Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

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.

Immune signatures underlying post-acute COVID-19 lung sequelae.

Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)­specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8+ T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.

Proinflammatory circulating markers: new players for evaluating asymptomatic acute cardiovascular toxicity in breast cancer treatment.

PURPOSE: This study aimed to evaluate markers of cardiac damage (total CK, CKMB and CRP), inflammatory markers (free iron, homocysteine and TNF-α) as well as lipidogram in breast cancer patients undergoing acute cycles of doxorubicin (DOX), paclitaxel (PTX) or trastuzumab (TZ) and to verify if there is an association between these markers and the toxicity of the chemotherapeutic treatment. Methods: Included in the study were 120 breast cancer patients and 50 healthy controls. All analyzes were performed on automated systems. For the statistical analysis, each group was compared with the controls according to their normality by Student's t-test and Mann-Whitney test. Results: Our results showed that DOX treatment led to increased hsCRP (4.80 ± 1.23 mg/dL, p = 0.0005), triglycerides (187.6 ± 25.06, p = 0.0231), TNF-α (42.31 ± 17.96 pg/mL, p = 0.01) and Fe levels (138.8 ± 18.6 µg/dL, p = 0.0193). In the meantime, PTX induced changes in CK-MB (8.78 ± 4.2 U/L, p = 0.0361), hsCRP (7.12 ± 1.87 mg/dL, p = 0.0006), cholesterol (201.7 ± 19.54, p = 0.05), triglycerides (201.7 ± 19.54, p = 0.0277), TNF-α (38.27 ± 9.12 pg/mL, p = 0.023), homocysteine (10.95 ± 0, 86 µmol/L, p = 0.005), and free iron (113 ± 18 6 µg/dL, p = 0.045) while TZ augmented CK-MB (6.9 ± 1.97 U/L, p < 0.00), hsPCR (3.12 ± 0.68 mg/dL, p = 0.095), cholesterol (218.3 ± 16.79, p = 0.0317), triglycerides (218.3 ± 16.79, p = 0.0127), TNF-α (89.6 ± 12.11, p = 0.032), homocysteine (9.95 ± 1.15 µmol/L, p = 0.0396), free iron (120.5 ± 4.64 µg/dl, p = 0.0058) as well. Conclusions: Our data demonstrated the existence of a proinflammatory net triggered by breast cancer chemotherapy that could increase cardiomyocytes permeability and allow the leakage of circulating proteins as CK-MB and induce the production of hsCRP.

Executive summary of EPOS 2020 including integrated care pathways.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012(1-3). The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings.

Ruminal transcript abundance of the centromere-associated protein E gene may influence residual feed intake in beef steers.

A better understanding regarding the mechanisms by which the rumen processes feed may assist us in identifying animals with superior feed efficiency. Studies to evaluate the gene expression of rumen tissue have previously been performed to analyze their relationship with feed efficiency. Continuing this research is critical to determine whether the expression of the genes identified is associated with feed efficiency in additional populations of beef cattle to ensure that they are robust across breed and environment. A previous rumen-transcriptome study on Hereford × Angus steers identified 122 differentially expressed genes (PFDR  < 0.05) associated with residual feed intake (RFI), a measure of feed efficiency. The purpose of our study was to test the most divergent, up- and down-regulated genes in the rumen tissue of an unrelated population of Hereford × Angus steers that included two contemporary groups. A total of 13 genes were evaluated by quantitative real-time PCR. The centromere-associated protein E (CENPE) gene was expressed in lower concentrations in the rumen epithelium of steers in the more efficient (low RFI) group in both contemporary groups of animals, which was the same as the previous study. In addition, CENPE, a gene involved in chromosome alignment during mitosis, has also been associated with growth traits in cattle and pigs. There was no relationship between the expression of the other 12 genes tested with RFI in the population of steers in this study, which illustrates the importance of validating gene expression data in additional populations.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

MCCB cognitive profile in Spanish first episode schizophrenia patients.

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB cognitive profile in a Spanish sample of FESz was similar to the cognitive profile of CSz with some discrepancies in select domains. The scores of both patient samples were about 1-2 SD below the scores of non-psychiatric control subjects.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

Longitudinal evaluation of clustering of chronic sinonasal and related symptoms using exploratory factor analysis.

BACKGROUND: Sinonasal symptoms are common and can have several underlying causes. When symptoms occur in specified patterns lasting 3 months or more they meet criteria for chronic rhinosinusitis (CRS). Approaches to CRS symptom measurement do not specify how to measure symptoms and treat specified sinonasal symptoms as generally interchangeable, suggesting that such symptoms should cluster on 1 or 2 latent factors. METHODS: We used questionnaire responses to 37 questions on the presence, severity, bother, and frequency of cardinal sinonasal and related symptoms lasting 3 months, from 3535 subjects at 3 time points over 16 months. We completed 5 exploratory factor analyses (EFA) to identify symptom clustering, 1 for each time point and 2 for the differences between adjacent questionnaires. The baseline EFA was used to provide factor scores that were described longitudinally and examined by CRS status. RESULTS: Five EFAs identified the same 5 factors (blockage and discharge, pain and pressure, asthma and cold/flu symptoms, smell loss, and ear and eye [mainly allergy] symptoms), with clustering determined by symptom frequency, severity, and degree of bother. Responses to individual questions showed changes over time but when combined into factor scores showed less longitudinal change. All symptom factor scores were progressively higher from never to past to current CRS status. CONCLUSIONS: Although the current approaches to symptom characterization in CRS imply a single underlying latent construct, our results suggest that there are at least 3 latent constructs relevant to CRS. Further studies are needed to evaluate whether these clusters have identifiable underlying pathobiologies.

Short-chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down-regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs. OBJECTIVE: The objective of this study was to determine whether short-chain fatty acids (SCFAs) can induce t-PA in airway epithelial cells via their known receptors GPR41 and GPR43. METHODS: We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein-coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t-PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA. RESULTS: Immunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t-PA expression from two- to tenfolds. The strongest inducer of t-PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t-PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43. CONCLUSIONS AND CLINICAL RELEVANCE: Short-chain fatty acids were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.

Prevalence, severity, and risk factors for acute exacerbations of nasal and sinus symptoms by chronic rhinosinusitis status.

BACKGROUND: Nasal and sinus symptoms (NSS) are common to many health conditions, including chronic rhinosinusitis (CRS). Few studies have investigated the occurrence and severity of, and risk factors for, acute exacerbations of NSS (AENSS) by CRS status (current, past, or never met European Position Paper on Rhinosinusitis [EPOS] criteria for CRS). METHODS: Four seasonal questionnaires were mailed to a stratified random sample of Geisinger primary care patients. Logistic regression was used to identify individual characteristics associated with AENSS occurrence and severity by CRS status (current long-term, current recent, past, never) using EPOS subjective symptoms-only (EPOSS ) CRS criteria. We operationalized 3 AENSS definitions based on prescribed antibiotics or oral corticosteroids, symptoms, and symptoms with purulence. RESULTS: Baseline and at least 1 follow-up questionnaires were available from 4736 subjects. Self-reported NSS severity with exacerbation was worst in the current long-term CRS group. AENSS was common in all subgroups examined and generally more common among those with current EPOSS CRS. Seasonal prevalence of AENSS differed by AENSS definition and CRS status. Associations of risk factors with AENSS differed by definition, but CRS status, body mass index, asthma, hay fever, sinus surgery history, and winter season consistently predicted AENSS. CONCLUSIONS: In this first longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were both common, sometimes severe, and differed by EPOSS CRS status. Contrasting associations of risk factors for AENSS by the different definitions suggest a need for a standardized approach to definition of AENSS.

Perceptions on the value of bodily functions in multiple sclerosis.

BACKGROUND: In neurological diseases presenting with a plethora of symptoms, the value of bodily functions for a given patient might be a guide for clinical management. Multiple sclerosis (MS) is paradigmatic in this respect, and little is known about the value of different bodily functions of patients and their physicians' perceptions. METHODS: In a multicenter study, 171 patients with relapsing-remitting multiple sclerosis (RRMS), 61% with a clinically active disease within the last 2 years were followed over up to 3 years and yearly patients and their study physician rated on the perceived value of 13 bodily functions via a priority list. Differences between patients and physicians as well as modulating disease demographic factors were analyzed. RESULTS: Patients with RRMS rated visual function followed by thinking and memory and walking highest while physicians stressed mobility, followed by thinking and memory and alertness most. Ratings were independent from disease duration or disability. Strongest value judgment differences were seen in swallowing regarded more relevant by patients and hand function regarded more relevant by physicians. In general, patients' and physicians' ratings through time were quite stable. Collapsing physical items into a physical functioning scale and mental items in a mental function scale, both dimensions were regarded equally important by patients while physicians underscored physical functioning (P = .016). CONCLUSION: There are differences between patients and physicians in value statements of bodily functions in MS. In particular, visual functioning is under-recognized by physicians.

Genetically driven brain serotonin deficiency facilitates panic-like escape behavior in mice.

Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings. Our findings indicate that constitutive Tph2 inactivation and consequential lack of 5-HT synthesis in Tph2 null mutant mice (Tph2-/-) results in increased freezing to associated foot shock and a differential c-Fos activity pattern in the basolateral complex of the amygdala. This is accompanied by altered GABAergic transmission as observed by recordings of inhibitory postsynaptic currents on principal neurons in the basolateral nucleus, which may explain increased fear associated with hyperlocomotion and escape-like responses in aversive inescapable contexts. In contrast, lifelong 5-HT deficiency as observed in Tph2 heterozygous mice (Tph+/-) is able to be compensated through reduced GABAergic transmission in the basolateral nucleus of the amygdala based on Slc6a4 mRNA upregulation in subdivisions of dorsal raphe neurons. This results in increased activity of the basolateral nucleus of the amygdala due to associated foot shock. In conclusion, our results reflect characteristic syndromal dimensions of panic disorder and agoraphobia. Thus, constitutive lack of 5-HT synthesis influence the risk for anxiety- and stressor-related disorders including panic disorder and comorbid agoraphobia through the absence of GABAergic-dependent compensatory mechanisms in the basolateral nucleus of the amygdala.

Developing an international scoring system for a consensus-based social cognition measure: MSCEIT-managing emotions.

BACKGROUND: Measures of social cognition are increasingly being applied to psychopathology, including studies of schizophrenia and other psychotic disorders. Tests of social cognition present unique challenges for international adaptations. The Mayer-Salovey-Caruso Emotional Intelligence Test, Managing Emotions Branch (MSCEIT-ME) is a commonly-used social cognition test that involves the evaluation of social scenarios presented in vignettes. METHOD: This paper presents evaluations of translations of this test in six different languages based on representative samples from the relevant countries. The goal was to identify items from the MSCEIT-ME that show different response patterns across countries using indices of discrepancy and content validity criteria. An international version of the MSCEIT-ME scoring was developed that excludes items that showed undesirable properties across countries. RESULTS: We then confirmed that this new version had better performance (i.e. less discrepancy across regions) in international samples than the version based on the original norms. Additionally, it provides scores that are comparable to ratings based on local norms. CONCLUSIONS: This paper shows that it is possible to adapt complex social cognitive tasks so they can provide valid data across different cultural contexts.

Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample.

BACKGROUND: The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general-population sample. METHODS: A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups. RESULTS: We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms. CONCLUSIONS: CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.

Ruminal expression of the NQO1, RGS5, and ACAT1 genes may be indicators of feed efficiency in beef steers.

Ruminal genes differentially expressed in crossbred beef steers from USMARC with variation in gain and feed intake were identified in a previous study. Several of the genes identified with expression patterns differing between animals with high gain-low feed intake and low gain-high feed intake were evaluated in a separate, unrelated population of Angus × Hereford beef steers from the University of Wyoming that was classified to differ in residual feed intake (RFI). Of the 17 genes tested, two were differentially expressed by RFI class in the Angus × Hereford animals. These genes included NAD(P)H dehydrogenase, quinone 1 (NQO1; P = 0.0009) and regulator of G-protein signaling 5 (RGS5; P = 0.01). A third gene, acetyl-CoA acetyltransferase 1 (ACAT1; P = 0.06), displayed a trend toward association with RFI. These data suggest that some of the genes identified in a previous rumen transcriptome discovery study may have utility for identifying or selecting for animals with superior feed efficiency phenotypes across cattle breeds and populations.

Chronic airway inflammation provides a unique environment for B cell activation and antibody production.

BACKGROUND: B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways. OBJECTIVE: We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation. METHODS: We analysed B cells from NP or tonsil, or after ILC2 coculture, by flow cytometry. Antibody production from tissue was measured using Luminex assays and the frequency of antibody-secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT-PCR. RESULTS: NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extrafollicular marker Epstein-Barr virus-induced protein 2 (EBI2), but significantly fewer germinal centre (GC) B cells compared with tonsil. Antibody production and the frequency of antibody-secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC-mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell-targeted therapies may provide new treatment options for CRSwNP.

Differential gene expression in the duodenum, jejunum and ileum among crossbred beef steers with divergent gain and feed intake phenotypes.

Small intestine mass and cellularity were previously associated with cattle feed efficiency. The small intestine is responsible for the digestion of nutrients and absorption of fatty acids, amino acids and carbohydrates, and it contributes to the overall feed efficiency of cattle. The objective of this study was to evaluate transcriptome differences among the small intestine from cattle with divergent gain and feed intake. Animals most divergent from the bivariate mean in each of the four phenotypic Cartesian quadrants for gain × intake were selected, and the transcriptomes of duodenum, jejunum and ileum were evaluated. Gene expression analyses were performed comparing high gain vs. low gain animals, high intake vs. low intake animals and each of the phenotypic quadrants to all other groups. Genes differentially expressed within the high gain-low intake and low gain-high intake groups of animals included those involved in immune function and inflammation in all small intestine sections. The high gain-high intake group differed from the high gain-low intake group by immune response genes in all sections of the small intestine. In all sections of small intestine, animals with low gain-low intake displayed greater abundance of heat-shock genes compared to other groups. Several over-represented pathways were identified. These include the antigen-processing/presentation pathway in high gain animals and PPAR signaling, starch/sucrose metabolism, retinol metabolism and melatonin degradation pathways in the high intake animals. Genes with functions in immune response, inflammation, stress response, influenza pathogenesis and melatonin degradation pathways may have a relationship with gain and intake in beef steers.