Consultant Report Securing Australia’s Future STEM : Country Comparisons

STEM Country Comparisons: JapanSecuring Australia’s Future Project 2. Australian Council of Learned Academies (ACOLA)This report can be found at www.acola.org.a

Proteasome-dependent decrease in Akt by growth factors in vascular smooth muscle cells

AbstractAkt is activated by growth factors to regulate various aspects of vascular smooth muscle cell function. Platelet-derived growth factor (PDGF) and insulin-like growth factor-1 activated Akt in vascular smooth muscle cells with a rapid reduction of total Akt protein that lasted for several hours. The downregulation of Akt required phosphatidylinositol 3-kinase activity, but not intrinsic Akt activity. The downregulation of Akt was abrogated by MG-132, a proteasome inhibitor, but not by inhibitors of calpain or cathepsins. Akt was found in ubiquitin immune complex after PDGF treatment. Proteasome-dependent degradation of Akt may provide a counter-regulatory mechanism against overactivation of Akt

Urinary Excretion of Inorganic and Organic Fluoride after Inhalation of Sevoflurane

This study was designed to investigate the defluorination of sevoflurane in patients. Five patients, scheduled for orthopedic surgery, were administered sevoflurane for 60 min during NLA-nitrous oxide-oxygen. The end-tidal concentration of sevoflurane was adjusted at 0.6% throughout the entire inhalation period. The serum concentration of inorganic F- increased significantly 15 min after the onset of inhalation and reached a plateau at 45 min with a mean value about 15 μM. The serum organic fluoride level increased significantly 45 min after the onset of inhalation and did not change significantly 4 hr later with a mean value of about 140 μM. The elimination half-lives and rate constants were calculated from urinary data to be 2040 min and 0.00034 for inorganic fluoride and 1800 min and 0.00038 for organic fluoride respectively. The ratio organic/inorganic fluoride was calculated to be 2.3.This study was supported in part by a Grant-in-aid for Science Research from the Ministry of Education, Science and Culture of Japan

Clinical Evaluation and Metabolism of Sevoflurane in Patients

Sevoflurane was submitted to Phase II studies in patients following Phase I studies. Sevoflurane, 2% inspired during maintenance, was administered with 50% N2O in oxygen to produce surgical anesthesia in 9 orthopedic patients of ASA Physical Status I. Under controlled ventilation, endotracheal concentration of sevoflurane was recorded. The blood concentration of sevoflurane was measured during and after the inhalation. Serum, urinary inorganic fluoride, and glucuronide of hexafluoroisopropanol were analysed with ion chromatographic analyzer. The patient inhaled sevoflurane for 3.5 ± 1.6 hr. All the patients were anesthetized and operated uneventfully. Postoperative laboratory findings showed no unexplainable abnormality. The end expiratory concentration of sevoflurane reached a plateau in 4.0 ± 0.8 min and fell rapidly after discontinuation of sevoflurane. Blood concentration of sevoflurane was about 500 μM during inhalation. It decreased promptly after termination of sevoflurane and was not correlated with anesthetic time. The time for verbal response after discontinuation was 11.8 ± 4.2 min. The serum concentration of inorganic fluoride increased after inhalation and reached a plateau (13.7 ± 8.2 μM) in 120 min. The level lasted for 120 min after anesthesia and fell by half at 12 hr after anesthesia. Urinary fluoride concentration varied from 20 to 3,000 μM during the first 12 hr urine, and showed its maximum in the first postoperative 12 or 24 hr urine. The findings that sevoflurane with nitrous oxide and oxygen produced surgical anesthesia without any sequelae and that the serum fluoride level did not exceed the nephrotoxic level warrent the further clinical evaluation in a wider range of subjects.A part of this work was supported by a Research Grant from the Japanese Ministry of Education, Science and Culture and presented at the 8th European Congress of Anaesthesiology, Vienna, Austria, in September, 1986

Machine learning-based prediction of relapse in rheumatoid arthritis patients using data on ultrasound examination and blood test

Recent effective therapies enable most rheumatoid arthritis (RA) patients to achieve remission; however, some patients experience relapse. We aimed to predict relapse in RA patients through machine learning (ML) using data on ultrasound (US) examination and blood test. Overall, 210 patients with RA in remission at baseline were dichotomized into remission (n = 150) and relapse (n = 60) based on the disease activity at 2-year follow-up. Three ML classifiers [Logistic Regression, Random Forest, and extreme gradient boosting (XGBoost)] and data on 73 features (14 US examination data, 54 blood test data, and five data on patient information) at baseline were used for predicting relapse. The best performance was obtained using the XGBoost classifier (area under the receiver operator characteristic curve (AUC) = 0.747), compared with Random Forest and Logistic Regression (AUC = 0.719 and 0.701, respectively). In the XGBoost classifier prediction, ten important features, including wrist/metatarsophalangeal superb microvascular imaging scores, were selected using the recursive feature elimination method. The performance was superior to that predicted by researcher-selected features, which are conventional prognostic markers. These results suggest that ML can provide an accurate prediction of relapse in RA patients, and the use of predictive algorithms may facilitate personalized treatment options

Characterization of an Acute Muscle Contraction Model Using Cultured C2C12 Myotubes

A cultured C2C12 myotube contraction system was examined for application as a model for acute contraction-induced phenotypes of skeletal muscle. C2C12 myotubes seeded into 4-well rectangular plates were placed in a contraction system equipped with a carbon electrode at each end. The myotubes were stimulated with electric pulses of 50 V at 1 Hz for 3 ms at 997-ms intervals. Approximately 80% of the myotubes were observed to contract microscopically, and the contractions lasted for at least 3 h with electrical stimulation. Calcium ion $(Ca^{2+})$ transient evoked by the electric pulses was detected fluorescently with Fluo-8. Phosphorylation of protein kinase B/Akt (Akt), 5′ AMP-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38), and c-Jun NH2-terminal kinase (JNK)1/2, which are intracellular signaling proteins typically activated in exercised/contracted skeletal muscle, was observed in the electrically stimulated C2C12 myotubes. The contractions induced by the electric pulses increased glucose uptake and depleted glycogen in the C2C12 myotubes. C2C12 myotubes that differentiated after exogenous gene transfection by a lipofection or an electroporation method retained their normal contractile ability by electrical stimulation. These findings show that our C2C12 cell contraction system reproduces the muscle phenotypes that arise in vivo (exercise), in situ (hindlimb muscles in an anesthetized animal), and in vitro (dissected muscle tissues in incubation buffer) by acute muscle contraction, demonstrating that the system is applicable for the analysis of intracellular events evoked by acute muscle contraction

Comprehensive behavioral analysis of mice repeatedly treated with propofol

Propofol, known as “milk of anesthesia”, is used for the induction and maintenance of anesthesia. Recently, propofol has attracted increasing concerns about its safety and abuse potential because of its psychostimulant effects such as euphoria and sexual hallucinations. Previous reports focused on the effects of postoperative and neonatal exposure to propofol. However, the lasting effects of repetitive propofol administration during adulthood have not been well investigated. It is conceivable that prolonged use of propofol affects brain function and the behavioral characteristics of the abused patient. Thus, we performed a comprehensive behavioral analysis of mice exposed to propofol. Adult male C57BL/6J mice were repeatedly administered with propofol (20 or 80 mg/kg/day i.p.), intralipos (vehicle control), or saline only once a day for seven days. We then performed a behavioral test battery to evaluate various behaviors. Afterwards, we resumed the propofol treatment for three days and subsequently conducted contextual and cued fear conditioning tests. In the three‐chamber social approach test, propofol treatment attenuated social novelty preference in mice. In the fear conditioning test, high dose-treated mice exhibited impaired long-term cued-dependent memory retention. In the rotarod test, propofol- and intralipos-treated mice tended to have decreased motor coordination than the saline-treated mice. Our results demonstrated that repetitive propofol treatment has the potential to induce some behavioral changes in mice. Additionally, the solvent itself might have effects different from that of propofol. Our findings provide basic data on the safe use and risk of propofol abuse. Highlights Propofol, known as “milk of anesthesia”, has attracted increasing concerns about its safety and abuse potential. The lasting effects of repetitive propofol administration during adulthood have not been well investigated. To clarify the effects of repetitive propofol use on brain function and behavioral characteristics, we performed a comprehensive behavioral analysis of mice exposed to propofol. In this study, propofol treatment attenuated the social novelty preference and the performance of the cued long-term memory task in mice. Additionally, treatment with propofol and intralipos tended to induce decreased motor coordination. Our results demonstrated that repetitive propofol treatment has the potential to induce some behavioral changes in mice. Furthermore, the solvent itself might have effects different from that of propofol. Our findings provide basic data for the safe use and risk of propofol abuse

T市内保育所・認定こども園の看護職配置の現状と期待される役割―医療的ケアの必要な障害児の受け入れ―

　本研究は、T市内保育所・認定こども園の看護職配置の現状と役割、医療的ケアの必要な障害児の受け入れの現状と課題を明らかにすることを目的とした。研究の調査対象者は、T市内にある保育所・認定こども園203施設に所属する所長（園長）・主任保育士・看護職者の内いずれか1名とした。2018年11月～12月の間に、無記名の自記式調査用紙を郵送法にて配布・回収した。本研究は研究者所属大学の人を対象とする研究倫理委員会の承認を得て実施した。　調査用紙116通（回収率57.1％）が回収された。看護職の配置は有が57施設（49.1％）、無は59施設（50.9％）であった。医療的ケアの必要な障害児を受け入れている施設は6施設（5.2％）で、今後受け入れ予定は有が5施設（4.3％）、無は85施設（73.3％）、状況に応じて検討するは21施設（18.1％）であった。受け入れ可能と考える医療的ケア（複数回答）で最も多かったのが、服薬管理26件（47.3％）、次いで気管切開部の管理7件（12.7％）であった。受け入れにあたり必要と考えられる準備（複数回答）は、保護者との話し合い64件（19.8％）、次いで嘱託医・主治医とのカンファレンス59件（18.2％）であった。　保育所・認定こども園の看護職配置は年々増加傾向にある。医療的ケアの必要な障害児の受け入れはまだ少ないが、受け入れを検討する施設が増えてきている。検討課題として、保育所看護職の期待は大きい。さらに、医療的ケア児等コーディネーター養成研究の周知、保育所関係者の受講への整備が今後の課題となる。また、障害児の状態を把握するためには、保護者との話し合いが最も重要であることが示唆された