The relation between paracetamol use and asthma:a GA2LEN European case-control study

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (2045 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations

Herpes Simplex Virus Type 1 Infection Facilitates Invasion of Staphylococcus aureus into the Nasal Mucosa and Nasal Polyp Tissue

Background: Staphylococcus aureus (S. aureus) plays an important role in the pathogenesis of severe chronic airway disease, such as nasal polyps. However the mechanisms underlying the initiation of damage and/or invasion of the nasal mucosa by S. aureus are not clearly understood. The aim of this study was to investigate the interaction between S. aureus and herpes simplex virus type 1 (HSV1) in the invasion of the nasal mucosa and nasal polyp tissue. Methodology/Principal Findings: Inferior turbinate and nasal polyp samples were cultured and infected with either HSV1 alone, S. aureus alone or a combination of both. Both in turbinate mucosa and nasal polyp tissue, HSV1, with or without S. aureus incubation, led to focal infection of outer epithelial cells within 48 h, and loss or damage of the epithelium and invasion of HSV1 into the lamina propria within 72 h. After pre-infection with HSV1 for 24 h or 48 h, S. aureus was able to pass the basement membrane and invade the mucosa. Epithelial damage scores were significantly higher for HSV1 and S. aureus co-infected explants compared with control explants or S. aureus only-infected explants, and significantly correlated with HSV1-invasion scores. The epithelial damage scores of nasal polyp tissues were significantly higher than those of inferior turbinate tissues upon HSV1 infection. Consequently, invasion scores of HSV1 of nasal polyp tissues were significantly higher than those of inferior turbinate mucosa in the HSV1 and co-infection groups, and invasion scores of S. aureus of nasal polyp tissues were significantly higher than those of inferior turbinate tissues in the co-infection group. Conclusions/Significance: HSV1 may lead to a significant damage of the nasal epithelium and consequently may facilitate invasion of S. aureus into the nasal mucosa. Nasal polyp tissue is more susceptible to the invasion of HSV1 and epithelial damage by HSV1 compared with inferior turbinate mucosa

The EUFOREA pocket guide for chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS

Gene Transcription Changes in Asthmatic Chronic Rhinosinusitis with Nasal Polyps and Comparison to Those in Atopic Dermatitis

Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma.Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD.Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases

Non-Image-Forming Light Driven Functions Are Preserved in a Mouse Model of Autosomal Dominant Optic Atrophy

Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1Q285STOP mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies

Role of Innate Immunity in the Pathogenesis of Chronic Rhinosinusitis: Progress and New Avenues

Chronic rhinosinusitis is a heterogeneous and multifactorial disease with unknown etiology. Aberrant responses to microorganisms have been suggested to play a role in the pathophysiology of the disease. Research has focused on the presence, detection, response to, and eradication of these potential threats. Main topics seem to center on the contribution of structural cells such as epithelium and fibroblasts, on the consequences of activation of pattern-recognition receptors, and on the role of antimicrobial agents. This research should be viewed not only in the light of a comparison between healthy and diseased individuals, but also in a comparison between patients who do or do not respond to treatment. New players that could play a role in the pathophysiology seem to surface at regular intervals, adding to our understanding (and the complexity) of the disease and opening new avenues that may help fight this incapacitating disease

The EUFOREA pocket guide for chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS

Model-Based Methods for Assessment, Learning, and Instruction: Innovative Educational Technology at Florida State University

Abstract In this chapter, we describe our research and development efforts relating to eliciting, representing, and analyzing how individuals and small groups conceptualize complex problems. The methods described herein have all been devel-oped and are in various states of being validated. In addition, the methods we describe have been automated and most have been integrated in an online model-based set of tools called HIMATT (Highly Interactive Model-based Assessment Tools and Technologies; available for research purposes a

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