Pathogenesis of nasal polyposis Hulse, K. E.; Stevens, W. W.; Tan, B. K. ...
Clinical and experimental allergy,
February 2015, Letnik:
45, Številka:
2
Journal Article
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Summary
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition that affects a large proportion of the population world‐wide and is associated with high cost of ...management and significant morbidity. Yet, there is a lack of population‐based epidemiologic studies using current definitions of CRSwNP, and the mechanisms that drive pathogenesis in this disease remain unclear. In this review, we summarize the current evidence for the plethora of factors that likely contribute to CRSwNP pathogenesis. Defects in the innate function of the airway epithelial barrier, including diminished expression of antimicrobial products and loss of barrier integrity, combined with colonization by fungi and bacteria likely play a critical role in the development of chronic inflammation in CRSwNP. This chronic inflammation is characterized by elevated expression of many key inflammatory cytokines and chemokines, including IL‐5, thymic stromal lymphopoietin and CCL11, that help to initiate and perpetuate this chronic inflammatory response. Together, these factors likely combine to drive the influx of a variety of immune cells, including eosinophils, mast cells, group 2 innate lymphoid cells and lymphocytes, which participate in the chronic inflammatory response within the nasal polyps. Importantly, however, future studies are needed to demonstrate the necessity and sufficiency of these potential drivers of disease in CRSwNP. In addition to the development of new tools and models to aid mechanistic studies, the field of CRSwNP research also needs the type of robust epidemiologic data that has served the asthma community so well. Given the high prevalence, costs and morbidity, there is a great need for continued research into CRS that could facilitate the development of novel therapeutic strategies to improve treatment for patients who suffer from this disease.
Working memory, a fundamental cognitive function that is highly dependent on the integrity of the prefrontal cortex, is known to show age-related decline across the typical healthy adult lifespan. ...Moreover, we know from work in neurophysiology that the prefrontal cortex is disproportionately susceptibly to the pathological effects of aging. The n-back task is arguably the most ubiquitous cognitive task for investigating working memory performance. Many functional magnetic resonance imaging (fMRI) studies examine brain regions engaged during performance of the n-back task in adults. The current meta-analyses are the first to examine concordance and age-related changes across the healthy adult lifespan in brain areas engaged when performing the n-back task. We compile data from eligible fMRI articles that report stereotaxic coordinates of brain activity from healthy adults in three age-groups: young (23.57 ± 5.63 years), middle-aged (38.13 ± 5.63 years) and older (66.86 ± 5.70 years) adults. Findings show that the three groups share concordance in the engagement of parietal and cingulate cortices, which have been consistently identified as core areas involved in working memory; as well as the insula, claustrum, and cerebellum, which have not been highlighted as areas involved in working memory. Critically, prefrontal cortex engagement is concordant for young, to a lesser degree for middle-aged adults, and absent in older adults, suggesting a gradual linear decline in concordance of prefrontal cortex engagement. Our results provide important new knowledge for improving methodology and theories of cognition across the lifespan.
•Normative meta-analyses of n-back functional correlates across the lifespan.•Insula and cerebellum are concordant for young, middle aged and older adults.•Prefrontal cortex not reliably implicated as a function of age.•Reorganization of functional areas supporting working memory in healthy aging.
Background:
Gaming disorder was included in the latest revision of the International Classification of Diseases (11th ed.). Worldwide, prevalence estimates of gaming disorder are considerably ...heterogeneous and often appear to be exceedingly high. However, few studies have examined the methodological, cultural and/or demographic factors that might explain this phenomenon. This review employed meta-analytic techniques to compute the worldwide-pooled prevalence of gaming disorder and evaluate the potential contributing factors for varied prevalence estimates.
Method:
Prevalence estimates were extracted from 53 studies conducted between 2009 and 2019, which included 226,247 participants across 17 different countries. Study findings were meta-analyzed using a random-effects model. Subgroup and moderator analyses examined potential sources of heterogeneity, including assessment tool and cut-off, participant age and gender, sample size and type, study region, and year of data collection.
Results:
The worldwide prevalence of gaming disorder was 3.05% (confidence interval: 2.38, 3.91); this figure was adjusted to 1.96% 0.19, 17.12 when considering only studies that met more stringent sampling criteria (e.g. stratified random sampling). However, these estimates were associated with significant variability. The choice of screening tool accounted for 77% of the variance, with the Lemmens Internet gaming disorder-9, Gaming Addiction Identification Test and Problematic Videogame Playing scales associated with the highest estimates. Adolescent samples, lower cut-off scores and smaller sample size were significant predictors of higher prevalence. Gaming disorder rates were approximately 2.5:1 in favor of males compared to females.
Conclusion:
The worldwide prevalence of gaming disorder appears to be comparable to obsessive-compulsive disorder and some substance-related addictions, but lower than compulsive buying and higher than problem gambling. Gaming disorder prevalence rates appear to be inflated by methodological characteristics, particularly measurement and sampling issues.
Human cognition is increasingly characterized as an emergent property of interactions among distributed, functionally specialized brain networks. We recently demonstrated that the antagonistic ...“default” and “dorsal attention” networks—subserving internally and externally directed cognition, respectively—are modulated by a third “frontoparietal control” network that flexibly couples with either network depending on task domain. However, little is known about the intrinsic functional architecture underlying this relationship. We used graph theory to analyze network properties of intrinsic functional connectivity within and between these three large-scale networks. Task-based activation from three independent studies were used to identify reliable brain regions (“nodes”) of each network. We then examined pairwise connections (“edges”) between nodes, as defined by resting-state functional connectivity MRI. Importantly, we used a novel bootstrap resampling procedure to determine the reliability of graph edges. Furthermore, we examined both full and partial correlations. As predicted, there was a higher degree of integration within each network than between networks. Critically, whereas the default and dorsal attention networks shared little positive connectivity with one another, the frontoparietal control network showed a high degree of between-network interconnectivity with each of these networks. Furthermore, we identified nodes within the frontoparietal control network of three different types—default-aligned, dorsal attention-aligned, and dual-aligned—that we propose play dissociable roles in mediating internetwork communication. The results provide evidence consistent with the idea that the frontoparietal control network plays a pivotal gate-keeping role in goal-directed cognition, mediating the dynamic balance between default and dorsal attention networks.
Gas separation membranes can be applied to a range of processing steps during natural gas treatment. This paper considers the current and future potential of polymeric membranes in acidic gas ...removal, heavy hydrocarbon recovery, water dehydration as well as nitrogen and helium separation. In particular, the current commercial membrane materials for CO2 removal (cellulose acetate, polyimides and perfluoropolymers) are reviewed, along with membrane process design and the conditions required to make membrane processes economically competitive with other technologies. The current application of membranes for heavy hydrocarbon recovery is also investigated. Issues affecting membrane viability are explored, such as competitive sorption, plasticization and the influence of module design on performance. In addition, for each application, comments are provided on the future progress of membranes in these areas. Membranes for dehydration, nitrogen separation and helium recovery are less developed, so the current potential for membranes in those applications are reviewed with a focus on the direction of future research to achieve commercially viable processes.
Summary Background Information about trends in adolescent health inequalities is scarce, especially at an international level. We examined secular trends in socioeconomic inequality in five domains ...of adolescent health and the association of socioeconomic inequality with national wealth and income inequality. Methods We undertook a time-series analysis of data from the Health Behaviour in School-aged Children study, in which cross-sectional surveys were done in 34 North American and European countries in 2002, 2006, and 2010 (pooled n 492 788). We used individual data for socioeconomic status (Health Behaviour in School-aged Children Family Affluence Scale) and health (days of physical activity per week, body-mass index Z score zBMI, frequency of psychological and physical symptoms on 0–5 scale, and life satisfaction scored 0–10 on the Cantril ladder) to examine trends in health and socioeconomic inequalities in health. We also investigated whether international differences in health and health inequalities were associated with per person income and income inequality. Findings From 2002 to 2010, average levels of physical activity (3·90 to 4·08 days per week; p<0·0001), body mass (zBMI −0·08 to 0·03; p<0·0001), and physical symptoms (3·06 to 3·20, p<0·0001), and life satisfaction (7·58 to 7·61; p=0·0034) slightly increased. Inequalities between socioeconomic groups increased in physical activity (−0·79 to −0·83 days per week difference between most and least affluent groups; p=0·0008), zBMI (0·15 to 0·18; p<0·0001), and psychological (0·58 to 0·67; p=0·0360) and physical (0·21 to 0·26; p=0·0018) symptoms. Only in life satisfaction did health inequality fall during this period (−0·98 to −0·95; p=0·0198). Internationally, the higher the per person income, the better and more equal health was in terms of physical activity (0·06 days per SD increase in income; p<0·0001), psychological symptoms (−0·09; p<0·0001), and life satisfaction (0·08; p<0·0001). However, higher income inequality uniquely related to fewer days of physical activity (−0·05 days; p=0·0295), higher zBMI (0·06; p<0·0001), more psychological (0·18; p<0·0001) and physical (0·16; p<0·0001) symptoms, and larger health inequalities between socioeconomic groups in psychological (0·13; p=0·0080) and physical (0·07; p=0·0022) symptoms, and life satisfaction (−0·10; p=0·0092). Interpretation Socioeconomic inequality has increased in many domains of adolescent health. These trends coincide with unequal distribution of income between rich and poor people. Widening gaps in adolescent health could predict future inequalities in adult health and need urgent policy action. Funding Canadian Institutes of Health Research.
Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an era focused on phenotype to ...include endotype‐based information. Phenotypic classification has identified clinical heterogeneity in CRS based on endoscopically observed features such as presence of nasal polyps, presence of comorbid or systemic diseases, and timing of disease onset. More recently, laboratory‐based findings have established CRS endotype based upon specific mechanisms or molecular biomarkers. Understanding the basis of widespread heterogeneity in the manifestations of CRS is advanced by findings that the three main endotypes, Type 1, 2, and 3, orchestrate the expression of three distinct large sets of genes. The development and use of improved methods of endotyping disease in the clinic are ushering in an expansion of the use of biological therapies targeting Type 2 inflammation now and perhaps other inflammatory endotypes in the near future. The purpose of this review is to discuss the phenotypic and endotypic heterogeneity of CRS from the perspective of advancing the understanding of the pathogenesis and improvement of treatment approaches and outcomes.
The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted ...a prospective study with Crohn’s disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community α-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function; 13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment.
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•Stool metagenomes of IBD patients starting biologic therapy were prospectively assessed•Higher abundance of butyrate producers at baseline in therapy-responsive CD patients•Baseline enrichment of 13 microbial pathways in therapy-responsive CD patients•Early microbial changes at week 14 persist up to 1 year in responders
Gut microbiome may predict responses to clinical therapy. Ananthakrishnan et al. conducted a prospective study with IBD patients initiating anti-integrin therapy. Higher abundance of butyrate producers and enrichment of 13 microbial pathways at baseline in therapy-responsive CD patients was observed. Early microbial changes persist up to 1 year in responders.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a chronic type 2 inflammatory response in the paranasal sinuses. Group 2 innate lymphoid cells (ILC2s) are potent innate immune ...cells that contribute to type 2 inflammation by producing cytokines such as interleukin (IL)-4, IL-5, and IL-13. There is increasing evidence suggesting that ILC2s play an important role in the CRSwNP pathogenesis.
We reviewed published literature obtained through PubMed inquiries.
Studies relevant to the presence, function, and activation of ILC2s in CRSwNP were included.
Nasal polyps (NPs) are one of the first tissues in which human ILC2s were discovered, and many groups have since reported that these cells are highly elevated in NPs. ILC2s in NPs are also highly activated and produce type 2 cytokines in vivo. Mediators known to activate ILC2s, including receptor activator of nuclear factor kappa-Β ligand, thymic stromal lymphopoietin, various lipid mediators (including prostaglandin D
and cysteinyl leukotrienes), IL-4, and IL-13 have also been shown to be elevated in NPs compared with healthy sinonasal tissue. Other well-known ILC2 activators, IL-25 and IL-33, are sometimes elevated in NPs in some countries. Furthermore, activation of ILC2s by means of 4 distinct transcriptional pathways (nuclear factor kappa-light-chain-enhancer of activated B cells, nuclear factor of activated T cells, signal transducer and activator of transcription 5, and signal transducer and activator of transcription 6) is needed for the most robust generation of type 2 cytokines.
ILC2-mediated type 2 inflammation plays a crucial role in the pathogenesis of CRSwNP. Targeting the upstream mediators responsible for activating ILC2s and the downstream products that these cells release may play an important role in modifying the inflammatory response and improving clinical outcomes in CRSwNP.
Tasks that demand externalized attention reliably suppress default network activity while activating the dorsal attention network. These networks have an intrinsic competitive relationship; ...activation of one suppresses activity of the other. Consequently, many assume that default network activity is suppressed during goal-directed cognition. We challenge this assumption in an fMRI study of planning. Recent studies link default network activity with internally focused cognition, such as imagining personal future events, suggesting a role in autobiographical planning. However, it is unclear how goal-directed cognition with an internal focus is mediated by these opposing networks. A third anatomically interposed ‘frontoparietal control network’ might mediate planning across domains, flexibly coupling with either the default or dorsal attention network in support of internally versus externally focused goal-directed cognition, respectively. We tested this hypothesis by analyzing brain activity during autobiographical versus visuospatial planning. Autobiographical planning engaged the default network, whereas visuospatial planning engaged the dorsal attention network, consistent with the anti-correlated domains of internalized and externalized cognition. Critically, both planning tasks engaged the frontoparietal control network. Task-related activation of these three networks was anatomically consistent with independently defined resting-state functional connectivity MRI maps. Task-related functional connectivity analyses demonstrate that the default network can be involved in goal-directed cognition when its activity is coupled with the frontoparietal control network. Additionally, the frontoparietal control network may flexibly couple with the default and dorsal attention networks according to task domain, serving as a cortical mediator linking the two networks in support of goal-directed cognitive processes.
►Spatiotemporal PLS and rsfcMRI analysis identified distributed brain networks.►The default mode network was engaged during goal-directed behavior.►Default activity was co-active, and coupled, with the frontoparietal control network.
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