Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids

Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map™ dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n\ua0=\ua07), PBS (n\ua0=\ua04) or LPS (n\ua0=\ua03) presented distinct gene expression profiles, with some overlap (R2Y\ua0=\ua00.70, Q2=\ua00.43). Addition of fecal supernatants from healthy subjects and IBS patients (n\ua0=\ua09) gave rise to different gene expression profiles of the colonoid monolayers (R2Y\ua0=\ua00.79, Q2=\ua00.64). Genes (n\ua0=\ua022) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions

The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

Innate sensing of bacterial flagellin in acute and chronic intestinal inflammation

Flagellin is a highly immunogenic, bacterial protein considered to be abundant in the intestinal lumen. It has been reported to be an immunodominant antigen in patients with inflammatory bowel disease (IBD). In the work presented in this thesis several complementary murine models of IBD were employed to elucidate the role of innate immune sensing of flagellin in the development of intestinal inflammation. Pattern recognition receptors (PRRs) enable mammals to discriminate self from non-self through the recognition of microbial signatures, such as bacterial flagellin. Flagellin is detected by at least two distinct PRRs, NOD-like receptor 4 (NLRC4) and Toll-like receptor 5 (TLR5). Our experiments revealed that NLRC4 promoted protective effects during acute intestinal inflammation mediated by infection with Citrobacter rodentium, a close relative of enteropathogenic E. coli. Following infection with C. rodentium, Nlrc4-/- mice developed more severe weight loss, increased bacterial colonisation levels and exacerbated intestinal inflammation compared to WT counterparts. Bone marrow chimera experiments revealed that NLRC4 expression in non-hematopoietic cells provided protection and intestinal epithelial cells expressed high NLRC4 mRNA levels. These results suggest that NLRC4 inflammasome activation in the intestinal epithelium provides potent, protective effects during infection with a mucosal pathogen. In contrast, TLR5 was shown to promote protective effects during chronic, T-cell mediated intestinal inflammation driven by adoptive transfer of naïve CD4+ T-cells into lymphopenic Rag-/- hosts. The absence of TLR5 in Rag-/- recipients resulted in accelerated and exacerbated IBD. Furthermore, chronic T-cell dependent colitis driven by Helicobacter hepaticus, a flagellated, enteric bacterium, was more severe in mice deficient in TLR5. Finally, construction of a H.hepaticus Type 6 secretion system deletion mutant revealed delayed pathogenicity in an innate model of intestinal inflammation, most likely due to reduced initial colonisation of mutant H.hepaticus

Underlättad omvårdnad med hjälp av fyra tassar : Vårdpersonalens upplevelse av vårdhundens betydelse för personer med demenssjukdom som bor på särskilt boenden- En empirisk intervjustudie

Bakgrund: Antalet personer med demenssjukdom ökar i Sverige på grund av den åldrande befolkningen. Demenssjukdomar är kroniska och påverkar hela individens livssituation. Utöver farmakologisk behandling används komplementära terapier med syfte att öka personens upplevelse av välbefinnande och livskvalité, exempelvis genom hundassisterad-terapi. Svenska riktlinjer understryker vikten av att omvårdnaden vid demenssjukdom utgår från ett personcentrerat förhållningssätt. Syfte: Att beskriva vårdpersonalens upplevelse av vårdhundens betydelse för personer med demenssjukdom som bor på särskilt boende. Metod: En kvalitativ intervjustudie, där åtta semistrukturerade intervjuer gjordes och analyserades. Resultat: Vårdhunden upplevdes vara en motivationsfaktor för personer med demenssjukdom och motiverade dem till att delta i fysiska aktiviteter, uppehålla samtal och att samarbeta med vårdpersonalen. Vårdhunden upplevdes ha förmåga att lindra symtom som oro, ångest och aggressivitet, vilket hade en positiv inverkan på omvårdnaden av personerna med demenssjukdom. Utöver det så upplevde vårdpersonalen att vårdhunden var en begränsad tillgänglighet och inte något som alla personer med demenssjukdom kunde dra nytta av. Slutsats: Vårdpersonalen upplever att vårdhunden har en övergripande positiv inverkan på personer med demenssjukdom som bor på särskilt boende och kan underlätta att uppnå en personcentrerad omvårdnad. Mer forskning krävs för att nå ökad kunskap om vårdhundens effekt på personer med demenssjukdom. Nyckelord: Demens, Personcentrerad omvårdnad, Upplevelser, Vårdhund, Vårdpersonal.Background: The number of people with dementia is increasing in Sweden due to the aging population. Dementia is a chronic disease that affects the whole life situation of the person. Beside pharmacological treatment there are complementary therapies which are used to increase the person's experience of well-being and life quality, for example through dog-assisted therapy. Swedish guidelines underline the importance of person centred approach in the nursing of people with dementia. Aim: To describe healthcare staff's experience of therapy dog's significance for people with dementia living in a nursing home. Method: A qualitative interview study, in which eight semi-structured interviews were conducted and analysed. Results: The healthcare staff perceived that the therapy dog became a motivational factor for persons living with dementia, leading to increase their will to participate in physical activity, maintain conversations with others and to cooperate with the healthcare staff. The therapy dog contributed to encrichment of nursing of the care environment at the nursing home. The therapy dog seem like to alleviate symptoms such as worry, anxiety and aggressiveness. Which had a positive effect on the nursing of persons with dementia. Further the staff experienced that the therapy dog currently had a limited availability and was something not all people with dementia could make use of. Conclusion: The healthcare staff experiences that the therapy dog has an overall positive impact on people with dementia living in a nursing home and that it supports the ability to accomplish person-centered nursing. More research needs to be done in order to increase the knowledge of the therapy dog’s effect on people with dementia. Keywords: Dementia, Experiences, Healthcare staff, Person-centered care, Therapy dog

Genomlysning av ett lager ur ett Leanperspektiv - fokus på effektivitet och värdekapande aktiviteter : En fallstudie på Svenska Fönster

The objective of this study is to examine how Lean can make the utilization of inventory more effective and, from a Lean perspective, examine how the value-adding activities related to inventory can increase. To examine this, a case study was perfomed at Svenska Fönster. The conclusions of this study are that Lean can advantageously be applied on inventory to increase the efficiency.

Innate sensing of bacterial flagellin in acute and chronic intestinal inflammation

Flagellin is a highly immunogenic, bacterial protein considered to be abundant in the intestinal lumen. It has been reported to be an immunodominant antigen in patients with inflammatory bowel disease (IBD). In the work presented in this thesis several complementary murine models of IBD were employed to elucidate the role of innate immune sensing of flagellin in the development of intestinal inflammation. Pattern recognition receptors (PRRs) enable mammals to discriminate self from non-self through the recognition of microbial signatures, such as bacterial flagellin. Flagellin is detected by at least two distinct PRRs, NOD-like receptor 4 (NLRC4) and Toll-like receptor 5 (TLR5). Our experiments revealed that NLRC4 promoted protective effects during acute intestinal inflammation mediated by infection with Citrobacter rodentium, a close relative of enteropathogenic E. coli. Following infection with C. rodentium, Nlrc4-/- mice developed more severe weight loss, increased bacterial colonisation levels and exacerbated intestinal inflammation compared to WT counterparts. Bone marrow chimera experiments revealed that NLRC4 expression in non-hematopoietic cells provided protection and intestinal epithelial cells expressed high NLRC4 mRNA levels. These results suggest that NLRC4 inflammasome activation in the intestinal epithelium provides potent, protective effects during infection with a mucosal pathogen. In contrast, TLR5 was shown to promote protective effects during chronic, T-cell mediated intestinal inflammation driven by adoptive transfer of naïve CD4+ T-cells into lymphopenic Rag-/- hosts. The absence of TLR5 in Rag-/- recipients resulted in accelerated and exacerbated IBD. Furthermore, chronic T-cell dependent colitis driven by Helicobacter hepaticus, a flagellated, enteric bacterium, was more severe in mice deficient in TLR5. Finally, construction of a H.hepaticus Type 6 secretion system deletion mutant revealed delayed pathogenicity in an innate model of intestinal inflammation, most likely due to reduced initial colonisation of mutant H.hepaticus.This thesis is not currently available in ORA

Early-Life Human Microbiota Associated With Childhood Allergy Promotes the T Helper 17 Axis in Mice

The intestinal microbiota influences immune maturation during childhood, and is implicated in early-life allergy development. However, to directly study intestinal microbes and gut immune responses in infants is difficult. To investigate how different types of early-life gut microbiota affect immune development, we collected fecal samples from children with different allergic heredity (AH) and inoculated germ-free mice. Immune responses and microbiota composition were evaluated in the offspring of these mice. Microbial composition in the small intestine, the cecum and the colon were determined by 16S rRNA sequencing. The intestinal microbiota differed markedly between the groups of mice, but only exposure to microbiota associated with AH and known future allergy in children resulted in a T helper 17 (Th17)-signature, both systemically and in the gut mucosa in the mouse offspring. These Th17 responses could be signs of a particular microbiota and a shift in immune development, ultimately resulting in an increased risk of allergy

COVID-19 and Hairy-Cell Leukemia: An EPICOVIDEHA Survey

International audienc