Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts

Insulin receptor substrates (IRS-1 and IRS-2) are essential for intracellular signaling by insulin and insulin-like growth factor-I (IGF-I), anabolic regulators of bone metabolism. Although mice lacking the IRS-2 gene (IRS-2−/− mice) developed normally, they exhibited osteopenia with decreased bone formation and increased bone resorption. Cultured IRS-2−/− osteoblasts showed reduced differentiation and matrix synthesis compared with wild-type osteoblasts. However, they showed increased receptor activator of nuclear factor κB ligand (RANKL) expression and osteoclastogenesis in the coculture with bone marrow cells, which were restored by reintroduction of IRS-2 using an adenovirus vector. Although IRS-2 was expressed and phosphorylated by insulin and IGF-I in both osteoblasts and osteoclastic cells, cultures in the absence of osteoblasts revealed that intrinsic IRS-2 signaling in osteoclastic cells was not important for their differentiation, function, or survival. It is concluded that IRS-2 deficiency in osteoblasts causes osteopenia through impaired anabolic function and enhanced supporting ability of osteoclastogenesis. We propose that IRS-2 is needed to maintain the predominance of bone formation over bone resorption, whereas IRS-1 maintains bone turnover, as we previously reported; the integration of these two signalings causes a potent bone anabolic action by insulin and IGF-I

Nephrotoxicity with VCM and Nephrotoxins

There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51–1.85]; VCM + ≥ 2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37–1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42–2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN

Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases

There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN

ニュースを対象にした手話マルチメディアコーパスの構築

NHK Science and Technology LaboratoriesNHK Science and Technology LaboratoriesNHK Science and Technology LaboratoriesNHK Science and Technology Laboratories会議名: 言語資源活用ワークショップ2018, 開催地: 国立国語研究所, 会期: 2018年9月4日-5日, 主催: 国立国語研究所 コーパス開発センターＮＨＫ・Ｅテレで放送されている手話ニュースをデータベース化した，手話マルチメディアコーパスについて述べる．ニュースは構文の逸脱も少ないため，手話の言語研究をする上で比較的扱いやすい対象である．しかし，ニュースを対象にした大規模な手話コーパスはない．我々が現在構築している手話マルチメディアコーパスは，2018年3月末現在で，約15万文（延語数3,036,000語，異なり語数76,000語）を有し，手話コーパスでは大規模なものである．手話では手や指の動作である手指動作とともに，それ以外の動作である非手指動作も重要な情報を持つことが指摘されているので，コーパスの一部には代表的な非手指動作である顔情報（顔表情と口型）も書き起こしている．本稿では，顔情報に関する統計的な分析結果についても報告する

Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model.

The recent clinical application of perfusion technology for the machine preservation of donation after cardiac death (DCD) grafts has some advantages. Oxygenation has been proposed for the preservation of DCD liver grafts. The aim of this study is to clarify whether the use of HbV-containing preservation solution during the subnormothermic machine perfusion (SNMP) of the liver graft improves the graft function of DCD porcine livers in an ex vivo reperfusion model. Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: 4°C cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) with UW gluconate solution (HMP group; N = 5), SNMP (21°C) with UW gluconate solution (SNMP group; N = 5), SNMP (21°C) with HbVs (Hb; 1.8 mg/dl) perfusate (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model (IRM). The oxygen consumption of the SNMP and SNMP+HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, the AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH after reperfusion was significantly lower in SNMP+HbV group than CS and HMP groups. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained in comparison to the CS, HMP and SNMP groups. The SNMP+HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver

研究公正に関する自己記述式尺度における質問文の検討 : 尺度作成における議論を通して

京都府立医科大学大学院医学研究科医学生命倫理学人文・社会科学教室京都府立医科大学大学院医学研究科生物統計学教室京都府立医科大学大学院保健看護学研究科東京医科歯科大学臨床医学教育学開発分野新潟大学創生学部日本医科大学医療管理学京都府立医科大学大学院医学研究科生命基礎数理学教室京都府立医科大学大学院医学研究科医療フロンティア展開学九州大学病院ARO次世代医療センター群馬パース大学教養部AMED研究公正高度化モデル開発支援事業「学際的アプローチによる研究倫理教育のモデル評価プログラムの開発と検証」（瀬戸山班）では、研究活動に関する倫理的意思決定を測定する尺度を開発している。本論文では、この開発中の尺度の質問文に着目し、自己記述式尺度が抱える問題点を克服するため、質問文の作成において検討した内容や、この質問文のオリジナリティ、課題について述べる

研究活動における「隠れたカリキュラム」の可視化の試み : 重回帰分析による分析と考察

京都府立医科大学大学院医学研究科医学生命倫理学人文・社会科学教室京都府立医科大学大学院医学研究科生命基礎数理学教室京都府立医科大学大学院医学研究科生物統計学教室京都府立医科大学大学院保健看護学研究科東京医科歯科大学臨床医学教育学開発分野新潟大学創生学部日本医科大学医療管理学京都府立医科大学大学院医学研究科医療フロンティア展開学九州大学病院ARO次世代医療センター群馬パース大学教養部本稿では，医学教育分野で注目されている「隠れたカリキュラム（hidden curriculum）」を，医学研究の倫理分野において倫理的意思決定やそれに影響を与える組織の環境に応用し，研究倫理に関する規範意識・行動様式を問う情意領域問題の測定尺度を作成したものを用いて，「あなたならばどう行動するか」と「あなたの周りの人ならばどう行動すると考えるか」についてそれぞれ質問を行い，その得点差を見ることで隠れたカリキュラムの影響を可視化することを試みた。その結果，全体及びすべてのカテゴリーにおいて「あなたならばどう行動するか」の得点が高いこと，属性との関連について調べたところ，一部のカテゴリーと性別，人に関わる研究の有無で有意な得点差がみられた