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High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population.This study used cross-sectional data from adult subjects aged 50-75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V-VII (2010-2011 and 2014-2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010-2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010-2011 dataset and any site SR-OA in the 2014-2016 dataset.Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (2, 2-3, 3-4, 4-5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.03-2.62) compared to the reference group (3-4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10-3.10) compared with the reference group. Regarding SR-OA at any site in the 2014-2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders.This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.

Future transport will change drastically with the introduction of automated vehicles. Here, Autonomous Mobility on Demand (AMoD) will play a major role, requiring a radical change of vehicle design, with many different conceivable concepts. This technology shift holds high potentials and high risks. Uncertainties about future usage profiles, operator and customer requirements have to be dealt with. An approach to elicit initial requirements for future vehicle concepts considering the entire ecosystem is introduced. The applicability is shown for a specific urban mobility scenario.

BackgroundLimited therapies are available for patients with idiopathic inflammatory myopathy (IIM), a heterogenous group of chronic, systemic, autoimmune inflammatory diseases characterized by progressive muscle weakness and/or distinct skin rashes.1 Abatacept, a selective co-stimulation modulator, may be a useful treatment option.2ObjectivesTo evaluate efficacy, safety, and tolerability of abatacept + standard of care (SOC) in patients with IIM compared with SOC alone (placebo).MethodsA 24-week, randomized, double-blind, placebo-controlled phase 3 trial of SC abatacept (125 mg weekly) + SOC (corticosteroids and immunosuppressants alone or combined; NCT02971683) in patients with active, treatment-refractory IIM (Manual Muscle Testing-8 [MMT-8] ≤ 135) was performed. Primary endpoint was proportion of patients meeting International Myositis Assessment and Clinical Studies definition of improvement (IMACS DOI) at week 24. Change from baseline in myositis Functional Index-2 (FI-2), HAQ-DI, Myositis Disease Activity Assessment Tool (MDAAT), and Myositis Response Criteria (MRC) were secondary endpoints with safety. Post hoc analyses by disease subtype were performed.ResultsOverall, 148 patients were randomized (75 abatacept; 73 placebo); IIM subtypes were dermatomyositis (DM; 53.3% vs 57.5%), polymyositis (PM; 25.3% vs 34.2%), and autoimmune necrotizing myopathy (ANM; 21.3% vs 8.2%). Mean baseline MMT-8 and HAQ-DI scores were 112.7 and 1.5, respectively. Approximately 90% of patients completed week 24. Week 24 IMACS DOI rates were abatacept 56.0% vs placebo 42.5% (adjusted odds ratio, 1.8 [95% CI, 0.9–3.5]; P = 0.083). Pre-specified IMACS DOI analysis showed no differences for patients with DM but notable benefit for those with non-DM subtypes, PM and ANM (Table 1). Secondary endpoints showed similar differences (Table 1). MRC at day 169 by category is shown in Figure 1. Proportion of AEs (69.3% and 75.3%) and serious AEs (5.3% and 5.5%) were similar in the abatacept and placebo arms.Table 1.Primary and secondary (mean change from baseline at week 24) endpointsOutcomeIIMAbataceptPlaceboNominal P value (abatacept vs placebo) or adjusted mean difference from placebo (95% CI)IMACS DOI,a n/N (%)All42/75 (56.0)31/73 (42.5)P = 0.083DM22/40 (55.0)21/42 (50.0)P = 0.679Non-DM20/35 (57.1)10/31 (32.3)P = 0.040FI-2All4.1 (1.3)1.2 (1.4)2.9 (0 to 5.8)DM2.3 (1.6)0.3 (1.4)1.9 (−2.3 to 6.2)Non-DM3.2 (1.4)−0.6 (1.5)3.7 (−0.3 to 7.8)HAQ-DIAll−0.31 (0.07)0.20 (0.07)−0.12 (−0.28 to 0.04)DM−0.31 (0.08)−0.19 (0.07)−0.11 (−0.32 to 0.10)Non-DM−0.25 (0.09)−0.07 (0.09)−0.18 (−0.44 to 0.07)MDAAT, Extramuscular Global Activity, (95% CI)bAll−1.56 (−1.96 to −1.16)−1.40 (−1.81 to −0.99)−0.16 (−0.63 to 0.30)DM−1.90 (−2.43 to −1.37)−1.85 (−2.35 to 1.36)−0.05 (−0.77 to 0.68)Non-DM−1.09 (−1.46 to −0.72)−0.85 (−1.27 to −0.43)−0.24 (−0.80 to 0.32)MMT-8All12.9 (1.9)11.0 (2.0)1.8 (−2.7 to 6.4)DM14.4 (2.2)14.0 (2.2)0.4 (−5.7 to 6.4)Non-DM12.1 (2.5)7.8 (2.7)4.3 (−3.0 to 11.7)Physician Global AssessmentbAll−2.89 (0.30)−2.69 (0.30)−0.20 (−0.92 to 0.52)DM−2.78 (0.29)−2.43 (0.28)−0.35 (−1.15 to 0.46)Non-DM−2.35 (0.43)−2.21 (0.48)−0.14 (−1.43 to 1.15)Patient Global AssessmentbAll−1.4 (0.31)−0.98 (0.32)−0.38 (−1.11 to 0.35)DM−1.4 (0.33)−1.4 (0.31)−0.00 (−0.91 to 0.90)Non-DM−1.2 (0.41)−0.3 (0.44)−0.93 (−2.14 to 0.29)Data are adjusted mean change from baseline score (SE) unless stated.aDefined as improvement of ≥ 20% in 3 IMACS core measures, worsening by ≥ 25% in ≤ 2 IMACS core measure scores, and a reduction of < 25% in MMT-8; b100 mm visual analog scale.ConclusionIn this double-blind trial of SC abatacept vs placebo, abatacept failed to meet primary or secondary endpoints. Post hoc analyses suggest a treatment benefit in patients with PM and ANM (not DM) when treated with abatacept. Abatacept use was well tolerated.References[1]Dalakas MC, Hohlfeld R. Lancet 2003;362:971–82.[2]Tjärnlund A, et al. Ann Rheum Dis 2018;77:55–62.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Medical writing and editorial assistance were provided by Fiona Boswell, PhD, of Caudex and were funded by Bristol Myers Squibb. Study execution was by Sandra Overfield and Robin Scully.Disclosure of InterestsRohit Aggarwal Consultant of: AbbVie, Alexion, Argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Corbus, CSL Behring, EMD Serono, Janssen, Jubilant, Kezar, Kyverna, Mallinckrodt, Octapharma, Orphazyme, Pfizer, Q32, Roivant (personal fees), Grant/research support from: Bristol Myers Squibb, EMD Serono, Genentech, Mallinckrodt, Pfizer, Q32, Ingrid E. Lundberg Shareholder of: Novartis, Roche, Consultant of: Argenx, AstraZeneca, Corbus, EMD Serono, Janssen, Kezar, Octapharma, Orphazyme (personal fees), Grant/research support from: Bristol Myers Squibb, Yeong Wook Song: None declared, Aziz Shaibani: None declared, Victoria P Werth Consultant of: AbbVie, Akari, Amgen, Argenx, AstraZeneca, Bayer, Beacon Bioscience, Biogen, Bristol Myers Squibb, Celgene, Corcept, Crisalis, CSL Behring, Cugene, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Horizon, Idera, Incyte, Janssen, Kezar, Kwoya Kirin, Lilly, Medimmune, Medscape, Merck, Nektar, Octapharma, Pfizer, Principia, Regeneron, Resolve, Rome Pharmaceuticals, Sanofi, UCB, Viela Bio, Grant/research support from: Amgen, Argenx, AstraZeneca, Biogen, Bristol Myers Squibb, Celgene, Corbus Pharmaceuticals, CSL Behring, Genentech, Gilead, Janssen, Pfizer, q32 Bio, Regeneron, Syntimmune, Ventus, Viela, Michael A Maldonado Employee of: Bristol Myers Squibb

Background Bilateral adrenal hemorrhage is a serious condition that can result in adrenal insufficiency, shock, acute adrenal crisis, and mortality if it is not managed with adequate treatment. We report a rare case of idiopathic bilateral adrenal hemorrhage. Case presentation A 50-year-old woman visited our hospital with complaints of right upper abdominal pain. A computed tomography (CT) revealed unilateral left adrenal gland hemorrhage. However, the results of rapid adrenocorticotropic hormone (ACTH) stimulation test and adrenomedullary hormone function test were normal. Since the patient did not show signs of adrenal insufficiency, corticosteroid therapy was postponed and only supportive management therapy was started. After 1 week, a follow- up CT showed a previously unseen adrenal hemorrhage on the right adrenal gland, but the rapid ACTH stimulation test result was normal. One year later, no hemorrhagic signs were observed on the follow-up CT. Conclusion In most cases of idiopathic bilateral adrenal hemorrhage, patients are treated with steroid replacement therapy due to adrenal insufficiency. In some other cases, patients are treated with steroids despite the absence of adrenal insufficiency. Here we reported a very rare case of idiopathic bilateral adrenal hemorrhage sequentially to emphasize that before initiation of adrenal hormone replacement therapy, it is important to determine whether adrenal insufficiency is present. If there is no evidence of adrenal insufficiency, adrenal replacement therapy should be postponed until the presence of adrenal insufficiency is confirmed.

Supplemental material, Supplementary Figure and tables for Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare by D J Go, J Y Lee, M J Kang, E Y Lee, E B Lee, E C Yi and Y W Song in Lupus

Observation at the room temperature the spectra of the resonant inelastic light scattering by the spatially confined optical phonons as well as the excitonic luminescence caused by confinement effects in the ensemble of isolated quantum dots (QDs) nc-Si/SiO2 is reported. It is shown that the samples investigated are high purity and high crystalline perfection quality nc-Si/SiO2 QDs without amorphous phase α-Si and contaminants. Comparison between the experimental data obtained and phenomenological model of the strong space confinement of optical phonons revealed the need of the more accurate form of the weighted function for the confinement of optical phonons. It is shown that simultaneous detection of the inelastic light scattering by the confinement of phonons and the excitonic luminescence spectra by the confined electron-hole pairs in the nc-Si/SiO2 QDs allows selfconsistently to determine more accurate values of the diameter of the nc-Si/SiO2 QDs.

Проанализирован состав тонких слоев рутения, синтезированных при импульсном осаждении из газовой фазы с участием комплексного карбонил-диенового прекурсора Ru(CO)3(C6H8), а также NH3, N2O, H2 в качестве второго реагента. Сформулированы схемы процессов роста низкотемпературных слоев рутения, объясняющие роль вторых реагентов в ходе процессов осаждения.

To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups.From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures.The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns.This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

An all-fiber-integrated, Q-switched thulium-doped fiber laser based on carbon nanotube (CNT) evanescent field interaction is experimentally demonstrated. It is shown that a saturable absorber based on a CNT-deposited D-shaped fiber can readily be incorporated into a thulium-doped fiber ring cavity for a passive Q-switching operation at a wavelength of ~ 1.89 μm. Using the laser scheme stable Q-switched pulses with a temporal width of ~ 7.155 μs could be obtained at a repetition rate of 14.18 kHz. The temporal stability of the output pulses was also investigated.

The results of measuring the first spectra of relative quantum efficiency for photoconversion in thin-film ZnO/CdS/Cu(In,Ga)Se2/Mo solar cells fabricated on rigid (glass) and flexible (polyimide) substrates are reported. The character of interband transitions has been studied and the values of the band gap for direct and indirect transitions in thin Cu(In,Ga)Se2 films are determined. It is found that a shift of the maximal photosensitivity for the obtained solar cells to shorter wavelengths is observed as rigid substrates are replaced by flexible ones. It is concluded that thin-film Cu(In,Ga)Se2 structures can be used as broad-band photoconverters of solar radiation.

Objective. Knee osteoarthritis (OA) is prevalent among the elderly in Asian countries; however, the utilization of total knee replacement (TKR) is unknown. Using data from a national registry, we sought to estimate the incidence of TKR by age and sex, and the trend for TKR utilization from 2002 to 2005 in South Korea. Methods. Reimbursement records from all hospitals in South Korea were extracted from the Health Insurance Review Agency (HIRA) database. Records with both the procedure code corresponding to a TKR and the diagnosis code of knee OA were selected. We estimated the age- and sex-specific rates of TKR. To compare the rate of TKR between men and women, we calculated age-standardized risk ratios. A TKR registry from a single centre containing more clinical information was analysed, and the differences in the clinical features between men and women were compared. Results. From 2002 to 2005, 47 961 TKRs were performed in subjects over the age of 40 yrs due to OA. The rate of TKR has increased over the 4 yrs and was much higher in women than in men. Compared with men, the age-standardized rate ratios for TKR in women ranged from 7.4 to 8.0. The single-centre registry data revealed that there was no difference in age, disease duration and the Kellgren-Lawrence grade at the time of surgery between men and women. Conclusion. Using a national database, we found that the rate of TKR increased steadily from 2002 to 2005 in South Korea. The TKR rate in women was much higher than that in men. Risk factors that account for such disparity in TKR utilization need to be further investigated.

Summary Human Toll-like receptors (TLRs) participate in innate immune response and signal the activation of adaptive immunity. The presence of a functional intronic polymorphism consisting of guanine–thymine repeats in TLR2 gene was recently reported. Here, we investigated a dinucleotide repeat polymorphism in intron II of TLR2 in Korean patients with rheumatoid arthritis (RA). The numbers of guanine–thymine [(GT)n] repeats in intron II of the TLR 2 gene were counted in 183 patients with RA and in 148 healthy controls, using the gene scanning technique. We classified alleles into two subclasses for further analysis, 12–16 GT repeats (S allele) and 17–28 repeats (L allele). By subgroup analysis, we also examined whether the S allele is associated with the presence of shared epitope (SE), rheumatoid factor (RF), joint erosion and extra-articular complications. S-allele frequency was significantly increased in patients with RA than in healthy controls [30.3% vs. 23.0%, P = 0.03, or 1.46, 95% confidence interval (CI) 1.03–2.07], and genotypes containing S alleles were more frequent in patients with RA than in healthy controls (54.4% vs. 46.5%. P = 0.04, or 1.57, 95% CI 1.01–2.42). A skewed S-allele distribution was not found to be related to the presence of SE. Subgroup analysis showed no genotypic or allele frequency differences between patients with/without RF, joint erosion, or extra-articular complications. Genotype containing shorter GT repeats in intron II of the TLR2 gene may confer susceptibility to RA in Koreans.

Radiation synovectomy is a useful treatment modality in patients with refractory synovitis. We have developed a 188Re-tin-colloid as a new radiopharmaceutical agent and investigated its efficacy and safety in patients with rheumatoid arthritis. Radiation synovectomy was performed using 188Re-tin-colloid in 22 knees from 21 rheumatoid arthritis patients refractory to intra-articular corticosteroid injection. The efficacy and safety of administration of 370-1110 MBq of 188Re-tin-colloid were evaluated after 1, 3, 6, 9 and 12 months. Pain intensity on a visual analogue scale decreased significantly 12 months after therapy (mean+/-SD: 68.0+/-26.1 mm vs. 25.1+/-23.4 mm; P=0.0001 by the paired t-test). Pain decreased in 19 cases (86.3%), joint tenderness improved in 14 cases (63.6%) and joint swelling was reduced in all cases (100%). 188Re-tin-colloid was safe. The residual activity of 188Re in the blood was 0.077%+/-0.25% of the injected dose. The radioactivity of 188Re in the urine was 0.14%+/-0.13% of the injected dose. Transient reactive synovitis was observed in 18 cases (81.8%). No clinical side-effects or abnormalities in leucocyte count, platelet count, liver function tests or urine analysis were observed in any patient. In conclusion, in this first study of radiation synovectomy using 188Re-tin-colloid for patients with rheumatoid arthritis, the treatment resulted in the improvement of arthritis and was well tolerated.

High-resolution MR angiography (HR-MRA) demonstrates blood flow in the digital arteries, which correlates with the severity of Raynaud's phenomenon (RP). This study investigates whether baseline HR-MRA of the hand can predict the treatment response to udenafil, a new PDE5-inhibitor, in patients with secondary RP.Baseline MRA and Doppler ultrasound were obtained in 12 patients with secondary RP. The patients were treated with udenafil 100 mg/day for 4 weeks and changes in blood flow were measured. Blood flow on MRA was scored on a 4-point scale: 0, no visible flow; 1, visible flow to the proximal phalanx; 2, to the middle phalanx; and 3, to the distal phalanx. Peak systolic velocity (PSV) was measured to determine blood flow. Paired t-test and ANOVA were used to determine the treatment response of the different MRA scores.On baseline MRA, 53.3% of digital arteries had an MRA score of 0, 25.8% MRA score of 1, 9.2% MRA score of 2, and 11.6% MRA score of 3. Overall, 4-week udenafil treatment improved digital flow (p0.05) in all MRA scores. Digital arteries with MRA score 2 showed the best response with improvement in PSV by 14.5 mm/sec (p0.01), whereas improvement in arteries of MRA scores 1 and 3 were not better than an MRA score of 0 (all, p0.05).Digital arteries with moderate blood flow observed on MRA respond best to treatment with udenalfil. Therefore, baseline MRA may help predict treatment response in patients with secondary RP.

Graphitic features are detected on 4H-SiC surface following oxidation and etching using surface enhanced Raman spectroscopy (SERS). The electronic state of the carbon is sp2 on both the Si- and C-faces of 4H-SiC. The structures of the “carbon clusters” consist of two-dimensional graphitic flakes less than 2 nm and one-dimensional polyenes. The degree of graphitization on the C-face SiC is higher than those on the Si-face SiC. This study provides experimental evidence for “carbon clusters” existing on SiC surfaces following oxidation at atmospheric pressure and demonstrates that SERS is an effective technique to probe low concentration species on the SiC surface.

Nitric oxide postoxidation anneal results in a significant decrease of defect state density (Dit) near the conduction bandedge of n-4H–SiC at the oxide/(1120) 4H–SiC interface. Comparison with measurements on the conventional (0001) Si-terminated face shows a similar interface state density following passivation. Medium energy ion scattering provides a quantitative measure of nitrogen incorporation at the SiO2/SiC interface.

e15000Background: To present an initial results of a phase III trial of Short Term radiotherapy (SCRT) followed by chEmotherapy (experimental group) versus Long-term chemoradiotherapy (CRT) (contro...

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N=579) and African-Americans (AAs) (N=407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P

Autoantibodies from the sera of Sjögren's syndrome patients (SS IgG) have been suggested to inhibit muscarinic receptor function. However, the acute nature of such an inhibitory effect remains controversial. In this study, we investigated the acute effects of SS IgG on muscarinic receptor function in human submandibular gland (HSG) cells.The effects of autoantibodies on muscarinic receptor function were studied using microspectrofluorimetry, whole-cell patch clamp, immunofluorescence confocal microscopy, and a co-immunoprecipitation assay.Carbachol (CCh) was found to consistently increase intracellular calcium concentration ([Ca(2+) ](i) ) and activate K(+) current in HSG cells. However, pretreatment of the cells with SS IgG for 5 or 30 min significantly attenuated these responses, with a substantially more prominent effect after 30 min of treatment. Like CCh, adenosine 5'-triphosphate (ATP) also increased [Ca(2+) ](i) and activated K(+) currents in HSG cells, although pretreatment with SS IgG did not affect the cellular response to ATP. CCh was found to reorganize α-fodrin in HSG cells in a Ca(2+) -dependent manner. However, pretreatment with SS IgG prevented the cytoskeletal reorganization of α-fodrin induced by CCh.SS IgG acutely and reversibly inhibited muscarinic receptor function, thereby inhibiting the Ca(2+) mobilization necessary for the activation of K(+) currents and α-fodrin reorganization in HSG cells.

Thermal-conductivity measurements are reported for the new refrigerants R134a, R152a und R123. Transient hot-wire experiments were performed which cover both the liquid and vapor states at temperatures and pressures ranging fromϑ=−20°C to 90°C and fromp=0.1 bar to 60 bar respectively. The results are correlated with density and temperature. In addition temperature dependent correlations are presented for (i) saturated liquid, (ii) saturated vapor, (iii) ideal gas (which equals approximately vapor state at ambient pressure). Finally the results are compared with data from the literature and also with the thermal conductivities of R12 and R11.

To investigate the role of sTREM-1 and PTX3 as markers of infection in febrile patients with SLE.In febrile (body temperatureor =38 degrees C) patients with SLE, blood samples of day 0, 1, 2, and 14 after presentation were drawn and relevant clinical data were collected. The patients were allocated to an infection group (n=19) or disease flare group (n=14). Serum levels of sTREM-1 and PTX3 were measured by ELISA using the serum samples of SLE patients and age- and sex-matched healthy controls (n=31).A total of 33 febrile episodes occurred in 32 SLE patients (19 infections, 14 flares) were studied. sTREM-1 levels on day 0 were significantly higher in the infection group than in the flare group (109.9 pg/ml (median) vs. 48.0 pg/ml, p=0.002), but PTX3 levels were similar in these two groups. The difference of sTREM-1 levels between infection group and flare group was persistent on day 1 and 2 (day 1, p=0.007; day 2, p=0.034). The highest diagnostic value (sensitivity=1.0, specificity=0.664) of sTREM-1 was obtained at the threshold value of 53.2 pg/mL.Serum sTREM-1 levels were significantly higher in the infection group than in the flare group of febrile SLE patients. Our findings suggest that serum sTREM-1 levels could be used to determine whether SLE patients have contracted an infection.

Behçet's disease (BD) is an autoimmune disease with an unknown etiology and mannose-binding lectin (MBL) is a pattern recognition receptor in the innate immune system, which is associated with some autoimmune diseases. We investigated MBL2 gene polymorphisms and serum MBL levels in BD patients and controls.MBL2 gene polymorphisms in exon 1 (MBL2 54 Gly/Asp, (A/B)), promoter (MBL2 H/L (G-550C), MBL2 Y/X (G-221C)), and 5' UTR region (MBL2 P/Q (C+4T)) were investigated using polymerase chain reaction and restriction fragment length polymorphism in 119 BD patients and 252 healthy controls. Serum MBL levels were measured by enzyme linked immunosorbent assay in 49 BD patients and 102 sex-/genotype-matched controls.No significant difference was found between BD patients and controls in terms of MBL2 polymorphisms and MBL serum levels. However, the presence of genital ulcer and neurologic involvement were found to be associated with MBL2 54 allele A (OR=2.415, OR=6.632, respectively). Eye involvement was found to be related to the presence of the MBL2 54 AA or AB genotypes (OR=12.46), MBL2-G-550C allele H (OR=1.829). High serum MBL level (or =500 ng/ml) was associated with skin lesions (p=0.002).The frequencies of the four MBL2 genetic polymorphisms examined were not different in BD patients and healthy controls. However, the presence of genital ulcer, eye involvement, and neuro-Behcet's disease were found to be associated with MBL2 polymorphisms that are associated with the production of high levels of MBL or functional MBL.

Ankylosing spondylitis (AS) is an inflammatory arthritis involving the axial skeleton. Decreased bone mineral density has also been reported in AS patients. This study sought to determine whether osteoclastogenesis and osteoclast activity are increased in AS.Twenty patients with AS were evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and other clinical parameters. Mononuclear cells were separated out from peripheral blood samples taken from AS patients and normal healthy controls and cultured with monocyte colony stimulating factor and receptor activator of the nuclear factor kappa B ligand (RANKL). Multi-nucleated, tartrate-resistant acid phosphatase stain-positive osteoclasts were counted after 9 days, and the areas of calcium absorption on calcium-coated plates were determined.Osteoclastogenesis was significantly greater in AS patients than in normal controls (number of osteoclasts/1106 mononuclear cells, median, 518.0 vs. 362.5, p=0.036). No differences were observed between AS patients and controls in terms of calcium absorption areas or the serum concentrations of tumor necrosis factor and RANKL. Osteoclastogenesis was greater in AS patients with sacroiliac joint ankylosis than in those without. Osteoclastogenesis and the calcium absorption area were not found to be correlated with BASDAI nor with other clinical parameters including age, erythrocyte sedimentation rate, and C-reactive protein levels.Osteoclastogenesis is elevated in AS patients, especially in those with sacroiliac joint ankylosis. Increased osteoclastogenesis may be related to osteopenia in AS patients.

To determine the serum levels of galectin-3 (Gal-3) and galectin-3 binding protein (G3BP) and to evaluate the associations between clinical features and these levels in patients with Behçet's disease (BD).Fifty patients with BD (mean age 40.6 +/- SEM 1.4 years; 21 males, 29 females; 26 active and 24 inactive patients), 20 patients with rheumatoid arthritis (RA), and 20 patients with systemic lupus erythematosus (SLE) were enrolled. Clinical features of BD patients including BD activity and severity over the previous 4 weeks were reviewed and serum levels of Gal-3 and G3BP were determined using enzyme-linked immunosorbent assays (ELISA).Serum Gal-3 levels were significantly higher in total BD patients than in healthy controls (mean +/- SEM, 10.68 +/- 0.93 versus 7.59 +/- 0.48 ng/mL; p = 0.0042 by Student's t-test), and active BD patients had significantly higher levels of serum Gal-3 than inactive patients and controls (13.08 +/- 1.53 in active BD, 8.08 +/- 0.71 ng/mL in inactive BD; p = 0.000039 by one way ANOVA). Although mean G3BP serum levels were not different in total BD patients and controls, active BD patients (6806.63 +/- 468.58 ng/mL) had higher G3BP levels than controls (5421.05 +/- 286.02 ng/mL; p = 0.031 by one way ANOVA). Additionally, serum Gal-3 significantly increased in patients with RA (p = 0.019 by t-test) and SLE (p = 0.00069) and G3BP increased in patients with SLE (p = 0.000012), compared to those in healthy controls. When we analyzed for associations with clinical features over the previous 4 weeks, Gal-3 was associated with orogenital ulcers (p = 0.036 by t-test) and time elapsed from symptom onset (p = 0.032, Pearson's coefficient = 0.314). Serum concentrations of Gal-3 (p = 0.013) and G3BP (p = 0.032) were positively correlated with the BD severity score for the previous 4 weeks. Gal-3 levels were significantly correlated with TNF-alpha (p = 0.048, Pearson's coefficient = 0.281) and G3BP levels were correlated with levels of C-reactive protein (p = 0.021, Pearson's coefficient = 0.329) in total BD patients. In multivariate analysis of all cytokines levels, only Gal-3 was significantly related to BD activity or severity for the previous 4 weeks.These results suggest that serum levels of Gal-3 and G3BP are increased in active BD patients and Gal-3 can be a new biomarker indicating disease activity in BD although their increments are not disease-specific.

The Behcet’s Disease Activity Form for Korean patients was easy to complete by patients without assistance.

New Concept of ion implantation technology, namely Locally‐Differentiated‐Scanning Ion Implantation (LDSI), is suggested for the first time in this report. The Vth variation caused by process non‐uniformity in each process variables such as gate Critical Dimension (CD), spacer deposition Uniformity and spacer etch CD, etc, becomes big huddle in scale down and larger diameter wafer. This LDSI technology has been developed for reducing the Threshold Voltage (Vth) variation within a wafer in nano‐scale FETs. The LDSI technology has the capability of implanting of the locally different dose at the desired region in wafer by controlling scan speed of X‐ or Y‐direction or by combining them with step‐wise rotation. By applied LDSI on S/D and halo implantation on 90nm era DRAM, the remarkable improvement in Vth variation has been achieved as much as 47%. Also, the Improvements in device yield and Idd fail rate by LDSI on 512M DDR3 product.By the evidences of this study, new implantation technology concept, LDSI, ...

Perturbations in genomic stability result in cancer, a reduced life span, and premature aging. MLH1 is a mismatch repair enzyme that acts to maintain genomic stability, and a loss of MLH1 increases cancer incidence and apoptosis resistance, which suggests a link between MLH1 and longevity. We found here that MLH1 is associated with longevity by comparing a centenarian group with a control group. Our data indicate a critical role for MLH1 in longevity.

We investigated the frequency and distribution of osteopenia according to the clinical severity in ankylosing spondylitis (AS). Bone mass was measured in men with mild (n = 45) and severe AS (n = 31) with dual-energy X-ray absorptiometry (DEXA). Definition of clinical severity was based on the Schober's test. Osteopenia was commonly detected (48% in mild AS and 39% severe AS) and, in mild disease, more frequently observed at the lumbar spine than any of the proximal femur sites. In severe AS, however, the frequency of osteopenia at the femoral neck and Ward's triangle was as high as at the lumbar spine. Both bone mineral density and T-scores in severe disease were lower than in mild disease at the femur neck, Ward's triangle, and total proximal femur, but not in the lumbar spine. The progression of osteopenia may be reflected more reliably at proximal femur sites than at the lumbar spine.

The rheumatoid synovium is a hypoxic environment, and hypoxia has been implicated as a factor in the pathogenesis of rheumatoid arthritis (RA). The purpose of this study was to investigate the effect of hypoxia on the expression of matrix metalloproteinase (MMP)-1, -3 and tissue inhibitor of metalloproteinase (TIMP)-1 in rheumatoid synovial fibroblasts.Synovial fibroblasts obtained from RA patients were cultured for 48 h under normoxic or hypoxic conditions. Assays included western blot analysis and enzyme-linked immunosorbent assay (ELISA) for MMP-1, -3 and TIMP-1, and northern blot analysis to measure TIMP-1 mRNA levels.Compared with normoxic culture, hypoxia increased MMP-1 and MMP-3 expression in rheumatoid synovial fibroblasts. Hypoxia decreased TIMP-1 expression in rheumatoid synovial fibroblasts, as measured by both protein and mRNA levels.These results suggest that microenvironmental conditions, such as hypoxia, may directly contribute to joint destruction in RA by increasing the ratio of MMP-1, -3 to TIMP-1 production in synovial fibroblasts.

Genetic factors and immune dysregulation play important roles in the development of systemic lupus erythematosus (SLE). Tumor necrosis factor receptor 2 (TNFR2) is suggested to be involved in the development of SLE because its genetic locus (1p36) encompasses one of the susceptible loci for SLE and its ligand (TNF) is associated with SLE. To investigate the role of TNFR2 in the pathogenesis of SLE, 139 Korean patients were genotyped with SLE, 137 healthy control subjects were genotyped for TNFR2 196 R/M polymorphism in exon 6 with PCR-SSCP, and the clinical characteristics of SLE were analyzed according to the genotypes. The genotype frequencies of 196 R/R, 196 R/M, and 196 M/M were 3.6%, 30.9%, and 65.5% in SLE patients and 4.4%, 26.3%, and 69.3% in healthy controls ( p = 0.676). The allelic frequency of 196 R was 19.1% in SLE patients and 17.5% in healthy controls ( p = 0.638, odds ratio = 1.109, and the 95% confidence interval = 0.720–1.708). The clinical characteristics were not different according to the genotypes. In conclusion, no skewed distribution of TNFR2 196 R/M polymorphism was found in Korean patients with SLE compared with healthy controls. Further studies in other populations will be needed to elucidate the role of the TNFR2 polymorphism in the development of SLE.

Chondrocyte apoptosis has been described in studies of the pathogenesis of various arthritides. Since matrix degradation is important in the pathology of arthritis, we investigated the effect of matrix depletion on chondrocyte apoptosis.Consecutive 1 mm sections of child's rib cartilage were cultured under 4 sets of conditions: (1) control; and treatment with (2) hyaluronidase, (3) collagenase, (4) hyaluronidase/collagenase alternately. Sections were harvested on Days 5, 8, and 11, and the proportion of apoptotic cells was measured by propidium iodide staining and flow cytometry. Changes of Fas and Fas ligand expression were verified by immunohistochemistry and Western blot.Collagenase treatment led to an increase of apoptosis, which began on Day 8, whereas hyaluronidase treatment had no effect on chondrocyte viability up to Day 11. Alternating hyaluronidase and collagenase treatment induced chondrocyte death earlier, but the difference in apoptotic rate was not significant on Days 8 or 11 compared to collagenase treatment alone. Immunohistochemistry showed the expression of Fas ligand in all enzymatically treated specimens. Expression of Fas receptor was ubiquitous in both control and treated specimens.The collagen framework is important in the maintenance of chondrocyte survival in human cartilage. Upregulation of Fas ligand in matrix depleted specimens suggested that the Fas pathway may have a role in apoptosis induced by matrix depletion.