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Yo Shimizu,1 Tsuyoshi Tsukada,2 Hiromi Sakata-Haga,2 Daisuke Sakai,3 Hiroki Shoji,3 Yutaka Saikawa,1 Toshihisa Hatta2 1Department of Pediatrics, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 2Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan; 3Department of Biology, Kanazawa Medical University, Uchinada, Ishikawa, JapanCorrespondence: Toshihisa HattaDepartment of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, JapanTel +81-76-281-8113Fax +81-76-218-8189Email thatta@kanazawa-med.ac.jpBackground: A number of childhood diseases have been identified, such as severe infection or autoinflammatory disease, in which immune overreaction against inflammation is a possible underlying mechanism. Previous reports have demonstrated that fetal cells exposed to maternal immune activation (MIA) induced by polyriboinosinic-polyribocytidylic acid [poly(I:C)] exhibited hypersensitivity to inflammation in vitro. However, the details of this mechanism remain unclear. Therefore, this study aimed to reveal the reaction to inflammation in offspring exposed to MIA in the prenatal period, as well as its molecular mechanism, using a viral infection mouse model.Materials and Methods: Pregnant mice at 12.5, 14.5, and 16.5 days post coitum were injected intraperitoneally with poly(I:C) 20 mg/kg body weight (BW) or saline. Offspring aged 3– 4 weeks received the second injection of 20 mg/kg BW or 4 mg/kg BW poly(I:C) or saline. Serum and tissues were collected at 2, 24, 48, and 72 h after the postnatal injection. The cytokine profile, histopathology of organs, and unfolded protein response (UPR) in offspring were examined.Results: The serum levels of interleukin (IL)-6, IL-17, and interferon-γ were significantly higher in the MIA group, and acute liver necrosis was detected. Moreover, failure in UPR was observed in the MIA group compared with that in the control group.Conclusion: Overall, MIA exposure in utero caused failure in UPR as well as immune overreaction to the second attack of inflammation in offspring. Our results suggested that prenatal exposure to MIA might contribute to the congenital inflammatory constitution after birth.Keywords: maternal immune activation, liver necrosis, immune overreaction, unfolded protein response defects

Reina Ozeki-Hayashi,1 Misao Fujita,2 Atsushi Tsuchiya,3 Taichi Hatta,2 Eisuke Nakazawa,1 Yoshiyuki Takimoto,1 Akira Akabayashi1,41Department of Biomedical Ethics, The University of Tokyo Faculty of Medicine, Tokyo, Japan; 2Uehiro Research Division for iPS Cell Ethics, Center for iPS Cell Research and Application Kyoto University, Kyoto, Japan; 3Industrial and Social Science, Tokushima University Graduate School of Technology, Tokushima, Japan; 4Division of Medical Ethics, Department of Population Health, New York University School of Medicine, New York, NY, USAIntroduction: Although guidelines do not recommend chemotherapy for patients with advanced cancer when death is imminent, many reports suggest the tendency to continue this treatment has been increasing every year. This study aimed to construct a model to clarify the beliefs and communication of doctors who administer chemotherapy to patients with recurrent or metastatic (hereafter, “recurrent/metastatic”) breast cancer, and determine how these beliefs are related to the process of treating patients.Materials and methods: Semi-structured interviews were conducted with 21 breast surgeons, and interview contents were analyzed using the grounded theory approach in order to conceptualize the treatment process.Results: The process of chemotherapy for patients with recurrent/metastatic breast cancer differed based on two beliefs held by doctors. One was a “belief that the patient is an entity who cannot accept death,” and throughout the treatment process, these doctors consistently avoided sharing bad news that might hurt patients, and always discussed aggressive chemotherapy. They proposed treatments as long as options remained, and when they ultimately judged that the physical condition of patients could not withstand further treatment, treatment was terminated despite the patient hoping for continuation. The other was a “belief that the patient is an entity who can accept death.” From early on after recurrence/metastasis, these doctors repeatedly gave patients information including bad news about prognosis, and when they judged that further treatment would hinder a patient’s ability to have a good death, they proposed terminating treatment.Conclusion: We demonstrated that breast surgeons treating recurrent/metastatic breast cancer patients have two beliefs and constructed a model of the treatment process based on those beliefs. This offered breast surgeons, who make decisions regarding treatment without clearly-defined guidelines, a chance to reflect on their own care style, which we believe will contribute to optimal patient care.Keywords: palliative chemotherapy, end-of-life, decision-making process, qualitative research

Examines kanji errors in handwriting of Japanese students and Australian learners of Japanese. Finds that Japanese students' phonologically-related kanji writing errors were most numerous, followed by orthographically-related errors and semantically-related errors; while Australian students wrote more non-existing kanji and made orthographically-related mistakes rather than semantically- and phonologically-related errors. Proposes suggestions for methods of teaching kanji writing. (SR)

Momentum distributions associated with ortho-positronium (o-Ps) pick-off annihilation photon are often influenced by light elements, as, e.g., carbon, oxygen, and fluorine. This phenomenon, so-called element specificity of o-Ps pick-off annihilation, has been utilized for studying the elemental environment around the open spaces. To gain an insight into the element specificity of o-Ps pick-off annihilation, the chemical shift of oxygen 1s binding energy and the momentum distributions associated with o-Ps pick-off annihilation were systematically investigated for alkali-metal loaded SiO2 glasses by means of X-ray photoelectron spectroscopy and positron-age-momentum correlation spectroscopy, respectively. Alkali metals introduced into the open spaces surrounded by oxygen atoms cause charge transfer from alkali metals to oxygen atoms, leading to the lower chemical shift for the oxygen 1s binding energy. The momentum distribution of o-Ps localized into the open spaces is found to be closely correlated with the oxygen 1s chemical shift. This correlation with the deepest 1s energy level evidences that the element specificity of o-Ps originates from pick-off annihilation with orbital electrons, i.e., dominantly with oxygen 2p valence electrons and s electrons with lower probability. [ABSTRACT FROM AUTHOR]