| 1. |
- Kanatsuna, N, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes
- 2015
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 82:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.
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| 2. |
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| 3. |
- Bornhöft, Lena, et al.
(författare)
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Health effects of direct triaging to physiotherapists in primary care for patients with musculoskeletal disorders: a pragmatic randomized controlled trial
- 2019
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Ingår i: Therapeutic Advances in Musculoskeletal Disease. - : SAGE Publications. - 1759-720X .- 1759-7218. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Physiotherapists and general practitioners (GPs) both act as primary assessors for patients with musculoskeletal disorders in primary care. Previous studies have shown that initial triaging to physiotherapists at primary healthcare centres has advantages regarding efficiency in the work environment and utilization of healthcare. In this study, we aimed primarily to determine whether triaging to physiotherapists affects the progression of health aspects over time differently than traditional management with initial GP assessment. The secondary aim was to determine whether triaging to physiotherapists affects patients' attitudes of responsibility for musculoskeletal disorders. Methods: This was a pragmatic trial where both recruitment and treatment strategies were determined by clinical, not study-related parameters, and was initiated at three primary care centres in Sweden. Working-age patients of both sexes seeking primary care for musculoskeletal disorders and nurse assessed as suitable for triaging to physiotherapists were randomized to initial consultations with either physiotherapists or GPs. They received self-assessment questionnaires before the initial consultation and were followed up at 2, 12, 26 and 52 weeks with the same questionnaires. Outcome measures were current and mean (3 months) pain intensities, functional disability, risk for developing chronic musculoskeletal pain, health-related quality of life and attitudes of responsibility for musculoskeletal conditions. Trends over time were analysed with a regression model for repeated measurements. Results: The physiotherapist-triaged group showed significant improvement for health-related quality of life at 26 weeks and showed consistent but nonsignificant tendencies to greater reductions of current pain, mean pain in the latest 3 months, functional disability and risk for developing chronic pain compared with traditional management. The triage model did not consistently affect patients' attitudes of responsibility for musculoskeletal disorders. Conclusions: Triaging to physiotherapists for primary assessment in primary care leads to at least as positive health effects as primary assessment by GPs and can be recommended as an alternative management pathway for patients with musculoskeletal disorders. ClinicalTrials.gov identifier: NCT148611.
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| 4. |
- Bornhöft, Lena, et al.
(författare)
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More cost-effective management of patients with musculoskeletal disorders in primary care after direct triaging to physiotherapists for initial assessment compared to initial general practitioner assessment.
- 2019
-
Ingår i: BMC musculoskeletal disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- A model for triaging patients in primary care to provide immediate contact with the most appropriate profession to treat the condition in question has been developed and implemented in parts of Sweden. Direct triaging of patients with musculoskeletal disorders (MSD) to physiotherapists at primary healthcare centres has been proposed as an alternative to initial assessment by general practitioners (GPs) and has been shown to have many positive effects. The aim of this study was to evaluate the cost-effectiveness from the societal perspective of this new care-pathway through primary care regarding triaging patients with MSD to initial assessment by physiotherapists compared to standard practice with initial GP assessment.Nurse-assessed patients with MSD (N=55) were randomised to initial assessment and treatment with either physiotherapists or GPs and were followed for 1year regarding health-related quality of life, utilization of healthcare resources and absence from work for MSD. Quality-adjusted life-years (QALYs) were calculated based on EQ5D measured at 5 time-points. Costs for healthcare resources and production loss were compiled. Incremental cost-effectiveness ratios (ICERS) were calculated. Multiple imputation was used to compensate for missing values and bootstrapping to handle uncertainty. A cost-effectiveness plane and a cost-effectiveness acceptability curve were construed to describe the results.The group who were allocated to initial assessment by physiotherapists had slightly larger gains in QALYs at lower total costs. At a willingness-to-pay threshold of 20,000 €, the likelihood that the intervention was cost-effective from a societal perspective including production loss due to MSD was 85% increasing to 93% at higher thresholds. When only healthcare costs were considered, triaging to physiotherapists was still less costly in relation to health improvements than standard praxis.From the societal perspective, this small study indicated that triaging directly to physiotherapists in primary care has a high likelihood of being cost-effective. However, further larger randomised trials will be necessary to corroborate these findings.ClinicalTrials.gov NCT02218749 . Registered August 18, 2014.
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| 5. |
- Kanatsuna, Norio, et al.
(författare)
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Doubly reactive INS-IGF2 autoantibodies in children with newly diagnosed autoimmune (type 1) diabetes.
- 2015
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 82:4, s. 361-369
-
Tidskriftsartikel (refereegranskat)abstract
- The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ, or both, in newly diagnosed type 1 diabetes patients and controls. Patients (n=676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n=363) were analyzed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA, and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than controls (p<0.001). Irrespective of age at diagnosis, 19 % (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (p<0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR=1.509; 95th CI 1.011, 2.252; p=0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans, rather than cis heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes. This article is protected by copyright. All rights reserved.
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| 6. |
- Nääv, Åsa, et al.
(författare)
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A1M Ameliorates Preeclampsia-Like Symptoms in Placenta and Kidney Induced by Cell-Free Fetal Hemoglobin in Rabbit.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most serious pregnancy-related diseases and clinically manifests as hypertension and proteinuria after 20 gestational weeks. The worldwide prevalence is 3-8% of pregnancies, making it the most common cause of maternal and fetal morbidity and mortality. Preeclampsia lacks an effective therapy, and the only "cure" is delivery. We have previously shown that increased synthesis and accumulation of cell-free fetal hemoglobin (HbF) in the placenta is important in the pathophysiology of preeclampsia. Extracellular hemoglobin (Hb) and its metabolites induce oxidative stress, which may lead to acute renal failure and vascular dysfunction seen in preeclampsia. The human endogenous protein, α1-microglobulin (A1M), removes cell-free heme-groups and induces natural tissue repair mechanisms. Exogenously administered A1M has been shown to alleviate the effects of Hb-induced oxidative stress in rat kidneys. Here we attempted to establish an animal model mimicking the human symptoms at stage two of preeclampsia by administering species-specific cell-free HbF starting mid-gestation until term, and evaluated the therapeutic effect of A1M on the induced symptoms. Female pregnant rabbits received HbF infusions i.v. with or without A1M every second day from gestational day 20. The HbF-infused animals developed proteinuria and a significantly increased glomerular sieving coefficient in kidney that was ameliorated by co-administration of A1M. Transmission electron microscopy analysis of kidney and placenta showed both intracellular and extracellular tissue damages after HbF-treatment, while A1M co-administration resulted in a significant reduction of the structural and cellular changes. Neither of the HbF-treated animals displayed any changes in blood pressure during pregnancy. In conclusion, infusion of cell-free HbF in the pregnant rabbits induced tissue damage and organ failure similar to those seen in preeclampsia, and was restored by co-administration of A1M. This study provides preclinical evidence supporting further examination of A1M as a potential new therapy for preeclampsia.
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| 7. |
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| 8. |
- Redelius, Karin, et al.
(författare)
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Physical education and teacher education in Sweden
- 2019
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Ingår i: European physical education teacher education practices: initial, induction, and professional development. - : Meyer & Meyer Sport. - 9781782551775 ; , s. 379-396
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Redelius, Karin, 1957-, et al.
(författare)
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Physical education teacher education in Sweden
- 2019
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Ingår i: European physical education teacher education practices. - : Meyer & Meyer Sport. - 9781782551775 ; , s. 379-396
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Ahluwalia, Bani, et al.
(författare)
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Effects of Aloe barbadensis Mill. extract (AVH200 (R)) on human blood T cell activity in vitro
- 2016
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Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 179, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- Ethnopharmacological relevance: Aloe barbadensis Mill. (Aloe vera) is a widely used medicinal plant well reputed for its diverse therapeutic applications. It has been used for thousands of years in folk medicine to treat various conditions and the Aloe vera gel has been reported to possess anti-inflammatory as well as immunostimulatory and immunomodulatory properties. However, the mode of action is still unclear. Aim of the study: The aim of this study was determine the effects of two well-defined A. barbadensis Mill. extracts AVH200 (R) and AVE200 on human blood T cells in vitro. Materials and methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in the presence or absence of AVH200 (R) and AVE200. The T cell phenotype was investigated by flow cytometry, cell proliferation was determined by CFSE dye and thymidine assay, respectively and cytokine secretion was determined by MSD (R) Multi-Spot Assay system and ELISA. Results: The presence of AVH200 (R) resulted in a reduced expression of CD25 among CD3(+) T cells and suppression of T cell proliferation in a dose dependent manner. Furthermore, AVH200 (R) reduced the expression of CD28 on CD3(+) T cells. AVH200 (R) also reduced the secretion of IL-2, IFN-gamma and IL-17A in PBMC cultures. The AVH200 (R) dose dependent reduction in T cell activation and proliferation recorded in the cell cultures was not due to apoptosis or cell death. Additionally, AVH200 (R) was found to be more effective as compared to AVE200 in reducing T cell activation and proliferation. Conclusion: AVH200 (R) has the potential to reduce the activation, proliferation and cytokine secretion of healthy human blood T cells. Our study suggests that AVH200 (R) has a suppressive effect on human blood T cells in vitro.
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| 11. |
- Ahrné, Karin, et al.
(författare)
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Tillstånd och trender för arter och deras livsmiljöer – rödlistade arter i Sverige 2015
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- 2015 års upplaga av den svenska rödlistan är den fjärde i ordningen. Den är baserad på IUCN:s rödlistningskriterier och revideras vart femte år. I rödlistan bedöms risken som enskilda arter av djur, växter och svampar löper att försvinna från Sverige. Bedömningen utförs av ArtDatabankens medarbetare i samverkan med över 100 externa experter, indelade i 14 expertkommittéer för olika organismgrupper. Under arbetet med 2015 års rödlista har tillstånd och trender bedömts för 21 600 arter och 1 318 lägre taxa (apomiktiska arter, underarter och varieteter), sammanlagt ca 22 900 taxa. Av de bedömda arterna klassificerades 2 029 som hotade (kategorierna CR, EN och VU) och 4 273 som rödlistade (inkluderar även kategorierna NT, RE och DD). Förhållandet mellan antalet rödlistade och antalet bedömda arter ar 19,8 %, vilket är ungefär samma värde som 2010 och 2005. I denna rapport jämförs antalet och andelen rödlistade arter mellan olika organismgrupper, biotoper, substrat och påverkansfaktorer. Texten ar indelad i en allmän del och åtta kapitel inriktade på olika landskapstyper. Landskapstyperna utgör en grov indelning av landets miljöer enligt följande kategorier: Skog, Jordbrukslandskap, Urbana miljöer, Fjäll, Våtmarker, Sötvatten, Havsstränder och Havsmiljöer. Skogen och jordbrukslandskapet är de artrikaste landskapstyperna med 1 800 respektive 1 400 arter som har en stark anknytning dit, och ytterligare flera hundra arter som förekommer där mer sporadiskt. De faktorer som påverkar flest rödlistade arter i Sverige är skogsavverkning och igenväxning, som båda utgör ett hot mot vardera ca 30 % av de rödlistade arterna. Avverkning minskar arealen av skog där naturliga strukturer och naturlig dynamik upprätthålls, och den orsakar därmed förlust av livsmiljöer. Igenväxning orsakas av ett antal faktorer, bland annat upphörande hävd (bete och slåtter), gödsling, trädplantering och brist på naturliga störningsregimer som t.ex. regelbundna översvämningar kring vattendrag och sjöar. Andra viktiga påverkansfaktorer är fiske, torrläggning av våtmarker, tillbakagång hos värdarter (främst alm och ask som drabbats av invasiva svampsjukdomar), klimatförändringar och konkurrens från invasiva arter. IUCN:s rödlisteindex beräknas för ett urval av de bedömda organismgrupperna. Rödlisteindex visar att skillnaderna mellan rödlistorna från 2000, 2005, 2010 och 2015 är små. Ett par undantag finns dock. Groddjur och stora däggdjur har fått en något förbättrad situation sedan 2000. Totalt förefaller det ändå som att trycket mot Sveriges artstock har förblivit relativt konstant under de senaste 15 åren.
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| 12. |
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| 13. |
- Alizadehgharib, Sara, et al.
(författare)
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The Immunomodulatory Properties of 2-Hydroxyethyl Methacrylate are Mediated by the NLRP3 Inflammasome.
- 2018
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Ingår i: The journal of adhesive dentistry. - 1461-5185. ; 20:3, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- The methacrylate monomer 2-hydroxyethyl methacrylate (HEMA), commonly used in dentistry, has multiple effects on the immune system. This study examined whether HEMA affects the immune system by inducing formation of the NLRP3 inflammasome.Human peripheral blood mononuclear cells (PBMCs) and the human monocyte cell line THP1 were cultured with or without 1000 μM HEMA. To block NLRP3 inflammasome activation, 130 mM KCl was also added to some of the cultures. For the in vivo studies, two different experimental setups were used. In the first experimental setup, mice were injected subcutaneously at the base of the tail with 20 μmol HEMA with or without 100 mM KCl. After 3 weeks, the animals were given an identical booster injection. Two weeks after the last injection, the mice were sacrificed and splenectomized. In the second experimental setup, HEMA (20 μmol), with or without 100 mM KCl, was injected subcutaneously into the tails of BALB/c mice. The mice were given two similar injections at 3-week intervals to allow evaluation of the local inflammation induced by HEMA. After the last inoculation, the injection site was examined daily for 4 days, after which the mice were sacrificed.Cultures of PBMCs and THP1 cells exposed to HEMA in vitro produced more IL-1ß and IL-18 than did control cells. Increased extracellular concentration of KCl inhibited the secretion of IL-1ß. HEMA exposure did not induce cytokine production in variants of the THP1 cell line unable to form the NLRP3 inflammasome. For the first experimental setup, the level of unstimulated basic splenocyte proliferation in vitro was significantly higher in cultures from mice exposed in vivo to HEMA only than in cultures from mice injected with HEMA plus KCl. In the second experimental setup of the in vivo studies, the HEMA-treated mice developed more pronounced inflammation at the site of injection compared to the group of mice given HEMA plus KCl.HEMA affects the immune system by inducing formation of the NLRP3 inflammasome.
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| 14. |
- Andersson, Martin, et al.
(författare)
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Thin film metal sensors in fusion bonded glass chips for high-pressure microfluidics
- 2017
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- High-pressure microfluidics offers fast analyses of thermodynamic parameters for compressed process solvents. However, microfluidic platforms handling highly compressible supercritical CO2 are difficult to control, and on-chip sensing would offer added control of the devices. Therefore, there is a need to integrate sensors into highly pressure tolerant glass chips. In this paper, thin film Pt sensors were embedded in shallow etched trenches in a glass wafer that was bonded with another glass wafer having microfluidic channels. The devices having sensors integrated into the flow channels sustained pressures up to 220 bar, typical for the operation of supercritical CO2. No leakage from the devices could be found. Integrated temperature sensors were capable of measuring local decompression cooling effects and integrated calorimetric sensors measured flow velocities over the range 0.5-13.8 mm/s. By this, a better control of high-pressure microfluidic platforms has been achieved.
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| 15. |
- Anmyr, Lena, et al.
(författare)
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Parents' Stress and Coping Related to Children's Use of a Cochlear Implant : A Qualitative Study
- 2016
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Ingår i: Journal of Social Work in Disability & Rehabilitation. - 1536-710X .- 1536-7118. ; 15:2, s. 150-167
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to increase understanding of parents' experiences of having a child with cochlear implant (CI) and to explore how these related to children's use of CI. Twelve parents of children, full-time users or limited users of CI, participated in the study. Qualitative content analysis showed that the parents of children who used their CI differed from the parents with limited users in how they handled stressors. Support from health care professionals was seen as insufficient. Parents need to get involved in dynamic processes, where health care resources promote parental coping.
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| 16. |
- Anmyr, Lena, et al.
(författare)
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Sense of coherence, social networks, and mental health among children with a cochlear implant
- 2015
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Ingår i: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876 .- 1872-8464. ; 79:4, s. 610-615
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore the personal and social resources of children with a cochlear implant from a child's perspective. Method: This descriptive cross-sectional study included 19 children with cochlear implants, aged 9-12 years. Data was collected, using the children's sense of coherence (CSOC) scale, the Network map, and the strengths and difficulties questionnaire (SDQ). The data was analyzed using descriptive and correlation statistics. Results: Most children had a strong sense of coherence. School life was an important arena for their social network. The mental health was comparable to normal hearing children. Still, some of the children with implants had low SOC and poor mental health. High SOC and closeness of the social network, especially in school, were associated with good mental health. Conclusion: This study shows that Swedish school-aged children with cochlear implants as a group have access to personal and social resources as strong sense of coherence and social networks. Still, there are individual children with psychosocial problems who need support and treatment.
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| 17. |
- Antonsson, Malin, 1986, et al.
(författare)
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High-level language ability in healthy individuals and its relationship with verbal working memory
- 2016
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 30:12, s. 944-958
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the study were to investigate healthy subjects' performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20-79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegard, Hartelius, & Ahlsen, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL.
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| 18. |
- Asa'ad, Farah, 1983, et al.
(författare)
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Role of epigenetics in alveolar bone resorption and regeneration around periodontal and peri-implant tissues.
- 2019
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Ingår i: European journal of oral sciences. - : Wiley. - 1600-0722 .- 0909-8836. ; 127:6, s. 477-493
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis and peri-implantitis are multifactorial diseases characterized by alveolar bone destruction mediated by the host response to a microbial challenge. Alveolar bone resorption mediated by epigenetics could be one of the mechanismsresponsible for this destruction of alveolar bone. The relationship between epigenetic modifications and bone metabolism has been thoroughly investigated in bone remodeling, cancer, and rheumatoid arthritis, but evidence is low regarding the relationship between epigenetic modifications and alveolar bone loss related to periodontal and peri-implant diseases. Therefore, we conducted a review of the pertinent literature based on a priori-formulated focused questions and ascreening strategy, in an attempt to comprehend the role of different epigenetic mechanisms in alveolar bone loss and to determine the current state with respect to their possible therapeutic applications in regenerative medicine. The review showed that the roles of DNA methylation, histone modifications, and non-coding RNAs in bone loss have been investigated. The results indicate that epigenetic mechanisms can participate in periodontal and peri-implant alveolar bone breakdown, suggesting their potential as therapeutic targets in alveolar bone regeneration. However, there is still only preliminary information regarding the possible therapeutic utility of these epigenetic mechanisms, suggesting a need for basic and translational research to assess the potential of such mechanisms in promoting alveolar bone regeneration.
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| 19. |
- Asa'ad, Farah, 1983, et al.
(författare)
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Scaffolds for periodontal tissue engineering
- 2019
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Ingår i: Handbook of Tissue Engineering Scaffolds: Volume One 1st Edition. - Cambridge, UK : Elsevier. - 9780081025642 ; , s. 479-496
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Bokkapitel (refereegranskat)
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| 20. |
- Aspegren, Henrik, et al.
(författare)
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Nationell styrning behövs för at förebygga översvämningar och vattenbrist
- 2018
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Ingår i: Göteborgs-Posten. - 1103-9345.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DebattTillgången till vatten kan inte längre ses som en lokal fråga utan måste ses ur ett bredare perspektiv, som kräver en samordning som är ny för Sverige. Det behövs sammanhängande nationell styrning och en strategi med helhetssyn på vattenfrågan, skriver nio svenska vattenexperter som kommer att debattera detta ämne under politikerveckan i Almedalen.
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| 21. |
- Blom, Kristin, et al.
(författare)
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Mebendazole-induced M1 polarisation of THP-1 macrophages may involve DYRK1B inhibition
- 2019
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Ingår i: BMC Research Notes. - : Springer Nature. - 1756-0500. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity by inducing a M2 to M1 phenotype switch in monocyte/macrophage models. In the present study we investigated the potential role of protein kinases in mediating this effect.Results: MBZ potently binds and inhibits Dual specificity tyrosine-phosphorylation-regulated kinase 1B (DYRK1B) with a Kd and an IC50 of 7 and 360 nM, respectively. The specific DYRK1B inhibitor AZ191 did not mimic the cytokine release profile of MBZ in untreated THP-1 monocytes. However, in THP-1 cells differentiated into macrophages, AZ191 strongly induced a pro-inflammatory cytokine release pattern similar to MBZ and LPS/IFNγ. Furthermore, like MBZ, AZ191 increased the expression of the M1 marker CD80 and decreased the M2 marker CD163 in THP-1 macrophages. In this model, AZ191 also increased phospho-ERK activity although to a lesser extent compared to MBZ. Taken together, the results demonstrate that DYRK1B inhibition could, at least partly, recapitulate immune responses induced by MBZ. Hence, DYRK1B inhibition induced by MBZ may be part of the mechanism of action to switch M2 to M1 macrophages.
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| 22. |
- Blom, Kristin, et al.
(författare)
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The anticancer effect of mebendazole may be due to M1 monocyte/macrophage activation via ERK1/2 and TLR8-dependent inflammasome activation
- 2017
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Ingår i: Immunopharmacology and immunotoxicology. - : Informa UK Limited. - 0892-3973 .- 1532-2513. ; 39:4, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Mebendazole (MBZ), a drug commonly used for helminitic infections, has recently gained substantial attention as a repositioning candidate for cancer treatment. However, the mechanism of action behind its anticancer activity remains unclear. To address this problem, we took advantage of the curated MBZ-induced gene expression signatures in the LINCS Connectivity Map (CMap) database. The analysis revealed strong negative correlation with MEK/ERK1/2 inhibitors. Moreover, several of the most upregulated genes in response to MBZ exposure were related to monocyte/macrophage activation. The MBZ-induced gene expression signature in the promyeloblastic HL-60 cell line was strongly enriched in genes involved in monocyte/macrophage pro-inflammatory (M1) activation. This was subsequently validated using MBZ-treated THP-1 monocytoid cells that demonstrated gene expression, surface markers and cytokine release characteristic of the M1 phenotype. At high concentrations MBZ substantially induced the release of IL-1 beta and this was further potentiated by lipopolysaccharide (LPS). At low MBZ concentrations, cotreatment with LPS was required for MBZ-stimulated IL-1 beta secretion to occur. Furthermore, we show that the activation of protein kinase C, ERK1/2 and NF-kappaB were required for MBZ-induced IL-1 release. MBZ-induced IL-1 release was found to be dependent on NLRP3 inflammasome activation and to involve TLR8 stimulation. Finally, MBZ induced tumor-suppressive effects in a coculture model with differentiated THP-1 macrophages and HT29 colon cancer cells. In summary, we report that MBZ induced a pro-inflammatory (M1) phenotype of monocytoid cells, which may, at least partly, explain MBZ's anticancer activity observed in animal tumor models and in the clinic.
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| 23. |
- Boork, Magdalena, et al.
(författare)
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Solbruket: Batterilager för ökad solelproduktion i det moderna lantbruket
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The potential for solar power production in the Swedish agriculture is significant but is highly limited by the capacity in the low-voltage grid. The use of battery storages may be a possibility to increase the self-consumption of solar power and reduce the power exchange to the grid, and thereby avoid expensive grid reinforcements.In order to build knowledge about both technical and user-related possibilities and challenges with grid-connected battery storages for Swedish farms with PV, RISE and Vattenfall have built a pilot plant on a farm in Hälsingland and conducted two sociotechnical studies with interviews and questionnaires concerning obstacles, drivers and benefits associated with battery storages, as they are perceived by Swedish farmers at present.The results point at a number of challenges for battery storages to become an attractive investment for farmers, which include:- Reliability: lifetime and performance of the battery technology is unclear.- Economy: profit versus investment costs.- Long-term storage: seasonal storage of energy is perceived as more attractive than short-term storage.- Supporting backup power: an added value that may motivate higher investment costs.- Climate and environmental benefits: important aspects that are unclear for the present battery technology.These challenges need to be addressed in technical system solutions, services and business models in order to motivate this particular group to invest in battery storages to complement their existing PV power plants.The results from the pilot plant also points at a number of practical benefits and possibilities associated with the system solution. Apart from creating value by cutting power peaks and enable increased self-consumption of solar power, the farmers appreciate the increased convenience provided by the batteries. Since the battery storage cuts the highest power peaks and thereby reduces the risk of local power failures, it is no longer crucial when in time power-consuming equipment is used. This offers a new flexibility in the daily routines. The main economic benefit raised by the farmers is the possibility of a lower fuse subscription.The results from Solbruket provide increased knowledge about farmers with PV and how battery storages can create value for the specific target group. This knowledge can be used by product and services developers to develop attractive technical solutions, services and business models targeting the specific market. However, it is crucial to keep in mind that the battery technology is perceived as immature, and that an investment is regarded as a significant risk. Only when there is balance between technical maturity and investment costs, it is reasonable for the consumer to consider different business models.
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| 24. |
- Bornhöft, Lena, et al.
(författare)
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Physiotherapy in Primary Care Triage - the effects on utilization of medical services at primary health care clinics by patients and sub-groups of patients with musculoskeletal disorders: a case-control study
- 2015
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Ingår i: Physiotherapy Theory and Practice. - : Informa UK Limited. - 0959-3985 .- 1532-5040. ; 31:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary Care Triage is a patient sorting system used in some primary health care clinics (PHCCs) in Sweden where patients with musculoskeletal disorders (MSD) are triaged directly to physiotherapists. The purpose of this study was to investigate whether sorting/ triaging patients seeking a PHCC for MSD directly to physiotherapists affects their utilization of medical services at the clinic for the MSD and to determine whether the effects of the triaging system vary for different sub-groups of patients. Methods: A retrospective case-control study design was used at two PHCCs. At the intervention clinic, 656 patients with MSD were initially triaged to physiotherapists. At the control clinic, 1673 patients were initially assessed by general practitioners (GPs). The main outcome measures were the number of patients continuing to visit GPs after the initial assessment, the number of patients receiving referrals to specialists/external examinations, doctors' notes for sick-leave or prescriptions for analgesics during one year, all for the original MSD. Results: Significantly fewer patients triaged to physiotherapists required multiple GP visits for the MSD or received MSD-related referrals to specialists/external examinations, sick-leave recommendations or prescriptions during the following year compared to the GP-assessed group. This applies to all sub-groups except for the group with lower extremity disorders, which did not reach significance for either multiple GP visits or sick-leave recommendations. Conclusions: The reduced utilization of medical services by patients with MSD who were triaged to physiotherapists at a PHCC is likely due to altered management of MSD with initial assessment by physiotherapists.
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| 25. |
- Bosaeus, Marja, et al.
(författare)
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A randomized longitudinal dietary intervention study during pregnancy: effects on fish intake, phospholipids, and body composition
- 2015
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Fish and meat intake may affect gestational weight gain, body composition and serum fatty acids. We aimed to determine whether a longitudinal dietary intervention during pregnancy could increase fish intake, affect serum phospholipid fatty acids, gestational weight gain and body composition changes during pregnancy in women of normal weight participating in the Pregnancy Obesity Nutrition and Child Health study. A second aim was to study possible effects in early pregnancy of fish intake and meat intake, respectively, on serum phospholipid fatty acids, gestational weight gain, and body composition changes during pregnancy. Methods In this prospective, randomized controlled study, women were allocated to a control group or to a dietary counseling group that focused on increasing fish intake. Fat mass and fat-free mass were measured by air-displacement plethysmography. Reported intake of fish and meat was collected from a baseline population and from a subgroup of women who participated in each trimester of their pregnancies. Serum levels of phospholipid arachidonic acid (s-ARA), eicosapentaenoic acid (s-EPA), and docosahexaenoic acid (s-DHA) were measured during each trimester. Results Weekly fish intake increased only in the intervention group (n=18) from the first to the second trimester (median difference 113 g, p=0.03) and from the first to the third trimester (median difference 75 g, p=0.01). In the first trimester, fish intake correlated with s-EPA (r=0.36, p=0.002, n=69) and s-DHA (r=0.34, p=0.005, n=69), and meat intake correlated with s-ARA (r=0.28, p=0.02, n=69). Fat-free mass gain correlated with reported meat intake in the first trimester (r=0.39, p=0.01, n=45). Conclusions Dietary counseling throughout pregnancy could help women increase their fish intake. Intake of meat in early pregnancy may increase the gain in fat-free mass during pregnancy.
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