Tarmmykobiota, serum anti-Saccharomyces cerevisiae antikroppar och calprotectin koncentrationer hos patienter med inflammatorisk tarmsjukdom som får infliximab medicinering

Inflammatory bowel disease (IBD) is a globally increasing chronic disease, for which the pathogenesis still is unclear. The most common subtypes of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). It is widely known that, in addition to the genetics, an altered immune response against the gut microbiome plays an important role in the development of the disease. For the IBD patients, to whom conventional medication is not sufficient, the TNF-α blocker infliximab, is given. However, about one third of the patients receiving infliximab treatment, do not respond to the drug, or lose response over time. Since there to this day are no reliable diagnostic markers available, the finding of such is of great importance. The goal of this study was to investigate possible markers for drug response in the gut mycobiota composition of IBD patients. The gut mycobiota composition of 72 IBD patients receiving infliximab was studied by MiSeq sequencing of fungal DNA from fecal samples, collected during one year. The sequencing data was analyzed using the mare package in R. In addition, anti-Saccharomyces cerevisiae antibody (ASCA) concentrations were measured from baseline serum samples by ELISA. Finally, calprotectin concentrations were measured from baseline and twelve weeks post infliximab serum samples by ELISA to study whether serum samples could be used instead of fecal samples for measuring calprotectin values. Results show an increase of the Candida and Spiromyces genera in the gut mycobiota of non-responding patients at baseline. At all timepoints, the Spiromyces genus was observed at a higher abundance, compared to the group of patients responding well or partially to the medication. Interestingly, the increase of Candida was seen only in Crohn’s disease patients, when looking at the composition at all timepoints. ASCA values did not differ between the response groups. The serum calprotectin values did not correlate with fecal calprotectin, and serum calprotectin can thus not be used as a marker of gut inflammation. In conclusion, the gut mycobiota can offer predictive markers for drug response prediction to infliximab in IBD patients, which can with further studies offer a clinical diagnostic tool for prediction of drug response.Inflammatorisk tarmsjukdom (IBD) är en kronisk inflammation i tarmarna som är allt mer förekommande i hela världen. De vanligaste typerna av IBD är Crohn’s sjukdom och ulcerös colit. En tydlig orsak till sjukdomen har inte blivit hittad, men man vet att IBD delvis orsakas av en ovanlig immunreaktion mot tarmens mikrobiom hos en genetiskt belagd person. Åt patienter, för vilka den vanliga inflammationshämmande medicineringen inte är tillräcklig, ges den biologiska medicinen infliximab. Upp till en tredjedel av patienterna som får infliximab får ingen läkemedelsrespons mot medicinen, antingen på grund av brist på respons från början, eller avfall av respons efter medicinering. Det är mycket viktigt att forska i prediktiva markörer, eftersom det i nuläget inte finns diagnostiska metoder för undersökning av respons mot infliximab. Målet med denna studie var att undersöka möjliga markörer för läkemedelsrespons i tarmmykobiotan hos IBD patienter. Tarmmykobiotans komposition undersöktes hos 72 IBD patienter, som får denna medicinering, genom MiSeq sekvensering av svamp DNA i avföringsprov tagna under ett år. Koncentrationen av anti-Saccharomyces cerevisiae antikroppar (ASCA) har mätts från serumprov tagna före medicineringen började genom ELISA. Slutligen mättes även koncentrationen av calprotectin från serumprov tagna före medicineringen började samt tolv veckor efter medicinering för att undersöka om dessa kunde användas istället för calprotectin värden mätta från avföring. I studien observeras en ökning av släkten Candida och Spiromyces i tarmmykobiotan hos gruppen av patienter för vilka infliximab inte fungerade i prover tagna innan påbörjad medicinering. En ökning av släktet Spiromyces var observerad även i prover tagna under medicinering, medan ökningen av Candida bara var observerad hos patienter som lider av Crohn’s sjukdom i prover tagna under medicineringen. Det observerades ingen korrelation mellan calprotectinvärden mätta från serum och avföring, vilket betyder att serum calprotectinvärden inte fungerar som inflammationsmarkör för tarmen. Slutligen observerades inga skildaktigheter i ASCA-värden i de olika grupperna. Sammanfattningsvis visar studien att tarmmykobiotan erbjuder möjliga prediktiva markörer för läkemedelsrespons mot infliximab hos IBD patienter som kan användas i diagnostiken

Making Magic: (Hetero)sexual (In)visibility in Scandinavian Young Adult Novels

In lieu of abstract, here is the first paragraph of the article: In Scandinavia, there is a commonly held assumption that gender equality has already been accomplished. In fictional representations, however, gender and sex roles are more problematic. This study of the depiction of girlhood in Scandinavian young adult novels demonstrates socially and culturally driven constructions of gender power that are markedly conservative. The girl protagonists typically deal with conventional issues of growing up, including coming to terms with what it means to be a girl and how to relate to (hetero)sexuality. However, the complexities of this maturational process can be extrapolated when their otherness is embodied in the trope of a witch-girl

The Effect of Antibiotics on the Infant Gut Fungal Microbiota

Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There are only a few studies on the infant gut fungal microbiota, the mycobiota, in relation to antibiotic treatment. Here, the aim was to investigate the impact of antibiotics on the infant gut mycobiota, and the interkingdom associations between bacteria and fungi. We had 37 antibiotic-naïve patients suffering from respiratory syncytial virus, of which 21 received one to four courses of antibiotics due to complications, and 16 remained antibiotic-naïve throughout the study. Fecal samples were collected before, during and after antibiotic treatment with a follow-up period of up to 9.5 months. The gut mycobiota was studied by Illumina MiSeq sequencing of the ITS1 region. We found that antibiotic use affected the gut mycobiota, most prominently seen as a higher relative abundance of Candida (p < 0.001), and a higher fungal diversity (p = 0.005–0.04) and richness (p = 0.03) in the antibiotic-treated infants compared to the antibiotic-naïve ones at multiple timepoints. This indicates that the gut mycobiota could contribute to the long-term consequences of antibiotic treatments

Bacterial and Fungal Profiles as Markers of Infliximab Drug Response in Inflammatory Bowel Disease

Tulehdukselliset suolistosairaudet (IBD) Crohnin tauti (CD) ja haavainen paksusuolentulehdus (UC) ovat maailmanlaajuisesti lisääntyviä sairauksia, joihin liittyy muuntunut suoliston mikrobisto. Infliksimabi (IFX) on TNF-alfan estäjä, jota käytetään IBD:n hoidossa, vaikkakin kolmas osa potilaista voi jäädä ilman hoitovastetta tai menettää sen. Luotettavia testejä hoitovasteen ennustamiseksi ei ole vielä saatavilla. Tutkimuksemme tavoitteena oli selvittää potilaiden ulosteen bakteerit, sienet ja hiivat infliksimabihoidon aikana sekä etsiä hoitovastetta ennustavia mittareita IBD potilailta. Tutkimuksessamme 72 IBD-potilasta (25 CD ja 47 UC) aloitti infliksimabihoidon ja heitä seurattiin vuoden ajan hoidon aloituksesta tai hoidon keskeytykseen saakka. Potilaiden ulostenäytteistä määritettiin sekvensointia hyödyntäen erikseen suoliston bakteerit (16S rRNA geenistä) sekä hiivat ja sienet (ITS1 geenin alueesta). Mikrobiston profiilit määritettiin ennen hoidon aloitusta, 2, 6, 12 viikkoa sekä 1 vuosi hoidon aloituksen jälkeen. IFX hoidon vaste määritettiin kolonoskopialla ja kliinisesti 12 viikon hoidon jälkeen. Tutkimuksessa havaittiin, että potilaiden ulosteen bakteerit sekä sienet ja hiivat erosivat merkittävästi toisistaan infliksimabihoitovasteen mukaan jo ennen hoidon aloitusta. Potilailla, jotka eivät saaneet vastetta hoidosta, oli vähemmän lyhytketjuisia rasvahappoja tuottavia bakteereja erityisesti Clostridia-luokasta sekä enemmän tulehdusta aiheuttavia bakteereja ja sieniä mm. Candida-suvusta. Tämä tulos testattiin bakteerien osalta myös ennustetestillä (ROC), joka erotti toisistaan ne potilaat, jotka saivat hyvän vasteen ja ne, jotka eivät saaneet vastetta (area under the curve > 0.8). Tulosten perusteella ulosteen bakteerit ja hiivat voisivat sopia ennustaviksi mittareiksi IBD-potilaiden infliksimabihoidon vasteen ennustamiseen.Peer reviewe

The gut fungal and bacterial microbiota in pediatric patients with inflammatory bowel disease introduced to treatment with anti-tumor necrosis factor-α

Publisher Copyright: © 2022, The Author(s).Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.Peer reviewe

The Effect of Antibiotics on the Infant Gut Fungal Microbiota

Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There are only a few studies on the infant gut fungal microbiota, the mycobiota, in relation to antibiotic treatment. Here, the aim was to investigate the impact of antibiotics on the infant gut mycobiota, and the interkingdom associations between bacteria and fungi. We had 37 antibiotic-naïve patients suffering from respiratory syncytial virus, of which 21 received one to four courses of antibiotics due to complications, and 16 remained antibiotic-naïve throughout the study. Fecal samples were collected before, during and after antibiotic treatment with a follow-up period of up to 9.5 months. The gut mycobiota was studied by Illumina MiSeq sequencing of the ITS1 region. We found that antibiotic use affected the gut mycobiota, most prominently seen as a higher relative abundance of Candida (p < 0.001), and a higher fungal diversity (p = 0.005–0.04) and richness (p = 0.03) in the antibiotic-treated infants compared to the antibiotic-naïve ones at multiple timepoints. This indicates that the gut mycobiota could contribute to the long-term consequences of antibiotic treatments

The Effect of Antibiotics on the Infant Gut Fungal Microbiota

Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There are only a few studies on the infant gut fungal microbiota, the mycobiota, in relation to antibiotic treatment. Here, the aim was to investigate the impact of antibiotics on the infant gut mycobiota, and the interkingdom associations between bacteria and fungi. We had 37 antibiotic-naive patients suffering from respiratory syncytial virus, of which 21 received one to four courses of antibiotics due to complications, and 16 remained antibiotic-naive throughout the study. Fecal samples were collected before, during and after antibiotic treatment with a follow-up period of up to 9.5 months. The gut mycobiota was studied by Illumina MiSeq sequencing of the ITS1 region. We found that antibiotic use affected the gut mycobiota, most prominently seen as a higher relative abundance of Candida (p < 0.001), and a higher fungal diversity (p = 0.005-0.04) and richness (p = 0.03) in the antibiotic-treated infants compared to the antibiotic-naive ones at multiple timepoints. This indicates that the gut mycobiota could contribute to the long-term consequences of antibiotic treatments

Male reproductive health statement:(XIIIth international symposium on Spermatology, May 9th--12th 2018, Stockholm, Sweden

International audienc

Apolipoprotein CIII and Ljungan virus in diabetes

It has been shown that there are patients with type 1 diabetes (T1D), whose sera induce an increased activity of voltage-gated Ca2+-channels in pancreatic beta-cells, resulting in increased cytoplasmic free Ca2+ concentration ([Ca2+]i) and apoptosis. Purification of the protein in the active fraction of T1D sera revealed that the observed effects were mediated by apolipoprotein CIII (apoCIII), and this protein was shown to be increased in serum from T1D patients. To be able to evaluate the importance of apoCIII in vivo for the development of T1D there is a need for a suitable animal model. We used the animal model diabetes-prone BB rat (DPBB) that spontaneously, at the age of around 60 days, develops a human-like T1D. Isolated islet cells cultured overnight in the presence of 10% sera from 60 days old prediabetic BB rats had a higher increase in [Ca2+]i upon depolarization with K+, an impaired glucose-induced insulin secretion and a decreased viability, compared to cells exposed to age-matched control sera. The prediabetic sera with this effect are referred to as positive (pos). The effect on [Ca2+]i was abolished when an antibody against apoCIII was present during culture. The relative amounts of apoCIII in pos, neg and control sera from 60 days old rats were evaluated and the content in pos sera was significantly higher. To investigate the effects of apoCIII in vivo, DPBB rats were treated with either active or inactive antisense against apoCIII between the age of 12 to 40 days. The apoCIII antisense treatment significantly delayed the onset of diabetes. Wild bank voles (Myodes glareolus) develop T1D and a picornavirus, named Ljungan virus (LV), has been isolated from these animals. If CD-1 mice, that normally do not carry LV, are infected with this virus in utero and exposed to stress after birth, the male offspring get type 2 diabetes. In BB rats LV was found in both prediabetic- and diabetic DPBB rats, as well as in diabetes-resistant rats. To evaluate if the presence of virus influences the onset of T1D, prediabetic rats were given antiviral treatments, which prolonged the prediabetic phase with approximately one week. The interplay between LV and diabetes is complicated and still not understood, and our data does not exclude a role of this virus in the development of diabetes

A qualitative method with a focus on science teaching for second language learners using a translanguage perspective in Sweden in grades 4-6

Syftet med uppsatsen var att undersöka hur lärare upplever den naturvetenskapliga undervisningen för flerspråkiga elever genom att besvara forskningsfrågorna: På vilket/vilka sätt arbetar läraren för att undervisa i naturvetenskap för flerspråkiga elever? Hur upplever lärare att flerspråkiga elevers ordförråd i svenska hämmar den naturvetenskapliga ämnesförståelsen? Studien baserades på semi-strukturerade intervjuer med fem verksamma lärare i åk 4–6. Studien vilar på teorin om ett transspråkande arbetssätt där elevens modersmål ses som en resurs för språk- och kunskapsutveckling i de naturvetenskapliga ämnena. I resultatet framkom det att lärarna upplever att de flerspråkiga eleverna har svårt med ämnesspecifika ord och begrepp. Lärarna hade gärna arbetat mer stöttande för de flerspråkiga eleverna men menar att det finns varken tid, kompetens eller resurser för det. Fynden från datainsamlingen antyder att lärarna inte har den kunskap som krävs för att stötta de flerspråkiga eleverna. Mycket av den tidigare forskning och teori som arbetet utgår från pekar åt samma håll. Med denna studie menar jag att transspråkande kan och bör användas i naturvetenskaplig undervisning i syfte att utveckla de flerspråkiga elevernas ämneskunskap och sitt första- och andraspråk.The purpose of the thesis was to investigate how teachers experience the education in science for multilingual students with the support of the research questions: In what / which ways does the teacher work to teach science for multilingual students? How do teachers experience that multilingual students' vocabulary in Swedish inhibits the understanding of scientific subjects? The study was based on semi-structured interviews with five active teachers in years 4-6. The study is based on the theory of translanguaging where the student's mother tongue is seen as a resource for language and knowledge development in the natural science subjects. The results showed that the teachers experience that the multilingual students have difficulty with subject-specific words and concepts. The teachers would have liked to have worked more supportively for the multilingual students, but believe that there is neither time, competence nor resources for that. The findings from the data collection suggest that teachers do not have the knowledge required to support multilingual students. Much of the previous research and theory that the work is based on points in the same direction. By this study, I mean that translanguaging can, and should be, used in science teaching to develop the multilingual students' subject knowledge as well as their first and second language