| 1. |
- Dicksved, Johan, et al.
(författare)
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Molecular analysis of the gut microbiota of identical twins with Crohn's disease
- 2008
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Ingår i: The ISME Journal. - : Nature Publishing Group. - 1751-7362 .- 1751-7370. ; 2:7, s. 716-727
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6 and concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.
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| 2. |
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| 3. |
- Jansson, Janet, et al.
(författare)
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Metabolomics reveals metabolic biomarkers of Crohn's disease
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6386-
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Tidskriftsartikel (refereegranskat)abstract
- The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.
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| 4. |
- Linton, Steven J., et al.
(författare)
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A randomized controlled trial of exposure in vivo for patients with spinal pain reporting fear of work-related activities
- 2008
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Ingår i: European Journal of Pain. - : Elsevier. - 1090-3801 .- 1532-2149. ; 12:6, s. 722-730
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pain-related fear is related to disability in persistent pain conditions. Exposure treatment has been reported to be of great benefit in replicated single case experiments.AIM: To evaluate the effects of exposure in vivo on fear and function in patients with persistent pain and work disability.METHOD: We recruited 46 patients suffering from long-term back pain and reduced function, who also were deemed fearful according to standardized measures. Participants were randomized into either an exposure plus usual treatment or waiting list control plus usual treatment group. After the waiting period the control group crossed over and received the exposure treatment.RESULTS: Between group comparisons showed a significantly better result for the exposure group on function, but not for fear or pain and effect sizes were modest (function=.6; fear=.4; pain=.1). When the control group crossed over to treatment significant treatment effects were noted for fear and function. For all patients treated, the pre to post-treatment effect sizes were large (function=.7; fear=1.1; pain=.9). There were 12 dropouts (8 in exposure and 4 in the control) during the first treatment phase and an additional 4 when the control group crossed over to exposure.CONCLUSIONS: Compared to a group receiving usual treatment and waiting for exposure, the exposure in vivo group demonstrated a significantly larger improvement on function. Overall exposure had moderate effects on function, fear and pain intensity. We conclude that exposure may be important in treatment, but is not recommended as a "stand alone" adjunct to usual treatment.
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| 5. |
- Nilsson, Johan, et al.
(författare)
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The influence of acute-phase levels of haemostatic factors on reperfusion and mortality in patients with acute myocardial infarction treated with streptokinase
- 2008
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Ingår i: Journal of Thrombosis and Thrombolysis. - Berlin : Springer. - 0929-5305 .- 1573-742X. ; 26:3, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- Background The fibrinolytic system and von Willebrand factor (vWF) have been shown to play a role as risk factors for myocardial infarction. We performed this prospective cohort study to determine if components in the fibrinolytic system or vWF before or during treatment of AMI with streptokinase (SK) could predict reperfusion, recurrent ischaemia, reinfarction or mortality at one year, or mortality at five years. Reperfusion and recurrent ischaemia were assessed by continuous vectorcardiography. The setting was Umeå university hospital and Skellefteå county hospital, Sweden. Results 139 patients were included; successful reperfusion was obtained in 53%. tPA activity, PAI-activity, PAI-mass concentration and vWF were analysed immediately on arrival and after 4 and 10 h. High fibrinolytic activity, measured as tPA activity > 25 U/L after the start of treatment, was associated with reperfusion. No significant associations between pre-treatment levels of the fibrinolytic variables or vWF and reperfusion or recurrent ischaemia were found. Elevated levels of PAI-1 mass concentration and PAI-1 activity after the start of SK treatment were associated with a higher risk for death at one year, but not at five years. High levels of vWF were associated with worse prognosis but not when corrected for age. Conclusion Pre-treatment levels of PAI-1, vWF and tPA activity showed no association with reperfusion or recurrent ischaemia. Elevated levels of PAI-1 activity after the start of treatment were associated with worse prognosis.
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| 6. |
- Temnerud, Johan, et al.
(författare)
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Spatial variation in discharge and concentrations of organic carbon in a catchment network of boreal streams in northern Sweden
- 2007
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 342:1-2, s. 72-87
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Tidskriftsartikel (refereegranskat)abstract
- Total organic carbon (TOC) is an important feature of water quality in Fenno-Scandia's till catchments. In this study we estimated the contribution of headwater streams to downstream TOC, tested the hypothesis that TOC-concentration decreases downstream and explored mechanisms for the observed patterns. The drainage network of a boreal catchment (66 sites) in northern Sweden, with subcatchment sizes 0.1178 km(2), was sampled in August 2002. In the headwaters there was a large variation in TOC-concentration (4-66 mg l(-1)) as well as other chemical parameters and specific discharge (0.13-8.21 s(-1) km(-2)). Further downstream there was less variation in both chemistry and specific discharge. Both flow and chemistry stabilized at catchment areas larger than 5 km2. No clear indication of in-stream processing effects on downstream TOC was observed, though there was TOC loss at takes and some stream junctions. To test whether the observed downstream decrease is different than that expected from conservative mixing along the stream network, we used a Monte Carlo approach to simulate downstream conservative mixing. The observed spatial variability was higher than the simulated, indicating that landscape-scale patterns are more than conservative mixing of random inputs. While the importance of in-stream processes that after TOC- concentrations cannot be ruled out, and loci of TOC loss do exist, we propose that headwater/ downstream patterns in TOC, and related parameters depend largely on the mosaic of landscape elements (mires, takes and forest) together with specific discharge. (c) 2007 Elsevier B.V. All. rights reserved.
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| 7. |
- Willing, Ben, et al.
(författare)
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Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease
- 2009
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Ingår i: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).METHODS: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).RESULTS: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.CONCLUSIONS: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.
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