A CLINICAL STUDY OF INHALANT ANAESTHESIA IN DOGS

A clinical trial was undertaken using three different inhalant anaesthetic agents and one intravenous anaesthetic agent in dogs undergoing routine desexing surgery. Healthy adult dogs undergoing either ovariohysterectomy or castration were assessed as to their demeanour, with the more excitable dogs being placed in groups receiving premedication with acepromazine and morphine. All dogs were then randomly assigned an anaesthetic agent for induction of general anaesthesia. The agents were the inhalants halothane, isoflurane and sevoflurane, and the intravenous agent propofol. Inhalant inductions were undertaken using a tight fitting mask attached to a standard anaesthetic machine with a rebreathing circuit, with the maximum dose of inhalant available from a standard vaporiser. Propofol inductions were undertaken via intravenous catheter. Dogs induced with propofol were randomly assigned one of the three inhalant agents for maintenance. Those induced by inhalant agent were maintained using the same agent. The surgical procedure was undertaken in standard fashion, as was recovery from anaesthesia. All dogs received the non-steroidal anti-inflammatory agent meloxicam. Data collection was divided into three stages: induction, maintenance, and recovery from anaesthesia. Variables measured at induction of anaesthesia were time to intubation, number of intubation attempts, tolerance of mask, quality of induction and quality of transfer to the maintenance stage. Standard variables for monitoring of anaesthesia were recorded throughout the maintenance of anaesthesia. Variables measured at recovery were time to righting, time to standing and quality of recovery. The mean time to intubation when using the newer inhalant sevoflurane (196.2 ± 14.8sec, mean ± SE) was not significantly different to that for halothane (221.4 ± 14.0sec) or isoflurane (172.4 ± 15.0sec). Time to intubation with isoflurane was significantly faster than with halothane. Mean time to intubation with propofol (85.4 ± 7.7sec) was significantly faster than that for any of the three inhalants. Choice of inhalant had no effect on quality of induction. The use of premedication significantly improved the quality of induction. The use of propofol for induction likewise significantly improved the quality of induction. Standard cardiorespiratory variables measured during the maintenance phase of anaesthesia remained within normal clinical ranges for all three inhalants, and were therefore not further analysed. Choice of inhalant agent had no significant effect on the time to righting or standing in recovery. The use of propofol for induction had no effect on these variables. Animals placed in groups receiving premedication had significantly longer times to righting and standing. The oesophageal temperature at the end of the procedure had a significant effect on times to righting and standing, with lower temperatures contributing to slower recoveries. Independent of procedure time, male dogs had shorter times to righting than female dogs

Fresh-blood-free diet for rearing malaria mosquito vectors

Mosquito breeding depends on the supply of fresh vertebrate blood, a major bottleneck for large-scale production of Anopheles spp. Feeding alternatives to fresh blood are thus a priority for research, outdoor large-cage trials and control interventions. Several artificial meal compositions were tested and Anopheles oogenesis, egg laying and development into the next generation of adult mosquitoes were followed. We identified blood-substitute-diets that supported ovarian development, egg maturation and fertility as well as, low progeny larval mortality, and normal development of offspring into adult mosquitoes. The formulated diet is an effective artificial meal, free of fresh blood that mimics a vertebrate blood meal and represents an important advance for the sustainability of Anopheles mosquito rearing in captivity.Agência financiadora / Número do subsídio Bill and Melinda Gates Foundation OPP1138841 Fundacao para a Ciencia e Tecnologia GHTM - UID/Multi/04413/201 CCMAR - UID/Multi/04326/2013 UID/Multi/04326/2013 RF SFRH/BPD/89811/2012 FAPEAM, Brazil 19716.UNI472.2459.20022014info:eu-repo/semantics/publishedVersio

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds

The treatment of Trypanosoma cruzi infection (the cause of human Chagas disease) remains a significant challenge. Only two drugs, both with substantial toxicity, are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy rather than to true lack of efficacy. For these reasons relatively few individuals infected with T. cruzi actually have their infections treated. In this study, we report on innovative methods that will facilitate the discovery of new compounds for the treatment of T. cruzi infection and Chagas disease. Utilizing fluorescent and bioluminescent parasite lines, we have developed in vitro tests that are reproducible and facile and can be scaled for high-throughput screening of large compound libraries. We also validate an in vivo screening test that monitors parasite replication at the site of infection and determines the effectiveness of drug treatment in less than two weeks. More importantly, results in this rapid in vivo test show strong correlations with those obtained in long-term (e.g. 40 day or more) treatment assays. The results of this study remove one of the obstacles for identification of effective and safe compounds to treat Chagas disease

Regulation of IL-2 gene expression by Siva and FOXP3 in human T cells

<p>Abstract</p> <p>Background</p> <p>Severe autoinflammatory diseases are associated with mutations in the <it>Foxp3 </it>locus in both mice and humans. <it>Foxp3 </it>is required for the development, function, and maintenance of regulatory T cells (T_regs), a subset of CD4 cells that suppress T cell activation and inflammatory processes. <it>Siva </it>is a pro-apoptotic gene that is expressed across a range of tissues, including CD4 T cells. Siva interacts with three tumor necrosis factor receptor (TNFR) family members that are constitutively expressed on T_regcells: CD27, GITR, and OX40.</p> <p>Results</p> <p>Here we report a biophysical interaction between FOXP3 and Siva. We mapped the interaction domains to Siva's C-terminus and to a central region of FOXP3. We showed that <it>Siva </it>repressed IL-2 induction by suppressing <it>IL-2 </it>promoter activity during T cell activation. Siva-1's repressive effect on <it>IL-2 </it>gene expression appears to be mediated by inhibition of NFkappaB, whereas FOXP3 repressed both NFkappaB and NFAT activity.</p> <p>Conclusions</p> <p>In summary, our data suggest that both <it>FOXP3 </it>and <it>Siva </it>function as negative regulators of IL-2 gene expression in T_regcells, via suppression of NFAT by <it>FOXP3 </it>and of NFkappaB by both <it>FOXP3 </it>and <it>Siva</it>. Our work contributes evidence for <it>Siva's </it>role as a T cell signalling mediator in addition to its known pro-apoptotic function. Though further investigations are needed, evidence for the biophysical interaction between FOXP3 and Siva invites the possibility that Siva may be important for proper T_regcell function.</p