| 1. |
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| 2. |
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| 3. |
- Hommel, A, et al.
(author)
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Lägg förslaget om förändrad utbildning i papperskorgen
- 2016
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In: Dagens medicin. - 1104-7488.
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Journal article (pop. science, debate, etc.)abstract
- Skapa specialistutbildningar för sjuksköterskor som motsvarar vårdens behov både i dag och i framtiden, skriver Ami Hommel, ordförande Svensk sjuksköterskeförening, och nio vårdprofessorer.
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| 4. |
- Hommel, A, et al.
(author)
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Lägg förslaget om förändrad utbildning i papperskorgen
- 2016
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In: Dagens medicin. - 1104-7488.
-
Journal article (other academic/artistic)abstract
- Skapa specialistutbildningar för sjuksköterskor som motsvarar vårdens behov både i dag och i framtiden, skriver Ami Hommel, ordförande Svensk sjuksköterskeförening, och nio vårdprofessorer.
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| 5. |
- Hommel, Ami, et al.
(author)
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Öka satsningarna på forskning i omvårdnad
- 2017
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In: Dagens Medicin. - 1104-7488. ; :19 januari
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Journal article (pop. science, debate, etc.)abstract
- Långsiktiga satsningar för välfärdsforskning är bra, men för att nå ända fram och minimera hälsoklyftorna är det nödvändigt att även forskning inom omvårdnad prioriteras, skriver tio debattörer.
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| 6. |
- Hommel, Ami, et al.
(author)
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Öka satsningarna på forskning i omvårdnad
- 2017
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In: Dagens medicin. - 1104-7488. ; :19 januari
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Journal article (other academic/artistic)abstract
- Långsiktiga satsningar för välfärdsforskning är bra, men för att nå ända fram och minimera hälsoklyftorna är det nödvändigt att även forskning inom omvårdnad prioriteras, skriver tio debattörer.
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| 7. |
- Månsdotter, Anna, et al.
(author)
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Towards capability-adjusted life years in public health and social welfare : results from a Swedish survey on ranking capabilities
- 2020
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In: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 15:12
-
Journal article (peer-reviewed)abstract
- INTRODUCTION: The aim of this study was to rank capabilities and suggest a relevant set of capabilities for the Swedish context to inform the development of capability-adjusted life years (CALYs). CALYs is a quality of life measure for policy making based on the capability approach by Amartya Sen.MATERIALS AND METHODS: A Swedish governmental review proposed the following 10 relevant capabilities: time, financial situation, mental/physical health, political resources, knowledge, living environment, occupation, social relations, security, and housing. Researchers in health-related disciplines from 5 universities ranked these capabilities from 1 to 10 (most to least important) in a web-based cross-sectional survey; 115 of 171 responses were eligible.RESULTS: Health, social relations, and financial situation were deemed most important. Stratification by gender, research field, and age group revealed few differences. We found that it was possible to rank capabilities and that health, social relations, and financial situation were ranked highest by a non-representative sample of researchers and doctoral students from health-related disciplines at five Swedish universities.CONCLUSIONS: The revealed ranking is dependent on the metric and must be further explored. The findings support continued development of CALYs for monitoring and evaluating outcomes in public health and social-welfare interventions.
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| 8. |
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| 9. |
- Arlien-Soborg, Mai C., et al.
(author)
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Acromegaly management in the Nordic countries: A Delphi consensus survey
- 2024
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In: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
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Journal article (peer-reviewed)abstract
- ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 10. |
- Arlien-Søborg, Mai C., et al.
(author)
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Acromegaly management in the nordic countries : a Delphi consensus survey
- 2024
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In: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265.
-
Journal article (peer-reviewed)abstract
- Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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| 11. |
- Belfrage, Henrik, 1955-, et al.
(author)
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Assessing risk of patriarchal violence with honour as a motive : six years experience using the PATRIARCH checklist
- 2012
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In: International Journal of Police Science and Management. - : Sage Publications. - 1461-3557 .- 1478-1603. ; 14:1, s. 20-29
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Journal article (peer-reviewed)abstract
- Few crimes are as complicated to investigate and understand as honour-based crimes. The planning and execution often involves multiple family members, usually without personality disorders or major mental disorders, and can include mothers, sisters, brothers, male cousins, uncles and grandfathers whose actions are by many, themselves included, considered as good or necessary. Investigations often have to be carried out transnational, involving many authorities and sometimes several countries. This paper describes the process of developing an evidence-based checklist which has been used for six years in Sweden as an aid for law enforcement and social authorities in cases with suspected risk for honour-based violence. Data from 56 recent cases are presented and discussed.
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| 12. |
- Belfrage, Henrik, et al.
(author)
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The PATRIARCH. Six years experiences from the use of a checklist for the assessment of risk for patriarchal violence with honor as motive.
- 2012
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In: International Journal of Police Science and Management. - 1461-3557 .- 1478-1603. ; 14:1, s. 20-29
-
Journal article (peer-reviewed)abstract
- Few crimes are as complicated to investigate and understand as honour-based crimes.The planning and execution often involves multiple family members, usually without personality disorders or major mental disorders, and can include mothers, sisters, brothers, male cousins, uncles and grand- fathers whose actions are by many, themselves included, considered as good or necessary. Invest- igations often have to be carried out trans- national, involving many authorities and sometimes several countries. This paper describes the process of developing an evidence-based check- list which has been used for six years in Sweden as an aid for law enforcement and social author- ities in cases with suspected risk for honour-based violence. Data from 56 recent cases are presented and discussed.
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| 13. |
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| 14. |
- Carlström, Maria, et al.
(author)
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Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility
- 2012
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In: Experimental dermatology. - : John Wiley and Sons. - 0906-6705 .- 1600-0625. ; 21:12, s. 932-937
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Journal article (peer-reviewed)abstract
- NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the inflammasome by regulating caspase-1 activity and interleukin (IL)-1 beta processing. The contribution of IL-1 beta in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domaincontaining protein (CARD)8, a negative regulator of caspase-1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohns disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan (R) Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.11.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.
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| 15. |
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| 16. |
- Dahan, Diana, et al.
(author)
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Induction of angiotensin converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility.
- 2014
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In: American Journal of Physiology: Cell Physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 307:12, s. 1093-1101
-
Journal article (peer-reviewed)abstract
- MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that phenotype switching depends on a tissue-specific target of miR-143/145, we found induction of angiotensin converting enzyme in the aorta but not in the bladder where angiotensin converting enzyme was expressed at a low level. Chronic treatment with angiotensin type-1 receptor antagonist restored contractility in miR-143/145-deficient aorta while leaving bladder contractility unaffected. This shows that tissue-specific targets are critical for the effects of miR-143/145 on smooth muscle differentiation and that angiotensin converting enzyme is one such target.
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| 17. |
- Edman, David, et al.
(author)
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Cyklisters hastighet på sträcka
- 2024
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In: Sammanställning av referat från Transportforum 2024. - Linköping : Statens väg- och transportforskningsinstitut. ; , s. 491-492
-
Conference paper (other academic/artistic)abstract
- Om målen med att nå ett hållbart transportsystem uppnås kommer vi att se allt fler cyklande. Fordonsutvecklingen leder också i riktning mot en allt bredare flora av cykeltyper med olika egenskaper. Vi kommer därför troligtvis att se såväl fler cyklande som en större variation av cykeltyp inom gruppen cyklande. Bland annat syns detta i en större spridning i hastighet. För att få fler att cykla är både trafiksäkerhet och framkomlighet viktiga faktorer. I detta perspektiv är det därför viktigt att skapa starka cykelstråk med hög framkomlighet och bibelållen trafiksäkerhet. Syftet med projektet är öka kunskapen om hur cyklisters hastighet och hastighetsspridning påverkas av kapacitet och utformning.Frågeställningar:Vilka krav på funktion ställs beroende på typ eller klass på stråken? Vilken fördröjning, i form av lägre hastighet än önskat, är acceptabel?I vilken omfattning fördröjs cyklister på grund av bristande kapacitet? Vilka krav ställs på utformningen för att skapa en tillräckligt hög trafiksäkerhet med dimensionerande hastigheter enligt VGU?Studien baseras på litteraturgenomgång samt analyser av beteendestudier i fält. Arbetet inleddes med en litteraturgenomgång och syftar till att få en djupare inblick i det aktuella kunskapsläget. Resultatet från litteraturgenomgången visar att kunskapen kring medelhastigheter är god. Från de svenska och utländska studierna kunde man se en mindre skillnad i hastigheter mellan cykling på cykelbana och cykelväg. Kunskapen om hastoghetsfördelning och kopplingen till utformningen på cykelbanor var dock mindre stark. Fältstudier genomförs fyra platser, tre platser i tätort och en plats med landsbygdscykling. Platserna i tätort spänner från cengrala delar till yttermiljöer. Fältstudierna har genomförts på platser med cykelbanor för att fånga cyklisterna interaktion med varandra utan påverkan av motortrafik. Studierna i fält fokuserar på i vilken utsträckning cyklister själva väljer sin hastighet. De kvantitativa mätningarna visar hur många omkörningar som görs på en given sträcka, hur långa fordonståg av cyklar som skapas och ”fria ” cyklar, det vill säga cyklande som inte interagerar med andra cyklar på den givna sträckan.
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| 18. |
- Einberg, Afrodite Psaros, et al.
(author)
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Prevalence of chronic hepatitis C virus infection among childhood cancer survivors in Stockholm, Sweden
- 2019
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In: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 58:7, s. 997-1002
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Journal article (peer-reviewed)abstract
- Background: Childhood cancer survivors treated before 1992, when blood donor screening for hepatitis C virus (HCV) infection was introduced, are at risk of transfusion-transmitted HCV infection. A national HCV screening campaign targeting blood transfusion recipients was launched in Sweden in 2007-2010. The aims of this study were to, among adult childhood cancer survivors in Stockholm County, investigate the prevalence of HCV infection, the natural course of infection, treatment outcome and anti-HCV testing frequency before, during and after the screening campaign and finally to actively screen the untested ones.Material and Methods: This was a combined retrospective register based and prospective screening study of adult childhood cancer survivors (n=686) treated for malignancy in Stockholm before 1992. In the first part, we investigated the prevalence of HCV infection and previous anti-HCV testing, and in the second part, we actively traced and HCV-screened the remaining untested cohort living in Stockholm. Analysis of previous documented anti-HCV tests in medical records, laboratory records, and the national communicable disease registry was performed. In the second part, 231 presumably untested individuals were contacted by mail and offered an anti-HCV test. The natural course of HCV infection and treatment outcome was analyzed for those found to be chronically infected.Results: In total, 235 patients were tested and 11 were HCV-RNA positive. The overall prevalence of chronic HCV infection among the tested childhood cancer survivors was thus 4.7% (95% CI = 2.6-8.2%), which is almost 10 times higher than the national prevalence of 0.5%. Only 12% of the Stockholm cohort were tested during the screening campaign in 2007-2010, while the test uptake using active tracing screening within this study was 40% (p<.001).Conclusion: With today's effective treatment options, active tracing and HCV screening of childhood cancer survivors are recommended.
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| 19. |
- Ekman, Anna-Karin, et al.
(author)
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Allergen-Induced Accumulation of CD68(-), CD123(+) Dendritic Cells in the Nasal Mucosa
- 2011
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 155:3, s. 234-242
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Journal article (peer-reviewed)abstract
- Background: Dendritic cells are antigen-presenting cells central to the immune system. They activate and orchestrate the innate and the adaptive immune systems. This phenotypically diverse group can be further divided into 2 subsets, the CD11c(+) myeloid dendritic cells (mDCs) and the CD123(+) plasmacytoid dendritic cells (pDCs). The aim of the study was to investigate the effect of allergen exposure on dendritic cells in subjects with allergic rhinitis. Methods: Atopic and non-atopic subjects were challenged intranasally with birch or timothy allergen. Nasal biopsies were taken before and 24 h after challenge, and were, after CD68 exclusion, stained for expression of CD11c and CD123 to identify dendritic cell subsets. The effect of allergic mediators on CD68(-), CD123(+) cells was studied with flow cytometry analysis in peripheral blood. Results: The amount of CD68(-), CD123(+) cells increased in the nasal sub-epithelium upon allergen challenge, whereas the number of CD68(-), CD11c(+) cells was unaffected. In vitro study of the effect of inflammatory mediators on pDC phenotype showed an increased activation in response TNF-alpha, IL-4 and CpG. Furthermore, TNF-alpha caused a higher activation among atopic than non-atopic subjects. Conclusions: An increased number of CD68(-), CD123(+) dendritic cells along with the positive pDC response following stimulation with inflammatory mediators suggest that the increased pDCs may be of an activated phenotype. It also suggests that the inflammatory response by pDCs to mediators such as TNF-alpha may be markedly higher in atopic subjects. These data support the notion of pDCs as important participants in allergic rhinitis. Copyright (C) 2011 S. Karger AG, Basel
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| 20. |
- Ekman, Anna-Karin, et al.
(author)
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Genetic variations of NLRP1 : susceptibility in psoriasis
- 2014
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In: British Journal of Dermatology. - : Wiley-Blackwell. - 0007-0963 .- 1365-2133. ; 171:6, s. 1517-1520
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Journal article (peer-reviewed)abstract
- BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.
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| 21. |
- Ekman, Anna-Karin, et al.
(author)
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IL-17 and IL-22 Promote Keratinocyte Stemness in the Germinative Compartment in Psoriasis
- 2019
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In: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 139:7, s. 1564-
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Journal article (peer-reviewed)abstract
- Psoriasis is an inflammatory skin disorder characterized by the hyperproliferation of basal epidermal cells. It is regarded as T-cell mediated, but the role of keratinocytes (KCs) in the disease pathogenesis has reemerged, with genetic studies identifying KC-associated genes. We applied flow cytometry on KCs from lesional and nonlesional epidermis to characterize the phenotype in the germinative compartment in psoriasis, and we observed an overall increase in the stemness markers CD29 (2.4-fold), CD44 (2.9-fold), CD49f (2.8-fold), and p63 (1.4-fold). We found a reduced percentage of cells positive for the early differentiation marker cytokeratin 10 and a greater fraction of CD29(+) and involucrin thorn cells in the psoriasis KCs than in nonlesional KCs. The up-regulation of stemness markers was more pronounced in the K10(+) cells. Furthermore, the psoriasis cells were smaller, indicating increased proliferation. Treatment with IL-17 and IL-22 induced a similar expression pattern of an up-regulation of p63, CD44, and CD29 in normal KCs and increased the colony-forming efficiency and long-term proliferative capacity, reflecting increased stem cell-like characteristics in the KC population. These data suggest that IL-17 and IL-22 link the inflammatory response to the immature differentiation and epithelial regeneration by acting directly on KCs to promote cell stemness.
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| 22. |
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| 23. |
- Ekman, Anna-Karin, et al.
(author)
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Nasal Challenge with LPS Stimulates the Release of Macrophage Inflammatory Protein 1 alpha
- 2009
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 149:2, s. 154-160
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Journal article (peer-reviewed)abstract
- Background: Bacterial infections can cause a variety of airway diseases. Toll-like receptors (TLRs) directly respond to the presence of microbes and partake in the innate immune defense. TLR4 is activated by lipopolysaccharide (LPS), and has been detected in sinonasal tissue, epithelial cells and various inflammatory cells. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a chemokine released during the inflammatory process. The present study investigated the potential role and regulation of MIP-1 alpha in LPS-induced nasal inflammation. Methods: Thirty-two healthy individuals were intranasally challenged with LPS or vehicle. Nasal lavage was performed, followed by a nasal biopsy. Inflammatory cells were counted, MIP-1 alpha levels analyzed and expression of MIP-1 alpha mRNA in biopsies quantified. Neutrophils isolated from peripheral blood were treated with LPS and effects on MIP1 alpha release, cell survival, and the involved signal pathways, were investigated. Results: LPS challenge caused an increase of MIP-1 alpha in nasal lavage. No corresponding change in mRNA expression was seen in nasal biopsies, suggesting the increase was not due to epithelial synthesis. Neutrophil numbers increased after LPS provocation. Treatment of isolated neutrophils with LPS delayed neutrophil apoptosis and resulted in a time-and concentration-dependent release of MIP-1 alpha, which was reduced by inhibitors of transcription and of nuclear factor (NF)-kappa B, protein kinase C (PKC) and p38 MAPK pathways. Conclusions: Nasal LPS challenge results in release of MIP-1 alpha. The release most likely originates from recruited neutrophils, via NF-kappa B-, PKC-and p38 MAPK-dependent pathways. LPS stimulation delayed neutrophil apop tosis. MIP-1 alpha may constitute an important mediator in neutrophilic airway disease. Copyright (C) 2009 S. Karger AG, Basel
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| 24. |
- Ekman, Anna-Karin, et al.
(author)
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Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.
- 2017
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In: Acta Dermato-Venereologica. - : Society for the Publication of Acta Dermato - Venereologica. - 0001-5555 .- 1651-2057. ; 97:4, s. 441-448
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Journal article (peer-reviewed)abstract
- Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.
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| 25. |
- Ekman, Anna-Karin
(author)
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Pattern-recognition receptors in airway inflammation
- 2011
-
Doctoral thesis (other academic/artistic)abstract
- Airway inflammation is a defining feature of allergic rhinitis and asthma. Bacterial and viral infections are known to cause exacerbations of both diseases, but knowledge about the mechanisms involved is limited. The pattern-recognition receptors (PRRs) comprise several receptor families which recognize microbial structures or host-derived danger signals, and trigger an immune response. The Toll-like receptors (TLRs) are the best characterized set of receptors, but another family of PRRs, the Nod-like receptors (NLRs), has recently been described. The TLRs and NLRs are found both in leukocytes and structural cells throughout the airways and are becoming increasingly implicated in airway inflammation. This thesis characterizes the presence and functional response of various members of the TLR and NLR families. Lipopolysaccharide (LPS) is found in the cell wall of Gram-negative bacteria and exerts its effects through TLR4. In the first three papers nasal LPS challenge was used as a method to study neutrophil inflammatory responses in the nose. In the first paper we explored if the upper airways could be used as a model for inflammatory events in the lung. LPS-induced neutrophil inflammation in the nose was inhibited and the results compared with findings in a study of similar design on the lower airways. The nasal model was found to mimic the responses seen in the lower airway study, with no signs of systemic activation or adverse effects. This suggests the nasal LPS model to be a safe and convenient method for studying neutrophilic airway inflammation. The nasal model was subsequently used in the second paper to analyze the role of macrophage inflammatory protein (MIP)-1α in LPS-induced local inflammation. The LPS challenge resulted in a neutrophil-mediated secretion of MIP-1α, dependent on the nuclear factor (NF)-κB, protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK) pathways. LPS also delayed neutrophil apoptosis in vitro, suggesting that the secretion of MIP-1α may be boosted by a prolonged neutrophil survival. This indicates that MIP- 1α plays a role in neutrophilic airway disease. In the third paper we investigated whether symptomatic allergic rhinitis affected the expression of TLR4 in nasal lavage, blood and bone marrow. Provocation with LPS in a milieu of allergic inflammation, caused by allergen challenge, resulted in a release of cytokines like interleukin (IL)-4, IL-5, IL-10, IL-13, Interferon (IFN)-γ and tumor necrosis factor (TNF)-α. No such cytokine release was seen with either allergen or LPS alone, nor when LPS preceded allergen. The systemic up-regulation of TLR4 seen during on-going allergic rhinitis might contribute to the presently seen increase in LPS response. It is therefore tempting to extrapolate these findings to a clinical situation in which a local infection can cause exacerbation or aggravation of allergic symptoms. The systemic up-regulation of TLR4 seen during symptomatic allergic rhinitis might contribute to the observed increase in response when LPS was applied following allergen challenge. The results strengthen the suggestion that a local infection may exacerbate allergic inflammation. The fourth study aimed to visualize the effects of allergen on two major populations of dendritic cells, the myeloid (mDCs) and the plasmacytoid dendritic cells (pDCs), in the nose of patients with allergic rhinitis. Allergen challenge increased the number of pDCsin the nasal sub-epithelium. In vitro studies of pDCs revealed that they could be activated by TNF-α, IL-4 and CpG stimulation, and that TNF-α caused a higher activation among atopic than non-atopic subjects. The data support the notion of mDCs and pDCs as distinct populations with different roles in the allergic process. Further, it suggests that the pDCs observed upon allergen challenge might be of an activated phenotype and play a role in the course of allergic rhinitis. The fifth study focused on the effects of TLR7 stimulation on airway smooth muscle contraction. Guinea pig tracheas were stimulated with the TLR7 agonists R837 and R848 for three days, and the contractile response along with the underlying signal pathways were investigated in a myograph model. TLR7 stimulation was found to reduce airway smooth muscle contraction in an epithelium-independent manner, dependent on p38 MAPK and NF-κB pathways. This indicates that TLR7 stimulation can be part of a protective mechanism against virus infection and that TLR7 deficiency might be a cause of airway disease. Further, it suggests that TLR7 ligands might be a future option for treatment of airway hyperresponsiveness. The sixth study characterized the expression and function of NLRs in neutrophils, with focus on Nucleotide-binding oligomerization domain (NOD)1, NOD2 and NACHTLRR- PYD binding protein (NLRP)3. An expression of NOD2 and NLRP3 protein and mRNA was found in isolated neutrophils. NOD2 activation resulted in IL-8 secretion and a change in neutrophil phenotype, while activation of NLRP3 caused secretion of IL-1β. Both receptors caused an increased neutrophil migration. The findings might reflect a previously unknown pathway for activation of these cells.
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| 26. |
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| 27. |
- Ekman, Anna-Karin, et al.
(author)
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Systemically elevated Th1-, Th2- and Th17-associated chemokines in psoriasis vulgaris before and after ultraviolet B treatment
- 2013
-
In: Acta Dermato-Venereologica. - : Society for Publication of Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 93:5, s. 527-531
-
Journal article (peer-reviewed)abstract
- Chemokines may contribute to the systemic inflammation that is linked to the increased risk of co-morbidities in patients with psoriasis. The aim of this study was to investigate circulating chemokines in patients with psoriasis and their relationship to disease severity. Analysis of plasma levels of chemokines in patients with psoriasis before narrowband ultraviolet B (UVB) therapy revealed increased expression of Th1-associated CXCL9 and -10, Th2-associated CCL17 and CCL22, and Th17-associated CCL20. CCL20 correlated with disease severity. UVB therapy reduced skin symptoms, but did not affect the chemokine levels in plasma. Anti-CD3 and anti-CD28-mediated activation of peripheral blood mononuclear cells (PBMCs) caused a higher secretion of Th2 cytokine interleukin (IL)-13 by PBMCs from patients with psoriasis than from healthy controls. The sustained high expression of inflammatory chemokines is a potential link to systemic inflammation in psoriasis. UVB therapy may be a more effective treatment of local rather than systemic inflammation.
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| 28. |
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| 29. |
- Ekman, Agneta, 1947-
(author)
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On dental health and related factors in Finnish immigrant children in Sweden
- 1989
-
Doctoral thesis (other academic/artistic)abstract
- In the postwar period Swedish communities have become more multicultural. Although there are about 120,000 Finnish immigrant children below the age of 18 in Sweden, knowledge about their dental health is rather sparse.Dental health and related factors were studied in Finnish immigrant children aged 5,8 and 14 years, living in the city of Luleå, northern Sweden. The effect of early dental health education to parents at the Child Health Centres was studied in one age group in Luleå and in one in the municipality of Botkyrka, Stockholm county. All groups of Finnish children were compared to Swedish children matched for age, sex and social class.At the age of 5 the prevalence of dental caries was higher than in Swedish control children. At the age of 8, this difference persisted, but was less pronounced in the permanent than in the primary dentition. The net mean caries increment between 5 and 8 years of age was 11.2 in the Finnish group compared to 7.4 in the Swedish. The proportion of children selected for individual prophylaxis and the time used between age 5 and 8 did not differ between the Finnish and the Swedish groups.In the Finnish teenagers, the prevalence of dental caries was higher than in the Swedish teenagers. Periodontal health was equally good in all age groups of Finnish and Swedish children. The difference in caries prevalence between the two groups was mainly explained by a more frequent between-meal eating and a higher intake of sucrose-containing products between meals in the Finnish children. Even though they had been included in organized dental care with individual prophylaxis, this was obviously not enough to guarantee them as good a dental health as in the Swedish children.Flourides were used to an equal extent in the Finnish and Swedish groups. Toothbrushing was less frequent in all Finnish age groups than in the Swedish controls.The Finnish parents were less convinced than the Swedish about their ability to influence the child’s dental health, and more Finnish than Swedish parents also found it necessary to visit a dentist only when they had toothache.The Finnish teenagers who had received almost twice as many hours of individual prophylaxis as the Swedish, knew less about the etiology of dental caries but equally much about the etiology of gingivitis.The best result of early dental health education to parents, evaluated by comparing prevalence of dental caries of the children at the age of 3, was obtained when information was given three times in Finnish. If information in the mother tongue cannot be offered, an extra session of information in Swedish can also benefit the dental health of the child.
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| 30. |
- Ekman Nilsson, Anna, et al.
(author)
-
A review of carbon footprint of Cu and Zn production from primary and secondary sources
- 2017
-
In: Minerals. - : MDPI AG. - 2075-163X. ; 7:9, s. 168-
-
Journal article (peer-reviewed)abstract
- Copper (Cu) and zinc (Zn) with their unique propertiesare central for economic growth, quality of life and creation of new jobs. The base-metalproducing sector is, however, under growing public pressure in respect toenergy and water requirements and needs to meet several challenges, includingincreased demand and lower ore grades generally associated with larger resourceuse. The development of technologies for metal production from secondarysources is often motivated by increased sustainability and this paper aims to providefurther insights about one specific aspect of sustainability, namely climatechange. The paper presents a review of carbon footprints (CF) for Cu and Znproduced from primary and secondary raw materials, by analyzing data taken fromscientific literature and the Ecoinvent database. Comparisons are carried outbased on the source of data selected as reference case. In the case of Cu,reduced CF of secondary production is indicated, although there is large datavariation. As for Zn, production of this metal from secondary sources seems to bebeneficial but the number of data and cases to be compared is much smallercompared to Cu. The general variation of data suggests that standardization ofcomparison is needed when assessing the environmental benefits of production inline with the principles of waste valorization, zero waste approach andcircular economy.
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| 31. |
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| 32. |
- Hamberg, Anna-Karin, 1964-, et al.
(author)
-
Warfarin dose prediction in children using pharmacometric bridging : comparison with published pharmacogenetic dosing algorithms
- 2013
-
In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 69:6, s. 1275-1283
-
Journal article (peer-reviewed)abstract
- PurposeNumerous studies have investigated causes of warfarin dose variability in adults whereas studies in children are limited both in numbers and size. Mechanism-based population modelling provides an opportunity to condense and propagate prior knowledge from one population to another. The main objectives with this study were to evaluate the predictive performance of a theoretically bridged adult warfarin model in children, and to compare accuracy in dose prediction relative to published warfarin algorithms for children.MethodAn adult population PK/PD-model for warfarin, with CYP2C9 and VKORC1 genotype, age and target INR as dose predictors, was bridged to children using allometric scaling methods. Its predictive properties were evaluated in an external dataset of children 0-18 years old, including comparison of dose prediction accuracy with three pharmacogenetics-based algorithms for children.ResultsOverall, the bridged model predicted INR response well in 64 warfarin treated Swedish children (median age 4.3 years), but with a tendency to over predict INR in children ≤ 2 years old. The bridged model predicted 20 of 49 children (41%) within ± 20% of actual maintenance dose (median age 7.2 years). In comparison the published dosing algorithms predicted 33-41% of the children within ± 20% of actual dose. Dose optimization with the bridged model based on up to three individual INR observations increased the proportion within ± 20% of actual dose to 70%.ConclusionA mechanism-based population model developed on adult data provides a promising first step towards more individualized warfarin therapy in children.
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| 33. |
- Himonakos, Christos, et al.
(author)
-
Long-term Follow-up of 84 Patients With Giant Prolactinomas-A Swedish Nationwide Study.
- 2023
-
In: The Journal of clinical endocrinology and metabolism. - : Oxford University Press. - 1945-7197 .- 0021-972X. ; 108:12
-
Journal article (peer-reviewed)abstract
- To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018.Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively).DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.
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| 34. |
- Martínez-Sanz, Marta, et al.
(author)
-
Alternative protocols for the production of more sustainable agar-based extracts from Gelidium sesquipedale
- 2021
-
In: Algal Research. - : Elsevier B.V.. - 2211-9264. ; 55
-
Journal article (peer-reviewed)abstract
- Agar-based extracts from Gelidium sesquipedale were obtained by applying a conventional hot water treatment and alternative ultrasound- and microwave-assisted methods, with and without the application of an alkaline pre-treatment. The alkaline pre-treatment produced refined extracts with higher purity; however, extraction yields increased from 2–5% to 7–19% by omitting this step. In particular, the ultrasound-assisted extraction allowed reducing 4-fold the extraction time, while keeping constant or even increasing the yield (up to 19% for the 1 h extraction) with respect to the conventional protocol. Interestingly, the presence of proteins and polyphenols conferred the semi-refined extracts a relatively high antioxidant capacity (19–24 μmol TE/g extract). The refined extract produced by the standard protocol formed the strongest hydrogels (>1000 g/cm2). On the other hand, the semi-refined extracts produced by the alternative protocols formed slightly stronger hydrogels (337–438 g/cm2) than the refined counterparts (224–311 g/cm2), due to their greater molecular weights of the former ones. LCA assessment showed lower global warming potential for the semi-refined extracts, especially the ultrasound-assisted extraction, hence highlighting the potential of this method to produce more sustainable agar-based extracts for food-related applications.
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| 35. |
- Papakokkinou, Eleni, et al.
(author)
-
Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
- 2020
-
In: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
-
Journal article (peer-reviewed)abstract
- Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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| 36. |
- Raghavan, Sukanya, 1974, et al.
(author)
-
Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach. : Sublingual immunization against H. pylori infection
- 2010
-
In: Infection and immunity. - 1098-5522. ; 78:10, s. 4251-60
-
Journal article (peer-reviewed)abstract
- Sublingual (SL) immunization has been described as an effective novel way to induce mucosal immune responses in the respiratory and genital tracts. We examined the potential of SL immunization against Helicobacter pylori to stimulate immune responses in the gastrointestinal mucosa and protect against H. pylori infection. Mice received two SL immunizations with H. pylori lysate antigens and cholera toxin as an adjuvant, and after challenge with live H. pylori bacteria, their immune responses and protection were evaluated, as were immune responses prior to challenge. SL immunization induced enhanced proliferative responses to H. pylori antigens in cervicomandibular lymph nodes and provided at least the same level of immune responses and protection as corresponding intragastric immunization. Protection in SL-immunized mice was associated with strong H. pylori-specific serum IgG and IgA antibody responses in the stomach and intestine, with strong proliferation and gamma interferon (IFN-γ) and interleukin-17 (IL-17) production by spleen and mesenteric lymph node T cells stimulated with H. pylori antigens in vitro, and with increased IFN-γ and IL-17 gene expression in the stomach compared to levels in infected unimmunized mice. Immunohistochemical studies showed enhanced infiltration of CD4(+) T cells and CD19(+) B cells into the H. pylori-infected stomach mucosa of SL-immunized but not unimmunized H. pylori-infected mice, which coincided with increased expression of the mucosal addressin cell adhesion molecule (MAdCAM-1) and T and B cell-attracting chemokines CXCL10 and CCL28. We conclude that, in mice, SL immunization can effectively induce protection against H. pylori infection in association with strong T and B cell infiltration into the stomach.
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| 37. |
- Ragnarsson, Oskar, 1971, et al.
(author)
-
Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study
- 2019
-
In: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 104:6, s. 2375-2384
-
Journal article (peer-reviewed)abstract
- Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
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| 38. |
- Ragnarsson, Oskar, 1971, et al.
(author)
-
The incidence of Cushing’s disease : a nationwide Swedish study
- 2019
-
In: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
-
Journal article (peer-reviewed)abstract
- Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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| 39. |
- Sigurdardottir, Gunnthorunn, 1975-, et al.
(author)
-
Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.
- 2018
-
In: Dermatology. - Basel : S. Karger. - 1018-8665 .- 1421-9832. ; 234:5-6, s. 173-179
-
Journal article (peer-reviewed)abstract
- BACKGROUND: In psoriasis, a common immune-mediated disease affecting 2-3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment.OBJECTIVE: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis.METHODS: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response.RESULTS: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10-12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction.CONCLUSION: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.
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| 40. |
- Sigurdardottir, Gunnthorunn, et al.
(author)
-
Systemic treatment and narrowband ultraviolet B differentially affect cardiovascular risk markers in psoriasis.
- 2014
-
In: The Journal of American Academy of Dermatology. - : Elsevier. - 0190-9622 .- 1097-6787. ; 70:6, s. 1067-1075
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Psoriasis is associated with a systemic inflammation and an increased frequency of the metabolic syndrome, both of which are believed to link psoriasis to an increased risk of cardiovascular disease.OBJECTIVE: The study aimed to investigate the systemic expression of markers of cardiovascular risk and determine their response to ultraviolet B therapy and treatment with the tumor necrosis factor-alfa inhibitor, etanercept.METHODS: Six markers of cardiovascular risk were measured in 28 patients with psoriasis and 28 control subjects.RESULTS: Five of the 6 investigated markers were elevated in patients with psoriasis. Four of these correlated to the body mass index and waist-hip ratio, suggesting a link to the metabolic syndrome. Total plasminogen activator inhibitor-1 remained elevated independently of these factors. The levels of the investigated risk markers decreased considerably after tumor necrosis factor-alfa inhibitor treatment but remained unaffected by ultraviolet therapy.LIMITATIONS: A relatively limited study population and nonrandomization are limitations.CONCLUSION: These findings suggest that the choice of treatment in psoriasis may influence the cardiovascular risk in patients with psoriasis and the metabolic syndrome.
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| 41. |
- Ström, Kristoffer, et al.
(author)
-
N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism
- 2018
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
-
Journal article (peer-reviewed)abstract
- Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.
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| 42. |
- Svensson, Elin, 1980, et al.
(author)
-
Economic and environmental analysis of an emerging biorefinery concept as a guide for early technology development
- 2015
-
Conference paper (other academic/artistic)abstract
- This paper presents a biorefinery concept based on emerging conversion processes by which forestry residues and micro-algae are converted into an array of bulk and specialty chemicals. Due to the early development status of the individual processes and conversion routes investigated for the concept, not only is there a lack of fundamental process data, but even the spectrum of products to be obtained from the bioconversion processes is currently unknown. This paper elaborates on the opportunities and challenges associated with linking technology development to systems analysis for a process at a very early development stage, with examples from the biorefinery project described above. Examples of key assumptions for the system studied will be presented. Furthermore, a reasonable size for the plant will be proposed and the feasibility of the biorefinery will be evaluated based on general mass balances and techno-economic estimations for the system and a discussion about environmental impacts.
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| 43. |
- Unger, M. M., et al.
(author)
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Unimpaired postprandial pancreatic polypeptide secretion in Parkinson's disease and REM sleep behavior disorder
- 2013
-
In: Movement Disorders. - : Wiley. - 0885-3185. ; 28:4, s. 529-533
-
Journal article (peer-reviewed)abstract
- Background: Pancreatic polypeptide is released immediately after food ingestion. The release is operated by vagal-abdominal projections and has therefore been suggested as a test for vagal nerve integrity. Pathoanatomical and clinical studies indicate vagal dysfunction in early Parkinson's disease (PD). Methods: We assessed the postprandial secretion of pancreatic polypeptide and motilin in healthy controls (n = 18) and patients with idiopathic rapid-eye-movement sleep behavior disorder (iRBD, n = 10), a potential premotor stage of PD, as well as in drug-naive (n = 19) and treated (n = 19) PD patients. Results: The postprandial pancreatic polypeptide secretion showed a physiological pattern in all groups and even an enhanced response in drug-naive PD and iRBD. Motilin concentrations correlated with pancreatic polypeptide concentrations. Conclusions: Postprandial pancreatic polypeptide secretion is not a suitable test for vagal nerve integrity in PD. The unimpaired pancreatic polypeptide response in iRBD and PD might be explained by partially intact vagal-abdominal projections or compensatory mechanisms substituting a defective neuronal brain–gut axis.
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| 44. |
- Vegfors, Jenny, 1984-
(author)
-
Psoriasin For Better or for Worse in Sickness and in Health : The Role of Psoriasin in Angiogenesis and Differentation of Epithelial Cells
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyper-proliferative skin disorder psoriasis. Both breast cancer and psoriasis are diseases which are characterized by hyperproliferation and a disturbed differentiation of the epithelial cells as well as a pronounced angiogenesis. The potential role of psoriasin in angiogenesis and the epithelial differentiation remain unclear.The aim of this thesis was to investigate the cellular effects of psoriasin in angiogenesis and the differentiation processes, with special emphasis on breast cancer and psoriasis.We found that psoriasin expression was induced in mammary epithelial cells and keratinocytes by oxidative stress. Psoriasin expression was shown to induce vascular endothelial growth factor (VEGF) expression and several other pro-angiogenic factors in epithelial cells. Upon down-regulation of psoriasin, H2O2-induced expression of VEGF was decreased as well as the pro-angiogenic factors heparin-binding EGF-like growth factor (HBEGF) and matrix metalloproteinase (MMP)-1. Extracellular psoriasin contributed to the subsequent induction of proliferation, migration and tube formation of endothelial cells. The proliferative effect of psoriasin was shown to be mediated by the receptor for advanced glycation end products (RAGE). Furthermore, psoriasin induced reactive oxygen species (ROS) in both endothelial and epithelial cells through the action of RAGE, and contributed to the expression of the pro-angiogenic factors in endothelial cells.The expression of psoriasin was up-regulated in mammary epithelial cells and keratinocytes in response to differentiation-inducing stimuli and was shown to be regulated by pathways involved in epithelial cell differentiation. Upon psoriasin down-regulation the shift towards a more differentiated CD24+-phenotype of mammary epithelial cells was abolished. Furthermore, the expression of the differentiation markers involucrin, desmoglein 1, transglutaminase 1 and CD24 was decreased in keratinocytes upon down-regulation of psoriasin expression. In vivo we demonstrated a gradient of psoriasin expression in the psoriatic epidermis, with intense expression in the suprabasal differentiated layers, and a similar staining pattern between psoriasin and the differentiation marker CD24 in DCIS tumors.In conclusion, our findings describe psoriasin as a mediator in the angiogenic process and a contributor of epithelial cell differentiation. Consequently, psoriasin is possibly a contributor to the development and progression of breast cancer and psoriasis and a potential target in the treatment of these diseases.
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| 45. |
- Vegfors, Jenny, et al.
(author)
-
Psoriasin (S100A7) contributes to stress-induced angiogenesis in psoriasis by the regulation of angiogenic factors in keratinocytes and promotion of angiogenic properties of dermal endothelial cells
- 2014
-
Other publication (other academic/artistic)abstract
- The S100 protein psoriasin, S100A7, is highly expressed in psoriasis. Vascular modifications occur early in the development of psoriasis and angiogenesis is one of the key features in the pathogenesis of the disease. This study aims to define the angiogenic properties of psoriasin in keratinocytes and to investigate the effects on dermal endothelial cells, thereby promoting angiogenesis in psoriasis. We showed that psoriasin expression, demonstrated by qPCR, is induced by hydrogen peroxide (H2O2) in keratinocytes and by cellular stress, such as hypoxia and cobalt chloride (CoCl2). Down-regulation of psoriasin, by siRNA, decreased the H2O2-induced expression of VEGF, heparin-binding EGF-like growth factor (HB-EGF) and matrix metalloproteinase (MMP)-1, and counteracted the reduction of the anti-angiogenic factor thrombospondin (THBS)-1. Extracellularly psoriasin was found to induce cell proliferation, migration and tube formation to a similar degree as VEGF and to induce the pro-angiogenic factors VEGF and IL-8 in dermal endothelial cells. Furthermore, we demonstrated that psoriasin-induced migration was mediated by the phosphoinositide-3-kinase (PI3K) and nuclear factor-kappa beta (NF-κB) signaling pathways. In conclusion, psoriasin is induced by cellular stress conditions and amplifies H2O2-induced expression of angiogenic factors relevant for psoriasis in keratinocytes. Moreover, psoriasin contributes to key features of the angiogenic process by inducing proliferation, migration and tube formation and increasing pro-angiogenic factors in dermal endothelial cell. Altogether, our data suggest that psoriasin is promoted by oxidative stress and mediate angiogenesis in psoriasis.
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| 46. |
- Vegfors, Jenny, et al.
(author)
-
Psoriasin (S100A7) is regulated by protein kinase C (PKC) and contributes to keratinocyte differentiation by regulating the expression of epidermal differentiation markers
- 2014
-
Other publication (other academic/artistic)abstract
- Psoriasis is a chronic inflammatory skin disease that is characterized by hyperproliferation and a disturbed maturation of the epidermal cells. The differentiation process of keratinocytes in active psoriatic lesions differs from that of normal epidermis, denoted by an altered expression of differentiation markers. Psoriasin, a protein which is highly expressed in psoriasis, is located within the epidermal differentiation complex (EDC), a gene cluster that contains several genes that are important in the terminal differentiation of the human epidermis. The potential role of psoriasin in keratinocyte differentiation remain however unclear. The aim of this present study was to investigate the possible involvement of psoriasin in keratinocyte differentiation. We demonstrated, by immunohistochemical staining, a gradient of psoriasin expression in the psoriatic epidermis, from an undefined or weak expression in the basal layer to an intense expression in the suprabasal differentiated layers. The expression of psoriasin was up-regulated in cultured keratinocytes in response to stimuli known to induce differentiation, such as an elevation of extracellular calcium or 12-Otetradecanoylphorbol-13-acetate (TPA). Down-regulation of psoriasin expression, by siRNA, resulted in decreased expression of the differentiation markers involucrin, desmoglein 1, transglutaminase 1 and CD24. Inhibition of protein kinase C (PKC) counteracted the calciuminduced expression of psoriasin and involucrin. In summary, our data demonstrate that psoriasin is regulated by the PKC signaling pathway and contributes to keratinocyte differentiation by the regulation of differentiation markers.
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| 47. |
|
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| 48. |
- Vegfors, Jenny, et al.
(author)
-
Psoriasin (S100A7) promotes stress-induced angiogenesis.
- 2016
-
In: British Journal of Dermatology. - : John Wiley & Sons. - 0007-0963 .- 1365-2133. ; 175:6, s. 1263-1273
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Journal article (peer-reviewed)abstract
- BACKGROUND: Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease.OBJECTIVES: To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis.METHODS: The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated.RESULTS: Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways.CONCLUSIONS: These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.
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- Verma, Deepti, et al.
(author)
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Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Uninvolved Psoriatic Epidermis
- 2018
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In: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 138:5, s. 1088-1093
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Journal article (peer-reviewed)abstract
- Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one-third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls. We performed an exhaustive genome-wide DNA methylation profiling using reduced representation bisulfite sequencing, which interrogates the methylation status of approximately 3-4 million CpG sites. More than 2,000 strongly differentially methylated sites were identified and a striking overrepresentation of the Wnt and cadherin pathways among the differentially methylated sites was found. In particular, we observe a strong differential methylation in several psoriasis candidate genes. A substantial number of differentially methylated sites present in the uninvolved versus healthy epidermis suggests the presence of a pre-psoriatic state in the clinically healthy skin type. Our exploratory study represents a starting point for identifying biomarkers for psoriasis-prone skin before disease onset.
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