Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

AbstractLaninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20mg of laninamivir octanoate once daily for 2 days (LO-2), 20mg of laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group (P<0.001 for each of the laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0 % [95 % confidence interval (CI) 62.7–85.8] and 78.1 % (95 % CI 64.1–86.7 %) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20mg of laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts

Visualizing Relief Funds Flow for the Great East Japan Earthquake: Trial Study to Construct an Inflow and Outflow Matrix Model

The Great East Japan Earthquake in 2011 caused unprecedented damage. During this time, several nonprofit organizations conducted voluntary emergency support activities in damaged areas. Although there was a magnificent giving, donations to nonprofit organizations’ disaster relief funds still seemed to be low. As streams of donations are very complex, people cannot acquire enough information about their donations’ use by nonprofit organizations. Moreover, a primary method for grasping the framework or streams of donations has not yet been clearly determined. To examine these problems, we aim to aggregate the flow of disaster relief funds by constructing a matrix model of the inflows and outflows of relief funds at various disaster support organizations. Throughout this process, we discuss statistical methods for accounting for the various relief fund streams. Using this matrix model, we found that donations given by people amounted to over 675 billion yen (8.4 billion U.S. dollars), and each had a different stream leading to final use.This paper is partially supported by JSPS KAKENHI Grant Number JP 15J02955 (Takako Nakajima) and 15K11981 (Yu Ishida).This paper was originally published in Japanese as Nakajima and Baba (2015), Trial study to aggregate the relief funds flow for the Great East Japan Earthquake: Matrix of relief funds inflow and outflow [Higashinihondaishinsai ni okeru enjyoshikin furoh hosoku no kokoromi: infuroh to autofuroh ni kansuru enjyoshikin matorikkusu], in Planning and Public Management, vol.38, no.4, pp.39–49.This revised paper in English is permitted by Japan Association for Planning and Public Management

The Molecular Mechanism Underlying Continuous Exercise Training-Induced Adaptive Changes of Lipolysis in White Adipose Cells

Physical exercise accelerates the mobilization of free fatty acids from white adipocytes to provide fuel for energy. This happens in several tissues and helps to regulate a whole-body state of metabolism. Under these conditions, the hydrolysis of triacylglycerol (TG) that is found in white adipocytes is known to be augmented via the activation of these lipolytic events, which is referred to as the “lipolytic cascade.” Indeed, evidence has shown that the lipolytic responses in white adipocytes are upregulated by continuous exercise training (ET) through the adaptive changes in molecules that constitute the lipolytic cascade. During the past few decades, many lipolysis-related molecules have been identified. Of note, the discovery of a new lipase, known as adipose triglyceride lipase, has redefined the existing concepts of the hormone-sensitive lipase-dependent hydrolysis of TG in white adipocytes. This review outlines the alterations in the lipolytic molecules of white adipocytes that result from ET, which includes the molecular regulation of TG lipases through the lipolytic cascade

Effects of CEACAM1 in oral keratinocytes on HO-1 expression induced by Candida β-glucan particles

Objective: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the carcinoembryonic antigen family. Although its expression has been found in chronic oral inflammatory epithelium, this study aimed to know whether CEACAM1 in oral keratinocytes participates in host immune response against Candida albicans . Methodology: We investigated CEACAM1 expression in oral keratinocytes induced by C. albicans as well as by Candida cell wall component β-glucan particles (β-GPs). Furthermore, the effects of CEACAM1 on β-GPs-induced heme oxygenase-1 (HO-1) expression and its related signals were examined. Results: Fluorescence staining showed CEACAM1 expression in oral keratinocytes (RT7) cells, whereas quantitative reverse transcription (RT)-PCR indicated that both live and heat-killed C. albicans increased CEACAM1 mRNA expression in RT7 cells. Examinations using quantitative RT-PCR and western blotting indicated that CEACAM1 expression was also increased by β-GPs derived from C. albicans . Specific siRNA for CEACAM1 decreased HO-1 expression induced by β-GPs from C. albicans as well as the budding yeast microorganism Saccharomyces cerevisiae . Moreover, knockdown of CEACAM1 decreased β-GPs-induced ROS activity in the early phase and translocation of Nrf2 into the nucleus. Conclusion: CEACAM1 in oral keratinocytes may have a critical role in regulation of HO-1 for host immune defense during Candida infection

The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue

Obesity is recognized as a risk factor for lifestyle-related diseases such as type 2 diabetes and cardiovascular disease. White adipose tissue (WAT) is not only a static storage site for energy; it is also a dynamic tissue that is actively involved in metabolic reactions and produces humoral factors, such as leptin and adiponectin, which are collectively referred to as adipokines. Additionally, because there is much evidence that obesity-induced inflammatory changes in WAT, which is caused by dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein 1, contribute to the development of insulin resistance, WAT has attracted special attention as an organ that causes diabetes and other lifestyle-related diseases. Exercise training (TR) not only leads to a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the inflammation-related adipokines in WAT. Therefore, TR is widely used as a tool for preventing and improving lifestyle-related diseases. This review outlines the impact of TR on the expression and secretory response of adipokines in WAT

An Examination into Measurement for Changes of Gender Cognition

publisher奈良本稿では、近年におけるわが国のジェンダー認知の変容について、心理学的にこの認知的変容の事実をより的確に測ること、さらには、変容の事実が確認された場合、その変容を規定する要因や条件を明らかにするためにはどうすべきかを、測定方法の問題を中心に検討した。具体的には、以下の4点について考察した。まず第1に、わが国において近年、「性別役割分業観」や「男らしさ・女らしさ」のステレタイプなどに代表される伝統的な性別意識あるいはジェンダー規範への準拠意識から、これらを否定する平等主義的な態度やジェンダー・フリーな価値観へと人々の認知が変化してきている傾向を最近の心理学的研究知見から示唆した。第2に、こうした変化をより的確に測定するために吟味すべき心理学上の研究方法の問題点を指摘した。第3に、ジェンダー認知の変容を規定する要因や変数としてどのような概念や指標が有効かを、ジェンダー規範や社会制度・システムと、人間の生物学的・生殖的性との関係から考察した。第4点目に、現在、心理学でよく利用されている尺度として「両性性尺度」と「平等主義尺度」を取り上げ、それらの妥当性と有用性を、上記3点の考察を受けて検討した

DIDS, a chemical compound that inhibits RAD51-mediated homologous pairing and strand exchange

RAD51, an essential eukaryotic DNA recombinase, promotes homologous pairing and strand exchange during homologous recombination and the recombinational repair of double strand breaks. Mutations that up- or down-regulate RAD51 gene expression have been identified in several tumors, suggesting that inappropriate expression of the RAD51 activity may cause tumorigenesis. To identify chemical compounds that affect the RAD51 activity, in the present study, we performed the RAD51-mediated strand exchange assay in the presence of 185 chemical compounds. We found that 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) efficiently inhibited the RAD51-mediated strand exchange. DIDS also inhibited the RAD51-mediated homologous pairing in the absence of RPA. A surface plasmon resonance analysis revealed that DIDS directly binds to RAD51. A gel mobility shift assay showed that DIDS significantly inhibited the DNA-binding activity of RAD51. Therefore, DIDS may bind near the DNA binding site(s) of RAD51 and compete with DNA for RAD51 binding

Current Status and Future Potential of Robotic Surgery for Gastrointestinal Cancer

　Robotic surgery has built on innovations in areas such as medical engineering and optical technology. Laparoscopic surgery has been successfully adapted for gastric, colon, and rectal cancer surgeries over the past two decades with numerous clinical trials showing oncological results comparable to those of open surgery. These trials have also shown that the laparoscopic approach shortens postoperative recovery time and decreases complication rates. Another advantage of minimally invasive techniques for the resection of gastric, colon, and rectal cancers is improved visualization of the surgical field. Despite the near absence of tactile feedback, robotic surgery has overcome many of the challenges inherent in laparoscopic surgery through features such as 3D vision, stable magnification, EndoWrist instruments, physiological tremor filtering, and motion scaling. Robotic surgery is not yet widely used in esophageal cancer surgery or in a pancreaticoduodenectomy for pancreatic cancer due to anatomical difficulties and the lack of a suitable approach.　Comparative studies of robotic and laparoscopic surgery have shown similar results in terms of perioperative management, oncologic evaluation, and functional outcomes. However, it is also true that the high cost and lack of tactile feedback in robotic surgery are major limitations in terms of current robotic technology becoming the worldwide standard for minimally invasive surgery. The future of robotic surgery will require cost reduction, the development of new platforms and technologies, the creation and validation of curricula and virtual simulators, and confirmation through appropriate randomized controlled clinical trials

GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination

RAD51 is a key factor in homologous recombination (HR) and plays an essential role in cellular proliferation by repairing DNA damage during replication. The assembly of RAD51 at DNA damage is strictly controlled by RAD51 mediators, including BRCA1 and BRCA2. We found that human RAD51 directly binds GEMIN2/SIP1, a protein involved in spliceosome biogenesis. Biochemical analyses indicated that GEMIN2 enhances the RAD51–DNA complex formation by inhibiting RAD51 dissociation from DNA, and thereby stimulates RAD51-mediated homologous pairing. GEMIN2 also enhanced the RAD51-mediated strand exchange, when RPA was pre-bound to ssDNA before the addition of RAD51. To analyze the function of GEMIN2, we depleted GEMIN2 in the chicken DT40 line and in human cells. The loss of GEMIN2 reduced HR efficiency and resulted in a significant decrease in the number of RAD51 subnuclear foci, as observed in cells deficient in BRCA1 and BRCA2. These observations and our biochemical analyses reveal that GEMIN2 regulates HR as a novel RAD51 mediator

コンピュータシステムを使った本学学生の食生活調査(自然科学)

本学学生534名を対象に食物摂取状況の調査を行い,特に今回は栄養素摂取量および食品群別摂取量について検討した。1)栄養摂取状況は,男女とも三大栄養素についてはおおむね好ましい摂取傾向であったが,ミネラル,ビタミン類は著しい摂取不足であった。2)動物性たん白質比は,女性48.4%,男性41.5%,植物性脂肪と動物性脂肪の割合は,男女とも1.5:1.0であった。また,PECエネルギー比は,女性13.1%,27.0%,58.0%,男性12.6%,25.3%,61.9%でいずれも適正比率であった。3)食品群別摂取状況は,男女とも肉類,魚介類,砂糖類は基準に達しており,その他の食品群は不足傾向であった。特に果実類,いも類,緑黄色野菜の摂取量が極めて少なかった。4)住形態別では,居住の違いが大きく影響することが示された。下宿生,寮生は自宅生に比べてかなりの摂取不足が認められた