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.
MULTIFILE
Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2α. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.
DOCUMENT
IL22 is an important cytokine involved in the intestinal defense mechanisms against microbiome. By using ileum-derived organoids, we show that the expression of anti-microbial peptides (AMPs) and anti-viral peptides (AVPs) can be induced by IL22. In addition, we identified a bacterial and a viral route, both leading to IL22 production by T cells, but via different pathways. Bacterial products, such as LPS, induce enterocyte-secreted SAA1, which triggers the secretion of IL6 in fibroblasts, and subsequently IL22 in T cells. This IL22 induction can then be enhanced by macrophage-derived TNFα in two ways: by enhancing the responsiveness of T cells to IL6 and by increasing the expression of IL6 by fibroblasts. Viral infections of intestinal cells induce IFNβ1 and subsequently IL7. IFNβ1 can induce the expression of IL6 in fibroblasts and the combined activity of IL6 and IL7 can then induce IL22 expression in T cells. We also show that IL22 reduces the expression of viral entry receptors (e.g. ACE2, TMPRSS2, DPP4, CD46 and TNFRSF14), increases the expression of anti-viral proteins (e.g. RSAD2, AOS, ISG20 and Mx1) and, consequently, reduces the viral infection of neighboring cells. Overall, our data indicates that IL22 contributes to the innate responses against both bacteria and viruses.
DOCUMENT
A first episode of psychosis (FEP) is a stressful, often life-changing experience. Scarce information is available about personal preferences regarding their care needs during and after a FEP. Whereas a more thorough understanding of these preferences is essential to aid shared decision-making during treatment and improve treatment satisfaction. Methods: Face-to-face interviews with participants in remission of a FEP were setup, addressing personal preferences and needs for care during and after a FEP. The interviews were conducted by a female and a male researcher, the latter being an expert with lived experience. Results: Twenty individuals in remission of a FEP were interviewed, of which 16 had been hospitalized. The distinguished themes based on personal preferences were tranquility, peace and quietness, information, being understood, support from significant others, and practical guidance in rebuilding one's life. Our findings revealed that the need for information and the need to be heard were often not sufficiently met. For 16/20 participants, the tranquility of inpatient treatment of the FEP was pre-dominantly perceived as a welcome safe haven. The presence and support of family and close friends were mentioned as an important factor in the process of achieving remission.
MULTIFILE
This study is part of the WHeelchair ExercisE and Lifestyle Study (WHEELS) project and aims to identify determinants of dietary behaviour in wheelchair users with spinal cord injury or lower limb amputation, from the perspectives of both wheelchair users and rehabilitation professionals. Results of focus groups with wheelchair users (n = 25) and rehabilitation professionals (n = 11) are presented using an integrated International Classification of Functioning, Disability and Health and Attitude, Social influence and self-Efficacy model as theoretical framework.
LINK
This study aims to explore the experiences and needs of individuals after a first episode of psychosis with regard to the way in which information about diagnosis, treatment options and prognosis is communicated with them. psychosis, communicating, stigma, needs, individual’s perception
MULTIFILE
Introduction Physical activity levels of children with disabilities are low, as these children and their parents face a wide variety of both personal and environmental barriers. Behavior change techniques support pediatric physical therapists to address these barriers together with parents and children. We developed the What Moves You?! intervention Toolkit (WMY Toolkit) filled with behavioral change tools for use in pediatric physical therapy practice. Objective To evaluate the feasibility of using the WMY Toolkit in daily pediatric physical therapy practice. Methods We conducted a feasibility study with a qualitative approach using semi-structured interviews with pediatric physical therapists (n = 11). After one day of training, the pediatric physical therapists used the WMY Toolkit for a period of 9 weeks, when facilitating physical activity in children with disabilities. We analyzed the transcripts using an inductive thematic analysis followed by a deductive analysis using a feasibility framework. Results For acceptability, pediatric physical therapists found that the toolkit facilitated conversation about physical activity in a creative and playful manner. The working mechanisms identified were in line with the intended working mechanisms during development of the WMY Toolkit, such as focusing on problem solving, self-efficacy and independence. For demand, the pediatric physical therapists mentioned that they were able to use the WMY Toolkit in children with and without disabilities with a broad range of physical activity goals. For implementation, education is important as pediatric physical therapists expressed the need to have sufficient knowledge and to feel confident using the toolkit. For practicality, pediatric physical therapists were positive about the ease of which tools could be adapted for individual children. Some of the design and materials of the toolkit needed attention due to fragility and hygiene. Conclusion The WMY Toolkit is a promising and innovative way to integrate behavior change techniques into pediatric physical therapy practice.
LINK
Stimulating patients to approach their pain from a biopsychosocial perspective is central to chronic pain rehabilitation. However, conversations between patients and their healthcare professionals about the social and psychological factors that may contribute to the continuation of pain and disability can be challenging. The current scientific literature does not sufficiently pinpoint the difficulties in patient–practitioner interaction on chronic pain, and it falls short of answering the question of how a joint exploration of the social and psychological factors that might be involved in the patient’s pain and evolving disability can be enhanced. In this theoretical article, we introduce discursive psychology as a potentially valuable research perspective to gain a better understanding of the difficulties in patient–practitioner interaction in the context of chronic pain rehabilitation. Discursive psychology focuses on features of people’s talk (e.g. that of patients and practitioners) and is concerned with the social practices that people perform as part of a specific interactional context. In this paper, we provide an introduction to the main theoretical notions of discursive psychology. We illustrate how discursive psychological analyses can inform our understanding of the specific sensitivities in conversations between patients with chronic pain and their practitioners. Finally, we address how a better understanding of these sensitivities offers a gateway towards improving these conversations. Een belangrijk principe in revalidatie bij chronische pijn is de benadering van de pijn vanuit een biopsychosociaal perspectief. Het blijkt echter een uitdaging voor patiënten en behandelaars om de sociale en psychologische factoren die een rol spelen bij chronische pijn te bespreken. In de huidige wetenschappelijke literatuur is hier nog niet voldoende aandacht voor; en wordt geen perspectief geboden voor verbetering van de gezamenlijke verkenning van sociale en psychologische factoren. In dit theoretische artikel introduceren we discursieve psychologie als een mogelijk waardevol onderzoeksperspectief om een beter begrip tot stand te brengen van de complexiteit van interactie in de context van chronische pijn revalidatie. Discursieve psychologie richt zich op kenmerken van interactie, in het bijzonder de sociale praktijken die tot stand worden gebracht binnen een specifieke interactionele context. We beschrijven de belangrijkste theoretische principes van discursieve psychologie en illustreren hoe een DP analyse licht kan werpen op de specifieke gevoeligheden in conversaties tussen patiënten met chronische pijn en hun behandelaars. Tot slot bespreken we hoe een beter begrip van deze gevoeligheden een ingang biedt tot het verbeteren van deze conversaties.
DOCUMENT
Moral food lab: Transforming the food system with crowd-sourced ethics
LINK
The objective of this thesis is to make a first step towards prevention of the progression of chronic venous disease and the development of a first venous leg ulcer in chronic venous disease patients. The aim is to identify chronic venous disease patients at risk of developing more severe clinical stages, provide insight in the lifestyle related risk factors, and provide an overview of current chronic venous disease care in the Netherlands.
DOCUMENT