Spontaneous Eosinophilic Nasal Inflammation in a Genetically-Mutant Mouse: Comparative Study with an Allergic Inflammation Model

Background: Eosinophilic inflammation is a hallmark of chronic rhinosinusitis with nasal polyps. To model this disease process experimentally, nasal sensitization of mice with ovalbumin or aspergillus has been described. Here, we describe a genetically mutant mouse that develops robust spontaneous nasal eosinophilic inflammation. These mice lack the enzyme SHP-1 that down-regulates the IL-4Ra/stat6 signaling pathway. We compared nasal inflammation and inflammatory mediators in SHP-1 deficient mice (mev) and an ovalbumin-induced nasal allergy model. Methods: A novel technique of trans-pharyngeal nasal lavage was developed to obtain samples of inflammatory cells from the nasal passages of allergic and mev mice. Total and differential cell counts were performed on cytospin preparations. Expression of tissue mRNA for IL-4, IL-13, and mouse beta-defensin-1 (MBD-1) was determined by quantitative PCR. Eotaxin in the lavage fluid was assessed by ELISA. Results: Allergic and mev mice had increased total cells and eosinophils compared with controls. Expression of IL-4 was similarly increased in both allergic and mev mice, but expression of IL-13 and eotaxin was significantly greater in the allergic mice than mev mice. Eotaxin was significantly up-regulated in both allergic rhinitis and mev mice. In both models of eosinophilic inflammation, down-regulation of the innate immune marker MBD-1 was observed. Conclusions: The mev mice display spontaneous chronic nasal eosinophilic inflammation with potential utility for chroni

A uniform procedure for the purification of CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1

We have established a uniform procedure for the expression and purification of the cyclin-dependent kinases CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1. We attach a His(6)-tag to one of the subunits of each complex and then co-express it together with the other subunits in Spodoptera frugiperda insect cells. The CDK complexes are subsequently purified by Ni(2+)-NTA and Mono S chromatography. This approach generates large amounts of active recombinant kinases that are devoid of contaminating kinase activities. Importantly, the properties of these recombinant kinases are similar to their natural counterparts (Pinhero et al. 2004, Eur J Biochem 271:1004-14). Our protocol provides a novel systematic approach for the purification of these three (and possibly other) recombinant CDKs

Social media and sensemaking patterns in new product development: demystifying the customer sentiment

Artificial intelligence by principle is developed to assist but also support decision making processes. In our study, we explore how information retrieved from social media can assist decision-making processes for new product development (NPD). We focus on consumers’ emotions that are expressed through social media and analyse the variations of their sentiments in all the stages of NPD. We collect data from Twitter that reveal consumers’ appreciation of aspects of the design of a newly launched model of an innovative automotive company. We adopt the sensemaking approach coupled with the use of fuzzy logic for text mining. This combinatory methodological approach enables us to retrieve consensus from the data and to explore the variations of sentiments of the customers about the product and define the polarity of these emotions for each of the NPD stages. The analysis identifies sensemaking patterns in Twitter data and explains the NPD process and the associated steps where the social interactions from customers can have an iterative role. We conclude the paper by outlining an agenda for future research in the NPD process and the role of the customer opinion through sensemaking mechanisms

A mixed-data evaluation in group TOPSIS with differentiated decision power

[[abstract]]This main objective of this paper is to provide decision support for mixed data in group Technique for Order Preference by Similarity to Idea Solution (TOPSIS) with differentiated decision power. We use a signum function to compare the ordinal performance of alternatives on any qualitative criterion, or the partial information provided by decision makers. The proposed process for ordinal information is uniformly coherent with the traditional TOPSIS steps, preserving the characteristic of distance-based utilities. Ordinal weights are also considered herein, and the decision power of the group members is formulated by their weights under an agreement in the group. Two examples demonstrate that the proposed approach has some benefits and achieves robustness with two types of sensitivity analyses. Some discussions and their limitations to the approach are also provided.[[notice]]補正完

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

Canadian 24-hour movement guidelines for the early years (0–4 years): exploring the perceptions of stakeholders and end users regarding their acceptability, barriers to uptake, and dissemination

Background: It is important to engage stakeholders and end users in the development of guidelines for knowledge translation purposes. The aim of this study was to examine stakeholders’ (experts in pediatric and family medicine, physical activity knowledge translation, and research) and end users’ (parents and early childhood educators) perceptions of the Canadian 24-Hour Movement Guidelines for the Early Years (0–4 years). Methods: Stakeholders (n = 10) engaged in telephone interviews and end users (n = 92) participated in focus groups (n = 14) to discuss perceived clarity and need for the guidelines, potential barriers to implementation, identification of credible messengers, and methods for dissemination of the guidelines. A thematic analysis was conducted. Results: The proposed guidelines were very well received by both stakeholders and end users. A clear need for such guidelines was identified, and most believed the guidelines were achievable. Stakeholders and end users identified several potential barriers to uptake, including low awareness of current guidelines; ‘daily challenges’ such as allure of screen time, lack of time, and competing priorities; and challenges in the context of shifting social norms. A range of methods and messengers of dissemination were identified. Medical and child care settings were the most frequently cited places for dissemination, and physicians and early childhood educators were the most common suggestions for messengers. Conclusions: There was consistent support for the Canadian 24-Hour Movement Guidelines for the Early Years (0–4 years) from both stakeholders and end users. Moving forward, it is important to dedicate appropriate support and funding toward dissemination efforts in order to reach end users, particularly parents and early childhood educators.Education, Faculty ofNon UBCKinesiology, School ofReviewedFacult