| 1. |
- Persson, I., et al.
(author)
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Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix : a population- and registry-based cohort study with over 2 years of follow-up
- 2014
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In: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 275:2, s. 172-190
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Journal article (peer-reviewed)abstract
- Objectives: To investigate the association between vaccination with Pandemrix and risk of selected neurological and immune-related diseases including narcolepsy.Design: Population-based prospective cohort study using data from regional vaccination registries and national health registries.Setting: Seven healthcare regions in Sweden comprising 61% of the Swedish population.Subjects: Study population of 3347467 vaccinated and 2497572 nonvaccinated individuals (vaccination coverage approximate to 60%) followed between 2009 and 2011 for 6.9 million person-years after exposure and 6.0 million person-years without exposure.Main outcome measure and analysis: First recorded diagnosis of neurological and immune-related diseases. Relative risks [hazard ratios (HRs) with 95% confidence intervals (CIs)] assessed using Cox regression, adjusted for covariates.Results: For all selected neurological and immune-related outcomes under study, other than allergic vaccine reactions (for which we verified an expected increase in risk) and narcolepsy, HRs were close to 1.0 and always below 1.3. We observed a three-fold increased risk of a diagnosis of narcolepsy (HR: 2.92, 95% CI: 1.78-4.79; that is, four additional cases per 100000 person-years) in individuals 20years of age at vaccination and a two-fold increase (HR: 2.18, 95% CI: 1.00-4.75) amongst young adults between 21 and 30years of age. The excess risk declined successively with increasing age at vaccination; no increase in risk was seen after 40years of age.Conclusions: For a large number of selected neurological and immune-related diseases, we could neither confirm any causal association with Pandemrix nor refute entirely a small excess risk. We confirmed an increased risk for a diagnosis of narcolepsy in individuals 20years of age and observed a trend towards an increased risk also amongst young adults between 21 and 30years.
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| 2. |
- Bybrant, M. C., et al.
(author)
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Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- de Winter, J M, et al.
(author)
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KBTBD13 is an actin-binding protein that modulates muscle kinetics
- 2020
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In: Journal of Clinical Investigation. - : Stanford University Press. - 0021-9738 .- 1558-8238. ; 130:2, s. 754-767
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Journal article (peer-reviewed)abstract
- The mechanisms that modulate the kinetics of muscle relaxation are critically important for muscle function. A prime example of the impact of impaired relaxation kinetics is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addition to weakness, NEM6 patients have slow muscle relaxation, compromising contractility and daily life activities. The role of KBTBD13 in muscle is unknown, and the pathomechanism underlying NEM6 is undetermined. A combination of transcranial magnetic stimulation-induced muscle relaxation, muscle fiber- and sarcomere-contractility assays, low-angle x-ray diffraction, and superresolution microscopy revealed that the impaired muscle-relaxation kinetics in NEM6 patients are caused by structural changes in the thin filament, a sarcomeric microstructure. Using homology modeling and binding and contractility assays with recombinant KBTBD13, Kbtbd13-knockout and Kbtbd13(R408c)-knockin mouse models, and a GFP-labeled Kbtbd13-transgenic zebrafish model, we discovered that KBTBD13 binds to actin - a major constituent of the thin filament - and that mutations in KBTBD13 cause structural changes impairing muscle-relaxation kinetics. We propose that this actin-based impaired relaxation is central to NEM6 pathology.
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| 4. |
- Hyvonen, R., et al.
(author)
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The likely impact of elevated [CO2], nitrogen deposition, increased temperature and management on carbon sequestration in temperate and boreal forest ecosystems: a literature review
- 2007
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In: New Phytologist. - Cambridge : Wiley. - 0028-646X .- 1469-8137. ; 173:3, s. 463-480
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Research review (peer-reviewed)abstract
- Temperate and boreal forest ecosystems contain a large part of the carbon stored on land, in the form of both biomass and soil organic matter. Increasing atmospheric [CO2], increasing temperature, elevated nitrogen deposition and intensified management will change this C store. Well documented single-factor responses of net primary production are: higher photosynthetic rate (the main [CO2] response); increasing length of growing season (the main temperature response); and higher leaf-area index (the main N deposition and partly [CO2] response). Soil organic matter will increase with increasing litter input, although priming may decrease the soil C stock initially, but litter quality effects should be minimal (response to [CO2], N deposition, and temperature); will decrease because of increasing temperature; and will increase because of retardation of decomposition with N deposition, although the rate of decomposition of high-quality litter can be increased and that of low-quality litter decreased. Single-factor responses can be misleading because of interactions between factors, in particular those between N and other factors, and indirect effects such as increased N availability from temperature-induced decomposition. In the long term the strength of feedbacks, for example the increasing demand for N from increased growth, will dominate over short-term responses to single factors. However, management has considerable potential for controlling the C store.
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| 5. |
- Klevebro, F., et al.
(author)
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Morbidity and mortality after surgery for cancer of the oesophagus and astro-oesophageal junction : a randomized clinical trial of neoadjuvant hemotherapy vs. neoadjuvant chemoradiation
- 2015
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 41:7, s. 920-926
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Journal article (peer-reviewed)abstract
- Objective: To compare the incidence and severity of postoperative omplications after oesophagectomy for carcinoma of the oesophagus and astro-oesophageal junction (GOJ) after randomized accrual to eoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). ackground: Neoadjuvant therapy improves long-term survival after esophagectomy. To date, evidence is insufficient to determine whether ombined nCT, or nCRT alone, is the most beneficial. ethods: Patients with carcinoma of the oesophagus or GOJ, resectable ith a curative intention, were enrolled in this multicenter trial onducted at seven centres in Sweden and Norway. Study participants re andomized to nCT or nCRT followed by surgery with two-field ymphadenectomy. Three cycles of cisplatin/5-fluorouracil was dministered in all patients, while 40 Gy of concomitant radiotherapy as administered in the nCRT group. esults: Of the randomized 181 patients, 91 were assigned to nCT and 90 o nCRT. One-hundred-and-fifty-five patients, 78 nCT and 77 nCRT, nderwent resection. There was no statistically significant difference etween the groups in the incidence of surgical or nonsurgical omplications (P-value = 0.69 and 0.13, respectively). There was no 0-day mortality, while the 90-day mortality was 3% (2/78) in the nCT roup and 6% (5/77) in the nCRT group (P = 0.24). The median lavien-Dindo complication severity grade was significantly higher in he nCRT. group (P = 0.001). onclusion: There was no significant difference in the incidence of omplications between patients randomized to nCT and nCRT. However, omplications were significantly more severe after nCRT. Registration rial database: The trial was registered in the Clinical Trials tabase registration number NCT01362127).
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| 6. |
- Ludvigsson, Jonas F., et al.
(author)
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Influenza H1N1 vaccination and adverse pregnancy outcome
- 2013
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 28:7, s. 579-588
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Journal article (peer-reviewed)abstract
- Although vaccines against influenza can reduce maternal morbidity and mortality, large-scale data on adverse effects in the offspring are scarce. Historical cohort study in Stockholm County, Sweden. We linked H1N1 vaccination data (Pandemrix(A (R)), a mono-valent AS03 adjuvanted H1N1 vaccine) with pregnancy and birth data from 21,087 women with singleton offspring conceived between February 2009 and January 2010 (vaccinated during pregnancy: n = 13,297 vs. unvaccinated: n = 7,790). Data were analysed by conceptualizing the observational cohort as a series of nested cohorts defined at each week of gestation. Logistic regression estimated odds ratios (ORs) for low birth weight (LBW, < 2,500 g), preterm birth (< 37 completed weeks), small-for-gestational age (SGA, < 10th percentile of the gestational age-specific birth weight within the cohort), low 5-min Apgar score (< 7), and caesarean section. Data were adjusted for potential confounders, including maternal age, body mass index, smoking, parity, civil status and comorbidities. Compared with infants of non-vaccinated women, infants of vaccinated women had similar adjusted ORs (95 % CI) for LBW (0.91; 0.79-1.04), preterm birth (0.99; 0.89-1.10), SGA (0.97; 0.90-1.05), low Apgar score (1.05, 0.84-1.31), and a marginal risk reduction for caesarean section (0.94, 0.89-0.99). H1N1 vaccination during pregnancy, using an AS03-adjuvanted vaccine, does not appear to adversely influence offspring risks of LBW, preterm birth, SGA, or low Apgar score. Our results suggest that this vaccine is safe for the offspring when used in different stages of pregnancy.
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| 7. |
- Mikusinska, Anna, et al.
(author)
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Response of ectomycorrhizal extramatrical mycelium production and isotopic composition to in-growth bag size and soil fauna
- 2013
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In: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 66, s. 154-162
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Journal article (peer-reviewed)abstract
- In-growth bags are increasingly used to study extramatrical mycelium (EMM) of ectomycorrhizal fungi in forest soils. In this paper we tested whether bag size and presence of soil fauna in bags influence the production, isotopic composition, carbon (C) and nitrogen (N) content of the EMM. Cylindrical in-growth mesh bags (2- or 5-cm-diameter; with or without openings - (1 or 2 mm), allowing faunal colonization or not) were harvested 37, 48, 81 and 283 days after installation in July and the EMM biomass was determined from elemental analyses of the extractable amount of mycelia. The occurrence of openings allowed animals to invade the bags but this did not affect the amount of EMM. We suggest further studies in this matter since the number of animals was low and variable. In the first harvest, mycelial biomass C was three times greater in 2-cm than in 5-cm-bags. After 81 days, mycelial biomass C was 54% greater in the 2-cm (54 kg ha(-1)) than in the 5-cm bags (35 kg ha(-1)). While total mycelial C did not change over winter, N content increased suggesting a role for the EMM in the storage of N from autumn to spring. The delta C-13 and delta N-15 of the EMM changed between the first three harvests. We hypothesize these changes to be mainly driven by changes in plant C and N sinks. The relation between the isotopic composition of sporocarp exploration type, plant roots and EMM is discussed. (C) 2013 Elsevier Ltd. All rights reserved.
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| 8. |
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| 9. |
- Persson, M L, et al.
(author)
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Aberrant amino acid transport in fibroblasts from patients with bipolar disorder
- 2009
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In: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 457:1, s. 49-52
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Journal article (peer-reviewed)abstract
- Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n=10) and healthy controls (n=10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (V(max)) and affinity constant (K(m)) were determined. A significantly lower V(max) for tyrosine (p=0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in K(m) for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low V(max)) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.
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