| 1. |
- Björck, Sara, et al.
(författare)
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Reduced Bone Mineral Density in Children with Screening-detected Celiac Disease
- 2017
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition. - 0277-2116. ; 65:5, s. 526-532
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of the study was to assess whether bone mass and metabolism are impaired in genetically at-risk children with screening-detected celiac disease. Methods: Included were 71 children with screening-detected celiac disease diagnosed at 10.0 ± 0.7 (mean ± standard deviation) years and 142 matched controls and 30 children with screening-detected celiac disease diagnosed at 3.3 ± 0.4 years of age presently on a gluten-free diet for 6.9 ± 1.1 years and 60 matched controls. All participants were assessed for bone mineral density (BMD) of total body and spine by dual X-ray absorptiometry, serum 25(OH) vitamin D3, parathyroid hormone (PTH), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, interferon gamma, and tumor necrosis factor alpha. Results: At diagnosis, screening-detected celiac disease children as compared to controls had a mean-0.03 g/cm 2 reduced BMD of both total body and spine (P = 0.009 and P = 0.005, respectively), a mean-11.4 nmol/L lower level of 25(OH) vitamin D3 (P < 0.001), and a mean +1.0 pmol/L higher PTH level (P < 0.001). Systemic levels of the cytokines IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were all increased in screening-detected celiac disease as compared to controls (P < 0.001). No difference in BMD, 25(OH) vitamin D3, PTH, and cytokine levels were detected in children on a gluten-free diet compared with controls. Conclusions: Children with screening-detected celiac disease have reduced BMD, lower levels of vitamin D3, higher levels of PTH, and signs of systemic inflammation compared with controls. These differences were not found in celiac disease children on a gluten-free diet, indicating that children with screening-detected celiac disease benefit from an early diagnosis and treatment.
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| 2. |
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| 4. |
- Björck, Sara
(författare)
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Searching for Celiac Disease Screening-detected celiac disease in an HLA-genotyped birth cohort
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Celiac disease is a common immune mediated enteropathy strongly associated with HLA-DQB1*02 (DQ2), *0302 (DQ8), or both and the presence of tissue transglutaminase autoantibodies (tTGA). Prevalence studies have revealed that most affected individuals go undetected because of subclinical signs or being asymptomatic rendering screening a method for identification. However, less is known about subclinical manifestations of screening-detected celiac disease during childhood and if these motivate identification and treatment. The overall aim of the present research was to identify children with screening-detected celiac disease in an HLA-genotyped birth cohort and to study systemic cytokines and bone mineral density (BMD) in these children. Methods: Children were HLA-genotyped at birth and offered screening at three and nine years of age by detection of tTGA in plasma using radioligand binding assays. Children repeatedly positive for tTGA underwent intestinal biopsy to confirm diagnosis of celiac disease. The cytokines IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, and TNF-α were analysed at time of diagnosis and after treatment with a gluten-free diet and compared with matched controls. At nine years of age, children with screening-detected celiac disease were examined by dual X-ray absorptiometry for analysis of BMD and for serum 25(OH) vitamin D3 and plasma parathyroid hormone (PTH) and compared to matched controls. Results: Screening-detected celiac disease was found in 3.5% (56/1618) of three year old children having HLA-risk alleles compared with none (0/1815) among children not having these risk alleles (p<0.001). A follow-up screening at nine years of age identified an additional 3.8% (72/1907) with celiac disease in the HLA-risk group compared with none (0/2167) in the control group (p<0.001). Three-year old children with screening-detected celiac disease had systemically elevated pro-inflammatory cytokines of both TH1 and TH2 pattern compared to controls of which most were down-regulated after starting a gluten-free diet. At nine years of age, children with screening-detected celiac disease had lower BMD, lower levels of vitamin D but higher PTH levels compared with matched controls. In contrast, children on a gluten-free diet did not differ from their matched controls. Conclusions: Screening-detected celiac disease is only found among children at genetic risk but repeated testing during childhood is necessary to detect new patients. HLA-genotyping could therefore be used to select large populations to be screened for celiac disease. Children with screening-detected celiac disease have systemically elevated pro-inflammatory cytokines and low BMD but normal values on a gluten-free diet, indicating that children with screening-detected celiac disease could benefit from early identification and treatment.
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| 5. |
- Björck, Sara, et al.
(författare)
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Serum cytokine pattern in young children with screening detected celiac disease.
- 2015
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 179:2, s. 230-235
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Tidskriftsartikel (refereegranskat)abstract
- Celiac disease is an autoimmune disease characterized by inflammation localized to the small bowel, but less is known about systemic signs of inflammation. The aim was to measure cytokines of the T helper 1 (Th1) and T helper 2 (Th2) cell patterns in children with screening detected celiac disease before and after treatment with a gluten free diet.
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| 6. |
- Ermert, David, et al.
(författare)
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The molecular basis of human igg-mediated enhancement of C4b-binding protein recruitment to group a streptococcus
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10:JUN
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes infects over 700 million people worldwide annually. Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. We recently showed that human IgG increased C4BP binding to the bacterial surface, which promoted streptococcal immune evasion and increased mortality in mice. We sought to identify how IgG promotes C4BP binding to Protein H, a member of the M protein family. Dimerization of Protein H is pivotal for enhanced binding to human C4BP. First, we illustrated that Protein H, IgG, and C4BP formed a tripartite complex. Second, surface plasmon resonance revealed that Protein H binds IgG solely through Fc, but not Fab domains, and with high affinity (IgG-Protein H: KD = 0.4 nM; IgG-Fc-Protein H: KD ≤1.6 nM). Each IgG binds two Protein H molecules, while up to six molecules of Protein H bind one C4BP molecule. Third, interrupting Protein H dimerization either by raising temperature to 41°C or with a synthetic peptide prevented IgG-Protein H interactions. IgG-Fc fragments or monoclonal human IgG permitted maximal C4BP binding when used at concentrations from 0.1 to 10 mg/ml. In contrast, pooled human IgG enhanced C4BP binding at concentrations up to 1 mg/ml; decreased C4BP binding at 10 mg/ml occurred probably because of Fab-streptococcal interactions at these high IgG concentrations. Taken together, our data show how S. pyogenes exploits human IgG to evade complement and enhance its virulence. Elucidation of this mechanism could aid design of new therapeutics against S. pyogenes.
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| 7. |
- Hvit Lindstrand, Sara
(författare)
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Små barns tecken- och meningsskapande i förskola : Multimodalt görande och teknologi
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores how activities that young children are engaged in within the preschool environment, can be understood in terms of early language and literacy processes. The overall aim is to construct knowledge about young children’s spontaneous sign processes as well as meaning making and early literacy processes in preschool. A wider aim is to contribute to the theoretical understanding of young children’s multimodal use of language. More specifically, there is an interest to show how preschool educators describe and analyse young children’s literacy and how young children construct language in interaction with other children and technology. The overall theoretical view of is a social constructionist perspective of language and knowledge. Young childrens’ early literacy is seen from Early Childhood Literacy and multimodal views. The results are presented in four studies that together construct knowledge about the overall aim. The first two studies, based on focus groups, give insight into preschool educators’ views, and professional language about young children’s literacy. Young children’s interactions with each other and an interactive board (IWB), were then explored by video recordings in the third and fourth studies. The interactions are discussed in relation to sign- and meaning making, imagination and creativity. The professional language of Swedish preschool educators is eventually discussed as a dialogism of earlier theoretical and leading voices. The use of concepts such as bodily alliterations and pictographic writing are proposed as ways to expand the theoretical approach to young children’s literacy processes in preschool.By observing childrens interactions and view their bodily activities and their use of resources as doing literacy- and language their literacy could be challenged in preschools in its own right, and seen as literacy education.
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| 8. |
- Livesey, Geoffrey, et al.
(författare)
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Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes : A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:6
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Forskningsöversikt (refereegranskat)abstract
- Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.
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| 9. |
- Livesey, Geoffrey, et al.
(författare)
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Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes : Assessment of Causal Relations
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:6
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Forskningsöversikt (refereegranskat)abstract
- While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.
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