International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

A novel allele of Alx4 results in reduced Fgf10 expression and failure of eyelid fusion in mice.

Normal fusion of developing eyelids requires coordination of inductive signals from the eyelid mesenchyme with migration of the periderm cell layer and constriction of the eyelids across the eye. Failure of this process results in an eyelids open at birth (EOB) phenotype in mice. We have identified a novel spontaneous allele of Alx4 that displays EOB, in addition to polydactyly and cranial malformations. Alx4 is expressed in the eyelid mesenchyme prior to and during eyelid fusion in a domain overlapping the expression of genes that also play a role in normal eyelid development. We show that Alx4 mutant mice have reduced expression of Fgf10, a key factor expressed in the mesenchyme that is required for initiation of eyelid fusion by the periderm. This is accompanied by a reduced number of periderm cells expressing phosphorylated c-Jun, consistent with the incomplete ablation of Fgf10 expression. Together, these data demonstrate that eyelid fusion in mice requires the expression of Alx4, accompanied by the loss of normal expression of essential components of the eyelid fusion pathway. Mamm Genome 2015 Apr; 26(3-4):173-8

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma

BACKGROUND AND AIMS: Cyclooxygenase 2 (COX‐2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX‐2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP‐1) and COX‐2 were determined by immunohistochemistry. The effects of MCP‐1, in the presence or absence of celecoxib, on COX‐2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP‐1 levels were markedly higher in adenoma with mild‐moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)‐1α and MIP‐1β, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP‐1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP‐1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP‐1 stimulated COX‐2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX‐2 inhibitor, inhibited MCP‐1‐induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP‐1 in adenoma epithelial cells might be involved in COX‐2 expression and subsequent macrophage activation. CONCLUSIONS: MCP‐1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX‐2 expression, leading to the subsequent development of colonic adenoma

Outdoor Advertising in Urban Context: Spatiality, Temporality and Individuality

This paper considers the interplay between outdoor advertising and the urban environment. This is conceptualised as a movement from traditional, two-dimensional outdoor advertising, through three dimensional and four dimensional, towards a more overt multimodal perspective. The paper highlights a series of interesting ontological shifts relating the visual, embodied and performative function of such advertising signs, whereby product marketing begins to increasingly incorporate place, encompassing a sophisticated use of ‘spatiality’ (e.g. buildings and spaces) as well as ‘temporality’ (e.g. movement and mapping) as integral elements of communications strategy. With emerging technology, we begin to observe an emphasis towards ‘interactive out-of-home experience’ (e.g. through locative and social media). This paper contributes to the debate in arguing that these aspects (in isolation or in combination) have the potential to change the relationship(s) between outdoor advertising, the urban environment and its people, with potentially very significant implications not only for marketing activity, but also our relationships with the towns and cities we inhabit. The paper concludes by introducing three tendencies – towards spectacle, portal and fluid space – as key constituents of present and future forms of outdoor advertising