate gyrus with topographical preferences. The expressions of PCDH1, PCDH9, PCDH10 and PCDH20 showed septal preferences, whereas the expressions of PCDH8, PCDH11, PCDH17 and PCDH19 showed temporal preferences, suggesting that they play roles in the formation/maintenance of intrahippocampal circuits. PCDHs also exhibited the region-specific expression patterns in the areas connected to hippocampal formation such as entorhinal cortex, lateral septum, and basolateral amygdaloid complex. Furthermore, the expression levels of three PCDHs (PCDH8, PCDH19 and PCDH20) were regulated by the electroconvulsive shock stimulation of the brain in the adult hippocampus and dentate gyrus. These results suggest that non-clustered PCDHs are involved in the maintenance and plasticity of adult hippocampal circuitry.

Objective To assess whether bioelectrical impedance analysis (BIA) can be used to evaluate the degree of hepatic steatosis in potential living liver donors. Material and Methods From May 2008 to April 2009, BIA was measured in 302 living donor candidates. Correlations among body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), total fatty changes at percutaneous needle liver biopsy, and BIA-derived fat composition were assessed. Results The median (range) BIA-derived fat proportion was 19.4% (4.8%–35.3%), BMI was 24 (17–39), and hepatic steatosis at liver biopsy was 2% (0%–75%). Crude correlations were observed between BIA-derived fat proportion and hepatic steatosis (r2 = 0.14; P = .000), between BMI and hepatic steatosis (r2 = 0.27; P = .000), and between BMI and BIA-derived fat proportion (r2 = .25; P = .000). Receiver operating characteristic curve analysis revealed that the area under the curve of BIA-derived fat proportion was smaller than that of BMI, and no significant cutoff value was identified. Conclusions These results suggest that BIA-derived fat composition alone cannot be used to accurately determine the degree of hepatic steatosis. However, a combination of BMI and BIA-derived fat composition may increase clinical ability to assess hepatic steatosis.