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1.
  • Nilsson, Kerstin, et al. (författare)
  • 54 forskare: Inte alla klarar höjd pensions-ålder
  • 2017
  • Ingår i: Svenska Dagbladet, Stockholm. - 1101-2412.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet, så att fler klarar att arbeta i högre ålder. Att enbart genom ekonomiska åtgärder höja pensionsåldern är inte långsiktigt hållbart, skriver 54 forskare.DEBATT | PENSIONForskning visar att cirka var fjärde har en diagnos eller skada orsakad av sitt arbete. Detta gör arbetsorsakad sjukdom och skada till ett betydelsefullt folkhälsoproblem. Att då enbart genom ekonomiska åtgärder höja pensionsåldern för samtliga (yrkes)grupper utifrån deras kronologiska ålder är inte långsiktigt hållbart när individers biologiska ålder är så olika bland annat till följd av arbetslivet. Detta är en demokratifråga. Forskning om äldre i arbetslivet och hållbart arbete visar att man då främst flyttar individer från pensionssystemet till sjukförsäkringssystemet och ökar klyftorna i samhället.Debatt Det här är en argumenterande text med syfte att påverka. Åsikterna som uttrycks är skribentens egna.Vi är 54 forskare som nu gemensamt har skrivit denna debattartikel. Anledningen är att vi är oroade över att cirka var fjärde blir sjuk av sitt arbete samtidigt som man i det förslag som ligger om att senarelägga ålderspensionen i princip utgår ifrån att arbetskraftsdeltagande enbart styrs av ekonomin. Vi vill trycka på betydelsen av åtgärder i arbetslivet för att komma tillrätta med ohälsan, det vill säga inte enbart ekonomiska restriktioner som tvingar folk som inte kan, vill och orkar att stanna kvar i arbetslivet till en högre kronologisk ålder.Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att förtjäna möjligheter till pension. Vi bör dock inte enbart utgå ifrån antalet år sedan en person föddes, då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Den svenska sjukförsäkringsreformen 2008 avsåg att få tillbaka människor i arbete. Men studien fann att den faktiskt bidrog till att fler gick i tidig ålderspension av dem som var i åldern 55–64 år. Ökningen var störst bland korttidsutbildade. Mer än 5 procent fler gick i tidig ålderspension då det blev svårare att få sjukpenning och sjukersättning. Vi kan notera att det är vanligare att manliga chefer tar ut tidig ålderspension, jämfört med kvinnliga maskinskötare inom tillverkningsindustrin. I vissa yrken är det dessutom vanligare att människor, trots pension, både orkar och faktiskt ges möjlighet att arbeta vidare om de har en specialkompetens som efterfrågas. Om vi endast kombinerar ekonomiska morötter med piskor finns en stor risk att vi ökar klyftan mellan grupper som både kan och vill fortsätta att yrkesarbeta och personer som av olika skäl inte längre kan eller orkar.Ta nytta av den forskning som vi har tagit fram. Ett hållbart och acceptabelt pensionssystem måste utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas och våra attityder som är kopplade till ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.”Morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi.Forskning visar att pedagogik som bygger på ”morötter” oftast är betydligt bättre än ”piskor” för att nå framgångsrika och långsiktiga mål. ”Morötter” i samhället, för organisationer, företag och individer är därför viktiga för god arbetshälsa och fortsatt produktivitet och kan bidra till ett längre arbetsliv även för grupper som tidigare inte ens klarat av att arbeta fram till pensionsåldern. Genom forskning inom området har bland annat swage-modellen utarbetats. Detta är ett verktyg som visar på komplexiteten i ett hållbart arbetsliv och tillsammans med systematiskt arbetsmiljöarbete, handlingsplaner och åtgärder syftar till ett mer hållbart arbetsliv. Morötter är enligt forskningen i detta sammanhang åtgärder för en god fysisk och mental arbetsmiljö, avpassad arbetsbelastning, stödjande teknik, att man kan anpassa arbetstakten, alternativa arbetstidsmodeller vid behov. Det är viktigt att man känner sig trygg och förväntas och tillåts vara delaktig, att man blir sedd av chefen och arbetskamraterna. Att de egna arbetsuppgifterna upplevs som meningsfulla och behövda av andra skapar självförverkligande och tillfredsställelse i arbetet. Att man känner att ens arbetsuppgifter och man själv är viktig för organisationen och företaget. Att man trots högre ålder inkluderas i olika nysatsningar och får tillgång till kompetensutveckling och inte blir åsidosatt eller åldersdiskriminerad. Utvärderingar visar att de äldre medarbetarna som fick några av dessa anpassningar och möjligheter var mer effektiva, utvilade, stimulerade när de var på arbetet samtidigt som sjukfrånvaron minskade. Vilket i sin tur bidrar till ett längre arbetsliv för grupper som tidigare inte klarat av att arbeta fram till pensionsåldern. I organisationer som bygger på en deltagar- och lärandekultur rustas de anställda för att klara omställningar, nya arbetsuppgifter och vid behov även yrkesbyten.Med en åldrande befolkning där allt fler lever allt längre behöver vi arbeta till en högre ålder i framtiden för att pensionssystemet ska hålla. Men ”morötter” är viktigare för en god arbetshälsa och hög produktivitet än en piska i form av oron för en dålig ekonomi. Det kräver också att vi ändrar våra attityder och förhållningssätt till äldre på arbetsmarknaden, vilket vi bäst gör genom att organisationer och företag får incitament till och erbjuder mer individanpassade arbetsvillkor, särskilt för personer i högre ålder. Låt oss därför använda den framtagna kunskapen i praktiken för att göra arbetslivet friskt och hållbart för alla åldrar.
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2.
  • Nilsson, Kerstin, et al. (författare)
  • Vi är oroade över senare ålderspension
  • 2017
  • Ingår i: Dagens Samhälle. - 1652-6511.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Var fjärde person blir i dag sjuk till följd av sitt arbete. Att höja pensionsåldern för alla yrkesgrupper, utan konkreta åtgärder för att minska ohälsan, är därför problematiskt och mycket oroande. Det är, enligt forskarna, inte långsiktigt samhällsekonomiskt lönsamt att utan andra åtgärder höja pensionsåldern för alla. Vi – 54 forskare – är mycket oroade över konsekvenserna av att, som föreslagits, senarelägga ålderspensionen.Förslaget utgår i princip från arbetskraftsdeltagande i princip enbart styrs av ekonomin, medan forskningen visar att det bara är en av flera faktorer som styr hur länge och hur mycket människor väljer att arbeta.Det här sättet att lösa problemet med en åldrande befolkning och ett sviktande pensionssystem är inte samhällsekonomiskt lönsamt på lång sikt, utan riskerar bara att flytta runt folk mellan olika ersättningssystem. Pensionssystemet bygger på att vi ska arbeta en viss del av våra liv för att tjäna in vår pension. Vi bör dock inte enbart utgå ifrån ålder eller antalet år sedan en person föddes då korttidsutbildade generellt träder in på arbetsmarknaden tidigare än långtidsutbildade. De med kortare utbildningstid har alltså varit en del av arbetskraften från en yngre ålder. Människor med kortare utbildning har också oftare ett arbete som innebär påfrestningar som kan inverka negativt på hälsotillståndet och som till och med kan påskynda det biologiska åldrandet. Dessutom lever korttidsutbildade generellt sett inte lika länge som långtidsutbildade, vilket delvis även avspeglar skilda livs- och arbetsvillkor.Ta nytta av den forskning som vi har tagit fram. Ekonomin är självklart viktigt för att vi ska vilja arbeta, men den är som sagt enbart en av flera faktorer med betydelse vårt arbetsliv.Hälsotillståndet, både det fysiska och det mentala, har en avgörande betydelse för hur länge och hur mycket vi orkar arbeta. Ett fysiskt och mentalt belastande arbete är en stark riskfaktor för en nedsatt hälsa i slutet av arbetslivet. Arbetstid, arbetstakt och möjlighet till återhämtning spelar en allt större roll ju äldre vi blir. Andra aspekter är arbetsinnehåll, hur meningsfulla och stimulerande arbetsuppgifterna är, balansen mellan arbete och familjesituation och fritidsaktiviteter. Organisationskultur, ledarskapet, stöd i arbetet och kompetens har stor betydelse för om vi ska kunna och vilja arbeta till en högre ålder. Vi måste ta större hänsyn till olika förutsättningar och varierande funktionsförmåga och utifrån detta anpassa de åtgärder som gör att arbetslivet blir möjligt och hållbart för allt fler även i högre ålder.Ett hållbart och acceptabelt pensionssystem måste därför utformas utifrån personliga förutsättningar och förhållanden i arbetslivet. Ett hållbart arbetsliv för allt fler i vår åldrande befolkning fordrar att vi samtidigt beaktar faktorer som relaterar till biologisk/kroppslig ålder, mental/kognitiv ålder samt social ålder/livsloppsfas samt de attityder som är kopplade till ålder.
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3.
  • Engberg, Anna E., et al. (författare)
  • Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
  • 2015
  • Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 36, s. 55-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.
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  • Aeinehband, Shahin, et al. (författare)
  • Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.
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7.
  • Aronsson, Gunnar, et al. (författare)
  • Healthy workplaces for women and men of all ages
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this knowledge compilation is to contribute with knowledge about the work environment in relation to the ever-older workforce. How do employee needs and possibilities change from a course of life perspective? What should the employer and other work environment actors think about in order for the workforce to be able to and want to work to a high age?The Swedish Work Environment Authority wishes to give an overarching knowledge profile of different aspects of the work environment and the ageing workforce, and we therefore asked seven researchers to summarise the research-based knowledge within each of their areas, from a course of life and gender perspective. An eighth researcher acted as an editor for the anthology, and has also written the preface.In summary, the report shows that we are becoming even healthier, living ever longer and working to an ever higher age. Older people in the workforce are positive for the economy because productivity increases, and the business sector can make use of competent and experienced staff for a longer time. But for the older labour force to be healthy and want to work at higher ages, one needs to take into consideration how ageing influences health and the capacity to work. With age, all people are affected to different degrees by reduced vision, hearing and physical capacity, as well as longer reaction times. Even their cognitive capacity changes. Certain cognitive abilities are strengthened with rising age, while others deteriorate. With an ageing workforce, more employees have chronic illnesses, which, however, seldom affect the actual working ability. Changes in working life also affect health and wellbeing, for example deregulated work and the technical development. Age and previous experiences impact upon our ability to adapt to these changes. One factor that promotes adaptation is partly resilience (that is to say, resistance and the ability to adapt to the new), partly compensation strategies when the mental and physical resources change. There are no great differences between gender when it comes to the consequences of ageing on health and wellbeing in the work. On the other hand, the public health trend shows increasing differences in health between the lower educated and the higher educated - a difference increasing more quickly among women than among men. The gender-segregated labour market also means that more women than men work in physical and mentally burdensome work. Attitudes at the workplace also affect wellbeing and the will to continue working at higher ages. Men tend to be more sensitive to age discrimination while women run the risk of double discrimination, that is to say based upon both gender and age. Work environment and the attitude to an older workforce are central to the considerations that an employee makes in the choice between continuing to work and retiring. Other prerequisites that influence the decision are one’s own health, private finances and self-fulfilling activities.The employer can do a great deal to lengthen and improve their employees’ working life. Systematic work environment management benefits everyone, and it can contribute to everyone keeping their working ability and to older people wanting to and being able to work for longer. Occupational health services of good quality also play an important role. Technical aids and adaptation of the working pace and working tasks are other measures that improve the work environment for the older workforce. The employer can also contribute to stimulating work arrangements and organisational support for the employees in order to strengthen their resilience and promote the development of compensation strategies. 
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  • Ekstrand-Hammarström, Barbro, et al. (författare)
  • TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations
  • 2015
  • Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 51, s. 58-68
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. (C) 2015 Elsevier Ltd. All rights reserved.
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10.
  • Gyllensten, Kristina, 1977, et al. (författare)
  • Older assistant nurses’ motivation for a full or extended working life
  • 2019
  • Ingår i: Ageing and Society. - 0144-686X .- 1469-1779. ; 39:12, s. 2699-2713
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to explore older workers’ motivation for a full or extended working life. With particular focus on assistant nurses aged 55–64 years, working in the elderly care sector. Focus group interviews were conducted with five different groups of assistant nurses. Inductive thematic analysis was used to analyse the interviews and five main themes were developed from the data: ‘Organisational issues’, ‘Health-related problems’, ‘Private issues’, ‘Meaningfulness and appreciation’ and ‘Social support’. Several of the main themes concerned problems with too high work demands of the assistant nurses. These findings suggest that it is important to improve the working conditions of assistant nurses in order to create a more sustainable working life. Increasing the number of staff and improving recovery opportunities and work–life balance could be important steps to improving the working conditions for this group. Finally, upgrading the competency and professionalism of assistant nurses could help to increase the motivation for a full or extended working life.
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  • Huang, Shan, et al. (författare)
  • Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood
  • 2015
  • Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 8:1, s. 31-37
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.METHODS:The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.RESULTS:Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.CONCLUSIONS:Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.
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  • Huang, Shan, et al. (författare)
  • Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.
  • 2016
  • Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 77, s. 111-119
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.
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  • Idborg, Helena, et al. (författare)
  • Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjogren's syndrome differ in molecular signatures and treatment perspectives
  • 2019
  • Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362 .- 1478-6354. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPrevious studies and own clinical observations of patients with systemic lupus erythematosus (SLE) suggest that SLE harbors distinct immunophenotypes. This heterogeneity might result in differences in response to treatment in different subgroups and obstruct clinical trials. Our aim was to understand how SLE subgroups may differ regarding underlying pathophysiology and characteristic biomarkers.MethodsIn a cross-sectional study, including 378 well-characterized SLE patients and 316 individually matched population controls, we defined subgroups based on the patients' autoantibody profile at inclusion. We selected a core of an antiphospholipid syndrome-like SLE (aPL+ group; positive in the lupus anticoagulant (LA) test and negative for all three of SSA (Ro52 and Ro60) and SSB antibodies) and a Sjogren's syndrome-like SLE (SSA/SSB+ group; positive for all three of SSA (Ro52 and Ro60) and SSB antibodies but negative in the LA test). We applied affinity-based proteomics, targeting 281 proteins, together with well-established clinical biomarkers and complementary immunoassays to explore the difference between the two predefined SLE subgroups.ResultsThe aPL+ group comprised 66 and the SSA/SSB+ group 63 patients. The protein with the highest prediction power (receiver operating characteristic (ROC) area under the curve=0.89) for separating the aPL+ and SSA/SSB+ SLE subgroups was integrin beta-1 (ITGB1), with higher levels present in the SSA/SSB+ subgroup. Proteins with the lowest p values comparing the two SLE subgroups were ITGB1, SLC13A3, and CERS5. These three proteins, rheumatoid factor, and immunoglobulin G (IgG) were all increased in the SSA/SSB+ subgroup. This subgroup was also characterized by a possible activation of the interferon system as measured by high KRT7, TYK2, and ETV7 in plasma. In the aPL+ subgroup, complement activation was more pronounced together with several biomarkers associated with systemic inflammation (fibrinogen, -1 antitrypsin, neutrophils, and triglycerides).ConclusionsOur observations indicate underlying pathogenic differences between the SSA/SSB+ and the aPL+ SLE subgroups, suggesting that the SSA/SSB+ subgroup may benefit from IFN-blocking therapies while the aPL+ subgroup is more likely to have an effect from drugs targeting the complement system. Stratifying SLE patients based on an autoantibody profile could be a way forward to understand underlying pathophysiology and to improve selection of patients for clinical trials of targeted treatments.
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  • Kozarcanin, Huda, et al. (författare)
  • The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation
  • 2016
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 14:3, s. 531-545
  • Tidskriftsartikel (refereegranskat)abstract
    • The lectin pathway's MASP-1/2 activates coagulation factors but the trigger of the activation is unknown. MASP-1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1-inhibitor. Activated platelets and fibrin were demonstrated to activate MASP-1 and MASP-2 both invitro and invivo. These findings may represent a crossroad between the complement and the coagulation systems. Summary Background The activated forms of the complement lectin pathway (LP) proteases MASP-1 and MASP-2 are able to cleave the coagulation factors prothrombin, fibrinogen, factor XIII and thrombin-activatable fibrinolysis inhibitor invitro. In vivo studies also show that MASP-1 is involved in thrombogenesis. Objectives To clarify the not yet identified mechanisms involved in triggering activation of the LP during thrombotic reactions. Methods Novel sandwich-ELISAs for detection of complexes between MASP-1 or MASP-2 and the serpins C1 inhibitor (C1-INH) or antithrombin (AT), were used to specifically detect and quantify the activated forms of MASP-1 and MASP-2. Results Activated platelets were shown by flow cytometry to bind Ficolin-1, -2 and -3 but not MBL, which was associated with activation of MASP-1 and MASP-2. We also demonstrated that fibrin and the plasmin-generated fibrin fragment DD in plasma, bind and activate MASP-1 and MASP-2. As demonstrated by the ELISA and SDS-PAGE/Western blotting, the fibrin-associated activation was reflected in a specific inactivation by AT during clotting without the assistance of heparin. In all other cases the MASPs were, as previously reported, inactivated by C1-INH. In systemic lupus erythematosus patients with thrombotic disease and in polytrauma patients, the levels of activated MASP-1 and MASP-2 in complex with both AT and C1-INH were associated with markers of thrombotic disease and contact/coagulation system activation. Conclusions MASP-1 and MASP-2 are activated during blood clotting. This activation is triggered by activated platelets and by the generation of fibrin during thrombotic reactions invitro and invivo, and may represent a novel activation/amplification mechanism in thromboinflammation.
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  • Lindblom, Rickard, 1981-, et al. (författare)
  • Complement Receptor 2 is increased in cerebrospinal fluid of multiple sclerosis patients and regulates C3 function
  • 2016
  • Ingår i: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 166, s. 89-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Besides its vital role in immunity, the complement system also contributes to the shaping of the synaptic circuitry of the brain. We recently described that soluble Complement Receptor 2 (sCR2) is part of the nerve injury response in rodents. We here study CR2 in context of multiple sclerosis (MS) and explore the molecular effects of CR2 on 0 activation. Significant increases in sCR2 levels were evident in cerebrospinal fluid (CSF) from both patients with relapsing remitting MS (n = 33; 6.2 ng/mL) and secondary-progressive MS (n = 9; 7.0 ng/mL) as compared to controls (n = 18; 4.1 ng/mL). Furthermore, CSF sCR2 levels correlated significantly both with CSF C3 and C1q as well as to a disease severity measure. In vitro, sCR2 inhibited the cleavage and down regulation of Cab to iC3b, suggesting that it exerts a modulatory role in complement activation downstream of C3. These results propose a novel function for CR2/sCR2 in human neuroinflammatory conditions.
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21.
  • Mohebnasab, Maedeh, et al. (författare)
  • Current and Future Approaches for Monitoring Responses to Anti-complement Therapeutics
  • 2019
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10, s. 1-13
  • Forskningsöversikt (refereegranskat)abstract
    • Aberrations in complement system functions have been identified as either direct or indirect pathophysiological mechanisms in many diseases and pathological conditions, such as infections, autoimmune diseases, inflammation, malignancies, and allogeneic transplantation. Currently available techniques to study complement include quantification of (a) individual complement components, (b) complement activation products, and (c) molecular mechanisms/function. An emerging area of major interest in translational studies aims to study and monitor patients on complement regulatory drugs for efficacy as well as adverse events. This area is progressing rapidly with several anti-complement therapeutics under development, in clinical trials, or already in clinical use. In this review, we summarized the appropriate indications, techniques, and interpretations of basic complement analyses, exemplified by a number of clinical disorders.
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22.
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23.
  • Mohlin, Camilla, 1972-, et al. (författare)
  • The link between morphology and complement in ocular disease
  • 2017
  • Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 89, s. 84-99
  • Forskningsöversikt (refereegranskat)abstract
    • The complement system is a vital component of the immune-priveliged human eye that is always active at a low-grade level, preventing harmful intraocular injuries caused by accumulation of turnover products and controlling pathogens to preserve eye homeostasis and vision. The complement system is a double-edged sword that is essential for protection but may also become harmful and contribute to eye pathology. Here, we review the evidence for the involvement of complement system dysregulation in age-related macular degeneration, glaucoma, uveitis, and neuromyelitis optica, highlighting the relationship between morphogical changes and complement system protein expression and regulation in these diseases. The potential benefits of complement inhibition in age-related macular degeneration, glaucoma, uveitis, and neuromyelitis optica are abundant, as are those of further research to improve our understanding of complement-mediated injury in these diseases.
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24.
  • Nilsson, Emma, et al. (författare)
  • Time for Caring? Elderly care employees’ occupational activities in the cross draft between their work priorities, “must-do’s” and meaningfulness.
  • 2017
  • Ingår i: International Journal of Care Coordination. - : SAGE Publications. - 2053-4345 .- 2053-4353. ; 20:1-2, s. 8-16
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing number of older people in the population will bring new challenges for the society and care coordination. One of the most important questions in care coordination is the employees’ work performance. The overall aim of this study was to examine care employees’ experience of factors that rule how they allocate their time and tasks in the care work. The study was qualitative and consists of focus group interviews with 36 employees in elderly care in five Swedish municipalities. Much of the work that care employees perform is controlled by others in the municipality organised health care. The employees had a limited possibility to decide what should be given priority in their work. However, the employees who participated in the focus group interviews did not want to prioritise tasks and duties they felt were faulty or in direct conflict with their own convictions. When employees experienced that the assistance assessments were correct and helpful to the individual elderly patient this contributed to the employees’ priority and performance of the task. The formal and informal control systems caused the employees’ priority to be mainly quantitative and visible work tasks, rather than more qualitative tasks and care giving to the elderly. In the intention to organise good care coordination that fit each elderly patients’ need it is important that those who work closest to the patient to a greater extent are given the opportunity to make their voice heard in decisions of care planning and assistance assessments.
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25.
  • Nilsson Ekdahl, Kristina, et al. (författare)
  • Interpretation of Serological Complement Biomarkers in Disease
  • 2018
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Complement systemaberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls. However, due to the low degree of specificity and sensitivity of some of the assays used, it is not always possible to make predictions regarding the complement status of individual patients. Today, there are three main indications for determination of a patient's complement status: (1) complement deficiencies (acquired or inherited); (2) disorders with aberrant complement activation; and (3) C1 inhibitor deficiencies (acquired or inherited). An additional indication is to monitor patients on complement-regulating drugs, an indication which may be expected to increase in the near future since there is now a number of such drugs either under development, already in clinical trials or in clinical use. Available techniques to study complement include quantification of: (1) individual components; (2) activation products, (3) function, and (4) autoantibodies to complement proteins. In this review, we summarize the appropriate indications, techniques, and interpretations of basic serological complement analyses, exemplified by a number of clinical disorders.
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26.
  • Nilsson Ekdahl, Kristina, et al. (författare)
  • Is generation of C-3(H2O) necessary for activation of the alternative pathway in real life?
  • 2019
  • Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 114, s. 353-361
  • Tidskriftsartikel (refereegranskat)abstract
    • In the alternative pathway (AP) an amplification loop is formed, which is strictly controlled by various fluid-phase and cell-bound regulators resulting in a state of homeostasis. Generation of the "C3b-like" C3(H2O) has been described as essential for AP activation, since it conveniently explains how the initial fluid-phase AP convertase of the amplification loop is generated. Also, the AP has a status of being an unspecific pathway despite thorough regulation at different surfaces. During complement attack in pathological conditions and inflammation, large amounts of C3b are formed by the classical/lectin pathway (CP/LP) convertases. After the discovery of LP's recognition molecules and its tight interaction with the AP, it is increasingly likely that the AP acts in vivo mainly as a powerful amplification mechanism of complement activation that is triggered by previously generated C3b molecules initiated by the binding of specific recognition molecules. Also in many pathological conditions caused by a dysregulated AP amplification loop such as paroxysmal nocturnal hemoglobulinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), C3b is available due to minute LP and CP activation and/or generated by non-complement proteases. Therefore, C3(H2O) generation in vivo may be less important for AP activation during specific attack or dysregulated homeostasis, but may be an important ligand for C3 receptors in cell-cell interactions and a source of C3 for the intracellular complement reservoir.
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27.
  • Nilsson, Kerstin, et al. (författare)
  • The transfer of knowledge between younger and older employees in the health and medical care: An intervention study
  • 2017
  • Ingår i: Open Journal of Social Sciences. - : Scientific Research Publishing, Inc.. - 2327-5952 .- 2327-5960. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • In the ageing society more old employees need to stay in working life for longer. However, the society also needs to take care of the increased amount of elderly in a more effective and respectful way. To take care of older employees experience knowledge to make the elderly care and the care employees work situation better and self-crediting to go on in an extended working life, new methods and measures are needed to be developed and evaluated. The overall purpose of this article was to evaluate how the participant in the intervention project experienced the project and its methodology. The intervention project followed three different methods: i) through interviews of the participants and the supervisor; ii) through participant observation; and iii) through an evaluation questionnaire to participants after the project was completed. The intervention project did transfer knowledge between different fields, that are, between generations, between different departments and between the municipality and county. The participation was described as not only a place for reflection and knowledge, but also a protected zone where participants could talk about the kind of problems they would ponder over. Several participants felt that it was important to develop and continue the work that the intervention project set in motion. The participants’ experience was made to be visible and their professional competence has been strengthened. They indicated that there had been an exchange of knowledge and between not only the generations but also the different kinds of work. The organisations also seem to have gained from the project by allowing the participants to unload, become more positive, develop more knowledge of experience, increase their propensity for reflection and get a better consensus between the municipality and county. The intervention project seems to have fulfilled the stated purpose and also the expectations of the participants.
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28.
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29.
  • Nilsson, Maria Skyvell, 1961, et al. (författare)
  • Clinical Course Content As A Dynamic Variable In Supervision Of Medical Students
  • 2010
  • Ingår i: The Internet Journal of Medical Education. - 2155-6725. ; 1:2
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDuring clinical supervision, medical students are expected to gain experience through clinical work, with the support of their clinical supervisor. What each supervisor chooses to emphasize and considers important will have a decisive impact on students’ understanding of what is content necessary to master in order to gain clinical skills. Therefore, in this study, the focus of attention is on what supervisors choose to emphasise during clinical supervision of fourth year medical students during a surgical course. MethodAn ethnographic approach was used, including a selective intermittent time mode, where observation and informal interviews were conducted. Twelve supervisors and nine medical students at a teaching hospital in Sweden participated. Field notes were made during observation; these were transcribed and analysed qualitatively. ResultsThe analysis resulted in six topic areas describing what was emphasized during supervision. The topic areas were: 1) Identifying, collecting and combining information, 2) Problem-solving and decision-making, 3) Handling treatment of disease, 4) Practical skills and illustration of technical equipment, 5) Communicating with patients, and 6) Handling organisational demands.ConclusionsThe findings of this study show the existence of several areas that are focused on in supervision. In authentic clinical situations, these topic areas were intertwined and overlapped and often appeared simultaneously. The clinical situations were adjusted neither to the students’ clinical experience nor to the needs of the students. Consequently, the students may find it difficult to determine what to learn and what to achieve during supervision. They may also find it difficult to understand the situations in the same way as their supervisors, because students focus on handling situations with a more theoretical and declarative approach to a larger extent than do their supervisors. The students therefore need supervisor support to develop and integrate theoretical knowledge. One conclusion that can be made is that supervisor awareness of students’ understanding is of crucial significance for the effective supervision. Regarding the nature of the content chosen in supervised situations, research in other settings and specialties would be required to map and to determine a more general theory of what is focused during medical supervision.
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30.
  • Nilsson, Per A., 1957- (författare)
  • Studying abroad : exploring mobility, expectations and experiences among mobile students
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis deals with the experiences and outcomes of temporarily studying abroad, via follow-up studies, aiming to explore international student mobility with a focus on the individual’s perspective. The specific research questions, dealing with the individual students’ expectations and experiences, are addressed in three papers. The fourth paper is a framing of these studies, using results from a global study.The first research question connects to the attractiveness of international study experiences: Q1. What are the individual’s expectations for studying abroad, among inbound and outbound students, and what are the students’ reported experiences compared with these expectations? The second research question connects to the mobility culture of youth: Q2. Does students’ reported life satisfaction change in any way after studying abroad?A main finding for outbound students was an appreciation of courses offered at the destination higher education institution that were not available at Umeå University. The students also had a desire to change their environment and have new experiences. Conversely, the desire to work abroad in the future was lower after returning home. A major finding for inbound students was that they assigned higher value to personal development than academic development. The experience made the students positive in regard to working abroad. Inbound students reported significantly higher satisfaction at follow-up six months later for the domains somatic health and activities of daily living. For both in- and outbound students, experiencing a new culture was more important than pure academic experiences.When the experience was compared with the expectation, in most cases the outcomes were positively related for both in- and outbound students. The motives for international study were primarily related to personal achievements, indicating a fulfilment of one’s potential and curiosity about a sojourn abroad.Finally, the results from the Umeå studies were compared with a global survey. The Umeå studies shows that the respondents viewed studying abroad as an important experience and as a merit later in life. The global survey results indicate that the transition from education to the world of work is of increasing importance to students, and that it matters more for non-European students. The global study showed that employability, teaching ability, expert lectures, and course organization are important to international students.
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31.
  • Nilsson, Petra, 1980-, et al. (författare)
  • How to make a workplace health promotion questionnaire process applicable, meaningful, and sustainable
  • 2011
  • Ingår i: Journal of Nursing Management. - : Wiley-Blackwell. - 0966-0429 .- 1365-2834. ; 19:7, s. 906-914
  • Tidskriftsartikel (refereegranskat)abstract
    • Background  In workplace health promotion, a questionnaire could be of great use. Unfortunately, fatigue regarding answering questionnaires has recently become greater than before. An action research approach could be a possible way of increasing employee participation.Aim  This study reports an attempt to explore key aspects for participation in, and commitment to, a workplace health promotion questionnaire process.Method  The study was conducted at two wards in a Swedish hospital. Data was collected during an action research process. Data were analysed with regard to a framework of questions.Findings  The three key aspects for participation in, and commitment to, a workplace health promotion questionnaire process were: an applicable questionnaire, a meaningful questionnaire process and a continuous and sustainable questionnaire process. A structure is presented as practical advice to managers, describing how such a process could be established to be applicable, meaningful and sustainable.Conclusion  This study has identified key aspects and prerequisites for questionnaire processes. The prerequisites – share decision-making, involve a core group and follow a structure – are discussed and proposed for managers and workgroups to consider in further workplace health promotion questionnaire processes.Implications for nursing management  The key aspects and prerequisites presented could provide a stimulating standpoint or advice, useful for planning and accomplishing workplace questionnaire processes.
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32.
  • Sandholm, Kerstin, et al. (författare)
  • Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use
  • 2019
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: C1q is a valuable biomarker of disease activity in systemic lupus erythematosus (SLE). The "gold standard" assay, rocket immunoelectrophoresis (RIE), is time-consuming, and thus a shift to soluble immune precipitation techniques such as nephelometry has occurred. However, quantification of C1q with these techniques has been questioned as a result of the antibody binding properties of C1q. In the present work, we have compared results using various techniques (RIE, nephelometry, and ELISA) and have developed and validated a new magnetic bead-based sandwich immunoassay (MBSI). Methods: C1q was quantified by nephelometry and the new sandwich immunoassay in 45 serum samples analyzed using RIE. C1q was also assessed in plasma using RIE and sandwich immunoassay in samples from SLE patients with nephritis (n = 69), SLE patients without nephritis (n = 310) as classified by BILAG score, and matched controls (n = 322). In addition, cerebrospinal fluid (CSF) samples from 31 patients, previously analyzed with ELISA, were also analyzed with the MBSI to test the behavior of this new assay in the lower detection range. Results: We found a strong correlation between the new MBSI, RIE, and ELISA, but not with nephelometry. The MBSI demonstrated lower levels of C1q in SLE patients than in matched controls (p < 0.0001), and patients with nephritis had lower levels than patients without nephritis (p < 0.01). Similarily, RIE showed significant differences between the patient groups (p < 0.0001). An association was also found between the levels of C1q and the SLE disease activity index (SLEDAI). Furthermore, there was good correlation between the values obtained by MBSI and ELISA, in both serum (r = 0.960) and CSF (r = 0.786), underscoring the ability of both techniques to measure low concentrations of C1q with high accuracy. Conclusion: The sandwich immunoassay correlated well with RIE, but soluble immune precipitation techniques, such as nephelometry, did not appear suitable alternatives, since C1q itself, and possibly anti-C1q antibodies, interfered with the measurements. The new sandwich immunoassay is therefore a good replacement for RIE in monitoring SLE disease activity.
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33.
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34.
  • Schön Persson, Sophie, et al. (författare)
  • Resources for work-related well-being : A qualitative study about healthcare employees' experiences of relationships at work
  • 2018
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 27:23-24, s. 4302-4310
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims and objectives: To explore municipal healthcare employees' experiences of relationships with care recipients and colleagues. The specific research questions were when do the relationships enhance well-being, and what prerequisites are needed for such relationships to occur? Background: Employees in health and social care for older people often depict their work in negative terms, and they often take a high number of sick leaves. Despite the heavy workload, other employees express well-being at work and highlight social relationships as one reason for this. However, a greater understanding of how these relationships can act as resources for workplace well-being is needed. Design: The design of the study was qualitative and exploratory. Methods: Qualitative interview studies were conducted with 23 healthcare employees in municipal health care. Thematic analysis was used to analyse the data. Results: Two themes were identified as resources for promoting relationships between employees and care recipients or colleagues: (a) Being personal-a close interpersonal relationship to a care recipient-and (b) Colleague belongingness-a sense of togetherness within the working group. Spending quality time together, providing long-term care and providing additional care were prerequisites for a close interpersonal relationship with care recipients. Trust, mutual responsibility and cooperation were prerequisites for a sense of togetherness within the working group. Conclusions: The findings provide an empirical base to raise awareness of relationships with care recipients and colleagues as health aspects. Relationships among employees in health care are vital resources that must be considered to create sustainable workplaces and consequently improve the quality of care. Relevance to clinical practice: The results of this study advocate health promotion efforts based on interpersonal relationships at the workplace. Dialogues in the working groups, based on the employees' experiences of positive daily situations, may be a promoting method for the work-related well-being of the employees.
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35.
  • Skyvell Nilsson, Maria, 1961-, et al. (författare)
  • Attitudes Emphasizing in the Clinical Supervision of Medical Students : An Ethnographic Study in Sweden
  • 2012
  • Ingår i: The Open Medical Education Journal. - 1876-519X. ; 5, s. 5-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Medical student's professional attitudes are expected to be developed in medical school, and particularly during clinical education. In this study we focus on supervision in order to describe the attitudes emphasized in the clinical education of fourth-year medical students taking a surgical course.Methods: An ethnographic approach was applied where observation and interviews were conducted. Nine medical students and twelve supervisors at a teaching hospital in Sweden participated. Field notes were made during observation as well as interviews; these were transcribed and analysed qualitatively.Result: The analysis resulted in six topic areas describing the attitudes emphasized. The medical students were expected to be: 1) Informed and effective decision makers, 2) Sensitive to patients' needs and expectations, 3) Communicative, 4) Authoritative and patriarchal, 5) Adaptable to organizational demands, and 6) Mindful of nurse's knowledge and requests.Conclusions: This study reveals that the attitudes emphasised during supervision are: dualistic and complex to learn, developed by a former generation and influence student learning. Students need support in order to handle the state of tension that exists in the attitudes emphasized. Medical students might experience difficulties in adopting some attitudes belonging to a former generation. There is a need for competence development among supervisors concerning how students may experience the attitudes emphasized in supervision.
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36.
  • Svenugnsson, Elisabet, et al. (författare)
  • Decreased levels of autoantibodies against apolipoprotein B-100 antigens are associated with cardiovascular disease in systemic lupus erythematosus.
  • 2015
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 181:3, s. 417-426
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased production of autoantibodies is a characteristic feature of systemic lupus erythematosus (SLE) and there is evidence that several of these autoantibodies may contribute to the increased cardiovascular disease (CVD) in SLE. Autoantibodies against the apolipoprotein (apo) B-100 peptides p45 and p210 have been associated with a lower CVD risk in non-SLE cohorts. The aim of the present study was to investigate how SLE affects the occurrence of these potentially protective autoantibodies. The study cohort consisted of 434 SLE patients and 322 age and sex-matched population controls. Antibodies against native and malondialdehyde (MDA)-modified p45 and p210 were measured by ELISA. SLE patients had significantly lower levels of p210 IgG and p45 IgM (both the native and MDA-modified forms). SLE patients with manifest CVD (myocardial infarction, ischemic cerebrovascular disease or peripheral vascular disease) had lower levels p210 IgG and p45 IgM than SLE patients without CVD. Decreased levels of these autoantibodies were also observed in SLE patients with permanent organ damage as assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI). The present findings show that patients with SLE, a condition generally characterized by abundance of autoantibodies of multiple specificities, have reduced levels of antibodies against the apo B-100 antigens p45 and p210 and that the levels of these antibodies are further reduced in SLE patients with CVD. These observations suggest the possibility that an impaired antibody-mediated removal of damaged LDL particles may contribute to the development of vascular complications and organ damage in SLE. This article is protected by copyright. All rights reserved.
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37.
  • Végvári, Ákos, et al. (författare)
  • Essential tactics of tissue preparation and matrix nano-spotting for successful compound imaging mass spectrometry
  • 2010
  • Ingår i: Journal of Proteomics. - : Elsevier BV. - 1876-7737 .- 1874-3919. ; 73:6, s. 1270-1278
  • Tidskriftsartikel (refereegranskat)abstract
    • The ultimate goal of MALDI-Imaging Mass Spectrometry (MALDI-IMS) is to achieve spatial localization of analytes in tissue sections down to individual tissue compartments or even at the level of a few cells. With compound tissue imaging, it is possible to track the transportation of an unlabelled, inhaled reference compound within lung tissue, through the application of MALDI-IMS. The procedure for isolation and preparation of lung tissues is found to be crucial in order to preserve the anatomy and structure of the pulmonary compartments. To avoid delocalization of analytes within lung tissue compartments we have applied an in-house designed nano-spotter, based on a microdispenser mounted on an XY table, of which movement and spotting functionality were fully computer controlled. We demonstrate the usefulness of this platform in lung tissue sections isolated from rodent in vivo model, applied to compound tissue imaging as exemplified with the determination of the spatial distribution of (1 alpha,2 beta,4 beta,7 beta)-7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatric yclo[3.3.1.0(2,4)]nonane, also known as tiotropium. We provide details on tissue preparation protocols and sample spotting technology for successful identification of drug in mouse lung tissue by using MALDI-Orbitrap instrumentation.
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38.
  • Wigren, Maria, et al. (författare)
  • Cardiovascular disease in systemic lupus erythematosus is associated with increased levels of biomarkers reflecting receptor-activated apoptosis
  • 2018
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 270, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue degradation and repair, associate with cardiovascular disease (CVD) in subjects with systemic lupus erythematosus (SLE). Methods: We investigated 484 well-characterized SLE patients, 69 of whom had CVD (coronary artery disease, cerebrovascular disease or peripheral artery disease), and 253 controls. Occurrence of carotid plaques was investigated with ultrasound. Plasma levels of biomarkers reflecting apoptosis (Fas, TNF receptor 1, TRAIL receptor 2), inflammation (IL-6, IL-8, monocyte chemotactic protein-1), tissue degradation (matrix metalloproteinase (MMP)-1, MMP-3, MMP-7), and tissue repair (platelet-derived growth factor, epidermal growth factor and stem cell factor) were analyzed by Proximity Extension Assay. Results: Subjects with SLE had markedly elevated plasma levels of biomarkers reflecting apoptosis, inflammation and tissue degradation as compared to controls. SLE patients with CVD had higher levels of Fas, TNF receptor 1, TRAIL receptor 2, MMP-1 and -7 than those without CVD. The same associations were found for the presence of a carotid plaque. When controlling for the factors included in the Framingham risk score, all biomarkers except MMP-1 remained associated with the presence of a carotid plaque, while only TRAIL receptor 2 levels remained significantly associated with CVD. Conclusions: Our findings argue that the cardiovascular risk in SLE is associated with increased cell death by apoptosis and tissue degradation.
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41.
  • Aad, G., et al. (författare)
  • Commissioning of the ATLAS Muon Spectrometer with cosmic rays
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
  • Tidskriftsartikel (refereegranskat)abstract
    • The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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