7,824 research outputs found

    Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.

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    Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures

    Spatiotemporal Hemodynamic Complexity in Carotid Arteries: An Integrated Computational Hemodynamics and Complex Networks-Based Approach

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    Objective: The study of the arterial hemodynamics is essential for a better understanding of the risks associated with the onset/progression of vascular disease. However, conventional quantification and visualization paradigms are not sufficient to fully capture the spatiotemporal evolution of correlated blood flow patterns and their “sphere of influence” in complex vascular geometries. In the attempt to bridge this knowledge gap, an integrated computational hemodynamics and complex networks-based approach is proposed to unveil organization principles of cardiovascular flows. Methods: The approach is applied to ten patient-specific hemodynamic models of carotid bifurcation, a vascular bed characterized by a complex hemodynamics and clinically-relevant disease. Correlation-based networks are built starting from time-histories of two fluid mechanics quantities of physiological significance, respectively (1) the blood velocity vector axial component locally aligned with the main flow direction, and (2) the kinetic helicity density. Results: Unlike conventional hemodynamic analyses, here the spatiotemporal similarity of dynamic intravascular flow structures is encoded in a distance function. In the case of the carotid bifurcation, this study measures for the first time to what extent flow similarity is disrupted by vascular geometric features. Conclusion: It emerges that a larger bifurcation expansion, a hallmark of vascular disease, significantly disrupts the network topological connections between axial flow structures, reducing also their anatomical persistence length. On the contrary, connections in helical flow patterns are overall less geometry-sensitive. Significance: The integrated approach proposed here, by exploiting the connections of hemodynamic patterns undergoing similar dynamical evolution, opens avenues for further comprehension of vascular physiopathology

    Global rural temperature trends

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    Using rural/urban land surface classifications derived from maps and satellite observed nighttime surface lights, global mean land surface air temperature time series were created using data from all weather observing stations in a global temperature data base and from rural stations only. The global rural temperature time series and trends are very similar to those derived from the full data set. Therefore, the well-known global temperature time series from in situ stations is not significantly impacted by urban warming

    Global rural temperature trends

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    Using rural/urban land surface classifications derived from maps and satellite observed nighttime surface lights, global mean land surface air temperature time series were created using data from all weather observing stations in a global temperature data base and from rural stations only. The global rural temperature time series and trends are very similar to those derived from the full data set. Therefore, the well-known global temperature time series from in situ stations is not significantly impacted by urban warming

    Wall shear stress topological skeleton independently predicts long-term restenosis after carotid bifurcation endarterectomy

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    Wall Shear Stress (WSS) topological skeleton, composed by fixed points and the manifolds linking them, reflects the presence of blood flow features associated to adverse vascular response. However, the influence of WSS topological skeleton on vascular pathophysiology is still underexplored. This study aimed to identify direct associations between the WSS topological skeleton and markers of vascular disease from real-world clinical longitudinal data of long-term restenosis after carotid endarterectomy (CEA). Personalized computational hemodynamic simulations were performed on a cohort of 13 carotid models pre-CEA and at 1 month after CEA. At 60 months after CEA, intima-media thickness (IMT) was measured to detect long-term restenosis. The analysis of the WSS topological skeleton was carried out by applying a Eulerian method based on the WSS vector field divergence. To provide objective thresholds for WSS topological skeleton quantitative analysis, a computational hemodynamic dataset of 46 ostensibly healthy carotid bifurcation models was considered. CEA interventions did not completely restore physiological WSS topological skeleton features. Significant associations emerged between IMT at 60 months follow-up and the exposure to (1) high temporal variation of WSS contraction/expansion (R2 = 0.51, p < 0.05), and (2) high fixed point residence times, weighted by WSS contraction/expansion strength (R2 = 0.53, p < 0.05). These WSS topological skeleton features were statistically independent from the exposure to low WSS, a previously reported predictor of long-term restenosis, therefore representing different hemodynamic stimuli and potentially impacting differently the vascular response. This study confirms the direct association between WSS topological skeleton and markers of vascular disease, contributing to elucidate the mechanistic link between flow disturbances and clinical observations of vascular lesions

    WALL SHEAR STRESS TOPOLOGICAL SKELETON IDENTIFICATION IN CARDIOVASCULAR FLOWS: A PRACTICAL APPROACH

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    The observed co-localization of “disturbed” hemodynamics and atherosclerotic lesion prevalence has led to the identification of low and oscillatory Wall Shear Stress (WSS) as a biomechanical localizing factor for vascular dysfunction. However, recent evidences have underlined how consideration of only “low and oscillatory” WSS may oversimplify the complex hemodynamic milieu to which the endothelium is exposed. In this context, recent studies have highlighted the relevance of WSS fixed points, and the stable and unstable manifolds that connect them. These WSS topological features have a strong link with flow features like flow stagnation, separation, and recirculation, which are usually classified as “disturbed” flow. Technically, a fixed point of a vector field is a point where the vector field vanishes, while unstable/stable vector field manifolds identify contraction/expansion regions linking the fixed points. The set of fixed points and their connections form the topological skeleton of a vector field. The presence of WSS fixed points and of WSS contraction/expansion regions, highlighted by WSS manifolds, might induce focal vascular responses relevant for, e.g., early atherosclerosis, or, aneurysm rupture. For these reasons, the topological skeleton analysis of the WSS vector field is of great interest and motivates the study present herein. Lagrangian techniques have been recently proposed to identify WSS manifolds but have certain practical limitations. A Eulerian approach has also been suggested, but only for 2D analytical fields. Here we propose and demonstrate the use of a simple Eulerian approach for identifying WSS topological skeleton on 3D surfaces
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