Bench-to-bedside review: Paediatric viral lower respiratory tract disease necessitating mechanical ventilation – should we use exogenous surfactant?

Treatment of infants with viral lower respiratory tract disease (LRTD) necessitating mechanical ventilation is mainly symptomatic. The therapeutic use of surfactant seems rational because significantly lower levels of surfactant phospholipids and proteins, and impaired capacity to reduce surface tension were observed among infants and young children with viral LRTD. This article reviews the role of pulmonary surfactant in the pathogenesis of paediatric viral LRTD. Three randomized trials demonstrated improved oxygenation and reduced duration of mechanical ventilation and paediatric intensive care unit stay in young children with viral LRTD after administration of exogenous surfactant. This suggest that exogenous surfactant is the first beneficial treatment for ventilated infants with viral LRTD. Additionally, in vitro and animal studies demonstrated that surfactant associated proteins SP-A and SP-D bind to respiratory viruses, play a role in eliminating these viruses and induce an inflammatory response. Although these immunomodulating effects are promising, the available data are inconclusive and the findings are unconfirmed in humans. In summary, exogenous surfactant in ventilated infants with viral LRTD could be a useful therapeutic approach. Its beneficial role in improving oxygenation has already been established in clinical trials, whereas the immunomodulating effects are promising but remain to be elucidated

MetaTM - a consensus method for transmembrane protein topology prediction

Transmembrane (TM) proteins are proteins that span a biological membrane one or more times. As their 3-D structures are hard to determine, experiments focus on identifying their topology (i. e. which parts of the amino acid sequence are buried in the membrane and which are located on either side of the membrane), but only a few topologies are known. Consequently, various computational TM topology predictors have been developed, but their accuracies are far from perfect. The prediction quality can be improved by applying a consensus approach, which combines results of several predictors to yield a more reliable result. RESULTS: A novel TM consensus method, named MetaTM, is proposed in this work. MetaTM is based on support vector machine models and combines the results of six TM topology predictors and two signal peptide predictors. On a large data set comprising 1460 sequences of TM proteins with known topologies and 2362 globular protein sequences it correctly predicts 86.7% of all topologies. CONCLUSION: Combining several TM predictors in a consensus prediction framework improves overall accuracy compared to any of the individual methods. Our proposed SVM-based system also has higher accuracy than a previous consensus predictor. MetaTM is made available both as downloadable source code and as DAS server at http://MetaTM.sbc.su.se

Low agreement for assessing the risk of postoperative deep venous thrombosis when deciding prophylaxis strategies: a study using clinical vignettes

BACKGROUND: Several clinical practice guidelines (CPG) on antithrombotic prophylaxis in surgical patients help to decide about the prophylaxis strategy based on the patient risk of deep venous thrombosis (DVT). However, the physician risk estimates of DVT could have little inter-observer reproducibility, which could lead to different individual prophylaxis practices. METHODS: Physicians were asked to evaluate DVT risk in eight clinical vignettes, describing actual patients cared for in our hospital. The vignettes included all possible levels of DVT risk. RESULTS: The degree of prophylaxis strategies accuracy was 63% (95% CI 523–75%). Overall agreement was 0.32 (z = 7.61, p < 0.001) and for each level of risk kappa was 0.38 (z = 6.50, p < 0.001); 0.1 (z = 1.65, p < 0.049) and 0.5 (z = 8.45, p < 0.001) for small, moderate and high risk group respectively CONCLUSIONS: Our results showed that there is poor agreement when physicians have to evaluate the risk for postoperative DVT, and in the cases of low and moderate risks of DVT there is the smallest agreement. In addition, the data also showed that the overall accuracy of DVT prophylaxis strategy was only moderate and the risk evaluation did not correlate to the selection of the strategy. The issue of inter-observers variability should be taken into account when CPG performance are analysed, especially when considering the risk-evaluation to choose the appropriate actions

Elevated blood pressure, heart rate and body temperature in mice lacking the XL alpha s protein of the Gnas locus is due to increased sympathetic tone

NEW FINDINGS: What is the central question of this study? Previously, we showed that Gnasxl knock-out mice are lean and hypermetabolic, with increased sympathetic stimulation of adipose tissue. Do these mice also display elevated sympathetic cardiovascular tone? Is the brain glucagon-like peptide-1 system involved? What is the main finding and its importance? Gnasxl knock-outs have increased blood pressure, heart rate and body temperature. Heart rate variability analysis suggests an elevated sympathetic tone. The sympatholytic reserpine had stronger effects on blood pressure, heart rate and heart rate variability in knock-out compared with wild-type mice. Stimulation of the glucagon-like peptide-1 system inhibited parasympathetic tone to a similar extent in both genotypes, with a stronger associated increase in heart rate in knock-outs. Deficiency of Gnasxl increases sympathetic cardiovascular tone. Imbalances of energy homeostasis are often associated with cardiovascular complications. Previous work has shown that Gnasxl-deficient mice have a lean and hypermetabolic phenotype, with increased sympathetic stimulation of adipose tissue. The Gnasxl transcript from the imprinted Gnas locus encodes the trimeric G-protein subunit XLαs, which is expressed in brain regions that regulate energy homeostasis and sympathetic nervous system (SNS) activity. To determine whether Gnasxl knock-out (KO) mice display additional SNS-related phenotypes, we have now investigated the cardiovascular system. The Gnasxl KO mice were ∼20 mmHg hypertensive in comparison to wild-type (WT) littermates (P≤ 0.05) and hypersensitive to the sympatholytic drug reserpine. Using telemetry, we detected an increased waking heart rate in conscious KOs (630 ± 10 versus 584 ± 12 beats min(−1), KO versus WT, P≤ 0.05). Body temperature was also elevated (38.1 ± 0.3 versus 36.9 ± 0.4°C, KO versus WT, P≤ 0.05). To investigate autonomic nervous system influences, we used heart rate variability analyses. We empirically defined frequency power bands using atropine and reserpine and verified high-frequency (HF) power and low-frequency (LF) LF/HF power ratio to be indicators of parasympathetic and sympathetic activity, respectively. The LF/HF power ratio was greater in KOs and more sensitive to reserpine than in WTs, consistent with elevated SNS activity. In contrast, atropine and exendin-4, a centrally acting agonist of the glucagon-like peptide-1 receptor, which influences cardiovascular physiology and metabolism, reduced HF power equally in both genotypes. This was associated with a greater increase in heart rate in KOs. Mild stress had a blunted effect on the LF/HF ratio in KOs consistent with elevated basal sympathetic activity. We conclude that XLαs is required for the inhibition of sympathetic outflow towards cardiovascular and metabolically relevant tissues

When Anomaly Mediation is UV Sensitive

Despite its successes---such as solving the supersymmetric flavor problem---anomaly mediated supersymmetry breaking is untenable because of its prediction of tachyonic sleptons. An appealing solution to this problem was proposed by Pomarol and Rattazzi where a threshold controlled by a light field deflects the anomaly mediated supersymmetry breaking trajectory, thus evading tachyonic sleptons. In this paper we examine an alternate class of deflection models where the non-supersymmetric threshold is accompanied by a heavy, instead of light, singlet. The low energy form of this model is the so-called extended anomaly mediation proposed by Nelson and Weiner, but with potential for a much higher deflection threshold. The existence of this high deflection threshold implies that the space of anomaly mediated supersymmetry breaking deflecting models is larger than previously thought.Comment: 14 pages, 1 figure (version to appear in JHEP

In vitro bioactivity of titanium-doped bioglass

Previous studies have suggested that incorporating relatively small quantities of titanium dioxide into bioactive glasses may result in an increase in bioactivity and hydroxyapatite formation. The present work therefore investigated the in vitro bioactivity of a titanium doped bioglass and compared the results with 45S5 bioglass. Apatite formation was evaluated for bioglass and Ti-bioglass in the presence and absence of foetal calf serum. Scanning electron microscopy (SEM) images were used to evaluate the surface development and energy dispersive X-ray measurements provided information on the elemental ratios. X-ray diffraction spectra confirmed the presence of apatite formation. Cell viability was assessed for bone marrow stromal cells under direct and indirect contact conditions and cell adhesion was assessed using SEM

A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches

Functional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al

Virtual Blocks: a serious game for spatial ability improvement on mobile devices

This paper presents a novel spatial instruction system for improving spatial abilities of engineering students. A 3D mobile game application called Virtual Blocks has been designed to provide a 3D virtual environment to build models with cubes that help students to perform visualization tasks to promote the development of their spatial ability during a short remedial course. A validation study with 26 freshman engineering students at La Laguna University (Spain) has concluded that the training had a measurable and positive impact on students spatial ability. In addition, the results obtained using a satisfaction questionnaire show that Virtual Blocks is considered an easy to use and stimulating application.This work has been partially supported by the (Spanish) National Program for Studies and Analysis project "Evaluation and development of competencies associated to the spatial ability in the new engineering undergraduate courses" (Ref. 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