A Key Role of Dendritic Cells in Probiotic Functionality

BACKGROUND: Disruption of the intestinal homeostasis and tolerance towards the resident microbiota is a major mechanism involved in the development of inflammatory bowel disease. While some bacteria are inducers of disease, others, known as probiotics, are able to reduce inflammation. Because dendritic cells (DCs) play a central role in regulating immune responses and in inducing tolerance, we investigated their role in the anti-inflammatory potential of probiotic lactic acid bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Selected LAB strains, while efficiently taken up by DCs in vitro, induced a partial maturation of the cells. Transfer of probiotic-treated DCs conferred protection against 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Protection was associated with a reduction of inflammatory scores and colonic expression of pro-inflammatory genes, while a high local expression of the immunoregulatory enzyme indolamine 2, 3 dioxgenase (IDO) was observed. The preventive effect of probiotic-pulsed DCs required not only MyD88-, TLR2- and NOD2-dependent signaling but also the induction of CD4+ CD25+ regulatory cells in an IL-10-independent pathway. CONCLUSIONS/SIGNIFICANCE: Altogether, these results suggest that selected probiotics can stimulate DC regulatory functions by targeting specific pattern-recognition receptors and pathways. The results not only emphasize the role of DCs in probiotic immune interactions, but indicate a possible role in immune-intervention therapy for IBD

Networks or structures? : organizing cultural routes around heritage values : case studies from Poland

The most common way of managing cultural heritage recently takes form of cultural routes as they seem to offer a new model of participation in culture to their recipients; they are often a peculiar anchor point for inhabitants to let them understand their identity and form the future; they offer actual tours to enter into interaction with culture and history, to build together that creation of the heritage, which so is becoming not only a touristic product, but, first of all, the space for cultural, social and civic activity. Yet, so far, according to what we know, the research problem concerning the method of cultural route organization (points on the route) into solid structures or more of the networked nature, has not been deliberated. A question arises, what values are brought by routes and how to organize routes to be the carriers of the values important for communities, where routes are functioning. And, as a consequence, if, from the point of view of the values of local communities, organizing solid route structures or organizing more widely-spaced, network-based routes would bring effects and what those effects would be. Thus, the posed question is of course scientifically imprecise because a network is a type of structure but presents a given direction for the development of cultural route structures. Our objective here is to present a certain solidity and rigidity of structure with dynamic and smooth understanding of the network. The research presented in the article is based on 3 case studies. We have selected for this purpose the three largest cultural routes in Poland, organized to various degrees. The outcome of the research was referred also to other cultural route organization research

Australia's National Bowel Cancer Screening Program: does it work for Indigenous Australians?

<p>Abstract</p> <p>Background</p> <p>Despite a lower incidence of bowel cancer overall, Indigenous Australians are more likely to be diagnosed at an advanced stage when prognosis is poor. Bowel cancer screening is an effective means of reducing incidence and mortality from bowel cancer through early identification and prompt treatment. In 2006, Australia began rolling out a population-based National Bowel Cancer Screening Program (NBCSP) using the Faecal Occult Blood Test. Initial evaluation of the program revealed substantial disparities in bowel cancer screening uptake with Indigenous Australians significantly less likely to participate in screening than the non-Indigenous population.</p> <p>This paper critically reviews characteristics of the program which may contribute to the discrepancy in screening uptake, and includes an analysis of organisational, structural, and socio-cultural barriers that play a part in the poorer participation of Indigenous and other disadvantaged and minority groups.</p> <p>Methods</p> <p>A search was undertaken of peer-reviewed journal articles, government reports, and other grey literature using electronic databases and citation snowballing. Articles were critically evaluated for relevance to themes that addressed the research questions.</p> <p>Results</p> <p>The NBCSP is not reaching many Indigenous Australians in the target group, with factors contributing to sub-optimal participation including how participants are selected, the way the screening kit is distributed, the nature of the test and comprehensiveness of its contents, cultural perceptions of cancer and prevailing low levels of knowledge and awareness of bowel cancer and the importance of screening.</p> <p>Conclusions</p> <p>Our findings suggest that the population-based approach to implementing bowel cancer screening to the Australian population unintentionally excludes vulnerable minorities, particularly Indigenous and other culturally and linguistically diverse groups. This potentially contributes to exacerbating the already widening disparities in cancer outcomes that exist among Indigenous Australians. Modifications to the program are recommended to facilitate access and participation by Indigenous and other minority populations. Further research is also needed to understand the needs and social and cultural sensitivities of these groups around cancer screening and inform alternative approaches to bowel cancer screening.</p

Syndromic Autism: progressing beyond current levels of description

Genetic syndrome groups at high risk of autism comorbidity, like Down syndrome and fragile X syndrome, have been presented as useful models for understanding risk and protective factors involved in the emergence of autistic traits. Yet despite reaching clinical thresholds, these ‘syndromic’ forms of autism appear to differ in significant ways from the idiopathic or ‘non-syndromic’ autism profile. We explore alternative mechanistic explanations for these differences and propose a developmental interpretation of syndromic autism that takes into account the character of the genetic disorder. This interpretation anticipates syndrome-specific autism phenotypes, since the neurocognitive and behavioural expression of the autism is coloured by syndromically defined atypicalities. To uncover the true nature of comorbidities and of autism per se, we argue that it is key to extend definitions of autism to include the perceptual and neurocognitive characteristics of the disorder and then apply this multilevel conceptualization to the study of syndromic autism profiles