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- Tjonneland, A., et al.
(author)
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Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study
- 2009
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 58:12, s. 1606-1611
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Journal article (peer-reviewed)abstract
- Objective: Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis. Design and setting: Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30-74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre. Results: A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7-11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend). Conclusions: The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.
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- Deisenhammer, F, et al.
(author)
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Prediction of natalizumab anti-drug antibodies persistency
- 2019
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 25:3, s. 392-398
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Journal article (peer-reviewed)abstract
- Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency. Design/methods: We developed a highly sensitive natalizumab ADA titration assay on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We included 43 patients with a positive ELISA-ADA result within 6 months of treatment initiation (baseline) of whom a follow-up serum sample was available 12–30 months after treatment start. MSD-ADA titres and drug levels were measured. Results: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA persistency. Reversion to ADA negativity occurred in 10 patients with mean drug levels of 10.8 μg/mL. The median trough drug level in ADA-positive samples was 0 µg/mL. PK levels and ADA titres correlated strongly negatively ( r = −0.67). Conclusion: High baseline natalizumab ADA titres accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results.
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- Karadenizli, A., et al.
(author)
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Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012
- 2015
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In: Eurosurveillance. - 1025-496X .- 1560-7917. ; 20:21
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Journal article (peer-reviewed)abstract
- Waterborne epidemics of tularaemia caused by Francisella tularensis are increasingly reported in Turkey. We have used whole genome sequencing to investigate if F. tularensis isolated from patients could be traced back to drinking water sources. Tonsil swabs from 33 patients diagnosed with oropharyngeal tularaemia in three outbreaks and 140 water specimens were analysed. F. tularensis subsp. holarctica was confirmed by microagglutination and PCR in 12 patients and five water specimens. Genomic analysis of three pairs of patient and water isolates from outbreaks in Sivas, Corum, and Kocaeli showed the isolates to belong to two new clusters of the F. tularensis B. 12 genetic clade. The clusters were defined by 19 and 15 single nucleotide polymorphisms (SNPs) in a multiple alignment based on 507 F. tularensis genomes. One synonymous SNP was chosen as a new canonical SNP (canSNP) for each cluster for future use in diagnostic assays. No SNP was identified between the genomes from the patient-water pair of isolates from Kocaeli, one SNP between the pair of isolates from Sivas, whereas the pair from Corum differed at seven SNPs. These results illustrate the power of whole genome sequencing for tracing F. tularensis patient isolates back to their environmental source.
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| 7. |
- Toft, A., et al.
(author)
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Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation
- 2023
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In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
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Journal article (peer-reviewed)abstract
- IntroductionIncreasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. MethodsCombining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. ResultsCompared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. DiscussionLower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. HighlightsCSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
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- Wallin, Anders, 1950, et al.
(author)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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In: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Journal article (peer-reviewed)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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| 9. |
- Afset, J. E., et al.
(author)
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Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 2011
- 2015
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In: Eurosurveillance. - 1025-496X .- 1560-7917. ; 20:19, s. 9-14
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Journal article (peer-reviewed)abstract
- In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.
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| 10. |
- Anckarsäter, Henrik, et al.
(author)
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New evidence for an association between the CSF HVA:5-HIAA ratio and psychopathic traits
- 2003
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 74:7, s. 918-921
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To replicate the relation between the CSF HVA:5-HIAA ratio and psychopathic traits previously reported in a pilot group of 22 perpetrators of violent crimes. METHODS: CSF monoamine metabolite concentrations in another 28 violent and sexual offenders, aged 45 or below, referred to pretrial forensic psychiatric investigation, were compared to features of psychopathy according to the Psychopathy Checklist-Revised (PCL-R). RESULTS: Our previous finding was repeated in the new study group, where the HVA:5-HIAA ratio was strongly associated with psychopathic traits (r = 0.50, p = 0.010), particularly its behavioural aspects (r = 0.523, p = 0.004). In subsamples of individuals from both study groups who had no medication (n = 25) or no current axis I disorder, including a history of mood disorder or substance dependence (n = 21), the HVA:5-HIAA ratio remained strongly associated with all psychopathy factors but most closely with the behavioural features. Retrospective assessments of childhood disruptive symptomatology, such as attention deficit hyperactivity disorder or conduct disorder, analysed in relation to the monoamine metabolites, showed the same association with the HVA:5-HIAA ratio. CONCLUSIONS: Violent and aggressive behavioural traits with childhood onset and adult expression as psychopathic features are associated with changed activity in the brain dopaminergic system, possibly as a result of serotonergic dysregulation.
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