Non-Invasive Respiratory Support is a Pro-inflammatory Stimulus to the Upper and Lower Airways

Non-invasive respiratory support (NIV) is associated with a high prevalence of local side- effects which may be associated with induction of upper airway inflammation. This thesis examines the effect of NIV on the upper and lower airway by examining bronchial epithelial cell cultures, healthy subjects, obstructive sleep apnoea (OSA), and chronic obstructive pulmonary disease (COPD) patients. The rationale for this thesis is based on reports suggesting that continuous positive airway pressure (CPAP) may induce early upper airway inflammation, and discusses the relationship between upper and lower airways in COPD. To examine the addressed rationale we used both an in vitro and in vivo approach. In vitro, we examined the release of the inflammatory cytokines from a human bronchial epithelial cell line over time-intervals using CPAP therapy. In vivo studies investigated whether induction of nasal inflammation was associated with the development of systemic inflammation, nasal symptoms, and changes in nasal mucociliary clearance after a short period of CPAP therapy. Results were investigated further in OSA by investigating whether induction of nasal inflammation was associated with the development of systemic inflammation, nasal symptoms, airway obstruction, and impaired adherence to CPAP therapy and quality of sleepiness over a six months follow-up period. Additional pilot data obtained involved a comparison of local and systemic inflammatory indices in COPD patients using and not using NIV. The key finding was that CPAP is pro-inflammatory. The in vitro data showed that CPAP resulted in the release of inflammatory mediators from cultured human bronchial epithelial cells, in a time-and-pressure-dependent manner. Meanwhile, in vivo data from healthy control subjects showed CPAP was associated with dose (pressure) response changes in nasal and systemic inflammatory markers, reduced nasal function, and the development of nasal symptoms. The development of nasal symptoms was associated with the degree of functional impairment and nasal inflammatory response. These in vitro and in vivo results were novel in reporting the effects of CPAP in this way, providing new data on the mechanisms of CPAP intolerance in the crucial, early phase of therapy. Furthermore, the long-term CPAP study with OSA resulted in nasal inflammation, reduction in nasal mucociliary function, and significant other adverse effects. However, sleep quality and the perceived benefits of therapy improved over time, despite the presence of side-effects. These results have important implications for clinical practice, since it demonstrates a relationship between nasal symptoms, mucociliary clearance, inflammation and compliance in patients with OSA initiating and continuing CPAP therapy. Further investigation of strategies to combat the initial side-effects and nasal inflammation associated with this treatment modality might target the epithelial lining of the nose in an attempt to address the origin of the inflammatory response. In addition, educational and support strategies to improve patients‟ tolerance of side effects may further increase compliance with nasal CPAP treatment for OSA patients

Dental Anxiety and Fear among Patients in Jazan, Kingdom of Saudi Arabia: A Cross-sectional Study

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Comparison and Evaluation of Deadlock Prevention Methods for Different Size Automated Manufacturing Systems

In automated manufacturing systems (AMSs), deadlocks problems can arise due to limited shared resources. Petri nets are an effective tool to prevent deadlocks in AMSs. In this paper, a simulation based on existing deadlock prevention policies and different Petri net models are considered to explore whether a permissive liveness-enforcing Petri net supervisor can provide better time performance. The work of simulation is implemented as follows. (1) Assign the time to the controlled Petri net models, which leads to timed Petri nets. (2) Build the Petri net model using MATLAB software. (3) Run and simulate the model, and simulation results are analyzed to determine which existing policies are suitable for different systems. Siphons and iterative methods are used for deadlocks prevention. Finally, the computational results show that the selected deadlock policies may not imply high resource utilization and plant productivity, which have been shown theoretically in previous publications. However, for all selected AMSs, the iterative methods always lead to structurally and computationally complex liveness-enforcing net supervisors compared to the siphons methods. Moreover, they can provide better behavioral permissiveness than siphons methods for small systems. For large systems, a strict minimal siphon method leads to better behavioral permissiveness than the other methods

Multi-sensor Integrated System for Reverse Engineering

AbstractApplication of multiple sensors in Reverse Engineering (RE) has been effective approach to meet increasing demands of both complexity and accuracy. However, methodology to plan RE steps using systems combining different sensors has been a serious challenge. This paper presents hybrid system that integrates laser line scanning probe and touch trigger probe of coordinate measuring machine for RE of complex part. As a result of integration, this system utilizes strength of one system to overcome limitation of other. In this paper, RE methodology using hybrid system has been described through a part case study. The primary objective of this paper is to retrieve lost 2D drawings as well as damaged portion of mechanical part efficiently and accurately using hybrid system

Confusion Control in Generalized Petri Nets Using Synchronized Events

The loss of conflicting information in a Petri net (PN), usually called confusions, leads to incomplete and faulty system behavior. Confusions, as an unfortunate phenomenon in discrete event systems modeled with Petri nets, are caused by the frequent interlacement of conflicting and concurrent transitions. In this paper, confusions are defined and investigated in bounded generalized PNs. A reasonable control strategy for conflicts and confusions in a PN is formulated by proposing elementary conflict resolution sequences (ECRSs) and a class of local synchronized Petri nets (LSPNs). Two control algorithms are reported to control the appeared confusions by generating a series of external events. Finally, an example of confusion analysis and control in an automated manufacturing system is presented

Cryo-electron tomography of cells: connecting structure and function

Cryo-electron tomography (cryo-ET) allows the visualization of cellular structures under close-to-life conditions and at molecular resolution. While it is inherently a static approach, yielding structural information about supramolecular organization at a certain time point, it can nevertheless provide insights into function of the structures imaged, in particular, when supplemented by other approaches. Here, we review the use of experimental methods that supplement cryo-ET imaging of whole cells. These include genetic and pharmacological manipulations, as well as correlative light microscopy and cryo-ET. While these methods have mostly been used to detect and identify structures visualized in cryo-ET or to assist the search for a feature of interest, we expect that in the future they will play a more important role in the functional interpretation of cryo-tomograms

Rapid and Long-Lasting Increase in Sites for Synapse Assembly during Late-Phase Potentiation in Rat Hippocampal Neurons

Long-term potentiation in hippocampal neurons has stages that correspond to the stages of learning and memory. Early-phase (10–30 min) potentiation is accompanied by rapid increases in clusters or puncta of presynaptic and postsynaptic proteins, which depend on actin polymerization but not on protein synthesis. We have now examined changes in pre- and postsynaptic puncta and structures during glutamate-induced late-phase (3 hr) potentiation in cultured hippocampal neurons. We find that (1) the potentiation is accompanied by long-lasting maintenance of the increases in puncta, which depends on protein synthesis, (2) most of the puncta and synaptic structures are very dynamic, continually assembling and disassembling at sites that are more stable than the puncta or structures themselves, (3) the increase in presynaptic puncta appears to be due to both rapid and more gradual increases in the number of sites where the puncta may form, and also to the stabilization of existing puncta, (4) under control conditions, puncta of postsynaptic proteins behave similarly to puncta of presynaptic proteins and share sites with them, and (5) the increase in presynaptic puncta is accompanied by a similar increase in presumably presynaptic structures, which may form at distinct as well as shared sites. The new sites could contribute to the transition between the early and late phase mechanisms of plasticity by serving as seeds for the formation and maintenance of new synapses, thus acting as local “tags” for protein synthesis-dependent synaptic growth during late-phase plasticity

Analysis of Adhesion Molecules and Basement Membrane Contributions to Synaptic Adhesion at the Drosophila Embryonic NMJ

Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributions come from the extracellular matrix and its receptors. Most of these factors have been scrutinised by loss-of-function analyses in animal models. However, which adhesion factors establish the essential physical links across synaptic clefts and allow the assembly of synaptic machineries at the contact site in vivo is still unclear. To investigate these key questions, we have used the neuromuscular junction (NMJ) of Drosophila embryos as a genetically amenable model synapse. Our ultrastructural analyses of NMJs lacking different classes of CAMs revealed that loss of all neurexins, all classical cadherins or all glutamate receptors, as well as combinations between these or with a Laminin deficiency, failed to reveal structural phenotypes. These results are compatible with a view that these CAMs might have no structural role at this model synapse. However, we consider it far more likely that they operate in a redundant or well buffered context. We propose a model based on a multi-adaptor principle to explain this phenomenon. Furthermore, we report a new CAM-independent adhesion mechanism that involves the basement membranes (BM) covering neuromuscular terminals. Thus, motorneuronal terminals show strong partial detachment of the junction when BM-to-cell surface attachment is impaired by removing Laminin A, or when BMs lose their structural integrity upon loss of type IV collagens. We conclude that BMs are essential to tie embryonic motorneuronal terminals to the muscle surface, lending CAM-independent structural support to their adhesion. Therefore, future developmental studies of these synaptic junctions in Drosophila need to consider the important contribution made by BM-dependent mechanisms, in addition to CAM-dependent adhesion