554 research outputs found

    Potencial hidrogeniônico de antimicrobianos, segundo os fatores ambientais temperatura e luminosidade

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    The objective of this experimental study was to measure the pH of antibiotics administered by intravenous infusion - ceftriaxone sodium, vancomycin hydrochloride, metrodinazole, penicillin G potassium and amikacin sulfate - after reconstitution with sterile water and dilution with NaCl 0.9% or dextrose 5% in water, according to temperature and luminosity of the environment. The results showed that variation in the drugs' pH was less than 1.0 value and that some antibiotics remained acidic after dilution and maintained this chemical profile in all situations studied, suggesting that the studied environmental factors did not change the solutions' acid base characteristic. Some pH values measured characterize risk for the development of chemical phlebitis and infiltration, and it is important for clinical practice to emphasize the profile of intravenous solutions of antibiotics, considering method of dilution, and time to infusion.El objetivo de este estudio experimental fue medir el pH de los antibióticos de administración intravenosa ceftriaxona sódica, clorhidrato de vancomicina, metronidazol, penicilina G potásica y sulfato de amikacina, después de reconstitución con agua destilada y dilución con NaCl a 0,9%, o suero glucosado a 5%, considerando la influencia de la temperatura y luminosidad ambientales, así como el tiempo de exposición, en el comportamiento químico de esos fármacos. Los resultados demostraron variaciones que no ultrapasaron 1,0 (valor de pH) y que algunos antimicrobianos, eminentemente ácidos después de la dilución, mantuvieron ese comportamiento en todas las situaciones estudiadas, no sugiriendo la influencia de factores ambientales en el comportamiento químico de las soluciones. Considerando que algunos valores de pH encontrados pueden contribuir para el desarrollo de flebitis química e infiltración, es importante enfatizar que para la práctica clínica en salud, existe la necesidad de conocer las características de las soluciones de infusión intravenosa, considerando el tipo de dilución y el tiempo de infusión.O objetivo deste estudo experimental foi medir o pH dos antibióticos de administração intravenosa ceftriaxona sódica, cloridrato de vancomicina, metronidazol, penicilina G potássica e sulfato de amicacina, após reconstituição com água destilada e diluição com NaCl 0,9%, ou soro glicosado 5%, considerando a influência da temperatura e luminosidade ambientais, assim como do tempo de exposição, no comportamento químico desses fármacos. Os resultados demonstraram variações que não ultrapassaram 1,0 valor de pH e que alguns antimicrobianos, eminentemente ácidos após a diluição, mantiveram esse comportamento em todas as situações estudadas, não sugerindo a influência de fatores ambientais no comportamento químico das soluções. Como alguns valores de pH encontrados podem contribuir para o desenvolvimento de flebite química e infiltração, é importante enfatizar para a prática clínica em saúde, a necessidade de conhecer as características das soluções de infusão intravenosa, considerando tipo de diluição e tempo de infusão.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemCNPq: 476295/2004-1CNPq: 502382/2007-4SciEL

    Parents’ Beliefs about and Associations to their Elementary Children’s Home Technology Usage

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    This study sought to gather information through a survey of how newcomer parents’ beliefs about technology usage and how they engage with technology as they support their children with twenty-first century literacies. Parent respondents (N = 70) were drawn from two publicly funded schools in the Niagara Region, Ontario, Canada, where the population tends to be immigrant, visible minority, with post-secondary education, but unemployed and low income. Descriptive statistics quantified daily technology activities as being communication-oriented with the majority of parents holding distinct beliefs about the amount and type of their children’s technology usage. Chi-square tests indicated significant associations for demographic characteristics such as the gender, age, education, first language, and ethnicity of the parents as determinants of their beliefs about their children’s technology usage (e.g., social media, mobile phones, television). As well, levels of access and use varied in terms of the number of new technologies and the types of literacy practices that families engage in. Immigrant parents might hold misconceptions about twenty-first century literacies, therefore there should be an attempt to assist them to provide responsive twenty-first century literacy and technology support for their children

    Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

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    Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

    Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension.

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    Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. Here, we identify BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal model of PAH caused by BMPR-II deficiency, spontaneously developed PAH. Administration of BMP9 reversed established PAH in these mice, as well as in two other experimental PAH models, in which PAH develops in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a new therapeutic strategy for PAH

    Physiologic and molecular consequences of endothelial Bmpr2 mutation

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    <p>Abstract</p> <p>Background</p> <p>Pulmonary arterial hypertension (PAH) is thought to be driven by dysfunction of pulmonary vascular microendothelial cells (PMVEC). Most hereditary PAH is associated with BMPR2 mutations. However, the physiologic and molecular consequences of expression of BMPR2 mutations in PMVEC are unknown.</p> <p>Methods</p> <p>In vivo experiments were performed on adult mice with conditional endothelial-specific expression of the truncation mutation Bmpr2<sup>delx4+</sup>, with age-matched transactivator-only mice as controls. Phenotype was assessed by RVSP, counts of muscularized vessels and proliferating cells, and staining for thromboses, inflammatory cells, and apoptotic cells. The effects of BMPR2 knockdown in PMVEC by siRNA on rates of apoptosis were assessed. Affymetrix expression arrays were performed on PMVEC isolated and cultured from triple transgenic mice carrying the immortomouse gene, a transactivator, and either control, Bmpr2<sup>delx4+ </sup>or Bmpr2<sup>R899X </sup>mutation.</p> <p>Results</p> <p>Transgenic mice showed increased RVSP and corresponding muscularization of small vessels, with histologic alterations including thrombosis, increased inflammatory cells, increased proliferating cells, and a moderate increase in apoptotic cells. Expression arrays showed alterations in specific pathways consistent with the histologic changes. Bmpr2<sup>delx4+ </sup>and Bmpr2<sup>R899X </sup>mutations resulted in very similar alterations in proliferation, apoptosis, metabolism, and adhesion; Bmpr2<sup>delx4+ </sup>cells showed upregulation of platelet adhesion genes and cytokines not seen in Bmpr2<sup>R899X </sup>PMVEC. Bmpr2 mutation in PMVEC does not cause a loss of differentiation markers as was seen with Bmpr2 mutation in smooth muscle cells.</p> <p>Conclusions</p> <p>Bmpr2 mutation in PMVEC <it>in vivo </it>may drive PAH through multiple, potentially independent, downstream mechanisms, including proliferation, apoptosis, inflammation, and thrombosis.</p

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

    Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

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    The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models
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