Very Low Tidal Volume Ventilation with Associated Hypercapnia - Effects on Lung Injury in a Model for Acute Respiratory Distress Syndrome

BACKGROUND: Ventilation using low tidal volumes with permission of hypercapnia is recommended to protect the lung in acute respiratory distress syndrome. However, the most lung protective tidal volume in association with hypercapnia is unknown. The aim of this study was to assess the effects of different tidal volumes with associated hypercapnia on lung injury and gas exchange in a model for acute respiratory distress syndrome. METHODOLOGY/PRINCIPAL FINDINGS: In this randomized controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6 hours of mechanical ventilation with the following targets: Group 1: tidal volume = 8-10 ml/kg/PaCO(2) = 40 mm Hg; Group 2: tidal volume = 4-5 ml/kg/PaCO(2) = 80 mm Hg; Group 3: tidal volume = 3-4 ml/kg/PaCO(2) = 120 mm Hg; Group 4: tidal volume = 2-3 ml/kg/PaCO(2) = 160 mm Hg. Decreased wet-dry weight ratios of the lungs, lower histological lung injury scores and higher PaO(2) were found in all low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with conventional tidal volume/normocapnia (group 1). The reduction of the tidal volume below 4-5 ml/kg did not enhance lung protection. However, oxygenation and lung protection were maintained at extremely low tidal volumes in association with very severe hypercapnia and no adverse hemodynamic effects were observed with this strategy. CONCLUSION: Ventilation with low tidal volumes and associated hypercapnia was lung protective. A tidal volume below 4-5 ml/kg/PaCO(2) 80 mm Hg with concomitant more severe hypercapnic acidosis did not increase lung protection in this surfactant deficiency model. However, even at extremely low tidal volumes in association with severe hypercapnia lung protection and oxygenation were maintained

Pharmacotherapeutic intervention in impulsive preschool children: The need for a comprehensive therapeutic approach

Impulsive and aggressive behaviour symptoms often are serious problems in children, even already at preschool age. Thus, effective treatment approaches are requested. In this comment pharmacotherapeutic treatment approaches, first of all risperidone, their limitations and alternative psychotherapeutic approaches are outlined

Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use

A simulation study comparing supertree and combined analysis methods using SMIDGen

<p>Abstract</p> <p>Background</p> <p>Supertree methods comprise one approach to reconstructing large molecular phylogenies given multi-marker datasets: trees are estimated on each marker and then combined into a tree (the "supertree") on the entire set of taxa. Supertrees can be constructed using various algorithmic techniques, with the most common being matrix representation with parsimony (MRP). When the data allow, the competing approach is a combined analysis (also known as a "supermatrix" or "total evidence" approach) whereby the different sequence data matrices for each of the different subsets of taxa are concatenated into a single supermatrix, and a tree is estimated on that supermatrix.</p> <p>Results</p> <p>In this paper, we describe an extensive simulation study we performed comparing two supertree methods, MRP and weighted MRP, to combined analysis methods on large model trees. A key contribution of this study is our novel simulation methodology (Super-Method Input Data Generator, or <it>SMIDGen</it>) that better reflects biological processes and the practices of systematists than earlier simulations. We show that combined analysis based upon maximum likelihood outperforms MRP and weighted MRP, giving especially big improvements when the largest subtree does not contain most of the taxa.</p> <p>Conclusions</p> <p>This study demonstrates that MRP and weighted MRP produce distinctly less accurate trees than combined analyses for a given base method (maximum parsimony or maximum likelihood). Since there are situations in which combined analyses are not feasible, there is a clear need for better supertree methods. The source tree and combined datasets used in this study can be used to test other supertree and combined analysis methods.</p

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development

Does soil pyrogenic carbon determine plant functional traits in Amazon Basin forests?

Amazon forests are fire-sensitive ecosystems and consequently fires affect forest structure and composition. For instance, the legacy of past fire regimes may persist through some species and traits that are found due to past fires. In this study, we tested for relationships between functional traits that are classically presented as the main components of plant ecological strategies and environmental filters related to climate and historical fires among permanent mature forest plots across the range of local and regional environmental gradients that occur in Amazonia. We used percentage surface soil pyrogenic carbon (PyC), a recalcitrant form of carbon that can persist for millennia in soils, as a novel indicator of historical fire in old-growth forests. Five out of the nine functional traits evaluated across all 378 species were correlated with some environmental variables. Although there is more PyC in Amazonian soils than previously reported, the percentage soil PyC indicated no detectable legacy effect of past fires on contemporary functional composition. More species with dry diaspores were found in drier and hotter environments. We also found higher wood density in trees from higher temperature sites. If Amazon forest past burnings were local and without distinguishable attributes of a widespread fire regime, then impacts on biodiversity would have been small and heterogeneous. Alternatively, sufficient time may have passed since the last fire to allow for species replacement. Regardless, as we failed to detect any impact of past fire on present forest functional composition, if our plots are representative then it suggests that mature Amazon forests lack a compositional legacy of past fire

Utilização de diferentes níveis de suplementação de sódio para poedeiras comerciais no segundo ciclo de produção Utilization of different levels of sodium supplementation for commercial laying hens on second cycle of production

Realizou-se um experimento com o objetivo de estudar a suplementação de sódio para poedeiras comerciais no segundo ciclo de produção. Foram utilizadas 360 aves Lohmann - LSL, distribuídas em gaiolas convencionais, onde receberam 5 tratamentos experimentais (níveis de sódio suplementar de 0,05; 0,10; 0,15; 0,20 e 0,25%), com 6 repetições de 12 aves cada, avaliados em 3 períodos de 21dias. O delineamento experimental foi o inteiramente casualizado em esquema de parcelas subdivididas, sendo os tratamentos designados nas parcelas e as avaliações nos períodos, nas subparcelas. As rações foram isonutritivas à base de milho e farelo de soja e fornecidas à vontade. O sódio suplementar foi adicionado às dietas usando o NaCl contendo 39,7% desse elemento. Ao final de cada período experimental, foram avaliadas as características de desempenho, qualidade de casca dos ovos e percentagem de umidade das excretas. No final do experimento, foi realizada análise de sódio e potássio no plasma e o peso vivo das aves. Os níveis de sódio estudados influenciaram o desempenho das poedeiras, com redução no consumo de ração, peso vivo e produção de ovos nos níveis mais baixos de sódio e a umidade das excretas foi mais alta à medida que se elevou o nível de sódio fornecido na ração. Conclui-se que, para melhor desempenho das poedeiras no segundo ciclo de produção, a suplementação de sódio deve ser de 0,185% ou 0,219% de sódio total nas rações.<br>One experiment was conducted aiming to study the sodium supplementation for commercial laying hens on second cycle of production. A total of 360 Lohmann - LSL layers were randomly assigned to 30 conventional cages during 3 periods of 21 days, where 6 cages were placed on each of the 5 dietary treatments (sodium supplemental levels of 0.05, 0.10, 0.15, 0.20 and 0.25%) with 12 layers per cage. A completely randomized design was used in a split-plot schedule. The dietary treatments represented the parcels and the periods represented the split plot. The corn-soybean meal diets were isonutrient and were provided for "ad libitum" consumption. The supplemental sodium was added to the diets in the form of NaCl, with 39.7% of sodium. Performance, eggshell quality and excreta moisture traits were evaluated at the end of each 21 day period, whereas live weight and plasma sodium and potassium were measured at the end of the experiment. Sodium levels influenced the layers performance, which was characterized by reduction on feed consumption, live weight and egg production on the lower sodium levels and by the increase on excreta moisture on the higher sodium level. It follows that in order to achieve the best performance of the laying hens on the second cycle of production, the dietary sodium supplementation must be of 0.185% or 0.219% of total sodium