Surfactant protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model

Background Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated. Methods SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells), human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4+ T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array. Results SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake) and led to a decreased secretion of pro-inflammatory cytokines. Conclusion These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.

Obesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthma

Clinical and epidemiological studies show a close association between obesity and the risk of asthma development. The underlying cause-effect relationship between metabolism, innate and adaptive immunity, and inflammation remains to be elucidated.

Seeing Spaces: An Eye-Tracking Study Of Speech Segmentation

Speech is often a multimodal process, presented audiovisually through a talking face. One area of speech perception influenced by visual speech is speech segmentation, or the process of breaking a stream of speech into individual words. Mitchel and Weiss (2013) demonstrated that a talking face contains specific cues to word boundaries and that subjects can correctly segment a speech stream when given a silent video of a speaker. The current study expanded upon these results, using an eye tracker to identify highly attended facial features of the audiovisual display used in Mitchel and Weiss (2013). In Experiment 1, subjects were found to spend the most time watching the eyes and mouth, with a trend suggesting that the mouth was viewed more than the eyes. Although subjects displayed significant learning of word boundaries, performance was not correlated with gaze duration on any individual feature, nor was performance correlated with a behavioral measure of autistic-like traits. However, trends suggested that as autistic-like traits increased, gaze duration of the mouth increased and gaze duration of the eyes decreased, similar to significant trends seen in autistic populations (Boratston & Blakemore, 2007). In Experiment 2, the same video was modified so that a black bar covered the eyes or mouth. Both videos elicited learning of word boundaries that was equivalent to that seen in the first experiment. Again, no correlations were found between segmentation performance and SRS scores in either condition. These results, taken with those in Experiment, suggest that neither the eyes nor mouth are critical to speech segmentation and that perhaps more global head movements indicate word boundaries (see Graf, Cosatto, Strom, & Huang, 2002). Future work will elucidate the contribution of individual features relative to global head movements, as well as extend these results to additional types of speech tasks.

Visual Speech Segmentation: Using Facial Cues to Locate Word Boundaries in Continuous Speech

Speech is typically a multimodal phenomenon, yet few studies have focused on the exclusive contributions of visual cues to language acquisition. To address this gap, we investigated whether visual prosodic information can facilitate speech segmentation. Previous research has demonstrated that language learners can use lexical stress and pitch cues to segment speech and that learners can extract this information from talking faces. Thus, we created an artificial speech stream that contained minimal segmentation cues and paired it with two synchronous facial displays in which visual prosody was either informative or uninformative for identifying word boundaries. Across three familiarisation conditions (audio stream alone, facial streams alone, and paired audiovisual), learning occurred only when the facial displays were informative to word boundaries, suggesting that facial cues can help learners solve the early challenges of language acquisition.

Treatment response of airway clearance assessed by single-breath washout in children with cystic fibrosis

We studied the ability of 4 single-breath gas washout (SBW) tests to measure immediate effects of airway clearance in children with CF.

Vibrating Membrane Devices Deliver Aerosols More Efficient than Standard Devices: A Study in a Neonatal Upper Airway Model

Abstract Background: Aerosol therapy in preterm infants is challenging, as a very small proportion of the drug deposits in the lungs. Aim: Our aim was to compare efficiency of standard devices with newer, more efficient aerosol delivery devices. Methods: Using salbutamol as a drug marker, we studied two prototypes of the investigational eFlow(®) nebulizer for babies (PARI Pharma GmbH), a jet nebulizer (Intersurgical(®) Cirrus(®)), and a pressurized metered dose inhaler (pMDI; GSK) with a detergent-coated holding chamber (AeroChamber(®) MV) in the premature infant nose throat-model (PrINT-model) of a 32-week preterm infant (1,750 g). A filter or an impactor was placed below the infant model's "trachea" to capture the drug dose or particle size, respectively, that would have been deposited in the lung. Results: Lung dose (percentage of nominal dose) was 1.5%, 6.8%, and 18.0-20.6% for the jet nebulizer, pMDI-holding chamber, and investigational eFlow nebulizers, respectively (p<0.001). Jet nebulizer residue was 69.4% and 10.7-13.9% for the investigational eFlow nebulizers (p<0.001). Adding an elbow extension between the eFlow and the model significantly lowered lung dose (p<0.001). A breathing pattern with lower tidal volume decreased deposition in the PrINT-model and device residue (p<0.05), but did not decrease lung dose. Conclusions: In a model for infant aerosol inhalation, we confirmed low lung dose using jet nebulizers and pMDI-holding chambers, whereas newer, more specialized vibrating membrane devices, designed specifically for use in preterm infants, deliver up to 20 times more drug to the infant's lung.

SWIVIT--Swiss video-intubation trial evaluating video-laryngoscopes in a simulated difficult airway scenario: study protocol for a multicenter prospective randomized controlled trial in Switzerland

Video-laryngoscopes are marketed for intubation in difficult airway management. They provide a better view of the larynx and may facilitate tracheal intubation, but there is no adequately powered study comparing different types of video-laryngoscopes in a difficult airway scenario or in a simulated difficult airway situation.

Distance measures for image segmentation evaluation

The task considered in this paper is performance evaluation of region segmentation algorithms in the ground-truth-based paradigm. Given a machine segmentation and a ground-truth segmentation, performance measures are needed. We propose to consider the image segmentation problem as one of data clustering and, as a consequence, to use measures for comparing clusterings developed in statistics and machine learning. By doing so, we obtain a variety of performance measures which have not been used before in image processing. In particular, some of these measures have the highly desired property of being a metric. Experimental results are reported on both synthetic and real data to validate the measures and compare them with others.

Early assessment of brain maturation by MR imaging segmentation in neonates and premature infants

PURPOSE: We evaluated the impact of premature extrauterine life on brain maturation. PATIENTS AND METHODS: Twelve neonates underwent MR imaging at 40 (39.64 +/- 0.98) weeks (full term). Fifteen premature infants underwent 2 MR imaging examinations, after birth (preterm at birth) and at 40 weeks (41.03 +/- 1.33) (preterm at term). A 3D MR imaging technique was used to measure brain volumes compared with intracranial volume: total brain volume, cortical gray matter, myelinated white matter, unmyelinated white matter, basal ganglia (BG), and CSF. RESULTS: The average absolute volume of intracranial volume (269.8 mL +/- 36.5), total brain volume (246.5 +/- 32.3), cortical gray matter (85.53 mL +/- 22.23), unmyelinated white matter (142.4 mL +/-14.98), and myelinated white matter (6.099 mL +/-1.82) for preterm at birth was significantly lower compared with that for the preterm at term: the average global volume of intracranial volume (431.7 +/- 69.98), total brain volume (391 +/- 66,1), cortical gray matter (179 mL +/- 41.54), unmyelinated white matter (185.3 mL +/- 30.8), and myelinated white matter (10.66 mL +/- 3.05). It was also lower compared with that of full-term infants: intracranial volume (427.4 mL +/- 53.84), total brain volume (394 +/- 49.22), cortical gray matter (181.4 +/- 29.27), unmyelinated white matter (183.4 +/- 27.37), and myelinated white matter (10.72 +/- 4.63). The relative volume of cortical gray matter (30.62 +/- 5.13) and of unmyelinated white matter (53.15 +/- 4.8) for preterm at birth was significantly different compared with the relative volume of cortical gray matter (41.05 +/- 5.44) and of unmyelinated white matter (43.22 +/- 5.11) for the preterm at term. Premature infants had similar brain tissue volumes at 40 weeks to full-term infants. CONCLUSION: MR segmentation techniques demonstrate that cortical neonatal maturation in moderately premature infants at term and term-born infants was similar.

Mechanisms of airway obliteration after lung transplantation

Post-transplant bronchiolitis obliterans, also called bronchiolitis obliterans syndrome, affects up to 50-60% of patients who survive 5 yr after surgery according to its clinical definition, which is based on the degree of obstructive airway disease. Alloimmune-independent and -dependent mechanisms produce injuries and inflammation of epithelial cells and subepithelial structures, leading to aberrant tissue repair. The triggering of innate immunity by various infections or chemical injuries after, for example, gastroesophageal reflux, may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiation of rejection episodes. These phenomena may be limited in time and location or may be protracted. Reducing the risk of alloimmune-independent factors may be as important as treating acute episodes of lung rejection. Excessive immunosuppression may be deleterious by increasing the risk of infection, thereby triggering innate and adaptive immunity. New potential therapeutic targets are emerging from the research performed on leukotriene receptors, chemokine receptors, and growth factors. Neutralizing these molecules reduces the initial mononuclear and polynuclear infiltrates or the subsequent fibroproliferative process and the neovascular changes, feeding this process.