From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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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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From 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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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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Muscle fiber-type specific expression of UCP3-protein is reported here for the firts time, using immunofluorescence microscopy
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This text is structured as follows. Section 1 concerns the background to this public lecture: the fact that social participation is becoming increasingly important in our society. This is evident, for example, from the way we are evolving from a protective welfare state into an activational, participative society. This development has consequences for the social sector and therefore also for the professionals who work in it. Social work professionals are not necessarily expected to identify or solve participation problems; they are seen as intermediaries who enable citizens to take responsibility themselves. Social work professionals are therefore expected to provide the individual applicant with less direct support and to focus more on strengthening the social networks of people and the social contexts in which they find themselves. Section 2 connects sections 1 and 3, but may also be read independently. It is about the fact that social work professionals are not yet in the habit of providing systematic insight into the results of their actions, while policy makers, for example, are increasingly looking to them precisely for this. First of all, I set out the reasons why it is so important to make the products of their interventions more visible, not only to policy makers, but also to social work professionals themselves and to the customers/citizens who depend on them. Secondly, I set out how the results of social interventions can be made more visible than they are at present; and what research can contribute. In this, I advocate a change in thinking: from thinking in terms of the evidence to thinking in terms of the evident. This argument forms the basis of the type of research that is being taken up from within the research group. In section 3, I describe a number of research projects that will be conducted during my tenure. I also set out the main proposition of this address, which states that social work professionals should do more with the knowledge that peoples behaviour is determined to a significant degree by contexts. In particular, social contexts could play a bigger role in promoting citizen participation. At present, social work professionals normally intervene directly in peoples behaviour, such as with therapies for combating problem behaviour. Interventions in a broader, social, context are rare. Why is this? And couldnt citizen participation be more effectively promoted by these means than through direct behavioural interventions? I put forward four propositions in this regard, and explain each of them in reference to one of the current research projects within the research group. With this, in combination with the general outlines of the research presented in section 2, I hope to provide a clear and inspiring overview of the research that will be carried out within the research group in the coming years. Finally, in section 4, I will discuss the significance of the research group to the faculty of Society and Law at Hogeschool Utrecht University of Applied Sciences, and to parties outside of Hogeschool Utrecht University of Applied Sciences.
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Aim: Midwives are expected to identify and help resolve ethics problems that arise in practice, skills that are presumed to be taught in midwifery educational programs. In this study, we explore how midwives recognize ethical dilemmas in clinical practice and examine the sources of their ethics education. Methods: We conducted semi-structured, individual interviews with midwives from throughout the United States (U.S.) (n = 15). Transcripts of the interviews were analysed using an iterative process to identify themes and subthemes. Findings: Midwives described a range of professional ethical dilemmas, including challenges related to negotiating strained interprofessional relationships and protecting or promoting autonomy for women. Ethical dilemmas were identified by the theme of unease, a sense of distress that was expressed in three subthemes: uncertainty of action, compromise in action, and reflecting on action. Learning about ethics and ethical dilemmas occurred, for the most part, outside of the classroom, with the majority of participants reporting that their midwifery program did not confer the skills to identify and resolve ethical challenges. Conclusion: Midwives in this study reported a range of ethical challenges and minimal classroom education related to ethics. Midwifery educators should consider the purposeful and explicit inclusion of midwifery-specific ethics content in their curricula and in interprofessional ethics education. Reflection and self-awareness of bias were identified as key components of understanding ethical frameworks. As clinical preceptors were identified as a key source of ethics learning, midwifery educators should consider ways to support preceptors in building their skills as role models and ethics educators.
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At the beginning of the twenty first century obesity entered Dutch maternity care as a ‘new illness’ challenging maternity care professionals in providing optimal care for women with higher BMI’s. International research revealed that obese women had more perinatal problems than normal weight women. However, the effect of higher BMIs on perinatal outcomes had never been studied in women eligible for midwife-led primary care at the outset of their pregnancy. In the context of the Dutch maternity care system, it was not clear if obesity should be treated as a high-risk situation always requiring obstetrician-led care or as a condition that may lead to problems that could be detected in a timely manner in midwife-led care using the usual risk assessment tools. With the increased attention on obesity in maternity care there was also increased interest in GWG. Regarding GWG in the Netherlands, the effect of insufficient or excessive GWG on perinatal outcomes had never been studied and there were no validated guidelines for GWG. A midwife’s care for the individual woman in the context of the Dutch maternity care system - characterised by ‘midwife-led care if possible, obstetrician-led care if needed’ - is hampered by the lack of national multidisciplinary consensus regarding obesity and weight gain. Obesity has not yet been included in the OIL and local protocols contain varying recommendations. To enable sound clinical decisions and to offer optimal individual care for pregnant women in the Netherlands more insights in weight and weight gain in relation to perinatal outcomes are required. With this thesis the author intends to contribute to the body of knowledge on weight and weight gain to enhance optimal midwife-led primary care for the individual woman and to guide midwives’ clinical decision-making.
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Pupils with problem behaviours are challenging teachers as well as they are a challenge to teachers to find a way to teach them what curricula prescribe. Especially middle school teachers and those working in schools for special education are con-fronted with pupils with behavioural problems. There, teachers experience hard classes and find it difficult to fit classroom management with the pupils needs. In this paper we focus on two questions: is pullout an effective treatment to handle problem behaviour? do special classes have advantages for pupils who were pulled out or not? First we present a theoretical framework about pullout and we explicit our expectations. Then we describe the methods of our research in schools for special educa-tion during two months for students (N=759) when pulled out. We examined the reason of pulling out and the interactions during the process outside the classroom and the return. Because teachers noticed date and time of the removal, it was possible to use survival analysis to show the effects of the treatment. We found that pullout occurs under quite different circumstances, so the treatment integrity is a problem because deficiency of the intervention leads to repeated pullout. The data also showed that special classes for pupils who are pulled out seem to trigger and/or in-tensify the process itself. So, we conclude that these classes have a contra-productive effect.
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Breast cancer is the most prevalent form of cancer that affects women worldwide, posing a significant burden on public health. While advancements in early detection and improved treatments have led to a remarkable 90% five-year survival rate and an 83% ten-year survival rate, this has also resulted in more prophylactic mastectomies being performed. Despite advancements in breast-conserving techniques, immunotherapy, and hormone therapy, many women still undergo mastectomies as part of their cancer treatment. In all cases, this results in scarring, and additional side effects from treatment modalities may arise. The loss of a breast can profoundly impact health-related quality of life (HRQoL). Although HRQoL has improved greatly during the recent years, systematic and local therapy having side effects is not uncommon, and this needs more attention.
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