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AimFrom 1986 to 1996, there was a four-fold increase in coeliac disease among young Swedish children, known as the Swedish coeliac epidemic. Children with type 1 diabetes have an increased risk of developing coeliac disease. We studied whether the prevalence of coeliac disease differed in children with type 1 diabetes born during and after this epidemic.MethodsWe compared national birth cohorts of 240 844 children born in 1992-1993 during the coeliac disease epidemic and 179 530 children born in 1997-1998 after the epidemic. Children diagnosed with both type 1 diabetes and coeliac disease were identified by merging information from five national registers.ResultsThere was no statistically significant difference in the prevalence of coeliac disease among children with type 1 diabetes between the two cohorts: 176/1642 (10.7%, 95% confidence interval 9.2%-12.2%) in the cohort born during the coeliac disease epidemic versus 161/1380 (11.7%, 95% confidence interval 10.0%-13.5%) in the post-epidemic cohort.ConclusionThe prevalence of having both coeliac disease and type 1 diabetes was not significantly higher in children born during, than after, the Swedish coeliac epidemic. This may support a stronger genetic disposition in children who develop both conditions., Funding Agencies|Council of Skane; ALF

Tick-borne encephalitis virus is an enveloped, pathogenic, RNA virus in the family Flaviviridae, genus Flavivirus. Viral particles are formed when the nucleocapsid, consisting of an RNA genome and multiple copies of the capsid protein, buds through the endoplasmic reticulum membrane and acquires the viral envelope and the associated proteins. The coordination of the nucleocapsid components to the sites of assembly and budding are poorly understood. Here, we investigate the interactions of the wild-type and truncated capsid proteins with membranes with biophysical methods and model membrane systems. We show that capsid protein initially binds membranes via electrostatic interactions with negatively-charged lipids, which is followed by membrane insertion. Additionally, we show that membrane-bound capsid protein can recruit viral genomic RNA. We confirm the biological relevance of the biophysical findings by using mass spectrometry to show that purified virions contain negatively-charged lipids. Our results suggest that nucleocapsid assembly is coordinated by negatively-charged membrane patches on the endoplasmic reticulum and that the capsid protein mediates direct contacts between the nucleocapsid and the membrane.

Aims: Between 1985 and 1996, Sweden experienced an "epidemic" of celiac disease with a fourfold increase in incidence in young children. Timing and amount of gluten introduced during infancy have been thought to explain this "epidemic". We aimed to study whether the cumulative incidence of type 1 diabetes differs between children born during the "epidemic" compared to children born after. Methods: This is a national register study in Sweden comparing the cumulative incidence of type 1 diabetes in two birth cohorts of 240 844 children 0-17 years old born 1992-1993, during the "epidemic", and 179 530 children born 1997-1998, after the "epidemic". Children diagnosed with type 1 diabetes were identified using three national registers. Results: The cumulative incidence of type 1 diabetes by the age of 17 was statistically significantly higher in those born after the "epidemic" 0.77% than in those born during the "epidemic" 0.68% (p < 0.001). Conclusion: The incidence of type 1 diabetes is higher in those born after the epidemic compared to those born during the epidemic, which does not support the hypothesis that gluten introduction increases the incidence of T1D. Changes in gluten introduction did not halt the increased incidence of type 1 diabetes in Sweden.

Objective: To gain knowledge of underlying risk factors for vascular complications and their impact on life expectancy in myelofibrosis. Methods: From a cohort of 392 myelofibrosis patients registered in the Swedish MPN registry 58 patients with vascular complications during follow-up were identified. Patients with vascular complications were compared with both 1:1 matched controls and the entire myelofibrosis cohort to explore potential risk factors for vascular complications and their impact on survival. Results: Incidence of vascular complications was 2.8 events per 100 patient-years and the majority of complications were thrombotic. Patients with complications were significantly older and had lower hemoglobin when compared to the entire cohort. In the case–control analysis, no significant risk factor differences were observed. The major cause of death was vascular complications and median survival was significantly impaired in patients with vascular complications (48 months) compared to controls (92 months). Inferior survival in patients with vascular complications was found to be dependent on IPSS risk category in a Cox regression model. Conclusion: Vascular complications have a considerable impact on survival in MF. At diagnosis, risk assessment by IPSS does not only predict survival but is also associated with the risk of vascular complications.

Syfte: Syftet var att belysa kvinnors upplevelser av att leva med polycystiskt ovarialsyndrom. Bakgrund: Polycystiskt ovarialsyndrom är ett endokrint syndrom som drabbar 5-20% av kvinnor i fertil ålder. På grund av symptomens heterogena karaktär varierar upplevelserna och många aspekter av kvinnans liv påverkas. Metod: Vald metod är en litteraturstudie där tolv kvalitativa studier analyserades. Resultat: Fyra teman som beskriver kvinnors upplevelser av att leva med PCOS framkom; problem med psykosomatiska symptom, påverkad kvinnlighet, frustration gentemot vården och behov av copingstrategier. Slutsats: Diagnosen har en stor påverkan på livskvaliteten. Då det finns en kunskapsbrist om diagnosen bland vårdpersonal vore kompetensutveckling inom området samt forskning om det psykiska och medicinska omhändertagandet av stor betydelse. Kunskap om kvinnors upplevelser kan hjälpa sjuksköterskor att få ökad förståelse för vad som är viktigt i omvårdnaden av patienter med PCOS.

Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method., Funding Agencies|Barndiabetesfonden; Skane County Councils Research and Development Foundation

Publicerad på Lakartidningen.se 2021-09-07

Traumatisk hjärnskada är vanligt förekommande i alla åldrar och kan leda till behov av rehabiliteringsinsatser under många år. Kunskap och samarbete mellan flera specialiteter och samordning av insatser är viktiga för patienten genom hela vårdkedjan. Det finns ett behov av mer jämlik vård och stöd i att hantera hjärnskaderelaterade frågor genom hela livet. Vid specialiserad hjärnskaderehabilitering bedöms och behandlas komplexa förlopp med symtom som långvarig svår medvetandestörning, posttraumatisk agitation, kognitiva funktionsnedsättningar, fatigue, motoriska och kommunikativa svårigheter, synsvårigheter, yrsel och stimuluskänslighet efter traumatisk hjärnskada.

OBJECTIVES: Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were ≥10 times the upper limit of normal (10× ULN) predicted CD in T1D. METHODS: Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2,035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhüber classification. RESULTS: All of the 60 children with anti-tTG ≥10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2,003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2,035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. CONCLUSIONS: As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a non-invasive method., Funding Agency:Skane County Council's Research and Development Foundation

Publicerad online 2020-04-28

OBJECTIVE: To explore the relative importance of risk factors, treatments and blood counts for the occurrence of vascular complications and their impact on life expectancy in Essential Thrombocythemia (ET) and Polycythemia Vera (PV). METHODS: Nested case-control study within the Swedish MPN registry. From a cohort of 922 ET patients and 763 PV patients, 71 ET and 81 PV cases with vascular complications were compared to matched controls. RESULTS: Incidence of vascular complications were 2.0 and 3.4 events per 100 patient-years in ET and PV, respectively. At diagnosis, no significant risk factor differences were observed between cases and controls in neither of the diseases. At the time of vascular event, ET complication cases did not differ significantly from controls but in PV, cases had significantly higher WBCs and were to a lesser extent treated with antithrombotic and cytoreductive therapy. Life expectancy was significantly decreased in both ET and PV cases compared to controls. CONCLUSIONS: The risk of vascular complications is high in both ET and PV and these complications have a considerable impact on life expectancy. The protective effect of antithrombotic and cytoreductive therapy for vascular complications in PV underscores the importance of avoiding undertreatment., Funding Agency:Regional FOU Västra Götaland County

I denna rapport beskrivs hur matematikutvecklare, lärare, och elever arbetar för att elever som i början av årkurs 6 visade så låga resultat att de riskerade att bli underkända i slutet av år 6 ska bli godkända på Nationella provet i årskurs 6. I resultatet visas vilka faktorer som var positiva för elevernas lärande i matematik. Det handlade om att a) skapa tid för matematik (Ofta behöver dessa elever mer tid för att lära), b) fokusera på det som är det som är centralt (t.ex. räkning och problemlösning), c) läraren tror på den individuella eleven!, d) organisera er så att undervisningen snabbt kan anpassas för varje elev!, e) synliggöra elevens framsteg!, f) se till så att eleven arbetade intensivt vid matematiktillfällena! g) låta eleverna arbeta på lagom nivå, och med lagom mängd!

Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intraprotein "tunnel" as the main inhibitor binding site (A1), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix−turn−helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-A1 selective PrfA inhibitors with potent antivirulence properties.

An organizing structure that in recent years has had a major impact on how to work with students who don’t respond to regular instruction is Response to Intervention (RTI). Efforts in RTI are divided into three different tiers of instruction: primary, secondary and tertiary. In our study, we investigate the impact of intensive secondary-tier instruction on students’ knowledge of basic combinations of digits in addition. We also focus on how the students develop their use of more advanced calculations in addition during the intervention. The results showed that students became faster at performing simple addition tasks, which indicates that their fluency – declarative knowledge – developed during the intervention phase. Our results thereby strengthen suggestions that a secondary-tier intervention level should take place in a small group of students 20-40 minutes four to five times a week. Meanwhile, the students developed their ability to solve two-digit arithmetic tasks in addition and subtraction, which could be explained by the fact that students had automated simple number combinations and thus could focus on the calculation procedure.

BACKGROUND: Spasticity is a common consequence of injury to the central nervous system negatively affecting patients everyday activities. Treatment mainly consists of training and different drugs, often with side effects. There is a need for treatment options that can be performed by the patient in their home environment. AIM: The objective of this study was to assess the effectiveness of an assistive technology (AT), Mono, a garment with integrated electrodes for multifocal transcutaneous electrical stimulation intended for self-treatment of spasticity, in study participants with spasticity due to stroke or CP. DESIGN: The study was a randomized, controlled, double-blind study with a cross-over design. SETTING: Participants were recruited from two rehabilitation clinics. Treatments were performed in participants homes and all follow-ups were performed in the two rehabilitation clinics. POPULATION: Thirty-one participants were included in the study and 27 completed the study. Four participants discontinued the study. Two declined participation before baseline and two withdrew due to problems handling the garment. METHODS: Participants used the AT with and without electrical stimulation (active/non-active period) for six weeks each. followed by six weeks without treatment. Goal Attainment Scaling (GAS), change in mobility, arm-hand ability, spasticity and pain were measured at baseline and after 6, 12 and 18 weeks. RESULTS: Fifteen of the 27 participants fulfilled the treatment protocol in terms of recommended use. Deviations were frequent. No statistically significant differences in outcome were found between the active and the non-active treatment periods. During the active period, an improvement was seen in the 10-meter comfortable gait test, time and steps. An improvement was seen in both the active and non-active periods for the GAS. CONCLUSIONS: Compliance was low, partly due to deviations related to the garment, complicating the interpretation of the results., Funding Agencies|Region Ostergotland; Promobilia Foundation; Inerventions AB (Vinnova)

Several bacterial pathogens interact with their host through protein secretion effectuated by a type VI secretion system (T6SS). Francisella tularensis is a highly pathogenic intracellular bacterium that causes the disease tularemia. Proteins encoded by the Francisella pathogenicity island (FPI), which constitute a type VI secretion system, are essential for the virulence of the bacterium and a key mechanism behind this is the escape from the phagosome followed by productive cytosolic replication. It has been shown that T6SS in Francisella is distinct since all putative substrates of F. tularensis T6SS, except for VgrG, are unique to the species. Many of the FPI proteins are secreted into the macrophage cytosol and this is dependent on the functional components of DotU, VgrG, IglC and IglG. In addition, PdpC seems to have a regulatory role for the expression of iglABCD. Since previous results showed peculiar phenotypes of the Delta pdpC and Delta iglG mutants in mouse macrophages, their unique behavior was characterized in human monocyte-derived macrophages (HMDM) in this study. Our results show that both Delta pdpC and Delta iglG mutants of the live vaccine strain (LVS) of F. tularensis did not replicate within HMDMs. The Delta pdpC mutant did not escape from the Francisella containing phagosome (FCP), neither caused cytopathogenicity in primary macrophages and was attenuated in a mouse model. Interestingly, the Delta iglG mutant escaped from the HMDMs FCP and also caused pathological changes in the spleen and liver tissues of intradermally infected C57BL/6 mice. The Delta iglG mutant, with its unique phenotype, is a potential vaccine candidate.

This study, based on the sociocultural perspective, aims to show the significance of motivation and feedback concerning pupils with writing problems. The study was based on a writing task which lasted every school day for five weeks. Observations were made during the interventions and along with a survey they create the result. Eighteen pupils in fourth grade from two rural schools participated in the study and in each class were pupils who had special needs education previously. Pupils from school A wrote, read the text to and were given feedback by, a teacher. Pupils from school B wrote, read the text to and were given feedback by a dogassisted teacher. A dogassisted teacher has a living tool, who by the presence only, gives an entry to the pupil’s mind which can be hard for a teacher to achieve oneself. The pupil feels acknowledged by the dog and accept the feedback in a positive way thus the review might be experienced as negative. The study shows that a school dog enforces the confidence by letting the pupil be superior to the dog and at the same time the pupil embraces what the teacher delivers with the voice of the dog. The results of the study show that both pupils in school A and B experienced increased motivation and pleasure in writing. Charts and tests can provide answers regarding the cause of the difficulties but the real challenge is to develop various ways to work that encounters and suits every single pupil. There has been a wish not to pit methods or motivational efforts against each other, rather to find various success factors for pupils with special needs. Because of pupils diversity and hence the teachers methods need to offer alternatives. One of these alternatives could be dogassisted teaching because the study shows that The dog is more that man’s best friend – it could also be the best teacher.

Objective: To assess associations between real-world care pathways for working-age patients in the first year after severe traumatic brain injury and outcomes at 1 year. Setting and Design: Prospective, observational study with recruitment from 6 neurosurgical centers in Sweden and Iceland. Follow-up to 1 year, independently of care pathways, by rehabilitation physicians and paramedical professionals. Participants: Patients with severe traumatic brain injury, lowest (nonsedated) Glasgow Coma Scale score 3 to 8 during the first 24 hours and requiring neurosurgical intensive care, age 18 to 65 years, and alive 3 weeks after injury. Main Measures: Length of stay in intensive care, time between intensive care discharge and rehabilitation admission, outcome at 1 year (Glasgow Outcome Scale Extended score), acute markers of injury severity, preexisting medical conditions, and post-acute complications. Logistic regression analyses were performed. Results: A multivariate model found variables significantly associated with outcome (odds ratio for good outcome [confidence interval], P value) to be as follows: length of stay in intensive care (0.92 [0.87-0.98], 0.014), time between intensive care discharge and admission to inpatient rehabilitation (0.97 [0.94-0.99], 0.017), and post-acute complications (0.058 [0.006-0.60], 0.017). Conclusions: Delays in rehabilitation admission were negatively associated with outcome. Measures to ensure timely rehabilitation admission may improve outcome. Further research is needed to evaluate possible causation.

Syftet med examensarbetet är att undersöka hur några speciallärare och specialpedagoger ser på arbete med musik, språk och kommunikation för elever på tidig utvecklingsnivå. Fokuseringen är hur de ser på att använda musik för att nå språkliga och kommunikativa mål för elever i gymnasiesärskolan. Som metod i studien har kvalitativa intervjuer använts då den undersöker upplevelser. Datainsamlingsmaterialet har analyserats enligt fenomenologisk forskningsmetod. Sammanlagt har sex speciallärare och specialpedagoger intervjuats. Resultatet visar att speciallärarna och specialpedagogerna ser flera gemensamma nämnare i musik som medel att nå kommunikativa mål. Musik ses som ett mångsidigt och flexibelt medel som utvidgar till språkliga och kommunikativa sammanhang. Det beskrivs i motivationshöjande aktiviteter som genererar sociala möten. Musiken sociala forum ses som särskilt betydelsefull då det annars arbetas mycket på individuell nivå. Möjligheter beskrivs i att variera metoder där hela kroppen används utifrån en här- och nusituation. Musiksammanhang beskrivs också i att locka eleverna till något mer utmanande. Även den ordlösa kommunikationen som finns i musiken tas upp, en slags kommunikation men utan ord. Det ordlösa som finns i musiken ger utrymme för återhämtning i en kravlös gemenskap för dem som annars har svårt att utrycka sig i talat språk. Där blir eleverna deltagare i en passiv kommunikation genom att följa med i texten till en känd sång eller genom att bara lyssna på musikens uttryck.