Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.Laboratorio de Investigaciones del Sistema Inmun

Mechanisms of innate immune activation by gluten peptide p31-43 in mice

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD.Instituto de Estudios Inmunológicos y Fisiopatológico

Mechanisms of innate immune activation by gluten peptide p31-43 in mice

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Innate immunity contributes to the pathogenesis of CD, but the mechanisms remain poorly understood. Although previous in vitro work suggests that gliadin peptide p31-43 acts as an innate immune trigger, the underlying pathways are unclear and have not been explored in vivo. Here we show that intraluminal delivery of p31-43 induces morphological changes in the small intestinal mucosa of normal mice consistent with those seen in CD, including increased cell death and expression of inflammatory mediators. The effects of p31-43 were dependent on MyD88 and type I IFNs, but not Toll-like receptor 4 (TLR4), and were enhanced by coadministration of the TLR3 agonist polyinosinic:polycytidylic acid. Together, these results indicate that gliadin peptide p31-43 activates the innate immune pathways in vivo, such as IFN-dependent inflammation, relevant to CD. Our findings also suggest a common mechanism for the potential interaction between dietary gluten and viral infections in the pathogenesis of CD

Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.Laboratorio de Investigaciones del Sistema Inmun

Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice

Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency.Facultad de Ciencias Exacta

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia.

En el presente trabajo tomamos la imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia, donde damos a conocer la problemática de la violencia en Colombia que ha causado innumerables víctimas las cuales demandan ayuda profesional de forma inmediata. Esta ayuda se debe ofrecer en los momentos de crisis y posteriores al trauma ya que la vida del individuo y sus relaciones sociales se ven afectadas. Las víctimas de la violencia requieren intervenciones específicas que incluyan todos los sectores de la comunidad en la resolución de sus problemas; es decir, una mediación psicológica que pueda contribuir al bienestar de la salud mental de manera individual y colectiva. Las intervenciones psicosociales en el relato de Gloria y el caso Pandurí, fueron diseñadas teniendo en cuenta el tipo de violencia de la población afectada, el ímpetu y permanencia de la misma, la historia de la población y finalmente otros aspectos socioculturales; donde se evaluaron los recursos de la población y la regeneración de un sentido de unidad colectivo; garantizando un trabajo cooperativo que logre una reconstrucción integral de las víctimas a la vida social. En los casos analizados de Gloria y Panduri se identificó la importancia del psicólogo en los procesos de recuperación, brindando acompañamiento integral que incluya un análisis de la problemática social desde diferentes perspectivas; siendo un puente facilitador que genere ideas y acciones entorno al cambio, orientando a las víctimas en sus procesos de reconstrucción de identidad. Se identificó en los casos analizados una herramienta muy importante en los procesos de recuperación de las víctimas de la violencia, la cual es el enfoque narrativo como terapia que busca convertir las experiencias de victimización en historias de sobrevivencia, esperanza, y superación, permitiéndoles a la persona reconstruir sus historias, resaltar sus actos heroicos y logros, superar la adversidad, y apreciar los recursos de la experiencia, siendo esta un medio para comprender que las historias que contamos transforman nuestra identidad, generan sueños, crean nuevos propósitos, y convierten experiencias dolorosas en oportunidades de aprendizaje donde la violencia pierda el protagonismo que paraliza y afecta la vida del individuo.In the present work, we take the image and the narrative as tools for the psychosocial approach in scenarios of violence, where we present the problem of violence in Colombia that has caused innumerable victims who demand professional help immediately. This help should be offered in times of crisis and after the trauma of the individual's life and social relationships are affected. Victims of violence require specific interventions that include all sectors of the community in the resolution of their problems; that is, a psychological mediation that can contribute to the well-being of mental health individually and collectively. Psychosocial interventions in the story of Gloria and the Pandurí case, were designed taking into account the type of violence of the affected population, the impetus and permanence of it, the history of the population and finally other socio-cultural aspects; where the resources of the population were evaluated and the regeneration of a sense of collective unity; guaranteeing a cooperative work that achieves an integral reconstruction of the victims to the social life. In the analyzed cases of Gloria and Panduri, the importance of the psychologist in the recovery processes was identified, providing comprehensive accompaniment that includes an analysis of the social problems from different perspectives; being a facilitating bridge that generates ideas and actions around change, guiding the victims in their processes of identity reconstruction. In the cases analyzed, a very important tool was identified in the processes of recovery of the victims of violence, which is the narrative approach as a therapy that seeks to turn the experiences of victimization into stories of survival, hope, and improvement, allowing the person to reconstruct their stories, highlight their heroic acts and achievements, overcome adversity, and appreciate the resources of experience, this being a means to understand that the stories we tell transform our identity, generate dreams, create new purposes, and turn painful experiences in learning opportunities where violence loses the protagonist that paralyzes and affects the life of the individual

Assessing the content validity of the revised Health of the Nation Outcome Scales (HoNOS 2018)

The Health of the Nation Outcome Scales (HoNOS) comprises 12 scales that cover the kinds of problems that may be experienced by working-age adults in contact with specialised mental health services. Drawing on 20 years’ experience in clinical practice, a collaborative, international review of the HoNOS was undertaken and a revised measure (known as the HoNOS 2018) was published. In this study, 32 experts from Australia, England and New Zealand completed an anonymous web-based survey to assess the relevance, comprehensiveness and comprehensibility (aspects of content validity) of the HoNOS 2018. The experts rated 11 of the 12 HoNOS 2018 scales as ‘important’ or ‘very important’ for determining the overall clinical severity (item-level content validity index or I-CVI ≥ 0.75). Evaluations of the scales’ ability to capture change, comprehensiveness and comprehensibility were more variable, but generally positive. Experts’ comments provided further insights into this variability; for example, they noted that some scales combine multiple phenomena, which can result in ambiguity in item wording and assessment challenges. Results from this study suggest that the revisions have not altered the importance of the scales. Given the measure’s breadth of content, training remains important for ensuring rating fidelity. Inter-rater reliability and utility testing are indicated

Assessing the content validity of the revised Health of the Nation Outcome Scales 65+: the HoNOS Older Adults

Aims and method: Recently, the Health of the Nation Outcome Scales (HoNOS) 65+ was revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA). Results: All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested that additional older adult-specific examples be included in the glossary (e.g., for scales measuring depressed mood, problems with relationships, and problems with activities of daily living). Clinical implications: Experts agreed that the HoNOS OA measures important constructs. Training may be needed to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended

Assessing the content validity of the revised Health of the Nation Outcome Scales 65+: the HoNOS Older Adults

Aims and method: Recently, the Health of the Nation Outcome Scales (HoNOS) 65+ was revised. Twenty-five experts from Australia and New Zealand completed an anonymous web-based survey about the content validity of the revised measure, the HoNOS Older Adults (HoNOS OA). Results: All 12 HoNOS OA scales were rated by most (≥75%) experts as ‘important’ or ‘very important’ for determining overall clinical severity among older adults. Ratings of sensitivity to change, comprehensibility and comprehensiveness were more variable, but mostly positive. Experts’ comments provided possible explanations. For example, some experts suggested that additional older adult-specific examples be included in the glossary (e.g., for scales measuring depressed mood, problems with relationships, and problems with activities of daily living). Clinical implications: Experts agreed that the HoNOS OA measures important constructs. Training may be needed to orient experienced raters to the rationale for some revisions. Further psychometric testing of the HoNOS OA is recommended

Sensitization to gliadin induces moderate enteropathy and insulitis in nonobese diabetic-DQ8 mice

Celiac disease (CD) is frequently diagnosed in patients with type 1 diabetes (T1D), and T1D patients can exhibit Abs against tissue transglutaminase, the auto-antigen in CD. Thus, gliadin, the trigger in CD, has been suggested to have a role in T1D pathogenesis. The objective of this study was to investigate whether gliadin contributes to enteropathy and insulitis in NOD-DQ8 mice, an animal model that does not spontaneously develop T1D. Gliadin-sensitized NOD-DQ8 mice developed moderate enteropathy, intraepithelial lymphocytosis, and barrier dysfunction, but not insulitis. Administration of anti-CD25 mAbs before gliadin-sensitization induced partial depletion of CD25+Foxp3+ T cells and led to severe insulitis, but did not exacerbate mucosal dysfunction. CD4+T cells isolated from pancreatic lymph nodes of mice that developed insulitis showed increased proliferation and proinflammatory cytokines after incubation with gliadin but not with BSA. CD4+ T cells isolated from nonsensitized controls did not response to gliadin or BSA. In conclusion, gliadin sensitization induced moderate enteropathy in NOD-DQ8 mice. However, insulitis development required gliadin-sensitization and partial systemic depletion of CD25+Foxp3+ T cells. This humanized murine model provides a mechanistic link to explain how the mucosal intolerance to a dietary protein can lead to insulitis in the presence of partial regulatory T cell deficiency.Facultad de Ciencias Exacta