Relationships between the Use and Environment of an Unagi-nonedoko-like Green Space in Downtown Kyoto City

It is becoming necessary to consider the effective use of vacant lots that have developed due to the demolition of Kyo-machiya (traditional houses) in Kyoto. These long, narrow lots are called Unagi-no-nedoko (“beds of eel”). Their spatial characteristics might make them unsuitable as green spaces because there is the possibility of creating a dark, small, exclusive, and dangerous atmosphere. Thus, we investigated the influence of the environment of an Unagi–no-nedoko-like green space on user awareness and behavior. The results found that the inner area of the green space was as quiet as an indoor room and was recognized as a “relaxing” environment, which caused users to stay longer. Moreover, users found the whole area “large” and “open.” These findings demonstrate that the spatial characteristics of Unagi-no-nedoko do not necessarily make them uncomfortable as green spaces, and it is possible to use such lots as green spaces in downtown Kyoto

Beneficial effects of fingolimod in MS patients with high serum Sema4A levels.

We previously demonstrated that patients with multiple sclerosis (MS) of high serum Sema4A levels are resistant to IFN-β therapy. To further elucidate the role of serum Sema4A as a biomarker for therapeutic stratification in MS patients, it is important to clarify the efficacy of other disease-modifying drugs (DMD) in those with high serum Sema4A levels. Thus, in this study we investigated whether fingolimod has beneficial effects on MS patients with high Sema4A levels. We retrospectively analyzed annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change in 56 relapsing-remitting multiple sclerosis (RRMS) patients who had been treated with fingolimod, including those who switched from IFN-β therapy. The levels of Sema4A in the sera were measured by sandwich ELISA. The implications of Sema4A on the efficacy of fingolimod were investigated by administering recombinant Sema4A-Fc and fingolimod to mice with experimental autoimmune encephalomyelitis (EAE). Retrospective analysis of MS cohort (17 high Sema4A and 39 low Sema4A) demonstrated the effectiveness of fingolimod in those with high serum Sema4A levels, showing reduction of ARR (from 1.21 to 0.12) and EDSS progression (from 0.50 to 0.04). Consistent with this observation, improvement in the disease severity of EAE mice receiving recombinant Sema4A-Fc was also observed after fingolimod treatment. These data suggest that fingolimod could serve as a candidate DMD for managing the disease activity of MS patients with high Sema4A levels

Immunotherapy for ocular myasthenia gravis: an observational study in Japan

Background: Treatment for ocular myasthenia gravis (OMG) has not yet been well established. Few reports have been published on the clinical practice and outcomes of OMG. Objectives: We investigated treatment of OMG and its outcomes in Japan.We investigated treatment of OMG and its outcomes in Japan. Design: We performed a retrospective cross-sectional survey of OMG patients from eight hospitals in Japan. Methods: Clinical information, including sex, age at onset, initial symptoms, autoantibodies, clinical course, treatment history, complications, and outcomes, was obtained. In addition, we recorded the total number of patients with MG and OMG separately. Results: In total, 135 patients with OMG (67 men, 68 women) were included. Treatment of OMG was not simple and involved various immunotherapeutic strategies. Eight patients went into remission spontaneously without immunotherapy. A total of 117 patients showed improvements after treatment, whereas 10 patients showed refractory responses to treatment. Overall outcomes were good; however, symptoms persisted in 60.7% of patients even after treatment. Among 90 patients who received immunotherapy, only two showed a refractory response. Meanwhile, for 45 patients who did not receive immunotherapy, 8 were refractory. Thus, the rate of refractory disease in the group with immunotherapy was significantly lower ( p  = 0.001, u-test) than in the group without immunotherapy. The proportion of generalized MG patients among all MG cases was low in medical centers where immunotherapy for OMG was frequently performed. Conclusion: Although the overall prognosis for patients with OMG was good, symptoms remained in more than half of the patients. Immunotherapy, including corticosteroids, may be beneficial for patients with OMG. Plain language summary Is immunosuppressive therapy beneficial for myasthenia gravis patients with ocular symptoms only? Patients with ocular myasthenia gravis (OMG) have only eye symptoms for more than 2 years. Whether this condition is an initial stage of the disease before eventually progressing to generalized myasthenia gravis (gMG) is still uncertain. Different from gMG, OMG is not life-threatening. But eye symptoms often cause troublesome problems in life. Doctors have treated OMG patients similarly to patients with gMG. There is no standard clinical practice for OMG. In this study, we examined how patients with OMG were treated at eight different specialist centers in Japan. In 135 patients with OMG, 8 patients became symptom free without treatment, 117 patients showed improvements after treatment, whereas 10 patients did not get well. Overall outcomes were good, but symptoms remained in 60.7% of patients even after treatment. Among 90 patients who received one or more immunotherapies, only 2 did not get well. Meanwhile, for 45 patients who did not receive immunotherapy, 8 remained ill. We found that treatment of OMG was not simple and often needed multiple immunotherapies. Administering immunotherapy, including corticosteroids, may be beneficial for patients with OMG

Fingolimod is effective in IFN-β non-responder patients with high Sema4A.

<p>Relapses (A) and EDSS (B) of all the patients with high Sema4A in Osaka University Hospital who changed from IFN-β to fingolimod treatment are shown. (The orange and blue lines represent duration of treatment with fingolimod and IFN-β, respectively.) During IFN-β treatment, the patients had many relapses and disease progressed. However, fingolimod tended to be effective in reducing the relapse rate (1.36 ± 0.80 (IFN-β) to 0.27 ± 0.25 (FTY), p = 0.054; Mann-Whitney U test) and in preventing further increase in EDSS in all patients (0.45 ± 0.37 (annual EDSS change, IFN-β) to 0.0 ± 0.0 (annual EDSS change, FTY), p = 0.046; Mann-Whitney U test). The Sema4A levels (U/ml) of each patient are as follows: Pt.1; 24098, Pt.2; 3500, Pt.3; 3915, Pt.4; 6484, Pt.5; 21186, indicated within the parenthesis.</p

Effect of fingolimod on the levels of Sema4A and number of lymphocytes.

<p>(A) The levels of Sema4A are not affected by fingolimod. The serum Sema4A levels were measured before and 3 months after fingolimod therapy. Fingolimod therapy did not affect the Sema4A levels (p = 0.675, Welch’s t test). (B) The Sema4A levels did not affect lymphopenia under fingolimod treatment. The cell counts of lymphocytes were measured before and 3 months after fingolimod therapy. Fingolimod-induced lymphopenia were observed in both patients with high Sema4A levels and those with low Sema4A levels. Data represent the mean ± SD. *p ≤ 0.05.</p

Fingolimod is effective for mice with EAE given Sema4A-Fc.

<p>(A), (B) The mean clinical scores of mice with EAE are shown. Immunized mice were treated with PBS + human IgG (Control; filled squares, n = 10), PBS + Sema4A-Fc (Sema4A; filled triangles, n = 8), IFN-β + human IgG (IFN; filled diamonds, n = 7 in (A), 8 in (B)), IFN-β + Sema4A-Fc (IFN + Sema4A; open circles, n = 7), Fingolimod + human IgG (FTY720; open squares, n = 8) or Fingolimod + Sema4A-Fc (FTY720 + Sema4A; open triangles, n = 8). Fingolimod is effective in mice with EAE given Sema4A-Fc. Administration method of fingolimod was intraperitoneal (i.p.) in (A) and oral (p.o.) in (B, C). Data represent the mean score ± SEM of two independent experiments. *p ≤ 0.05 for Fingolimod versus Control; ¶p ≤ 0.05 for IFN versus Control.; §p ≤ 0.05 for IFN+ Sema4A versus IFN. (C) The ratio of peripheral blood lymphocytes of mice with EAE at day 22 after immunization. *p ≤ 0.05.</p

Clinical characteristics of subjects in fingolimod cohort.

<p>Clinical characteristics of subjects in fingolimod cohort.</p