A Phase III Multicenter, Open-Label, One-Arm Study to Evaluate the Efficacy and Safety of Remifentanil Hydrochloride for Pediatric Subjects under General Anesthesia

レミフェンタニル塩酸塩は4-アニリドピペリジン誘導体で選択的μ-オピオイド受容体作動薬として，国内では，成人における「全身麻酔の導入及び維持における鎮痛」の効能・効果で汎用されているが，小児の適応はない。今回，小児におけるレミフェンタニル塩酸塩の有効性，安全性及び薬物動態を評価するため，挿管による気道確保及びオピオイド鎮痛薬による鎮痛を必要とする全身麻酔下での手術を行った1～15歳の小児患者80例を対象に，第Ⅲ相多施設単群非盲検試験を実施した。主要評価項目の皮膚切開時の刺激への反応は11.3％で，年齢区分（1～6歳，7～15歳）による明らかな差は認められなかった。本剤の使用に関連する有害事象は30.0％で，主な事象は心拍数減少であった。レミフェンタニルのクリアランスと年齢に明らかな傾向は認められなかった。レミフェンタニル塩酸塩は全身麻酔下の小児患者において，十分な鎮痛効果を認め，安全に使用可能であった。Remifentanil is a potent, selective, 4-anilidopiperidine µ- opioid receptor agonist not licensed for analgesia in the maintenance of general anesthesia in pediatric subjects in Japan.　A phase III trial was conducted to evaluate remifentanil for pediatric subjects in Japan.　This multicenter, open-label, one-arm study in pediatric subjects between 1 and 15 years of age receiving general anesthesia included 80 subjects.　Nine subjects (11.3%) showed response to skin incision, which was the primary endpoint, and no apparent difference in response rate was found according to age (1–6, and 7–15 years old).　Drug-related treatment emergent adverse events were found in 24 subjects (30.0%) with the most common event being heart rate decreased (26.3%).　Remifentanil was found to be effective and safe for analgesia in maintenance of general anesthesia for pediatric subjects

Effects of soy phytoestrogens and New Zealand functional foods on bone health

New Zealand is a rich source of food components that may have bioactivity on bone. Docosahexaenoic acid (DHA) from fish oil has been shown to maintain bone in ovariectomised (OVX) rats. Kiwifruit, a source of fibre and carotenoids may also affect bone via a prebiotic as well as direct cell based mechanisms. We aimed to 1) ascertain the effects of DHA on two cell models, including interactions with soy isoflavones; 2) and investigate the specific effects of carotenoids from kiwifruit as well as whole kiwifruit in cell based and rodent models as well as in a human study. RAW 264.7 mouse monocytes or mouse bone marrow were used to generate osteoclasts (OC). Cells were exposed to the agents between 5 and 21 days and formation and activity of OC measured, including molecular markers. DHA inhibited OC formation in both cell models, including expression of cathepsin K, NFATc1 as well as actin ring formation. Combination with isoflavones enhanced these effects. In OVX rats and mice fed with kiwifruit for 8 weeks, green kiwifruit reduced rate of bone loss after OVX, and in mice it reduced C-telopeptide of Type 1 collagen (CTX) levels and RANKL expression while in menopausal women, green kiwifruit affected blood lipids and bone markers positively.http://www.jsnfs.or.jp/english/english_jnsv.htmlhb201

Increased Systemic Glucose Tolerance with Increased Muscle Glucose Uptake in Transgenic Mice Overexpressing RXRγ in Skeletal Muscle

BACKGROUND: Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes

Acute molecular responses to concurrent resistance and high-intensity interval exercise in untrained skeletal muscle

Concurrent training involving resistance and endurance exercise may augment the benefits of single-mode training for the purpose of improving health. However, muscle adaptations, associated with resistance exercise, may be blunted by a subsequent bout of endurance exercise, via molecular interference. High-intensity interval training (HIIT), generating similar adaptations to endurance exercise, may offer an alternative exercise mode to traditional endurance exercise. This study examined the influence of an acute HIIT session on the molecular responses following resistance exercise in untrained skeletal muscle. Ten male participants performed resistance exercise (4 9 8 leg extensions, 70% 1RM, (RE)) or RE followed by HIIT (10 x 1 min at 90% HRmax, (RE+HIIT)). Muscle biopsies were collected from the vastus lateralis before, 2 and 6 h post-RE to determine intramuscular protein phosphorylation and mRNA responses. Phosphorylation of Akt (Ser473) decreased at 6 h in both trials (P < 0.05). Phosphorylation of mTOR (Ser2448) was higher in RE+HIIT (P < 0.05). All PGC-1a mRNA variants increased at 2 h in RE+HIIT with PGC-1a and PGC-1a-ex1b remaining elevated at 6 h, whereas RE-induced increases at 2 and 6 h for PGC-1a-ex1b only (P < 0.05). Myostatin expression decreased at 2 and 6 h in both trials (P < 0.05). MuRF-1 was elevated in RE+HIIT versus RE at 2 and 6 h (P < 0.05). Atrogin-1 was lower at 2 h, with FOXO3A downregulated at 6 h (P < 0.05). These data do not support the existence of an acute interference effect on protein signaling and mRNA expression, and suggest that HIIT may be an alternative to endurance exercise when performed after resistance exercise in the same training session to optimize adaptations

Can biosecurity and local network properties predict pathogen species richness in the salmonid industry?

Salmonid farming in Ireland is mostly organic, which implies limited disease treatment options. This highlights the importance of biosecurity for preventing the introduction and spread of infectious agents. Similarly, the effect of local network properties on infection spread processes has rarely been evaluated. In this paper, we characterized the biosecurity of salmonid farms in Ireland using a survey, and then developed a score for benchmarking the disease risk of salmonid farms. The usefulness and validity of this score, together with farm indegree (dichotomized as 1 or > 1), were assessed through generalized Poisson regression models, in which the modeled outcome was pathogen richness, defined here as the number of different diseases affecting a farm during a year. Seawater salmon (SW salmon) farms had the highest biosecurity scores with a median (interquartile range) of 82.3 (5.4), followed by freshwater salmon (FW salmon) with 75.2 (8.2), and freshwater trout (FW trout) farms with 74.8 (4.5). For FW salmon and trout farms, the top ranked model (in terms of leave-one-out information criteria, looic) was the null model (looic = 46.1). For SW salmon farms, the best ranking model was the full model with both predictors and their interaction (looic = 33.3). Farms with a higher biosecurity score were associated with lower pathogen richness, and farms with indegree > 1 (i.e. more than one fish supplier) were associated with increased pathogen richness. The effect of the interaction between these variables was also important, showing an antagonistic effect. This would indicate that biosecurity effectiveness is achieved through a broader perspective on the subject, which includes a minimization in the number of suppliers and hence in the possibilities for infection to enter a farm. The work presented here could be used to elaborate indicators of a farm’s disease risk based on its biosecurity score and indegree, to inform risk-based disease surveillance and control strategies for private and public stakeholders.Consejo Nacional de InovacionCiencia y TecnologiaUniversity of California DavisMarine Harvest Irelan

Gradation: A pay-as-you-go style hybrid query language for structured and text data

There is an increasing number of Web data which consist of text and structured data, such as the combination of Wikipedia pages and DBpedia data. To issue queries to such data, we must choose one of the followings: (1) submit keyword queries against textual data part, or (2) submit structured queries in structured query languages like SPARQL, against structured data part. Keyword queries are easy for casual users to write, but they do not have expressive powers enough to fulfill the user’s information needs. On the other hand, structured queries are more expressive than keyword queries, but are not easy for casual users to write. This paper proposes a hybrid query language that seamlessly integrates the two types of queries, allowing us to write queries in a “pay-as-you-go” fashion.published or submitted for publicationis peer reviewe