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Characterising the role of Staphylococcus aureus and its toxins in chronic rhinosinusitis
No full textChronic rhinosinusitis (CRS) is a chronic inflammatory condition affecting the lining of the nose and paranasal sinuses. It is the second most common chronic disease worldwide, and impacts significantly on patients’ quality of life and healthcare resources. CRS is subdivided into two main disease categories: CRS with and without nasal polyps (CRSwNP and CRSsNP respectively). It is well established that bacteria, most notably Staphylococcus aureus (S. aureus), play an important role in the pathogenesis of CRS. Whilst much emphasis has been placed on surface bacteria, intracellular bacteria are gaining more prominence in relation to resistant disease. The intracellular environment may provide a protective niche for pathogenic bacteria to evade host immunity, and provide a reservoir for re-infection. Recently published findings from the Southampton Upper Airway Research Group reported the novel finding of intracellular S. aureus within nasal polyp mast cells, in addition to epithelial cells. Furthermore, the presence/addition of Staphylococcus aureus Enterotoxin B (SEB) further promoted the internalisation of S. aureus into mast cells. The aim of this work was to further characterise the host response towards S. aureus and its toxins, with particular emphasis on S. aureusmast cell interactions. A prospective study was performed using ex-vivo sinonasal mucosa and nasal polyp tissue from CRS patients, and sinonasal mucosa from non-CRS patients undergoing trans-sphenoidal pituitary surgery as a control. Pro-inflammatory cytokine profiles of these tissue sub-sites were measured using real time quantitative polymerase chain reaction (RT-qPCR). An explant tissue model was developed to study the immune response of nasal polyps, and control samples to SEB, with the resultant host immune response measured using RT-qPCR and Luminex. An in vitro cell culture model was developed to characterise interactions between a CRS-specific S. aureus isolate and the RPMI-2650 epithelial cell line, HMC-1 mast cell line and LAD2 mast cell line. S. aureus was cultured to the mid-log phase and combined with all three cell lines, at set time-points and multiplicity of infection ratios. Intracellular uptake of S. aureus was examined using confocal laser scanning microscopy, intracellular viability and its release was examined using colony forming unit (CFU) enumerations, and the associated host immune response was measured using RT-qPCR and Luminex. Study of the potential phenotypic change to S. aureus, from its continual uptake and release from mast cells, was undertaken in both HMC-1 and LAD2 cell lines, utilising CFUs, RT-qPCR and Luminex. For the study of IgE sensitisation and its effect on the activation of S. aureus infected LAD2 cells, the following techniques were used; LDH assays, degranulation (β-hexosaminidase) assays, protein kinase phosphorylation, RT-qPCR and Luminex. In comparison to control patients, CRSwNP patients display upregulated pro-inflammatory cytokines (IL-5, IL-8) toll-like receptors (TLR-4) and matrix metalloproteinases (MMP-28). In many cases the nonpolypoidal sinonasal mucosa of CRSwNP and nasal polyps display strikingly similar immune profiles, with no statistical difference found between the two sites. SEB was found to significantly upregulate nasal polyp gene expression ratios of IL-5, IL-17A, TNFα, TGF-β, and supernatant protein concentrations of IFNγ, IL-5, IL-17A, and TNFα. In cell line culture experiments, RPMI-2650 epithelial cells, as well as HMC-1 and LAD2 mast cells, readily internalised S. aureus. This intracellular uptake was significantly enhanced in the presence of SEB for both epithelial and mast cells at 24 hours. Intracellular S. aureus was found to be viable and capable of release, rapidly replenishing previously eradicated extracellular bacterial populations. Upon S. aureus exposure, both mast cells (HMC-1) and epithelial cells (RPMI-2650) contributed to inflammation through pro-inflammatory cytokine release vi into the culture supernatant (IFNγ, TNFα, IL-17A, IL-1β and IL-6). S. aureus was able to significantly downregulate both the gene expression (IL-8, IL-1β, TNFα, TGF-β1 and IL-5) and protein release (TNFα) of LAD2 mast cells through the sequential repeated intracellular uptake and release of S. aureus. In the presence of prior IgE sensitisation, S. aureus infected LAD2 mast cells were able to limit degranulation, the host immune response (TNFα gene expression and protein release), and the phosphorylation of Atk2 and GSK-3α/β. These findings demonstrate the importance of S. aureus and its toxins in the development of a chronic inflammatory reaction in CRS patients. Epithelial and mast cells appear to provide a protective niche, shielding S. aureusfrom immune mediated clearance, as well as acting as a reservoir of infection that can replenish eradicated bacterial populations. Through prior IgE sensitisation of mast cells, S. aureus was able to manipulate the subsequent host immune response, favouring its own survival. A similar response was also seen following repeated uptake and release of S. aureus from mast cells, suggesting bacterial phenotypic change. This is of particular relevance in patients with elevated IgE levels, as is seen in patients with S. aureus colonisation where IgE forms against both S. aureus and its enterotoxins. This may well facilitate the ongoing survival and submucosal persistence of S. aureus, and could contribute towards the development of a chronic disease process. These patients are likely to benefit from aggressive medical therapy, particularly in the post-operative period, to eradicate S. aureus, in order to improve long-term treatment outcomes.<br/
In response to Use of the lymphocyte count as a diagnostic screen in adults with suspected Epstein-Barr virus infectious mononucleosis
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis
No full textBackground: Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the upper airways, often associated with the formation of nasal polyps (CRSwNP). It is well established that macroscopically normal (non-polypoidal) sinonasal mucosa in CRSwNP patients can undergo polypoidal change over time, turning into frank polyps. However, little is known about what drives this process. This study aimed to investigate potential drivers of nasal polyp formation or growth through comparison of the immunological profiles of nasal polyps with contiguous non-polypoidal sinonasal mucosa, from the same patients.Methods: The immune profiles of three types of tissue were compared; nasal polyps and adjacent non-polypoidal sinonasal mucosa from 10 CRSwNP patients, and sinonasal mucosa from 10 control patients undergoing trans-sphenoidal pituitary surgery. Nasal polyp and control samples were also stimulated with Staphylococcus aureus enterotoxin B (SEB) using a nasal explant model, prior to cytokine analysis. Real time quantitative polymerase chain reaction (IL-5, T-bet, IL-17A, FoxP3, TLR-4, IL-8, IL-1β and IL-6) and Luminex (IFNγ, IL-5 and IL-17A) were used to quantify pro-inflammatory responses.Results: Nasal polyps and contiguous non-polypoidal sinonasal mucosa from CRSwNP patients displayed a very similar pro-inflammatory profile. When stimulated with SEB, nasal polyps displayed a Th2/Th17 mediated response when compared to controls.Conclusions: In CRSwNP, nasal polyps and non-polypoidal sinonasal mucosa from the same patient displayed a similar pro-inflammatory profile skewed towards the Th2/Th17 pathway in nasal polyps following SEB stimulation, with evidence of disordered bacterial clearance. These factors may contribute to enhanced survival of bacteria and development of a chronic inflammatory milieu, potentially driving new polyp formation and recurrence following surgical removal.<br/
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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