| 1. |
- Aldridge, Jonathan, et al.
(författare)
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T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3(+)Th2 phenotype
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The majority of CD4(+)T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA. Methods We examined the proportions of Th1, Th2, CXCR3(+)Th2, Th17, CXCR3(+)Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry. We also examined the cytokine/chemokine profile in paired SF and plasma (n = 8) and in culture supernatants of FLS from patients with chronic RA (n = 7) stimulated with Th-associated cytokines, by the use of cytometric bead arrays and ELISA. Cytokine receptor expression in FLS (n = 3) were assessed by the use of RNA sequencing and qPCR. Results The proportions of Th1 and CXCR3(+)Th2 cells were higher in SF than in blood (P < 0.05). TPh and PD-1(high)TFh in RA SF were primarily of a Th1 and a CXCR3(+)Th2 phenotype. Moreover, the levels of CXCL9, CXCL10, CCL20, CCL2, CXCL8, IL-6 and IL-10 were higher in SF than in plasma (P < 0.05). Lastly, IL-4, IL-13 and IL-17A induced RA FLS to secrete proinflammatory IL-6, CCL2, CXCL1 and CXCL8, while IFN gamma mainly induced CXCL10. Conclusion These findings indicate that not only Th1 but also CXCR3(+)Th2 cells may have a pathogenic role in RA synovial inflammation.
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| 2. |
- Alhamdow, Ayman, et al.
(författare)
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Low-level exposure to polycyclic aromatic hydrocarbons is associated with reduced lung function among Swedish young adults
- 2021
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to adverse pulmonary effects. However, the impact of low-level environmental PAH exposure on lung function in early adulthood remains uncertain. Objectives: To evaluate the associations between urinary PAH metabolites and lung function parameters in young adults. Methods: Urinary metabolites of pyrene, phenanthrene, and fluorene were analysed in 1000 young adults from Sweden (age 22–25 years) using LC-MS/MS. Lung function and eosinophilic airway inflammation were measured by spirometry and exhaled nitric oxide fraction (FeNO), respectively. Linear regression analysis was used to evaluate associations between PAH metabolites and the outcomes. Results: Median urinary concentrations of 1-OH-pyrene, ∑OH-phenanthrene, and ∑OH-fluorene were 0.066, 0.36, 0.22 μg/L, respectively. We found inverse associations of ∑OH-phenanthrene and ∑OH-fluorene with FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC ratio (adjusted P < 0.05; all participants). An increase of 1% in ∑OH-fluorene was associated with a decrease of 73 mL in FEV1 and 59 mL in FVC. In addition, ∑OH-phenanthrene concentrations were, in a dose-response manner, inversely associated with FEV1 (B from −109 to −48 compared with the lowest quartile of ∑OH-phenanthrene; p trend 0.004) and FVC (B from −159 to −102 compared with lowest quartile; p-trend <0.001). Similar dose-response associations were also observed between ∑OH-fluorene and FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC (p-trend <0.05). There was no association between PAH exposure and FeNO, nor was there an interaction with smoking, sex, or asthma. Conclusion: Low-level PAH exposure was, in a dose-response manner, associated with reduced lung function in young adults. Our findings have public health implications due to i) the widespread occurrence of PAHs in the environment and ii) the clinical relevance of lung function in predicting all-cause and cardiovascular disease mortality.
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| 3. |
- Bergström, Anna, 1983-, et al.
(författare)
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The use of the PARIHS framework in implementation research and practice-a citation analysis of the literature
- 2020
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Ingår i: Implementation science : IS. - : Springer Science and Business Media LLC. - 1748-5908. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: The Promoting Action on Research Implementation in Health Services (PARIHS) framework was developed two decades ago and conceptualizes successful implementation (SI) as a function (f) of the evidence (E) nature and type, context (C) quality, and the facilitation (F), [SI = f (E,C,F)]. Despite a growing number of citations of theoretical frameworks including PARIHS, details of how theoretical frameworks are used remains largely unknown. This review aimed to enhance the understanding of the breadth and depth of the use of the PARIHS framework. METHODS: This citation analysis commenced from four core articles representing the key stages of the framework's development. The citation search was performed in Web of Science and Scopus. After exclusion, we undertook an initial assessment aimed to identify articles using PARIHS and not only referencing any of the core articles. To assess this, all articles were read in full. Further data extraction included capturing information about where (country/countries and setting/s) PARIHS had been used, as well as categorizing how the framework was applied. Also, strengths and weaknesses, as well as efforts to validate the framework, were explored in detail. RESULTS: The citation search yielded 1613 articles. After applying exclusion criteria, 1475 articles were read in full, and the initial assessment yielded a total of 367 articles reported to have used the PARIHS framework. These articles were included for data extraction. The framework had been used in a variety of settings and in both high-, middle-, and low-income countries. With regard to types of use, 32% used PARIHS in planning and delivering an intervention, 50% in data analysis, 55% in the evaluation of study findings, and/or 37% in any other way. Further analysis showed that its actual application was frequently partial and generally not well elaborated. CONCLUSIONS: In line with previous citation analysis of the use of theoretical frameworks in implementation science, we also found a rather superficial description of the use of PARIHS. Thus, we propose the development and adoption of reporting guidelines on how framework(s) are used in implementation studies, with the expectation that this will enhance the maturity of implementation science.
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| 4. |
- Bergström, Lena, et al.
(författare)
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Klimatförändringar och biologisk mångfald : Slutsatser från IPCC och IPBES i ett svenskt perspektiv.
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- De stora miljö- och samhällsproblemen kommer inte ensamma. De är sammankopplade på olika sätt. Detta innebär utmaningar men ger också möjligheter att utveckla åtgärder och lösningar. Det gäller både för klimatfrågan och frågan om att motverka förlusten av biologisk mångfald och ekosystem. Kunskapens betydelse för att hantera dessa och andra aspekter är ovärderlig, såväl kring specifika frågeställningar som kring omständigheter och förutsättningar för åtgärdsarbetet.Den här kunskapssammanställningen har gjorts av forskare från Lunds universitet och Sveriges lantbruksuniversitet på uppdrag av Naturvårdsverket och SMHI. Forskarna har tagit avstamp i de omfattande kunskapsutvärderingar som gjorts av den mellanstatliga klimatpanelen (IPCC) och den mellanstatliga plattformen för biologisk mångfald (IPBES). Slutsatserna från IPCC och IPBES sätts i ett svenskt perspektiv, bland annat genom utvalda exempel vilka fungerar som aktuella illustrationer av hur klimatförändringar påverkar biologisk mångfald och ekosystem i Sverige.
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| 5. |
- Fuchs, David, et al.
(författare)
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Scoring the Risk of Having Systemic Mastocytosis in Adult Patients with Mastocytosis in the Skin
- 2021
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 9:4, s. 1705-1712.e4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a bone marrow biopsy is not performed, the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients. OBJECTIVE: To develop a risk score to predict SM in adults with MIS. METHODS: We examined 1145 patients with MIS from the European Competence Network on Mastocytosis Registry who underwent a bone marrow biopsy. A total of 944 patients had SM and 201 patients had cutaneous mastocytosis; 63.7% were female, and 36.3% were male. Median age was 44 +/- 13.3 years. The median serum tryptase level amounted to 29.3 +/- 81.9 ng/mL. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver-operating curves. RESULTS: In the multivariate model, the tryptase level (P < .001), constitutional/cardiovascular symptoms (P = .014), and bone symptoms/osteoporosis (P < .001) were independent predictors of SM (P < .001; sensitivity, 90.7%; specificity, 69.1%). A 6-point risk score was established (risk, 10.7%-98.0%) and validated. CONCLUSIONS: Using a large data set of the European Competence Network on Mastocytosis Registry, we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure cutaneous mastocytosis. (C) 2020 American Academy of Allergy, Asthma & Immunology
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| 6. |
- Grut, Viktor, et al.
(författare)
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Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis : a presymptomatic case-control study
- 2021
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 28:9, s. 3072-3079
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epstein-Barr virus (EBV) and Human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with Cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, we sought to increase the understanding of CMV in MS aetiology.METHODS: We performed a nested case-control study with presymptomatically collected blood samples identified through cross-linkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95 % confidence intervals (CI) for CMV seropositivity as risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating attributable proportion due to interaction (AP).RESULTS: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56-0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06-0.61) and EBV antigen EBNA-1 (amino acid 385-420) at age 20-39 years (AP 0.37, 95% CI 0.09-0.65).CONCLUSIONS: CMV seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.
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| 7. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 8. |
- Lambe, Mats, et al.
(författare)
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Reproductive patterns and maternal and pregnancy outcomes in women with psoriasis-A population-based study
- 2020
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Ingår i: The Journal of American Academy of Dermatology. - : MOSBY-ELSEVIER. - 0190-9622 .- 1097-6787. ; 82:5, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data on pregnancy outcomes in women with psoriasis are conflicting.Objective: We examined whether maternal psoriasis affects the risk of adverse maternal and pregnancy outcomes.Methods: We used population-based data to compare reproductive patterns in women with and without psoriasis. Odds ratios (ORs) with 95% confidence intervals (CIs) for adverse outcomes were estimated with adjustments for maternal age, period of childbirth, smoking, and prepregnancy body mass index.Results: Compared with women without psoriasis, women with psoriasis were younger at first birth and had longer interpregnancy intervals but did not differ in final parity. Risk estimates in women with psoriasis were elevated for pregnancy hypertension (OR, 1.37; 95% CI, 1.19-1.58), premature rupture of membranes (OR, 1.15; 95% CI, 1.04-1.27), large for gestational age (OR, 1.11; 95% CI, 1.01-1.21), cleft palate (OR, 1.69; 95% CI, 1.07-2.66), and unspecified malformations (OR, 1.08; 95% CI, 1.01-1.16).Limitations: No information was available on lifestyle, disease severity, or type and duration of treatment. Small numbers hampered the assessment of rare outcomes.Conclusion: Although there was no evidence that fertility is negatively affected, women with psoriasis were at an increased risk of several adverse maternal and pregnancy outcomes. Our findings add to a growing body of evidence that pregnancies in women with psoriasis need special monitoring.
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| 9. |
- Melen, Erik, et al.
(författare)
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Male sex is strongly associated with IgE-sensitization to airborne but not food allergens : results up to age 24 years from the BAMSE birth cohort
- 2020
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Ingår i: Clinical and Translational Allergy. - : BioMed Central. - 2045-7022 .- 2045-7022. ; 75, s. 161-162
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Tidskriftsartikel (refereegranskat)abstract
- Background Up to half of the population in high-income countries has allergen-specific IgE antibodies. However, data regarding sex differences of IgE-sensitization from childhood to adulthood is limited. Objective To explore IgE-sensitization to common foods and airborne allergens in relation to sex over time in a population-based cohort followed up to young adulthood. Methods The Swedish population-based birth cohort BAMSE includes 4089 subjects who have been followed regularly with questionnaires and clinical investigations. A recent 24-year follow-up included 3069 participants (75%). Sera collected at 4, 8, 16 and 24 years were analyzed for IgE-antibodies to 14 common foods and airborne allergens. Results At 24 years sensitization to foods had decreased compared to previous follow-ups affecting 8.4%, while sensitization to airborne allergens was more common, affecting 42.2%. Male sex was associated with IgE-sensitization to airborne allergens at all ages (overall OR: 1.68, 95% CI 1.46-1.94) while there was no statistically significant association between sex and sensitization to food allergens (overall OR: 1.10, 95% CI 0.93-1.32). Levels of allergen-specific IgE did not differ significantly between males and females for any of the tested foods or airborne allergens at any age, following adjustment for multiple comparisons. Conclusion IgE-sensitization to airborne allergens increases with age up to young adulthood, whereas sensitization to food allergens seems to level off. Male sex is strongly associated with IgE-sensitization to airborne allergens from early childhood up to young adulthood. In contrast, there is little evidence for associations between sex and IgE-sensitization to foods.
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| 10. |
- Mitselou, Niki, 1982-, et al.
(författare)
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Preterm birth reduces the risk of IgE sensitization up to early adulthood : A population-based birth cohort study
- 2022
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Munksgaard Forlag. - 0105-4538 .- 1398-9995. ; 77:5, s. 1570-1582
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunoglobulin E (IgE) sensitization is associated with asthma and allergic diseases. Gestational age influences early immune system development, thereby potentially affecting the process of tolerance induction to allergens.Objective: To study IgE sensitization to common allergens by gestational age from childhood up to early adulthood.Methods: Population-based birth cohort, data from the Swedish BAMSE study were used. Allergen-specific IgE antibodies to a mix of common food (fx5) and inhalant (Phadiatop) allergens were analysed at 4, 8, 16 and 24 years. Sensitization was defined as allergen-specific IgE >= 0.35 kU(A)/L to fx5 and/or Phadiatop at each time point. Using logistic regression and generalized estimated equations, adjusted odds ratios (aORs) for sensitization in relation to gestational age were calculated. Replication was sought within the Swedish twin study STOPPA.Results: In BAMSE, 3522 participants were screened for IgE antibodies during follow-up; of these, 197 (5.6%) were born preterm (<37 gestational weeks) and 330 (9.4%) post-term (>= 42 weeks). Preterm birth reduced the risk of sensitization to common food and/or inhalant allergens up to early adulthood by 29% (overall aOR = 0.71; 95% CI: 0.52-0.98), and to food allergens specifically by 40% (overall aOR = 0.60; 95% CI: 0.38-0.93). No relation was found between post-term birth and IgE sensitization at any time point. Replication analyses in STOPPA (N = 675) showed similar risk estimates for sensitization to food and/or inhalant allergens (aOR = 0.72; 95% CI: 0.42-1.21), which resulted in a combined meta-analysis aOR = 0.71 (95% CI: 0.54-0.94).Conclusions: Our study suggests an inverse association between preterm birth and long-term IgE sensitization.
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