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Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance–determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.

HD 44179 is a postasymptotic giant branch star with a biconical nebula known as the Red Rectangle. It shows the 3.3, 3.4, 6.2, 7.7, 8.6, and 11.3 μm infrared emission features (commonly known as the polycyclic aromatic hydrocarbon (PAH) emission bands and the Aromatic Infrared Bands). Previous observations of HD 44179 showed that the width of the 3.3 μm emission feature was narrower within 2″ of HD 44179 and wider further away from the star. This was interpreted as an indication that the 3.3 μm emission feature arises from two types of PAHs with spatially varying relative abundances. With new observations of HD 44179 taken with the NASA Infrared Telescope Facility we find that the width of the 3.3 μm emission feature profile is not narrower on HD 44179 and conclude that there is no evidence for two spatially varying components.

Polymyositis-dermatomyositis is extremely rare during pregnancy, and immunosuppressive therapy should be administered after carefully considering the effects on both the mother and fetus. Several reports have associated the disease activity with fetal prognosis, higher rates of eclampsia, preterm births, and fetal deaths. We report our experience with a patient who was diagnosed with polymyositis-dermatomyositis complicated by interstitial lung disease during pregnancy and was treated with a combination-immunosuppressant regimen. To the best of our knowledge, this is the first case wherein cyclosporine was used concomitantly with a steroid for the treatment of polymyositis diagnosed during pregnancy, with successful outcome of childbirth without any complications.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

We analyze the vertical component of GEONET GNSS measurements in Central Japan and clarify in some of the sites the origin of large annual time variations, as well as the secular variations. Many of these vertical movements may be attributable to the use of groundwater for agriculture, for snow melting, industrial, and hospital usages, etc. and the pumping up of the groundwater mining for refining natural gas and iodine at the production area of natural gas dissolved in water. For this reason, highly accurate monitoring of vertical variations by GNSS observations can provide new observation methods for understanding of not only geodynamics but also hydrology through monitoring groundwater fluctuation, and natural gas and oil resource development through monitoring ground movements caused by mining.

The "A disintegrin and metalloprotease" (ADAM) family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD). ADAM-17 in inflammatory myopathy serum [polymyositis (n = 26), dermatomyositis (n = 34), and clinically amyopathic dermatomyositis (n = 10)] and healthy control (n = 19) was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. Finally, we performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than that in healthy control (mean ± SEM, 1048 ± 312 and 36 ± 18 pg/ml, respectively; p

We examine the self-consistency of laboratory and observational data for potential carriers of the 3.3 $\mu$m infrared emission feature (IEF), a member of the ubiquitous family of strong interstellar IEFs at 3.3, 3.4, 6.2, 7.7, 8.6, 11.2, and 12.7 $\mu$m. Previous studies have shown that most Galactic sources (reflection nebulae, HII regions, and planetary nebulae) show 3.3 $\mu$m IEFs displaying similar central wavelengths, full widths at half maximum, and profiles. Our study is focused on the band profile designated as Class A, the most prevalent of four classes of observed band profiles. In contrast to the observations, laboratory spectra for gas phase polycyclic aromatic hydrocarbons (PAHs), the widely assumed carriers of the IEFs, display central wavelength shifts, widths, and profiles that vary with temperature and PAH size. We present an extrapolation of the laboratory band shifts and widths for smaller PAHs ($\le$32 carbon atoms) to the larger PAHs ($>$50 carbon atoms) that are thought to be the IEF carriers. The extrapolation leads to tight constraints on the sizes of the putative PAH carriers. Reconciling the observations with the implications of the laboratory spectra pose a significant challenge to the PAH and other IEF carrier hypotheses., Comment: Astrophysical Journal, in press. 24 pages, 7 figures

Recent volcanic activity has long been considered a distinct possibility that would place major constraints on the evolution of Mars’ interior. Volcanic activity would result in the outgassing of sulfur-bearing species. As part of our multi-band search for active release of volcanic gases on Mars, we looked for carbonyl sulfide (OCS) at its combination band ( ν 1 + ν 3 ) at 3.42 µ m (2924 cm − 1 ), and sulfur dioxide (SO 2 ) at 346.652 GHz, in two successive Mars years during its late Northern spring and mid Northern summer seasons (L s = 43°–144°). The targeted volcanic districts, Tharsis and Syrtis Major, were observed during the two intervals, 15 Dec. 2011 to 6 Jan. 2012 in the first year, and 23 May 2014 to 12 June 2014 in the second year using the high resolution infrared spectrometer CSHELL on the NASA Infrared Telescope Facility, and the high resolution heterodyne receiver HARP at the James Clerk Maxwell Telescope atop Maunakea, Hawaii. No active release of such gases was detected, and we report 2 σ upper limits of 1.8 ppbv and 3.1 ppbv for OCS and SO 2 , respectively, compared to 0.3 ppbv for SO 2 (Encrenaz, T. et al. [2011] Astron. & Astrophys. 530, A37; Krasnopolsky, V.A. [2012] Icarus 217, 144–152) over the disk of Mars. Our retrieved upper limit on the SO 2 outgassing rate of 156 tons/day (1.8 kg/s), corresponds to a mass rate of magma that is able to degas the SO 2 of 104 kilotons/day (1200 kg/s), or 40,000 m 3 /day (0.46 m 3 /s). Our campaign places stringent limits on the concentration of sulfur-bearing species into the atmosphere of Mars.

Advancing technology in near-infrared instrumentation and dedicated planetary telescope facilities have enabled nearly two decades of reconnoitering the spectral properties for near-Earth objects (NEOs). We report measured spectral properties for more than 1000 NEOs, representing >5% of the currently discovered population. Thermal flux detected below 2.5 µm allows us to make albedo estimates for nearly 50 objects, including two comets. Additional spectral data are reported for more than 350 Mars-crossing asteroids. Most of these measurements were achieved through a collaboration between researchers at the Massachusetts Institute of Technology and the University of Hawaii, with full cooperation of the NASA Infrared Telescope Facility (IRTF) on Mauna Kea. We call this project the MIT-Hawaii Near-Earth Object Spectroscopic Survey (MITHNEOS; myth-neos). While MITHNEOS has continuously released all spectral data for immediate use by the scientific community, our objectives for this paper are to: (1) detail the methods and limits of the survey data, (2) formally present a compilation of results including their taxonomic classification within a single internally consistent framework, (3) perform a preliminary analysis on the overall population characteristics with a concentration toward deducing key physical processes and identifying their source region for escaping the main belt. Augmenting our newly published measurements are the previously published results from the broad NEO community, including many results graciously shared by colleagues prior to formal publication. With this collective data set, we find the near-Earth population matches the diversity of the main-belt, with all main-belt taxonomic classes represented in our sample. Potentially hazardous asteroids (PHAs) as well as the subset of mission accessible asteroids (ΔV ≤ 7 km/s) both appear to be a representative mix of the overall NEO population, consistent with strong dynamical mixing for the population that interacts most closely with Earth. Mars crossers, however, are less diverse and appear to more closely match the inner belt population from where they have more recently diffused. The fractional distributions of major taxonomic classes (60% S, 20% C, 20% other) appear remarkably constant over two orders of magnitude in size (10 km to 100 m), which is eight orders of magnitude in mass, though we note unaccounted bias effects enter into our statistics below about 500 m. Given the range of surface ages, including possible refreshment by planetary encounters, we are able to identify a very specific space weathering vector tracing the transition from Q- to Sq- to S-types that follows the natural dispersion for asteroid spectra mapped into principal component space. We also are able to interpret a shock darkening vector that may account for some objects having featureless spectra. Space weathering effects for C-types are complex; these results are described separately by Lantz, Binzel, DeMeo. (2018, Icarus 302, 10–17). Independent correlation of dynamical models with taxonomic classes map the escape zones for NEOs to main-belt regions consistent with well established heliocentric compositional gradients. We push beyond taxonomy to interpret our visible plus near-infrared spectra in terms of the olivine and pyroxene mineralogy consistent with the H, L, and LL classes of ordinary chondrites meteorites. Correlating meteorite interpretations with dynamical escape region models shows a preference for LL chondrites to arrive from the ν6 resonance and H chondrites to have a preferential signature from the mid-belt region (3:1 resonance). L chondrites show some preference toward the outer belt, but not at a significant level. We define a Space Weathering Parameter as a continuous variable and find evidence for step-wise changes in space weathering properties across different planet crossing zones in the inner solar system. Overall we hypothesize the relative roles of planetary encounters, YORP spin-up, and thermal cycling across the inner solar system.

Background:Eosinophilic fasciitis (EF) is a rare disease that causes inflammation and fibrosis mainly in the fascia of the extremities with eosinophilia. It has been reported that the hypertrophied fascia in EF shows inflammatory cell infiltration by the lymphocytes and eosinophils and increased expression of fibrosis-related cytokines genes in fibroblast [1]. However, its pathophysiology in the fascia remains unresolved.Objectives:Therefore, we focused on fascial fibroblasts and aimed to determine the role of interleukin-4 (IL-4) in eosinophil and helper T cell infiltration and fibrosis in fascial fibroblast in EF.Methods:Fascial fibroblasts were obtained from fascia biopsy of a patient with EF, and were stimulated with pre- and post-treatment serum of a patient with EF and healthy control, followed by microarray to analyze gene expression. Fascial fibroblasts were stimulated with IL-4 10 ng/mL, and gene expression of IL-4 receptor and CCR3 ligands, CCL7 and CCL11 were measured by qPCR. Transforming growth factor (TGF) -β and periostin in the pre- and post-treatment serum of a patient with EF and conditioned medium of fascial fibroblasts stimulated with IL-4 were measured by ELISA. To examine the role of IL-4 in proliferation, we performed in proliferation assays using fascial fibroblasts treated with IL-4. CCR3-positive T cells in the fascial tissue of EF, dermatomyositis, and polymyositis patients were evaluated by immunostaining.Results:By microarray analysis, CCL7 and CCL11 expression of fascial fibroblasts stimulated with pre-treatment EF serum was higher than that in post-treatment EF serum and control serum. CCL7 and CCL11 mRNA in IL-4 stimulated facial fibroblasts were increased by 5.1-fold and 7.3-fold, respectively. TGF-β and periostin in IL-4 stimulated facial fibroblast conditioned medium were also increased. In addition, TGF-β and periostin in EF serum were gradually decreased by treatment for 4 and 10 weeks, compared to before treatment. Finally, fascial fibroblast proliferation was significantly increased by stimulation with IL-4. Furthermore, infiltration of CCR3-positive T cells was specific to the fascial tissue of EF.Conclusion:In EF, IL-4 enhances the production of CCR3 ligands, TGF-β, and periostin from fascial fibroblasts. As a result, it promotes the migration of eosinophils and CCR3-positive T helper cells to the fascia and fibrosis. These results suggest that inhibition of IL-4 pathway could be a novel strategy for eosinophilic fasciitis.References:[1]Igarashi A, Nashiro K, Kikuchi K, et al. Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders. J Invest Dermatol. 1996 Apr;106(4):729-33.Disclosure of Interests:None declared

Background:Hepatocyte growth factor (HGF) binds to the receptor tyrosine kinase c-Met and is a multifunctional cytokine that promotes processes such as cell proliferation, survival, differentiation, migration and angiogenesis [1]. We previously reported that HGF is produced by inflammation in the RA synovium, and activates monocyte migration to the synovium and promotes bone destruction through its own chemotactic effect and enhanced chemokine production in the synovium [2].Objectives:Therefore, we next aimed to determine the role of HGF in RA angiogenesis.Methods:The expression of HGF / c-Met in the serum and synovial tissues (STs) of RA patients and controls and human umbilical vein endothelial cells (HUVECs) was evaluated by ELISA and immunostaining. The effect of HGF/c-Met signaling on the promotion of CXCL16 production from HUVECs and RA fibroblast-like synoviocytes (FLSs) was determined by ELISA. To examine the role of HGF in angiogenesis, we performed in vitro Matrigel assays using HUVECs treated with HGF.Results:HGF in serum in treatment-naive RA patients was significantly higher than that in controls and HGF in serum in treatment-resistant RA showed a significant positive correlation with CXCL16. c-Met were expressed on vascular endothelial cells of RA STs and HUVECs. Stimulation of HUVECs with HGF dose-dependently increased CXCL16 production. c-Met signal inhibition by SU11274 suppressed TNF-α stimulation-enhanced CXCL16 production by RA FLSs in a dose-dependent manner. Furthermore, HGF induced HUVEC tube formation by 1.8-fold.Conclusion:HGF is produced by inflammation in the RA synovium, and activates angiogenesis through its own potent angiogenic effect and enhanced production of CXCL16 in the synovium. These results indicate that a strategy targeting c-Met signalling may be important for resolving treatment-resistant RA.References:[1]Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440-3.[2]Hosonuma M, Sakai N, Furuya H, et al. Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis. Rheumatology (Oxford). 2021 Jan 5;60(1):408-419.Disclosure of Interests:None declared

Background:Hepatocyte growth factor (HGF), originally discovered as a mitogen of hepatocytes, binds to receptor-tyrosine kinase c-Met and has been shown to be a multi-functional cytokine that promotes processes such as cell proliferation, survival, differentiation, migration, and angiogenesis1. Since HGF/c-Met signaling also leads to tumorigenesis and cancer invasion, that has recently attracted attention as a target for anticancer agents2. However, in reports of rheumatoid arthritis (RA), though anti-inflammatory and antiangiogenic mechanisms related to HGF/c-Met signal inhibition have been reported, the role of HGF in RA bone destruction through monocyte migration remains unclear3.Objectives:To determine the expression of HGF in RA biological fluids, the role it plays in monocyte migration and the therapeutic effect of a savolitinib, a specific c-Met inhibitor, in arthritis model mice.Methods:HGF/c-Met expression in serum, synovial fluid (SF), and synovial tissues (STs) obtained from RA patients and control subjects, as well as RA fibroblast-like synoviocytes (FLSs) was evaluated by ELISA and immunostaining. To determine the function of HGF in RA SFs, we preincubated RA SFs with a neutralizing anti-HGF antibody and measured the ability of these SFs to induce the human acute monocytic leukemia cell line (THP-1) chemotaxis. Additionally, examinations of SKG mice treated with savolitinib (2.5 mg/kg/day) for 4 weeks were conducted.Results:HGF level in serum from RA patients was significantly higher as compared to the controls (930 ± 97 vs. 476 ± 97 pg/mL, p Conclusion:HGF is produced by inflammation in synovium associated with RA, and then activates monocyte migration to synovium tissue and promotes bone destruction through its own chemotactic effect as well as enhanced chemokine production. These results indicate that a strategy that targets c-Met signaling may be important for resolving bone destruction in RA.References:[1] Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, Tashiro K, Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440-3[2] Lee D, Sung ES, Ahn JH, An S, Huh J, You WK. Development of antibody-based c-Met inhibitors for targeted cancer therapy. Immunotargets Ther. 2015 Feb 9;4:35-44.[3] Koch AE, Halloran MM, Hosaka S, Shah MR, Haskell CJ, Baker SK, Panos RJ, Haines GK, Bennett GL, Pope RM, Ferrara N. Hepatocyte growth factor. A cytokine mediating endothelial migration in inflammatory arthritis. Arthritis Rheum. 1996 Sep;39(9):1566-75Disclosure of Interests:None declared

Coastal areas are subject to flood hazards because of their topographic features, social development and related human activities. The Kujukuri Plain, Chiba Prefecture, Japan, is located nearby the Tokyo metropolitan area and it faces to the Pacific Ocean. In the Kujukuri Plain, widespread occurrence of land subsidence has been caused by exploitation of groundwater, extraction of natural gas dissolved in brine, and natural consolidation of the Holocene and landfill deposits. The locations of land subsidence include areas near the coast, and it may increase the flood hazard potential. Hence, it is very important to evaluate flood hazard potential by taking into account the temporal change of land elevation caused by land subsidence, and to prepare hazard maps for protecting the surface environment and for developing an appropriate land-use plan. In this study, flood hazard assessments at three different times, i.e., 1970, 2004, and 2013 are implemented by using a flood hazard model based on Multicriteria Decision Analysis with Geographical Information System techniques. The model incorporates six factors: elevation, depression area, river system, ratio of impermeable area, detention ponds, and precipitation. Main data sources used are 10 m resolution topography data, airborne laser scanning data, leveling data, Landsat-TM data, two 1:30 000 scale river watershed maps, and precipitation data from observation stations around the study area and Radar data. The hazard assessment maps for each time are obtained by using an algorithm that combines factors with weighted linear combinations. The assignment of the weight/rank values and their analysis are realized by the application of the Analytic Hierarchy Process method. This study is a preliminary work to investigate flood hazards on the Kujukuri Plain. A flood model will be developed to simulate more detailed change of the flood hazard influenced by land subsidence.

Objective : Sex-specific medicine has attracted attention in recent years, but no report on rheumatoid arthritis (RA) has examined sex differences in the effectiveness of biologics on activities of daily living (ADL), quality of life (QOL), or depressive state. Methods : The study subjects were 161 RA patients (female: 138; male: 23) attending regular doctor visits at our hospital. We compared the changes in disease activity, which was evaluated using the simplified disease activity index (SDAI), ADL (using the modified health assessment questionnaire; mHAQ), QOL (using short form-36; SF-36), and the Hamilton Depression Rating Scale (HAM-D) for RA patients between each sex over a six-month observation period while administering biologic treatment. Results : The female patients reported significant improvements in the following metrics: SDAI: from 22.1 ± 11.9 to 8.9 ± 7.8 (p < 0.001); mHAQ: from 0.46 ± 0.50 to 0.32 ± 0.45 (p < 0.001); and HAM-D: from 6.2 ± 4.8 to 3.8 ± 4.1 (p < 0.001). Moreover, all eight items of the SF-36 were significantly improved (p < 0.01). In contrast, the male patients improved on the SDAI (from 27.9 ± 11.7 to 12.7 ± 8.6 (p < 0.001)), but we did not observe significant improvements in the mHAQ or HAM-D scores or in any items on the SF-36. Conclusion : Both male and female patients with RA improved when using a biological drug. Sex differences in the improvement of depressive state were observed.

We surveyed the Tharsis and Syrtis volcanic regions on Mars during 23 November 2011 to 13 May 2012 which corresponded to its mid Northern Spring and early Northern Summer seasons (Ls = 34–110°). Strong submillimeter rotational transitions of sulfur dioxide (SO2), sulfur monoxide (SO) and hydrogen sulfide (H2S) were targeted. No active release was detected, and we infer 2 σ upper limits across the disk of the planet of 1.1 ppb, 0.7 ppb and 1.3 ppb for SO2, SO and H2S, respectively. Our derived upper limit for SO2 is comparable to previously reported limits, whereas for H2S we set a more stringent upper limit than previously measured, and we establish a limit for SO. Among the targeted molecules, SO2 is the strongest indicator for volcanic outgassing. Assuming a photochemical lifetime of 2 years for SO2, our upper limit of 1.1 ppb implies an outgassing rate less than 55 metric tons/day. This rate limits the daily amount of degassing magma to less than 12,000 m 3 . Our sensitivity is sufficient to detect a volcanic release on Mars that is 4 % the SO2 released continuously from Kilauea volcano in Hawaii or 5 % that of the Masaya volcano in Nicaragua. The non-detection of the sulfur compounds in the atmosphere of Mars indicates the absence of major volcanic outgassing.

Mapping Mars' water history We know the water cycle on Earth is complex. Neither is it simple on Mars. Infrared maps of water isotopes made by Villanueva et al. show the distribution of H2O and "semiheavy" water (HDO: deuterated water containing a mixture of hydrogen isotopes) across Mars. HDO enrichment varies with time and location; for example, irregular isotopic signals associate with different terrain features. The measurements also allow seasonal sublimation levels of the northern ice cap to be estimated and thus could be used to reveal past climate behavior. Science, this issue p. 218 We measured maps of atmospheric water (H2O) and its deuterated form (HDO) across the martian globe, showing strong isotopic anomalies and a significant high deuterium/hydrogen (D/H) enrichment indicative of great water loss. The maps sample the evolution of sublimation from the north polar cap, revealing that the released water has a representative D/H value enriched by a factor of about 7 relative to Earth's ocean [Vienna standard mean ocean water (VSMOW)]. Certain basins and orographic depressions show even higher enrichment, whereas high-altitude regions show much lower values (1 to 3 VSMOW). Our atmospheric maps indicate that water ice in the polar reservoirs is enriched in deuterium to at least 8 VSMOW, which would mean that early Mars (4.5 billion years ago) had a global equivalent water layer at least 137 meters deep. Maps of atmospheric water distribution reveal seasonal and spatial variations in the enrichment of deuterium to hydrogen. Maps of atmospheric water distribution reveal seasonal and spatial variations in the enrichment of deuterium to hydrogen.

We report the results of new survey of star-forming regions in the outer Galaxy at Galactocentric radius of more than 13.5 kpc, where the environment is significantly different from that in the solar neighborhood.

Background A disintegrin and metalloproteinases (ADAMs) are a family of transmembrane and secreted proteins. ADAM-10 has been reported to be the enzyme responsible for the release of a number of chemokines and cytokine receptors. We have shown that ADAM-10 is overexpressed on rheumatoid arthritis (RA) synovial tissue endothelial cells (ECs) and lining cells compared with osteoarthritis and normal tissues. We also demonstrated that ADAM-10 mediates EC migration and tube formed. Objectives In order to demonstrate for ADAM-10 in clinical side, we focused on ADAM-10 as predictive factor for treatment with biologics in RA. Methods The serum was collected from patients before the initial treatment with biological therapies. Fifteen patients were treated with adalimumab (ADA), and 20 patents were treated with tocilizumab (TCZ). ADAM-10 and fractalkine/CX3CL1 were measured by enzyme-linked immunosorbent assay at 0, 12, 24 and 54 weeks. Clinical disease activity was evaluated by clinical disease activity index (CDAI). Following biological therapies, we defined biologic-responders as patients whose DAS28 scores decreased by more than 1.2 at 24 weeks. ADAM-10 baseline was also compared between responders and nonresponders at 24 weeks. Results There were no significant differences were observed in the mean age, gender ratio, dosages of predonisolone and methotraxate between ADA and TCZ groups. In ADA group, baseline DAS28 for the 15 patients was 4.8±0.3 (2.5–7.2). On the other hands, baseline DAS28 for the 20 patients was 4.8±0.3 (2.5–6.8) in TCZ group. There were no differences between ADA and TCZ groups. RA patients with an insufficient response to ADA or TCZ showed highly significant improvement of DAS28 after 12 weeks (2.9±0.3 and 2.2±0.4, respectively), and 24 weeks (2.5±0.4 to 2.2±0.2, respectively). ADAM-10 highly correlates with CDAI, and fractalkine/CX3CL1. Serum ADAM-10 levels were no remarkable change after treatment with ADA despite decrease of disease activity of RA. On the other hand, serum ADAM-10 levels in patients who were treated with TCZ were significantly diminished following successful treatment and clinical improvement (baseline 408±88 pg/ml and 54 weeks 138±51 pg/ml, p Conclusions This study indicates that ADAM-10 is correlated with RA disease activity, and is higher in TCZ responders. These results suggest that ADAM-10 may be a predictor of treatment effectiveness for RA with TCZ. Disclosure of Interest None declared

Background The simplified disease activity index (SDAI) 50 has good agreement with the EULAR response measures for early rheumatoid arthritis (RA). Although there are reports on early RA, there have been no reports on long-established RA. Objectives In this study, we analyzed the relationships between various baseline factors and SDAI 50 after six months of biological disease-modifying antirheumatic drugs (bDMARDs) treatment to determine the prognostic factors for long-established RA. Methods The subjects were 332 RA patients who had been treated with bDMARDs for 6 months. The following characteristics were investigated: age, gender, disease duration, smoking history, body mass index, steroid and methotrexate dosage, previous bDMARDs use, combined csDMARDs use, ESR, CRP, serum matrix metalloproteinase-3 levels, SDAI score, health assessment questionnaire disability index score (for daily living activities) and short form-36 score (for quality of life). As a primary outcome index, SDAI response was defined as a 50% reduction in SDAI score between baseline and 6 months (SDAI 50). Results The group of RA patients who achieved SDAI 50 (Group A: 204 patients) had a higher tender joint count (p=0.041), swollen joint count (p=0.001), evaluator9s global assessment (p=0.027) and SDAI (p=0.006) than did those who did not achieve SDAI 50 (Group B: 152 patients). Before the start of the treatment, steroid dosage (p=0.0187, odds ratio: 1.119, 95% CI: 1.029–1.229) and SDAI (p=0.0003, odds ratio: 0.953, 95% CI: 0.928–0.978) were determined based on logistic regression analysis. Comparisons were performed between Groups A and B and between before treatment and after 6 months of SDAI. Group A showed a significant improvement compared to Group B by repeated measure analysis of variance (ANOVA) (Interaction: p=0.000, Group A vs. Group B: p=0.000, before vs. after treatment: p=0.000). Conclusions Our study demonstrated that RA patients with a lower steroid dosage and higher SDAI baseline are more likely to achieve SDAI 50 with bDMARD treatment. Acknowledgements ASHURA Resistry Groups Disclosure of Interest Y. Miwa Grant/research support from: Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, AbbVie CK, Pfizer Japan Inc., Chugai Pharmaceutical Co., Ltd., Eizai Co., Ltd, Asahi Kasei Pharm Co., Ltd, YL biologics Ltd., Japan Blood Products Organization,. Ono Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd., A. Nishimi: None declared, S. Nishimi: None declared, T. Tokunaga: None declared, S. Ishii: None declared, T. Kasama Grant/research support from: Mitsubishi Tanabe Pharma Corporation and AbbVie CK.

Background A disintegrin and metalloprotesase (ADAM) family is protease that is thought to have an important role in tissue destruction and inflammatory reaction. ADAMs are also involved in the amputation from the cell surface of inflammatory cytokines. ADAM-17 is one of the ADAM family, and is first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. The implication of ADAM-17 substrates in immunoregulation has made this enzyme an efficient therapeutic target in the treatment of a number of pathological conditions including airway inflammation and arthritis. Objectives The function of ADAM-17 in myositis is unclear. Therefore, we clarify the expression of ADAM-17 in inflammatory myopathy and the role of inflammation in interstitial lung diseases (ILD). Methods The serum were collected from the patients who were diagnosed with inflammatory myopathy in Showa University Hospital from 2003 to 2015. Twenty-six patients were diagnosed with polymyositis (PM), 34 patients were diagnosed with dermatomyositis (DM), and 10 patients were diagnosed clinically amyopathic dermatomyositis (CADM). Clinical manifestations and clinical data were also collected. The levels of ADAM-17 in the serum samples were measured using enzyme-linked immunosorbent assay (ELISA). ADAM-17 expression was determined in muscle tissues from DM using immunohistological staining. To determine that the role of lung fibrosis in inflammatory myopathy with ILD, we used human lung fibroblasts (HLF). ADAM-17 expression on HLF was also demonstrated by immunohistrogical staining. ADAM-17 expression in interleukine (IL)-6 and IL-6 receptor (IL-6R) stimulated HLF was performed by ELISA. Results ADAM-17 in inflammatory myopathy was significantly higher than in healthy control (n=19) (mean ± SEM; 1048±312 pg/ml and 36±18 pg/ml, respectively, p Conclusions ADAM-17 is expressed in inflammatory myopathies especially with ILD and expressed on HLF, suggesting that ADAM-17 may play the role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD. Disclosure of Interest None declared

A 68-year-old Japanese male presented with atrophic erythematous white lesions with peripheral dark reddish rims on his back. Multiple ulcers were detected from his stomach to his large intestine using endoscopy. Although the patient was given high doses of a steroid, aspirin, dipyridamole, and intravenous immunoglobulin therapy, he died of gastrointestinal hemorrhage, perforation and septic shock. An autopsy examination revealed pauci-inflammatory thrombotic microangiopathy with endothelial cell injury, fibrous occlusive arteriopathy, and vascular C5b-9 deposition in the wall of the gastrointestinal tract from the esophagus to the large intestine as well as in the dermis of the skin.

Objective: The purpose of this study was to prospectively assess the steroid-sparing effect and safety of Tacrolimus (TAC) combination treatment during the maintenance phase of SLE. Methods: Thirty-eight patients were studied over a 1-year period from 2009 to 2012. If manifestations of mild active SLE, such as skin eruptions, arthritis, or asymptomatic nephritis, worsened and/or decreasing levels of serum complement (C3c) were observed, TAC combination treatment (from 1 mg to 5 mg once daily) was carried out. This was accomplished by adding TAC to the patient’s existing treatment regimen and decreasing in the usage of prednisolone (PSL). Scores on the SLE Disease Activity Index (SLEDAI), PSL dosage, and proteinuria, serum levels of C3c, anti-dsDNA levels were researched. Results: Twenty-eight patients received to TAC combination therapy. 1) The PSL dose was decreased from 11.7 ± 5.6 to 8.2 ± 4.2 mg/day (P

The original version of this article, unfortunately, contained errors. Figure citation, caption, image and updated sentence in the Result section are now presented correctly in this article.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

iSHELL is 1.10-5.3 μm high spectral resolution spectrograph being built for the NASA Infrared Telescope Facility on Maunakea, Hawaii. Dispersion is accomplished with a silicon immersion grating in order to keep the instrument small enough to be mounted at the Cassegrain focus of the telescope. The white pupil spectrograph produces resolving powers of up to R=75,000. Cross-dispersing gratings mounted in a tilt-able mechanism allow observers to select different wavelength ranges and, in combination with a slit wheel and Dekker mechanism, slit lengths ranging from 5ʺ″ to 25ʺ″. One Teledyne 2048x2048 Hawaii 2RG array is used in the spectrograph, and one Raytheon 512x512 Aladdin 2 array is used in a slit viewer for object acquisition and guiding. First light is expected in mid-2016. In this paper we discuss details of the construction, assembly and laboratory testing.

In order to investigate the Galactic-scale environmental effects on the evolution of protoplanetary disks, we explored the near-infrared (NIR) disk fraction of the Quartet cluster, which is a young cluster in the innermost Galactic disk at the Galactocentric radius Rg ~ 4 kpc. Because this cluster has a typical cluster mass of ~10^3 M_sun as opposed to very massive clusters, which have been observed in previous studies (>10^4 M_sun), we can avoid intra-cluster effects such as strong UV field from OB stars. Although the age of the Quartet is previously estimated to be 3-8 Myr old, we find that it is most likely ~3-4.5 Myr old. In moderately deep JHK images from the UKIDSS survey, we found eight HAeBe candidates in the cluster, and performed K-band medium-resolution ($R \equiv \Delta \lambda / \lambda ~ 800$) spectroscopy for three of them with the Subaru 8.2 m telescope. These are found to have both Br\gamma absorption lines as well as CO bandhead emission, suggesting that they are HAeBe stars with protoplanetary disks. We estimated the intermediate-mass disk fraction (IMDF) to be ~25 % for the cluster, suggesting slightly higher IMDF compared to those for young clusters in the solar neighborhood with similar cluster age, although such conclusion should await future spectroscopic study of all candidates of cluster members., Comment: 15 pages, 8 figures, and 2 Tables. Accepted for publication in the Astrophysical Journal

We report the multi-epoch detections of the water ice in 2.8-4.2 micron spectra of two Herbig Ae stars, PDS 144N (A2 IVe) and PDS 453 (F2 Ve), which have an edge-on circumstellar disk. The detected water ice absorption is found to originate from their protoplanetary disks. The spectra show a relatively shallow absorption of water ice around 3.1 micron for both objects. The optical depths of the water ice absorption are ~0.1 and ~0.2 for PDS 144N and PDS 453, respectively. Compared to the water ice previously detected in low-mass young stellar objects with an edge-on disk with a similar inclination angle, these optical depths are significantly lower. It suggests that stronger UV radiation from the central stars effectively decreases the water ice abundance around the Herbig Ae stars through photodesorption. The water ice absorption in PDS 453 shows a possible variation of the feature among the six observing epochs. This variation could be due to a change of absorption materials passing through our line-of-sight to the central star., Comment: 9 figures, 2 tables, Accepted for publication in The Astrophysical Journal

Objective: Rheumatoid arthritis (RA) patients have a greater depressive tendency than normal subjects, and infliximab is known to provide quick therapeutic effects and to have high bioavailability for RA. We therefore investigated whether the depressive state of RA patients would be improved by infliximab. Material and Methods: The Self-Rating Depression Scale (SDS) was used to evaluate 34 RA patients before and 14 or 30 weeks after inflixi mab treatment using the SDS and Disease Activity Score (DAS) 28. The SDS and DAS28 results before and after treatment were compared. Results: We also included 42 cases treated with methotrexate as the control group. The SDS decreased in both groups, and the intraindividual vari ability was p