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Nao Enomoto,1 Sho Nakamura,2– 4 Satoru Kanda,3– 5 Hiroko Endo,1 Emiko Yamada,1 Sachiyo Kobayashi,1 Miki Kido,1 Rina Inoue,4 Junko Shimakura,6 Hiroto Narimatsu2– 4,7 1Section of Health and Longevity Service, Takahata Town Office, Takahata, Yamagata, Japan; 2Graduate School of Health of Innovation, Kanagawa University of Human Services, Kawasaki, Kanagawa, Japan; 3Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan; 4CIKOP, Specified Nonprofit Corporation, Yamagata, Japan; 5Department of Clinical Oncology, Yamagata University Faculty of Medicine, Yamagata, Japan; 6Section of Welfare and Child Service, Takahata Town Office, Takahata, Yamagata, Japan; 7Department of Genetic Medicine, Kanagawa Cancer Center, Yokohama, Kanagawa, JapanCorrespondence: Hiroto NarimatsuCancer Prevention and Cancer Control Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, JapanTel +81-45-520-2222Fax +81-45-520-2216Email hiroto-narimatsu@umin.orgPurpose: A tailored approach to individual risk factors for developing lifestyle-related diseases would help induce behavioral changes toward intervention acceptability. The addition of preventive healthcare programs to nationwide specific health guidance in Japan is adapted in a given region.Patients and Methods: We conducted a prospective parallel-group comparison study on 195 eligible residents from Takahata, Japan, with a high risk of lifestyle-related diseases from 2014 to 2017 to examine whether such an intervention could improve the body mass index (BMI) and estimated glomerular filtration rate (eGFR).Results: Of the 195 enrolled residents, 117 were assigned to the control group and 78 to the intervention group. They were ≤ 65 years old and had a BMI ≥ 25 kg/m2 and an eGFR ≤ 90 mL/kg/1.73 m2. We conducted certain interventions for each group, including additional blood testing, regular health guidance, and specific health guidance. After one year, neither BMI (intervention: 26.7 ± 2.17 kg/m2 vs control: 27.3 ± 2.12 kg/m2, p = 0.076) nor eGFR (intervention: 72.2 ± 11.1 mL/kg/1.73 m2 vs control: 73.1 ± 10.5 mL/kg/1.73 m2, p = 0.608) differed significantly between groups. However, after three years, the BMI in the intervention group (26.4 ± 2.05 kg/m2) was significantly reduced compared to that in the control group (27.4 ± 2.26 kg/m2; p = 0.005).Conclusion: The additional interventions might have contributed to a reduction in metabolic syndrome.Trial Registration: This study was registered in the UMIN-Clinical Trials Registry (ID:000013581). More information: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015868. The registration date was 31/03/2014.Keywords: personalized preventive medicine, body mass index, estimated glomerular filtration rate, medical cost

Rapid Asian economic development might engender secondary impacts of atmospheric aerosol particles over the western Pacific after conversion of gaseous pollutants such as SO2. To elucidate changes in aerosol concentrations in leeward areas undergoing remarkable industrialization, the number-size distributions of submicron (0.3- 1.0 μm) aerosols were measured at Murododaira (36.6°N, 137.6°E, 2450 ma.s.l.) on the western flank of Mount Tateyama in central Japan during January 1999-February 2009. Nighttime data obtained from 24:00 to 05:00 (local time) were used to analyze free-tropospheric aerosol concentration. Monthly average volume concentrations were calculated for months with >50% daily data coverage. Volume concentrations of submicron aerosols were high in spring to early summer and low in winter. Significant increasing trends at 5% level were found for volume concentrations during December-January and March-April. Simulated monthly SO2- 4 concentrations at Mt. Tateyama from results of regional aerosol modeling with SO2 emission inventory up to 2005 showed seasonal variation and winter-spring increasing trends similar to those of observed aerosol concentration. According to the model analyses, the contribution of Chinese SO2-4 concentration was high in winter-spring (ca. 80% of total SO2-4 at Mt. Tateyama). This accords with the increasing trend observed in winter-spring, suggesting that increasing SO2 emission in China engender enhancement of submicron aerosols over Japan, especially during winter-spring. [ABSTRACT FROM AUTHOR]

Human thymic stromal lymphopoietin (TSLP) promotes CD4+ T-cell proliferation both directly and indirectly through dendritic cell (DC) activation. Although human TSLP-activated DCs induce CD8+ T-cell proliferation, it is not clear whether TSLP acts directly on CD8+ T cells. In this study, we show that human CD8+ T cells activated by T-cell receptor stimulation expressed TSLP receptor (TSLPR), and that TSLP directly enhanced proliferation of activated CD8+ T cells. Although non-stimulated human CD8+ T cells from peripheral blood did not express TSLPR, CD8+ T cells activated by anti-CD3 plus anti-CD28 did express TSLPR. After T-cell receptor stimulation, TSLP directly enhanced the expansion of activated CD8+ T cells. Interestingly, using monocyte-derived DCs pulsed with a cytomegalovirus (CMV)-specific pp65 peptide, we found that although interleukin-2 allowed expansion of both CMV-specific and non-specific CD8+ T cells, TSLP induced expansion of only CMV-specific CD8+ T cells. These results suggest that human TSLP directly enhances expansion of CD8+ T cells and that the direct and indirect action of TSLP on expansion of target antigen-specific CD8+ T cells may be beneficial to adoptive cell transfer immunotherapy. [ABSTRACT FROM AUTHOR]

To evaluate the biological effect of ceramic fibres on the clearance function of alveolar macrophages (AMs) morphological changes and phagocytic activity of AMs were assessed. Rats were exposed to respirable ceramic fibres with a mass median aerodynamic diameter of 4.4 microns and a concentration of 20.1 mg/m3 in an exposure chamber. They were killed after one week (group A) and two weeks (group B) of exposure, and four weeks (group C) and 12 weeks (group D) after exposure for two weeks. The AMs recovered by bronchoalveolar lavage (BAL) from each test group were incubated with yeast and phagocytic activity was determined by counting the number of yeast cells in AMs. Morphological features of AMs were assessed by scanning electron microscopy and quantified according to morphological changes. Total cell counts in BAL fluid from exposed rats in group A were higher than in control rats. Phagocytic activity of exposed AMs in group B and C exceeded that of control AMs. Morphological changes of the exposed AMs in groups A, B, and C were greater than those of control AMs. These findings suggest that ceramic fibres induced the phagocytic activity and morphological changes in AMs, and that the clearance function of AMs was stimulated by the inhaled ceramic fibres. [ABSTRACT FROM AUTHOR]

Abstract Background The optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB) in intermediate-risk prostate cancer (PCa) patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT) with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS) provide no firm recommendations. Methods/Design Seed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment. The primary endpoint is biochemical progression-free survival (BPFS). Secondary endpoints are overall survival (OS), clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS]), quality of life (QOL) evaluation, and adverse events. In the correlative study (SHIP36B), we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy. Discussion These two multicenter trials (SHIP0804 & SHIP36B) are expected to provide crucial data regarding the efficacy, acceptability and safety of adjuvant ADT. SHIP36B will also provide important information about the prognostic implications of PSA levels in intermediate-risk PCa patients treated with 125I-TPPB. Trial registration NCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709

Abstract Background Physicians' mental health may be adversely affected by the number of days of work and time spent on-call, and improved by sleep and days-off. The aim of this study was to determine the associations of depressive symptoms with taking days of off duty, hours of sleep, and the number of days of on-call and overnight work among physicians working in Japanese hospitals. Methods A cross-sectional study as a national survey was conducted by mail. The study population was 10,000 randomly selected physicians working in hospitals who were also members of the Japan Medical Association (response rate 40.5%). Self-reported anonymous questionnaire was sent to assess the number of days off-duty, overnight work, and on-calls, and the average number of sleep hours on days not working overnight in the previous one month. Depressive state was determined by the Japanese version of the Quick Inventory of Depressive Symptomatology. Logistic regression analysis was used to explore the associations between depressive symptoms and the studied variables. Results Among the respondents, 8.3% of men and 10.5% of women were determined to be depressed. For both men and women, depressive state was associated with having no off-duty days and averaging less than 5 hours of sleep on days not doing overnight work. Depressive state was positively associated with being on-call more than 5 days per month for men, and more than 8 days per month for women, and was negatively associated with being off-duty more than 8 days per month for men. Conclusion Some physicians need some support to maintain their mental health. Physicians who do not take enough days-off, who reduced sleep hours, and who have certain number of days on-calls may develop depressive symptoms.

Abstract Background Alveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung. Calcitonin gene-related peptide (CGRP) has been reported to play an important role in the proliferation of various types of epithelial and endothelial cells. We investigated the effects of CGRP on the proliferation of alveolar epithelial cells in vitro and in vivo. Methods A549 cells were cultured in Dulbecco Modified Eagle Medium with 5% fatal bovin serum for 24 hours, then CGRP was added in vitro. The proliferation of DNA synthesis was measured using 5-bromo-2-deoxyuridine, an analog of thymidine, by enzyme-linked immunosorbent assay. As one intracellular response to CGRP, we examined activation of p44/42- extracellular signal-regulated kinase (ERK) pathway by adding CGRP, using western blotting method. Recombinant adenovirus encoding nuclear-targeted-human β-CGRP (rhCGRP) was administered into Male Wister rat (n = 5, 10 weeks old) lungs by intratracheal instillation in vivo. 7 days after the administration of CGRP, rat lungs were harvested and histological findings and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) were evaluated to examine cell proliferation. Results In vitro study, CGRP increased the proliferation of A549 cells in a dose and time dependent manner. CGRP8-37 (inhibitor of CGRP receptor) decreased CGRP induced proliferation of DNA synthesis. Phosphorylation of ERK pathway was observed within 15 minutes and peaked in one hour. U0126 (inhibitor of ERK pathway) decreased CGRP induced proliferation of DNA synthesis.In vivo study, histological examination of the lung indicated proliferation of alveolar epithelial cells in the rhCGRP-treated group and the nuclei of alveolar epithelial cells were positive for PCNA immunostaining. Conclusion In this study, we conclude that CGRP stimulates proliferation of human alveolar epithelial cells in vivo and in vitro.