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3From the publisher: "Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs." Authors: Jolanda H. M. van BilsenEmail author, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx and Erwin L. Roggen
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Background: The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists. Objectives: Designing the first set of classification criteria for the classification of central sensitization pain. Methods: A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain. Results: It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory). Limitations: Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies. Conclusion: Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain. Key words: Chronic pain, diagnosis, hypersensitivity, classification, neuropathic pain
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People make trait inferences based on facial appearance, and these inferences guide social approach and avoidance. Here, we investigate the effects of textural features on trait impressions from faces. In contrast to previous work, which exclusively manipulated skin smoothness, we manipulated smoothness and the presence of skin blemishes independently (Study 1) and orthogonally (Study 2). We hypothesized that people are particularly sensitive to skin blemishes because blemishes potentially indicate poor health and the presence of an infectious disease. We therefore predicted that the negative effect of blemished skin is stronger than the positive effect of smoothed skin. The results of both studies are in line with this reasoning. Across ratings of trustworthiness, competence, maturity, attractiveness, and health, the negative influence of skin blemishes was stronger and more consistent than the positive influence of skin smoothness (Study 1). Moreover, the presence of skin blemishes diminished the positive effect of skin smoothness on attractiveness ratings (Study 2). In sum, both facial skin blemishes and facial skin smoothness influence trait impression, but the negative effect of blemished skin is larger and more salient than the positive effect of smooth skin.
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Background: Dermoscopy is known to increase the diagnostic accuracy of pigmented skin lesions (PSLs) when used by trained professionals. The effect of dermoscopy training on the diagnostic ability of dermal therapists (DTs) has not been studied so far. Objectives: This study aimed to investigate whether DTs, in comparison with general practitioners (GPs), benefited from a training programme including dermoscopy, in both their ability to differentiate between different forms of PSL and to assign the correct therapeutic strategy. Methods: In total, 24 DTs and 96 GPs attended a training programme on PSLs. Diagnostic skills as well as therapeutic strategy were assessed, prior to the training (pretest) and after the training (post-test) using clinical images alone, as well as after the addition of dermatoscopic images (integrated post-test). Bayesian hypothesis testing was used to determine statistical significance of differences between pretest, post-test and integrated post-test scores. Results: Both the DTs and the GPs demonstrated benefit from the training: at the integrated post-test, the median proportion of correctly diagnosed PSLs was 73% (range 30–90) for GPs and 63% (range 27–80) for DTs. A statistically significant difference between pretest results and integrated test results was seen, with a Bayes factor>100. At 12 percentage points higher, the GPs outperformed DTs in the accuracy of detecting PSLs. Conclusions: The study shows that a training programme focusing on PSLs while including dermoscopy positively impacts detection of PSLs by DTs and GPs. This training programme could form an integral part of the training of DTs in screening procedures, although additional research is needed.
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From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "
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Chronic itching is a serious and uncomfortable condition. The scratch response might result in a vicious cycle of alternating itching and scratching. To develop psychological interventions for people suffering from chronic itching and to break the vicious itch-scratching-itch cycle, it is important to elucidate which environmental factors trigger itch sensations. Virtual reality (VR) techniques provide a useful tool to examine specific content characteristics in a three-dimensional (3D VR) environment and their influences on itch sensations and scratching behaviour. This article describes two experiments in which we focused on the effects of environmental information on itching and scratching behaviour. Additionally, in the second experiment, we examined the influence of having a chronic skin condition on sensitivity to itch induction. We found evidence for the importance of the content of audio–visual materials for the effectiveness in inducing feelings of itch in the observers. In both experiments, we observed significantly higher levels of perceived itch in the itch-inducing conditions than in the control condition. Moreover, the results showed that elevated levels of perceived itch were associated with an increase in scratching behaviours, which was especially salient in the contagious itch condition, in which perceived itch was accompanied by a significant increase in the number of scratches. Experiment 2 additionally showed increased perceived itch levels in participants who reported having a chronic skin condition, reflecting higher sensitivity to itch-inducing audio–visual stimuli in this group than in participants without a chronic skin condition. Based on the results we concluded that directing attention towards itch- or scratch aspects of related information in the environment and to the consequences for one’s own skin are effective tools to induce itch sensations and scratching behaviour. This knowledge provides tools for developing novel strategies in advising and treating people suffering from chronic itching and breaking the vicious itch-scratching-itch cycle.
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International Innovation is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the publication can be found at: www.researchmedia.eu
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Abstract Background Dermoscopy is known to increase the diagnostic accuracy of pigmented skin lesions (PSLs) when used by trained professionals. The effect of dermoscopy training on the diagnostic ability of dermal therapists (DTs) has not been studied so far. Objectives This study aimed to investigate whether DTs, in comparison with general practitioners (GPs), benefited from a training programme including dermoscopy, in both their ability to differentiate between different forms of PSL and to assign the correct therapeutic strategy. Methods In total, 24 DTs and 96 GPs attended a training programme on PSLs. Diagnostic skills as well as therapeutic strategy were assessed, prior to the training (pretest) and after the training (post-test) using clinical images alone, as well as after the addition of dermatoscopic images (integrated post-test). Bayesian hypothesis testing was used to determine statistical significance of differences between pretest, post-test and integrated post-test scores. Results Both the DTs and the GPs demonstrated benefit from the training: at the integrated post-test, the median proportion of correctly diagnosed PSLs was 73% (range 30–90) for GPs and 63% (range 27–80) for DTs. A statistically significant difference between pretest results and integrated test results was seen, with a Bayes factor>100. At 12 percentage points higher, the GPs outperformed DTs in the accuracy of detecting PSLs. Conclusions The study shows that a training programme focusing on PSLs while including dermoscopy positively impacts detection of PSLs by DTs and GPs. This training programme could form an integral part of the training of DTs in screening procedures, although additional research is needed
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This article gives information on an international ring trial of the epidermal-equivalent (EE) sensitizer potency assay.
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From Pubmed: " BACKGROUND: Antigen-specific immunotherapy (AIT) is a promising therapeutic approach for both cow's milk allergy (CMA) and peanut allergy (PNA), but needs optimization in terms of efficacy and safety. AIM: Compare oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and determine the dose of allergen needed to effectively modify parameters of allergy. METHODS: Female C3H/HeOuJ mice were sensitized intragastrically (i.g.) to whey or peanut extract with cholera toxin. Mice were treated orally (5 times/week) or subcutaneously (3 times/week) for three consecutive weeks. Hereafter, the acute allergic skin response, anaphylactic shock symptoms and body temperature were measured upon intradermal (i.d.) and intraperitoneal (i.p.) challenge, and mast cell degranulation was measured upon i.g. challenge. Allergen-specific IgE, IgG1 and IgG2a were measured in serum at different time points. Single cell suspensions derived from lymph organs were stimulated with allergen to induce cytokine production and T cell phenotypes were assessed using flow cytometry. RESULTS: Both OIT and SCIT decreased clinically related signs upon challenge in the CMA and PNA model. Interestingly, a rise in allergen-specific IgE was observed during immunotherapy, hereafter, treated mice were protected against the increase in IgE caused by allergen challenge. Allergen-specific IgG1 and IgG2a increased due to both types of AIT. In the CMA model, SCIT and OIT reduced the percentage of activated Th2 cells and increased the percentage of activated Th1 cells in the spleen. OIT increased the percentage of regulatory T cells (Tregs) and activated Th2 cells in the MLN. Th2 cytokines IL-5, IL-13 and IL-10 were reduced after OIT, but not after SCIT. In the PNA model, no differences were observed in percentages of T cell subsets. SCIT induced Th2 cytokines IL-5 and IL-10, whereas OIT had no effect. CONCLUSION: We have shown clinical protection against allergic manifestations after OIT and SCIT in a CMA and PNA model. Although similar allergen-specific antibody patterns were observed, differences in T cell and cytokine responses were shown. Whether these findings are related to a different mechanism of AIT in CMA and PNA needs to be elucidated."
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