Prevalence and predictive factors of difficult-to-treat rheumatoid arthritis: the KURAMA cohort

Difficult-to-treat rheumatoid arthritis (D2T RA) is a multifactorial condition in which disease activity of RA persists despite consecutive treatment with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). To evaluate the prevalence and predictive risk factors of D2T RA in our institution, a single-center, retrospective study was conducted. Medical records of RA patients, who visited our hospital from 2011 to 2020 and had a follow-up of more than 6 months, were retrospectively reviewed. D2T RA was defined as RA with a disease activity score of 28 - erythrocyte sedimentation rate (DAS28-ESR) of 3.2 or higher at the last visit, despite the use of at least two b/tsDMARDs. A logistic regression model was used to identify risk factors. A total of 672 patients were enrolled. The mean age at disease onset was 52.1 years and females were dominant (76.3%). After a mean follow-up of 46.6 months, patients with D2T RA accounted for 7.9% of overall patients. Multivariate analysis identified high rheumatoid factor (RF) levels (≥156.4 IU/mL, odds ratio [OR]: 1.95), DAS28-ESR (OR: 1.24), and coexisting pulmonary disease (OR: 2.03) as predictive risk factors of D2T RA. In conclusion, high RF levels, high DAS28-ESR, and coexisting pulmonary disease at baseline can predict the development of D2T RA

Excellent electrical properties of TiO2/HfSiO/SiO2 layered higher-k gate dielectrics with sub-1 nm equivalent oxide thickness

Equivalent oxide thickness (EOT) scaling, as well as improved interface properties, of metal/higher- k gate stacks for the sub- 1 nm region was achieved using a TiO_2/HfSiO/SiO_2 layered dielectric structure. Ti diffusion into the bottom oxides was found to form electrical defects, which lead to an increase of leakage current, fixed charge, interface trap density (Dit), and reliability degradation of the gate stacks. By controlling Ti diffusion and terminating Ti-induced defects using forming gas annealing, we successfully obtained a superior interface property (Dit =9.9× 10^{10} eV^{-1} cm^{-2}) and reduced gate leakage (Jg =7.2× 10^{-2} A/cm^2) at the 0.71-nm -EOT region.Hiroaki Arimura, Naomu Kitano, Yuichi Naitou, Yudai Oku, Takashi Minami, Motomu Kosuda, Takuji Hosoi, Takayoshi Shimura and Heiji Watanabe, "Excellent electrical properties TiO_2/HfSiO/SiO_2 of higher-k gate dielectrics with sub-1nm equivalent oxide thickness", Appl. Phys. Lett. 92, 212902 (2008) https://doi.org/10.1063/1.292968

Urinary sodium-to-potassium ratio associates with hypertension and current disease activity in patients with rheumatoid arthritis: a cross-sectional study

BACKGROUND: Excessive salt intake is thought to exacerbate both development of hypertension and autoimmune diseases in animal models, but the clinical impact of excessive salt in rheumatoid arthritis (RA) patients is still unknown. We performed a cross-sectional study to clarify the associations between salt load index (urinary sodium-to-potassium ratio (Na/K ratio)), current disease activity, and hypertension in an RA population. METHODS: Three hundred thirty-six participants from our cohort database (KURAMA) were enrolled. We used the spot urine Na/K ratio as a simplified index of salt loading and used the 28-Joint RA Disease Activity Score (DAS28-ESR) as an indicator of current RA disease activity. Using these indicators, we evaluated statistical associations between urinary Na/K ratio, DAS28-ESR, and prevalence of hypertension. RESULTS: Urinary Na/K ratio was positively associated with measured systolic and diastolic blood pressure and also with prevalence of hypertension even after covariate adjustment (OR 1.34, p <  0.001). In addition, increased urinary Na/K ratio was significantly and positively correlated with DAS28-ESR in multiple regression analysis (estimate 0.12, p <  0.001), as was also the case in gender-separated and prednisolone-separated sub-analyses. CONCLUSION: Urinary Na/K ratio was independently associated with current disease activity as well as with prevalence of hypertension in RA patients. Thus, dietary modifications such as salt restriction and potassium supplementation should be investigated as a potential candidate for attenuating both disease activity and hypertension in RA patients

Potential application of measuring serum infliximab levels in rheumatoid arthritis management: A retrospective study based on KURAMA cohort data

Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or the efficacy of the treatment diminishes over time. Although previous studies have reported a relationship between serum IFX levels and therapeutic efficacy, the potential applications of IFX therapeutic drug monitoring (TDM) in clinical practice remain unclear. The purpose of this study was to investigate the potential applications of IFX TDM by analyzing a Japanese cohort database. Data were collected retrospectively from the Kyoto University Rheumatoid Arthritis Management Alliance cohort between January 1, 2011, and December 31, 2018. Serum IFX levels were measured using a liquid chromatography-tandem mass spectrometer. Out of the 311 RA patients that used IFX, 41 were eligible for the analysis. Serum IFX levels were significantly higher in responders than in non-responders. An optimal cut-off value was determined to be 0.32 μg/mL based on a receiver operating characteristic curve. At the IFX measurement point, a better therapeutic response was observed in the high IFX group (n = 32) than in the low IFX group (n = 9). Conversely, at the maximum effect point, when DAS28-ESR was the lowest between IFX introduction and measurement points, there were no differences in responder proportions between the low and high IFX groups. IFX primary ineffectiveness could be avoided with appropriate dose escalation without blood concentration measurement in clinical practice. In conclusion, IFX TDM could facilitate the identification of secondary non-responders and in turn, proper IFX use

Involvement of integrin-linked kinase in capillary/tube-like network formation of human vascular endothelial cells

Angiogenesis is a complex process involving an ECM and vascular endothelial cells (EC), and is regulated by various angiogenic factors including VEGF. The ability to form a capillary/tube-like network is a specialized function of EC. Therefore, in vitro angiogenesis was assessed by a capillary/tube-like network formation assay. There are three angiogenic parameters: capillary length, number of capillaries, and relative capillary area per field. We evaluated capillary length per field in the assay. VEGF promoted capillary/tube-like network formation of EC in a type I collagen gel matrix in vitro. Moreover, we demonstrated the involvement of ILK in a VEGF signaling pathway mediating capillary/tube-like network formation of EC using dominant-negative, kinase deficient ILK. This is a straightforward assay to monitor responses of human vascular endothelial cells

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention

Simulating the carbon balance of a temperate larch forest under various meteorological conditions

<p>Abstract</p> <p>Background</p> <p>Changes in the timing of phenological events may cause the annual carbon budget of deciduous forests to change. Therefore, one should take such events into account when evaluating the effects of global warming on deciduous forests. In this article, we report on the results of numerical experiments done with a model that includes a phenological module simulating the timing of bud burst and other phenological events and estimating maximum leaf area index.</p> <p>Results</p> <p>This study suggests that the negative effects of warming on tree productivity (net primary production) outweigh the positive effects of a prolonged growing season. An increase in air temperature by 3°C (5°C) reduces cumulative net primary production by 21.3% (34.2%). Similarly, cumulative net ecosystem production (the difference between cumulative net primary production and heterotrophic respiration) decreases by 43.5% (64.5%) when temperatures are increased by 3°C (5°C). However, the positive effects of CO₂enrichment (2 × CO₂) outweigh the negative effects of warming (<5°C).</p> <p>Conclusion</p> <p>Although the model was calibrated and validated for a specific forest ecosystem, the implications of the study may be extrapolated to deciduous forests in cool-temperate zones. These forests share common features, and it can be conjectured that carbon stocks would increase in such forests in the face of doubled CO₂and increased temperatures as long as the increase in temperature does not exceed 5°C.</p

Research Activities in the Department of Nursing

Research activity at the Department of Nursing is overviewed from the point of research topics, the theme of the projects admitted for grant from the Ministry of Education and Science of Japan, and expected research topics, trying to clarify the needs and challenges of the Department from multilateral aspects in future research activities. The Department of Nursing, Aino University is currently divided into the five areas and further into 12 fields. On the other hand, according to the Scientific Research Grant Program (2015 fiscal year), the research topics in nursing science is subdivided into the five areas; a) basic nursing, b) clinical nursing, c) lifelong developmental nursing, d) elderly nursing, and e) community health nursing

Eosinophilic Granulomatosis with Polyangiitis: Latest Findings and Updated Treatment Recommendations

Eosinophilic granulomatosis with polyangiitis (EGPA) causes necrotizing vasculitis and eosinophil-rich granulomatous inflammation in small- to medium-sized vessels, resulting in multiple organ damage. EGPA is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, with myeloperoxidase-ANCA detected in approximately one-third of the patients. Conventional treatment of EGPA relies on systemic glucocorticoids (GCs) in combination with cyclophosphamide when poor prognostic factors are present; however, the dilemma between disease control and drug-related adverse effects has long been a challenge. Recent studies have revealed that the genetic background, pathophysiology, and clinical manifestations differ between ANCA-positive and ANCA-negative patients; however, mepolizumab, an interleukin (IL)-5 inhibitor, is effective in both groups, suggesting that the IL-5-eosinophil axis is deeply involved in the pathogenesis of both ANCA-positive and ANCA-negative EGPA. This review summarizes the latest knowledge on the pathophysiology of EGPA and focuses on the roles of eosinophils and ANCA. We then introduce the current treatment recommendations and accumulated evidence for mepolizumab on EGPA. Based on current unmet clinical needs, we discuss potential future therapeutic strategies for EGPA