| 31. |
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| 32. |
- Abdurrahman, G, et al.
(författare)
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Allergy-A New Role for T Cell Superantigens of Staphylococcus aureus?
- 2020
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Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus superantigens (SAgs) are among the most potent T cell mitogens known. They stimulate large fractions of T cells by cross-linking their T cell receptor with major histocompatibility complex class-II molecules on antigen presenting cells, resulting in T cell proliferation and massive cytokine release. To date, 26 different SAgs have been described in the species S. aureus; they comprise the toxic shock syndrome toxin (TSST-1), as well as 25 staphylococcal enterotoxins (SEs) or enterotoxin-like proteins (SEls). SAgs can cause staphylococcal food poisoning and toxic shock syndrome and contribute to the clinical symptoms of staphylococcal infection. In addition, there is growing evidence that SAgs are involved in allergic diseases. This review provides an overview on recent epidemiological data on the involvement of S. aureus SAgs and anti-SAg-IgE in allergy, demonstrating that being sensitized to SEs—in contrast to inhalant allergens—is associated with a severe disease course in patients with chronic airway inflammation. The mechanisms by which SAgs trigger or amplify allergic immune responses, however, are not yet fully understood. Here, we discuss known and hypothetical pathways by which SAgs can drive an atopic disease.
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| 33. |
- Abé, Christoph, et al.
(författare)
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Longitudinal Cortical Thickness Changes in Bipolar Disorder and the Relationship to Genetic Risk, Mania, and Lithium Use.
- 2020
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 87:3, s. 271-281
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a highly heritable psychiatric disorder characterized by episodes of manic and depressed mood states and associated with cortical brain abnormalities. Although the course of BD is often progressive, longitudinal brain imaging studies are scarce. It remains unknown whether brain abnormalities are static traits of BD or result from pathological changes over time. Moreover, the genetic effect on implicated brain regions remains unknown.Patients with BD and healthy control (HC) subjects underwent structural magnetic resonance imaging at baseline (123 patients, 83 HC subjects) and after 6 years (90 patients, 61 HC subjects). Cortical thickness maps were generated using FreeSurfer. Using linear mixed effects models, we compared longitudinal changes in cortical thickness between patients with BD and HC subjects across the whole brain. We related our findings to genetic risk for BD and tested for effects of demographic and clinical variables.Patients showed abnormal cortical thinning of temporal cortices and thickness increases in visual/somatosensory brain areas. Thickness increases were related to genetic risk and lithium use. Patients who experienced hypomanic or manic episodes between time points showed abnormal thinning in inferior frontal cortices. Cortical changes did not differ between diagnostic BD subtypes I and II.In the largest longitudinal BD study to date, we detected abnormal cortical changes with high anatomical resolution. We delineated regional effects of clinical symptoms, genetic factors, and medication that may explain progressive brain changes in BD. Our study yields important insights into disease mechanisms and suggests that neuroprogression plays a role in BD.
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| 34. |
- Abé, Christoph, et al.
(författare)
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Reply to: Tripping Over the Same Stone.
- 2020
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 88:2
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Tidskriftsartikel (refereegranskat)
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| 35. |
- Abelein, A, et al.
(författare)
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High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 235-
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Tidskriftsartikel (refereegranskat)abstract
- During storage in the silk gland, the N-terminal domain (NT) of spider silk proteins (spidroins) keeps the aggregation-prone repetitive region in solution at extreme concentrations. We observe that NTs from different spidroins have co-evolved with their respective repeat region, and now use an NT that is distantly related to previously used NTs, for efficient recombinant production of the amyloid-β peptide (Aβ) implicated in Alzheimer’s disease. A designed variant of NT from Nephila clavipes flagelliform spidroin, which in nature allows production and storage of β-hairpin repeat segments, gives exceptionally high yields of different human Aβ variants as a solubility tag. This tool enables efficient production of target peptides also in minimal medium and gives up to 10 times more isotope-labeled monomeric Aβ peptides per liter bacterial culture than previously reported.
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| 36. |
- Abidi, S, et al.
(författare)
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Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
- 2020
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:3
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Tidskriftsartikel (refereegranskat)abstract
- We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9–12 months (the “shorter regimen”) and individualised regimens of ≥20 months (“longer regimens”).We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD −0.15, 95% CI −0.17– −0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0–0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07–0.16), prothionamide/ethionamide (aRD 0.07, 95% CI −0.01–0.16) or ethambutol (aRD 0.09, 95% CI 0.04–0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
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| 37. |
- Abildgaard, J. S., et al.
(författare)
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Forms of participation : The development and application of a conceptual model of participation in work environment interventions
- 2020
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Ingår i: Economic and Industrial Democracy. - : SAGE Publications Ltd. - 0143-831X .- 1461-7099. ; 4:3, s. 746-769
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Tidskriftsartikel (refereegranskat)abstract
- In the realm of work environment improvements, the Nordic countries have led the way in demonstrating that employee participation is a key requisite for achieving improvements. Despite this, there is a lack of precision as to what ‘participatory’ in a participatory work environment intervention means. In this study, the authors present a conceptual model for participation in work environment interventions and apply it to protocols and manuals from eight participatory interventions to determine the form of participation used in each intervention. The authors suggest that the conceptual model can be applied in the design and assessment of participatory work environment interventions.
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| 38. |
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| 39. |
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| 40. |
- Abo Al Hayja, Muntasir
(författare)
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Sarcoidosis : expression of cell regulatory markers and the influence of patient phenotype on bronchoalveolar lavage cell differential counts
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sarcoidosis is a systemic inflammatory disease that can affect almost any organ, but the respiratory system is affected in more than 90% of the cases. To elicit an immune response, an antigen(s) is processed by antigen-presenting cells (APCs), e.g. alveolar macrophages (AMs), and is presented in association with HLAmolecules to specific T cells, using their T cell receptor (TCR). In sarcoidosis, this interaction between the innate and adaptive immune system leads to an exaggerated immune response and formation of non-caseating granulomas in affected organs. The causative antigen remains elusive. To generate the sarcoid inflammatory process, the genetic background as well as exposure for antigens, endogenous or exogenous, is it of importance. Clinically, sarcoidosis patients can be divided into two major groups, i.e. patients with Löfgren’s syndrome (LS) or with non-Löfgren’s syndrome (non-LS). LS is a clinically distinct and well-defined phenotype that is characterized by an acute onset and is associated with specific HLA molecules, i.e. HLA-DRB1*03. In most of the LS patients, the disease resolves within two years. On the other hand, non-LS patients constitute a heterogeneous group and are prone to develop a chronic disease course. Collecting cells from the deep lung compartment via bronchoalveolar lavage (BAL) enabled many researchers to explore immunological mechanisms in the alveolar space. In a healthy individual, BAL fluid (BALF) are mainly macrophages, some lymphocytes, and fewer neutrophils, and eosinophils; basophils and mast cells are rare. BALF from sarcoidosis patients contains an increased number of all these cell types, especially lymphocytes. The first two studies (I, II) aimed to shed some light on the expression of cell regulatory markers in LS and non-LS patients. Macrophages are classically subdivided into two major subtypes, i.e. M1 – known as proinflammatory macrophages – and M2 – known as remodeling macrophages. We found in the first study (I) reduced gene expression of toll-like receptor 2 (TLR2: M1 associated marker) – mainly in LS patients – and increased expression of CCL18 (M2 associated marker) in AM of sarcoidosis patients. This finding could indicate a shift toward M2-like macrophages in sarcoidosis. The reduced TLR2 expression in LS patients might allow for a more effective immune response leading to resolution of granulomas. The CCL18 chemokine is known to act as T cell chemoattractant and can also induce collagen production in fibroblasts. Hence, the increased expression of CCL18 in AM of patients might attract T cells to the lung in the early stages of the disease and exhibit a profibrotic role in more advanced disease. The second study (II) explored the expression of specific transcription factors/nuclear receptors known to have regulatory roles in inflammatory diseases, i.e. the peroxisome proliferator-activated receptors (PPARs): PPARα, PPARβ/δ and PPARγ. Compared to LS patients, PPARα expression was downregulated in BALF and blood CD4+ and CD8+ T cells in non-LS patients. Thus, CCL18 and PPARα could be used as biomarkers and might help in identifying patients at increased risk of developing more advanced lung disease. The third study (III) aimed to explore the influence of patient phenotypes on BALF cell differential counts. We found that genetic variants associated with risk of LS and clustered in the extended MHC region were associated with the quantitative levels of BALF macrophages, lymphocytes, and neutrophils. Genetic variants associated with non-LS and located in the MHC II region associated with the quantitative levels of BALF macrophages only. In addition, these genetic variants exhibit regulatory effects on other genes in the lung, blood, T cells, B cells, macrophages and neutrophils. The fourth study (IV) aimed to utilize data from a BALF registry of pulmonary sarcoidosis patients (LS and non-LS) to identify BALF cells that could predict disease severity (defined as advanced chest radiographs, reduced pulmonary function, or necessity for treatment) and/or chronicity (non-resolving course after two years). Compared with LS-resolving patients, LS-chronic patients exhibited higher BALF lymphocytes, neutrophils, and eosinophils. Additionally, in newly diagnosed LS patients, increased BALF neutrophils and basophils were more likely to associate with more severe disease; and increased BALF lymphocytes count was more likely to associate with a chronic disease course. In non-LS patients, increased BALF mast cells associated with a more severe and a chronic (nonresolving) disease, and increased BALF lymphocytes, neutrophils, eosinophils, and basophils associated with a more severe disease. In summary, searching for biomarkers, we identified two possible markers for severe and/or chronic disease, i.e. PPARα and CCL18. In study III and IV, we showed that genetic variants associated with LS and non-LS can influence BALF cell counts and that increased BALF neutrophils, eosinophils, lymphocytes, basophils and notably mast cells have prognostic implication in newly diagnosed sarcoidosis patients.
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