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  1. Arima Y, Matsui T
    PMID: 23908882 DOI: 10.5365/WPSAR.2011.2.2.005
    Dengue is an emerging vectorborne infectious disease that is a major public health concern in the Asia Pacific region. Official dengue surveillance data for 2010 provided by ministries of health were summarized as part of routine activities of the World Health Organization Regional Office for the Western Pacific. Based on reported data, dengue has continued to show an increasing trend in the Western Pacific Region. In 2010, countries and areas reported a total of 353 907 dengue cases, of which 1073 died, for a case fatality ratio of 0.30%. More than 1000 cases were reported each from Australia (North Queensland), Cambodia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore and Viet Nam. With the exception of Australia, the number of reported cases in 2010 was greater than that reported in 2009 for these countries. The elevated number of cases reported in 2010 in some countries, such as the Philippines, is likely due to several factors, such as enhanced reporting and continued epidemic activity. However, increases in reported number of cases in other areas, such as Singapore and Malaysia, appear to indicate sustained epidemic activity in those countries. The continued epidemic dengue activity in the Region highlights the need for timely and routine regional sharing of information.
  2. Arima Y, Edelstein ZR, Han HK, Matsui T
    Western Pac Surveill Response J, 2013 May 14;4(2):47-54.
    PMID: 24015372 DOI: 10.5365/WPSAR.2012.3.4.019
    Dengue is an emerging vectorborne infectious disease that is a major public health concern in the Asia and the Pacific. Official dengue surveillance data for 2011 provided by ministries of health were summarized as part of routine activities of the World Health Organization Regional Office for the Western Pacific. Based on officially reported surveillance data, dengue continued to show sustained activity in the Western Pacific Region. In 2011, Member States reported a total of 244,855 cases of which 839 died for a case fatality rate of 0.34%. More than 1000 cases were reported each from Cambodia, the Federated States of Micronesia, the Lao People's Democratic Republic, Malaysia, the Philippines, the Marshall Islands, Singapore and Viet Nam. Cambodia, the Federated States of Micronesia and the Marshall Islands reported higher activity relative to 2010. There continues to be great variability among the dengue-endemic countries and areas in the Region in the number of cases and serotype distribution. The continued high notification rate and complex dengue epidemiology in the Region highlight the need for information-sharing on a routine and timely basis.
  3. Nuriliani A, Nakahata Y, Ahmed R, Khaidizar FD, Matsui T, Bessho Y
    Genes Cells, 2020 Aug;25(8):593-602.
    PMID: 32533606 DOI: 10.1111/gtc.12794
    A main feature of aged organisms is the accumulation of senescent cells. Accumulated senescent cells, especially stress-induced premature senescent cells, in aged organisms lead to the decline of the regenerative potential and function of tissues. We recently reported that the over-expression of NAMPT, which is the rate-limiting enzyme in mammalian NAD+ salvage pathway, delays replicative senescence in vitro. However, whether Nampt-overexpressing cells are tolerant of stress-induced premature senescence remains unknown. Here, we show that primary mouse embryonic fibroblasts derived from Nampt-overexpressing transgenic mice (Nampt Tg-MEF cells) possess resistance against stress-induced premature senescence in vitro. We found that higher oxidative or endoplasmic reticulum (ER) stress is required to induce premature senescence in Nampt Tg-MEF cells compared to wild-type cells. Moreover, we found that Nampt Tg-MEF cells show acute expression of unfolded protein response (UPR)-related genes, which in turn would have helped to restore proteostasis and avoid cellular senescence. Our results demonstrate that NAMPT/NAD+ axis functions to protect cells not only from replicative senescence, but also from stress-induced premature senescence in vitro. We anticipate that in vivo activation of NAMPT activity or increment of NAD+ would protect tissues from the accumulation of premature senescent cells, thereby maintaining healthy aging.
  4. Iwata N, Ishigooka J, Kim WH, Yoon BH, Lin SK, Sulaiman AH, et al.
    Schizophr Res, 2020 01;215:408-415.
    PMID: 31471246 DOI: 10.1016/j.schres.2019.07.055
    BACKGROUND: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia.

    METHODS: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs).

    RESULTS: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p 

  5. Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, et al.
    Blood, 2018 06 07;131(23):2552-2567.
    PMID: 29685921 DOI: 10.1182/blood-2017-07-794529
    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
  6. Togami E, Chiew M, Lowbridge C, Biaukula V, Bell L, Yajima A, et al.
    PMID: 37064541 DOI: 10.5365/wpsar.2023.14.1.973
    The global burden of dengue, an emerging and re-emerging mosquito-borne disease, increased during the 20-year period ending in 2019, with approximately 70% of cases estimated to have been in Asia. This report describes the epidemiology of dengue in the World Health Organization's Western Pacific Region during 2013-2019 using regional surveillance data reported from indicator-based surveillance systems from countries and areas in the Region, supplemented by publicly available dengue outbreak situation reports. The total reported annual number of dengue cases in the Region increased from 430 023 in 2013 to 1 050 285 in 2019, surpassing 1 million cases for the first time in 2019. The reported case-fatality ratio ranged from 0.19% (724/376 972 in 2014 and 2030/1 050 285 in 2019) to 0.30% (1380/458 843 in 2016). The introduction or reintroduction of serotypes to specific areas caused several outbreaks and rare occurrences of local transmission in places where dengue was not previously reported. This report reinforces the increased importance of dengue surveillance systems in monitoring dengue across the Region.
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