Oseltamivir Prescription and Regulatory Actions Vis-à-Vis Abnormal Behavior Risk in Japan: Drug Utilization Study Using a Nationwide Pharmacy Database

BACKGROUND: In March 2007, a regulatory advisory was issued in Japan to restrict oseltamivir use in children aged 10-19 years because of safety concerns over abnormal behavior. The effectiveness and validity of regulatory risk minimization actions remain to be reviewed, despite their significant public health implications. To assess the impact of the regulatory actions on prescribing practices and safety reporting. METHODOLOY/PRINICPAL FINDINGS: In this retrospective review of a nationwide pharmacy database, we analyzed 100,344 dispensation records for oseltamivir and zanamivir for the period from November 2006 to March 2009. The time trend in dispensations for these antiviral agents was presented before and after the regulatory actions, contrasted with intensity of media coverage and the numbers of spontaneous adverse reaction reports with regard to antivirals. The 2007 regulatory actions, together with its intense media coverage, reduced oseltamivir dispensation in targeted patients in fiscal year 2008 to 20.4% of that in fiscal year 2006, although influenza activities were comparable between these fiscal years. In contrast, zanamivir dispensation increased approximately nine-fold across all age groups. The number of abnormal behavior reports associated with oseltamivir in children aged 10-19 years decreased from fiscal year 2006 to 2008 (24 to 9 cases); this decline was offset by the increased number of reports of abnormal behavior in children under age 10 (12 to 28 cases). The number of reports associated with zanamivir increased in proportion to increased dispensation of this drug (11 to 114 cases). CONCLUSIONS/SIGNIFICANCE: The 2007 actions effectively reduced oseltamivir prescriptions and the number of reports of abnormal behavior in the targeted group. The observed increase in abnormal behavior reports in oseltamivir patients under age 10 and in zanamivir patients suggests that these patient groups may also be at risk, calling into question the validity of the current discrimination by age and agent (Abstract translation is available in Japanese: Appendix S1)

Chemotherapy with low-dose capecitabine as palliative treatment in a patient with metastatic breast cancer: a case report

Chemotherapeutic agents are rarely used for symptom management in patients under palliative care setting. This is because chemotherapeutic agents not only have limited efficacy in palliative treatment but are also known to exert severe adverse effects. We describe our experience with a patient with metastatic breast cancer who was successfully treated with low-dose capecitabine, without the development of any severe toxicities and with significant improvement in activities of daily living (ADL) and quality of life (QOL)

Consumer Policy and Market Norms: Routes of socioeconomic development abstracted from literature concerning consumer fraud and product safety (Japanese)

In recent years, the evaluation of the public-private partnership (PPP) has been an important issue in discussions relating to public service reform. The increasing trend of an overwhelming number of public services being provided through the private sector lies in the government's traditional approach of outsourcing. Meanwhile, new methods of using the private sector such as the private finance initiative (PFI), the designated manager system, and market testing also draw attention, but it appears that the introduction of these methods into local governments is not always a smooth process. While an effort is being made to overcome the institutional restrictions and problems associated with the introduction of these initiatives, differing attitudes of local governments toward the promotion of PPPs seem to have a significant impact. This paper aims to analyze and evaluate PPPs from an empirical perspective, looking at the public services that the government outsourced to private companies in various forms and then deriving policy implications. This paper consists of the following four studies: I. Factors for promoting PPP in local governments (YAMAUCHI Naoto, ISHIDA Yu, OKUYAMA Naoko) II. Does government spending trigger private contributions? (MATSUNAGA Yoshiho, OKUYAMA Naoko) III. Evaluation of PPPs in home-visit nursing care services (SUZUKI Wataru, HOTTA Satoko) IV. Outsourcing of waste collection and factors for its promotion (IWATA Kenji)

Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV-2 and Exhibits Broad-Spectrum Antiviral Activity

There is a pressing need for host-directed therapeutics that elicit broad-spectrum antiviral activities to potentially address current and future viral pandemics. Apratoxin S4 (Apra S4) is a potent Sec61 inhibitor that prevents cotranslational translocation of secretory proteins into the endoplasmic reticulum (ER), leading to anticancer and antiangiogenic activity both in vitro and in vivo. Since Sec61 has been shown to be an essential host factor for viral proteostasis, we tested Apra S4 in cellular models of viral infection, including SARS-CoV-2, influenza A virus, and flaviviruses (Zika, West Nile, and Dengue virus). Apra S4 inhibited viral replication in a concentration-dependent manner and had high potency particularly against SARS-CoV-2 and influenza A virus, with subnanomolar activity in human cells. Characterization studies focused on SARS-CoV-2 revealed that Apra S4 impacted a post-entry stage of the viral life-cycle. Transmission electron microscopy revealed that Apra S4 blocked formation of stacked double-membrane vesicles, the sites of viral replication. Apra S4 reduced dsRNA formation and prevented viral protein production and trafficking of secretory proteins, especially the spike protein. Given the potent and broad-spectrum activity of Apra S4, further preclinical evaluation of Apra S4 and other Sec61 inhibitors as antivirals is warranted

Slitrk2 deficiency causes hyperactivity with altered vestibular function and serotonergic dysregulation

SLITRK2 encodes a transmembrane protein that modulates neurite outgrowth and synaptic activities and is implicated in bipolar disorder. Here, we addressed its physiological roles in mice. In the brain, the Slitrk2 protein was strongly detected in the hippocampus, vestibulocerebellum, and precerebellar nuclei—the vestibular-cerebellar-brainstem neural network including pontine gray and tegmental reticular nucleus. Slitrk2 knockout (KO) mice exhibited increased locomotor activity in novel environments, antidepressant-like behaviors, enhanced vestibular function, and increased plasticity at mossy fiber–CA3 synapses with reduced sensitivity to serotonin. A serotonin metabolite was increased in the hippocampus and amygdala, and serotonergic neurons in the raphe nuclei were decreased in Slitrk2 KO mice. When KO mice were treated with methylphenidate, lithium, or fluoxetine, the mood stabilizer lithium showed a genotype-dependent effect. Taken together, Slitrk2 deficiency causes aberrant neural network activity, synaptic integrity, vestibular function, and serotonergic function, providing molecular-neurophysiological insight into the brain dysregulation in bipolar disorders

Introduction for Fisheries and Aquatic Biology

Chapter I. Aquatic Environment. Ken FURUYA and Ichiro YASUDA : chapter_1.pdfChapter II. Biology and Ecology of Aqua-Shere. Toyoji KANEKO, Katsumi TSUKAMOTO, Atsushi TSUDA, Yuzuru SUZUKI and Katsufumi SATOH : chapter_2.pdfChapter III. Aquatic Resource and Production. Ichiro AOKI, Kazuo OGAWA, Taku YAMAKAWA and Tomoyoshi YOSHINAGA : chapter_3.pdfChapter IV. Chemistry of Aquatic Organism and Their Utilization. Hiroki ABE, Shugo WATABE, Yoshihiro OCHIAI, Shigeru OKADA, Naoko YOSHIKAWA, Yoshiharu KINOSHITA, Gen KANEKO and Shigeki MATSUNAGA : chapter_4.pdfChapter V. Relation between Aqua-Shere and Human Life. Hisashi KUROKURA, Hirohide MATSUSHIMA, Shingo KUROHAGI, Haruko YAMASHITA, Akinori HINO, Kazumasa IKUTA, Satoquo SEINO, Masahiko ARIJI, Ken FURUYA, Junichiro OKAMOTO and Nobuyuki YAGI : chapter_5.pdfPart of "Introduction for Fisheries and Aquatic Biology

試行カウンセリング実習の可能性と考慮点の実証的検討1-体験についての予備調査

The current study was conducted to demonstrate that trial counseling was an effective training method in graduate school clinical psychology courses. Here,the results of responses to a preliminary questionnaire by trainee counselors are reported.Usually,in courses to train clinical psychologists,role-playing is undertaken before taking practical cases,in which trainees play the role of client/therapist in a single session with students of the same school. In the present study,students were required to play the role of client/therapist successively in four sessions with students from other graduate school,so that they were meeting each other for the first time. Before and after the trial counseling session, students were asked to respond to yes-no questions and provide free descriptions on the substantial effects of the training. Results indicated self-awareness in students playing the role of the counselor and contented feelings about the psychological growth of the client. These results suggest that trial counseling is an important step in preparing for practical counseling. Results also indicated that to counsel students from another school was more similar to the real situation. Moreover, to observe the counseling experience from the viewpoint of a client in counseling was an important experience for the trainees