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2.
  • Ahuja, Sat pal, et al. (författare)
  • Glutathione S-transferase µ(GST) modifies activities of proteases and levels of cystatin C secreted by mouse retinal explants
  • 2004
  • Ingår i: Investigative Ophthalmology & Visual Science. - 1552-5783. ; 45, s. 352-352
  • Konferensbidrag (refereegranskat)abstract
    • Purpose: In one form of human autosomal recessive retinitis pigmentosa and in retinal degeneration (rd1) mouse, mutation occurs in the genes encoding ß subunit of rod photoreceptor cGMP phosphodiesterase. Therefore, rd1 mutant mouse is an appropriate model for human inherited retinal degeneration studies. Retinal explants are successfully cultured in serum free chemically defined R16 medium to evaluate effects of various rescue factors and retinal conditioned medium (RCM) for secreted molecules like proteases and their inhibitors. Cysteine protease inhibitor cystatin C has recently been identified in rodent neuroretina and RPE. RCM of explants treated with GST were analyzed for proteases and cystatin C to explain, in part, mode of action of GST in protection of degenerating retina. Methods: Postnatal day 2 (PN2) and PN7 control (wt) and rd1 were cultured with (10 ng / ml GST) and without GST in R16 medium, respectively, for 26 and 21 days in vitro (div). Retinal extracts (RE) and RCM were analyzed by fluorometry using casein green fluorescent labeled with BODIPY–FL (Molecular Probes) for total proteases; Z–Phe–Arg–NMec or Z–Arg–Arg–NMec for cysteine proteases and by ELISA for cystatin C, respectively, for levels and secretion of proteases and cystatin C. The protein content of RE was measured. Results: Protein content (µg) of RE from wt and rd1 retinal extracts respectively increased and decreased with age. Cystatin C (ng/ml RCM) content in wt and rd1 RE increased with age (was always higher in wt) up to PN14 and then decreased but was higher than that at PN2. Progressive secretion of cystatin C by PN2 explants was lower than that by PN7 explants; and that by rd1 PN2 and PN7 explants was initially lower up to in vitro age of PN19 and subsequently it was higher than that by wt explants. Secretion of total cystatin C by PN2 and PN7 wt and rd1 explants was similar and was increased by GST. During initial stage of culture total protease activity ({Delta} F / 100 µl RCM) in RCM of rd1 PN2 and PN7 explants was higher and was decreased in GST treated explants. Conclusions: Cystatin C content and secretion by wt RE is always higher and that of proteases is lower than that of rd1. Treatment with GST increases content of cystatin C and consequently decreases that of proteases especially cysteine proteases.
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3.
  • André, Malin, et al. (författare)
  • More physician consultations and antibiotic prescriptions in families with high concern about infectious illness-adequate response to infection-prone child or self-fulfilling prophecy?
  • 2007
  • Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 24:4, s. 302-307
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Respiratory tract infections (RTI) in children is the most common cause of prescription of antibiotics. It is important to describe and analyse non-medical factors in order to develop more rational use of antibiotics. Objectives. To compare families with high and low concern about infectious illness with regard to social variables, perception of infection proneness and beliefs in antibiotics and to relate the concern for infectious illness to reported morbidity, physician consultations and antibiotic prescriptions for the 18-month-old child in the family. Methods. A prospective, population-based survey was performed. During 1 month, all infectious symptoms, physician consultations and antibiotic treatments for 18-month-old children were noted. The 818 families also answered questions about their socio-economic situation, illness perception and concern about infectious illness. Results. High concern about infectious illness was associated with more frequent physicians consultations and more prescriptions of antibiotics. There was no significant difference in reported days with symptoms of RTI, but the parents more often experienced their children with RTI without fever as being ill. The variables of infection proneness in the child, inadequate beliefs in antibiotics and the factor of being the only child were important explanatory factors for concern about infectious illness. Conclusions. High concern about infectious illness is an important determining factor for physician consultations and antibiotic prescription for small children. An adequate consultation, where the doctor deals with the parents' worries and gives appropriate information about symptoms and disease, might contribute to less antibiotic prescribing with preserved parental satisfaction.
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6.
  • Bengtsson, Eva, et al. (författare)
  • Lack of the Cysteine-Protease Inhibitor Cystatin C Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.
  • 2005
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:10, s. 2151-2156
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective - Degradation of extracellular matrix plays an important role in growth and destabilization of atherosclerotic plaques. Cystatin C, inhibitor of the collagen- and elastin-degrading cysteine proteases of the cathepsin family, is produced by virtually all cell types. It is present in the normal artery wall but severely reduced in human atherosclerotic lesions. Methods and Results - To determine the functional role of cystatin C in atherosclerosis, we crossed cystatin C - deficient ( cysC(-/-)) mice with apolipoprotein E - deficient ( apoE(-/-)) mice. After 25 weeks of atherogenic diet, mice lacking apoE and cystatin C (cysC(-/-) apoE(-/-)) had larger subvalvular plaques compared with cysC(+/+) apoE(-/-) mice (766 000 +/- 20 000 mu m(2) per section versus 662 000 +/- 19 000 mu m(2) per section; P = 0.001), suggesting an atheroprotective role of cystatin C. The plaques from cysC(-/-) apoE(-/-) mice were characterized by increased total macrophage content. To determine which cellular source is important for the antiatherosclerotic effect of cystatin C, we performed bone marrow transplantations. ApoE(-/-) mice were transplanted with either cysC(-/-) apoE(+/+) or cysC(+/+) apoE(-/-) bone marrow. No significant differences in plaque area, macrophage, collagen, or lipid content of subvalvular lesions between the 2 groups were detected. Conclusions - The result suggests that the protective role of cystatin C in atherosclerosis is dependent primarily on its expression in nonhematopoietic cell types.
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7.
  • Bjork, Ingemar, et al. (författare)
  • The importance of the second hairpin loop of cystatin C for proteinase binding. Characterization of the interaction of Trp-106 variants of the inhibitor with cysteine proteinases
  • 1996
  • Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 35:33, s. 10720-10726
  • Tidskriftsartikel (refereegranskat)abstract
    • The single Trp of human cystatin C, Trp-106, is located in the second hairpin loop of the proteinase binding surface. Substitution of this residue by Gly markedly altered the spectroscopic changes accompanying papain binding and reduced the affinity for papain, actinidin, and cathepsins B and H by 300-900-fold. The decrease in affinity indicated that the side chain of Trp-106 contributes a similar free energy, -14 to -17 kJ·mol-1, to the binding to all four cysteine proteinases, corresponding to about 20-30% of the total binding energy. Replacement of Trp-106 by Phe led to a smaller (30-120-fold) decrease in affinity for the four enzymes than Gly substitution. The binding energy of the Phe residue corresponded to 20-45% of that of Trp, showing that a phenyl group can only partly substitute for the indole ring. The reduced affinities of the cystatin C Trp-106 variants for all proteinases studied were due almost exclusively to increased dissociation rate constants. The second hairpin loop thus contributes to the binding primarily by keeping cystatin C anchored to the proteinase once the complex has been formed. This role is partly in contrast to that of the N-terminal region, which increases the affinity of cystatin C for cathepsin B by increasing the association rate constant. Removal of the N-terminal region of the Trp-106Gly variant by proteolytic cleavage substantially weakened the binding to papain and cathepsin B. The resulting affinity indicated that the first hairpin loop (the "QVVAG-region"), which is the only region of the proteinase binding surface remaining intact in the truncated variant, contributes 40-60% of the total free energy of binding of cystatin C to both proteinases.
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8.
  • Brynjólfsson, Siggeir Fannar, et al. (författare)
  • An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD.
  • 2016
  • Ingår i: Inflammatory bowel diseases. - 1536-4844. ; 22:8, s. 1803-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potent amplifier of inflammation. Recently, the antimicrobial peptide PGLYRP-1 was shown to be the ligand of TREM-1. Here, the ability of an anti-TREM-1 antibody to dampen the release of proinflammatory cytokines by colon lamina propria cells (LPCs) from patients with IBD was investigated and correlated with PGLYRP-1 levels.Biopsies from patients with ulcerative colitis (UC, n = 45) or Crohn's disease (CD, n = 26) were compared with those from individuals undergoing colonoscopy for other reasons (n = 17). TREM-1 expression was analyzed on myeloid cells by flow cytometry. Cell culture experiments with LPCs were used to analyze PGLYRP-1 and inflammatory cytokine levels and assess the effect of anti-TREM-1 on cytokine secretion.The frequency of TREM-1-expressing neutrophils and recruited macrophages was higher in inflamed than in noninflamed biopsies. The PGLYRP-1 level in inflamed tissue was higher than in noninflamed tissue; it was produced primarily by neutrophils, and its level correlated with the secretion of proinflammatory cytokines. Secretion of myeloperoxidase, tumor necrosis factor-α, interleukin-1β, and interleukin-8 by LPCs stimulated with the potent TREM-1 agonist consisting of PGLYRP-1 complexed with peptidoglycan was reduced in the presence of anti-TREM-1. Moreover, a blocking effect of anti-TREM-1 was apparent when LPCs from a subset of inflamed individuals with elevated PGLYRP-1 were stimulated with killed bacteria.An anti-TREM-1 antibody can dampen secretion of proinflammatory cytokines in inflamed patients with elevated PGLYRP-1. Moreover, PGLYRP-1 + myeloperoxidase is a potential biomarker for predicting the effect of anti-TREM-1 therapy.
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9.
  • Bäcklund, A., et al. (författare)
  • Cystatin C influences the autoimmune but not inflammatory response to cartilage type II collagen leading to chronic arthritis development
  • 2011
  • Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Collagen-induced arthritis (CIA) is a mouse model for rheumatoid arthritis (RA) and is induced after immunization with type II collagen (CII). CIA, like RA, is an autoimmune disease leading to destruction of cartilage and joints, and both the priming and inflammatory phases have been suggested to be dependent on proteases. In particular, the cysteine proteases have been proposed to be detrimental to the arthritic process and even immunomodulatory. A natural inhibitor of cysteine proteases is cystatin C. METHODS: Cystatin C-deficient, sufficient and heterozygous mice were tested for onset, incidence and severity of CIA. The effect of cystatin C-deficiency was further dissected by testing the inflammatory effector phase of CIA; that is, collagen antibody-induced arthritis model and priming phase, that is, T cell response both in vivo and in vitro. In addition, in order to determine the importance of T cells and antigen-presenting cells (APCs), these cell populations were separated and in vitro T cell responses determined in a mixed co-culture system. Finally, flow cytometry was used in order to further characterize cell populations in cystatin C-deficient mice. RESULTS: Here, we show that mice lacking cystatin C, develop arthritis at a higher incidence and an earlier onset than wild-type controls. Interestingly, when the inflammatory phase of CIA was examined independently from immune priming then cystatin C-deficiency did not enhance the arthritis profile. However, in line with the enhanced CIA, there was an increased T cell and B cell response as delayed-type hypersensitivity reaction and anti-CII antibody titers were elevated in the cystatin C-deficient mice after immunization. In addition, the ex vivo naive APCs from cystatin C-deficient mice had a greater capacity to stimulate T cells. Interestingly, dendritic cells had a more activated phenotype in naive cystatin C-deficient mice. CONCLUSIONS: The lack of cystatin C enhances CIA and primarily affects in vivo priming of the immune system. Although the mechanism of this is still unknown, we show evidence for a more activated APC compartment, which would elevate the autoimmune response towards CII, thus resulting in an enhanced development of chronic arthritis.
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10.
  • Conti, David, V, et al. (författare)
  • Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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11.
  • deWeert, Michael J., et al. (författare)
  • Analysis of spatial variability in hyperspectral imagery of the uterine cervix in vivo
  • 2003
  • Ingår i: Proceedings of SPIE. - : SPIE. ; 4959, s. 67-76
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of fluorescence and reflectance spectroscopy in the analysis of cervical histopathology is a growing field of research. The majority of this research is performed with point-like probes. Typically, clinicians select probe sites visually, collecting a handful of spectral samples. An exception to this methodology is the Hyperspectral Diagnostic Imaging (HSDI®) instrument developed by Science and Technology International. This non-invasive device collects contiguous hyperspectral images across the entire cervical portio. The high spatial and spectral resolution of the HSDI instruments make them uniquely well suited for addressing the issues of coupled spatial and spectral variability of tissues in vivo. Analysis of HSDI data indicates that tissue spectra vary from point to point, even within histopathologically homogeneous regions. This spectral variability exhibits both random and patterned components, implying that point monitoring may be susceptible to significant sources of noise and clutter inherent in the tissue. We have analyzed HSDI images from clinical CIN (cervical intraepithelial neoplasia) patients to quantify the spatial variability of fluorescence and reflectance spectra. This analysis shows the spatial structure of images to be fractal in nature, in both intensity and spectrum. These fractal tissue textures will limit the performance of any point-monitoring technology.
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12.
  • El-Sukkari, D, et al. (författare)
  • The protease inhibitor cystatin C is differentially expressed among dendritic cell populations, but does not control antigen presentation
  • 2003
  • Ingår i: Journal of Immunology. - 1550-6606. ; 171:10, s. 5003-5011
  • Tidskriftsartikel (refereegranskat)abstract
    • Dendritic cells (DC) undergo complex developmental changes during maturation. The MHC class H (MHC H) molecules of immature DC accumulate in intracellular compartments, but are expressed at high levels on the plasma membrane upon DC maturation. It has been proposed that the cysteine protease inhibitor cystatin C (CyC) plays a pivotal role in the control of this process by regulating the activity of cathepsin S, a protease involved in removal of the MHC H chaperone E, and hence in the formation of MHC H-peptide complexes. We show that CyC is differentially expressed by mouse DC populations. CD8(+) DC, but not CD4(+) or CD4(-)CD8(-) DC, synthesize CyC, which accumulates in MHC II(+)Lamp(+) compartments. However, II processing and MHC H peptide loading proceeded similarly in all three DC populations. We then analyzed MHC H localization and Ag presentation in CD8(+) DC, bone marrow-derived DC, and spleen-derived DC lines, from CyC-deficient mice. The absence of CyC did not affect the expression, the subcellular distribution, or the formation of peptide-loaded MHC II complexes in any of these DC types, nor the efficiency of presentation of exogenous Ags. Therefore, CyC is neither necessary nor sufficient to control MHC II expression and Ag presentation in DC. Our results also show that CyC expression can differ markedly between closely related cell types, suggesting the existence of hitherto unrecognized mechanisms of control of CyC expression.
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13.
  • Gren, Susanne T, et al. (författare)
  • A Single-Cell Gene-Expression Profile Reveals Inter-Cellular Heterogeneity within Human Monocyte Subsets.
  • 2015
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Human monocytes are a heterogeneous cell population classified into three different subsets: Classical CD14++CD16-, intermediate CD14++CD16+, and non-classical CD14+CD16++ monocytes. These subsets are distinguished by their differential expression of CD14 and CD16, and unique gene expression profile. So far, the variation in inter-cellular gene expression within the monocyte subsets is largely unknown. In this study, the cellular variation within each human monocyte subset from a single healthy donor was described by using a novel single-cell PCR gene-expression analysis tool. We investigated 86 different genes mainly encoding cell surface markers, and proteins involved in immune regulation. Within the three human monocyte subsets, our descriptive findings show multimodal expression of key immune response genes, such as CD40, NFⱪB1, RELA, TLR4, TLR8 and TLR9. Furthermore, we discovered one subgroup of cells within the classical monocytes, which showed alterations of 22 genes e.g. IRF8, CD40, CSF1R, NFⱪB1, RELA and TNF. Additionally one subgroup within the intermediate and non-classical monocytes also displayed distinct gene signatures by altered expression of 8 and 6 genes, respectively. Hence the three monocyte subsets can be further subdivided according to activation status and differentiation, independently of the traditional classification based on cell surface markers. Demonstrating the use and the ability to discover cell heterogeneity within defined populations of human monocytes is of great importance, and can be useful in unravelling inter-cellular variation in leukocyte populations, identifying subpopulations involved in disease pathogenesis and help tailor new therapies.
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14.
  • Gunnarsson, A. Birgitta, et al. (författare)
  • Arbetsterapi för personer med depression och ångest : En randomiserad kontrollerad studie av Tree Theme Method®
  • 2015
  • Konferensbidrag (refereegranskat)abstract
    • Tema: InterventionStadier i livet: VuxnaProjekttyp: ForskningsarbeteBakgrund: Vid depression och ångest försvåras förmåga att klara vardagens aktiviteter liksom att relatera till andra. Svårigheterna bidrar till höga sjukskrivningstal. Tree Theme Method® (TTM) är en arbetsterapeutisk metod som syftar till ökad förmåga att utveckla strategier och struktur i vardagens aktiviteter. TTM består av 5 sessioner och innebär att måla och berätta sin livsberättelse med fokus på vardagslivets aktiviteter samt skapa en bild av framtida mål. Fokus i tidigare studier avseende TTM har varit processutvärdering. Nu är det viktigt att utvärdera eventuella effekter av interventionen. I den här studien prövas TTM mot kontroll. Kontrollgruppen får annan arbetsterapeutisk behandling, dvs 5 sessioner om vardagens aktiviteter och psykiskt välmående i den aktuella situationen. Hypotesen är att interventionsgruppen får högre grad av struktur i vardagens aktiviteter och förbättrad psykisk hälsa jämfört med kontrollgruppen.Syfte: Undersöka effekter av TTM jämfört med kontrollgrupp avseende aktivitet, psykiska symtom och självskattad hälsa.Metod: Randomiserad multicenterstudie i primärvård och vuxenpsykiatri. Totalt 130 patienter inkluderas. Inklusion är fastställd depression och/eller ångest, 18-65 år samt aktivitetsproblem. Patienter lottas till TTM alternativt annan arbetsterapeutisk behandling. Deltagarna besvarar självskattningsformulär avseende vardagens aktiviteter, psykiska symtom samt självskattad hälsa. Detta sker före och direkt efter behandling samt 3 och 12 månader efter avslutad behandling. Icke-parametrisk statistisk analys kommer att användas.Resultat/preliminärt resultat: Hittills har 55 patienter inkluderats. I nuläget finns inga preliminära resultat. Presentation av baslinjemätningar sker vid arbetsterapiforum.Slutsats: Det är betydelsefullt att kunna erbjuda patienter med depression och ångest olika behandlingsmetoder. Den här studien kan bidra till högre grad av evidens för arbetsterapeutisk behandling.
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15.
  • Gunnarsson, Anna Birgitta, et al. (författare)
  • Occupational performance problems in people with depression and anxiety
  • 2023
  • Ingår i: Scandinavian Journal of Occupational Therapy. - : Informa UK Limited. - 1103-8128 .- 1651-2014. ; 30:2, s. 148-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Depression and anxiety often reduce people's ability to cope with everyday occupations. There is a lack of knowledge about such problems in people of working age with depression and anxiety. Aim To describe which problems people with depression or anxiety disorders experience when performing everyday occupations and which occupations are affected. Materials and methods Data based on the Canadian Occupational Performance Measure was used in this cross-sectional study. A total of 118 participants aged 18-65 years, with depression or anxiety, were recruited from primary healthcare and general mental healthcare services. The data were analysed with descriptive statistics and directed content analysis. Results The participants rated a low level of occupational performance, and their satisfaction with performance even lower. They described a great number of problems with their everyday occupations. The most frequent problem areas concerned household management, socialization and personal care. Detailed descriptions of which type of problem they experienced during everyday occupations are included. Conclusions This study provides knowledge of which problems people with depression and anxiety disorders experience in everyday occupations within self-care, productivity, as well as leisure. Furthermore, they rate performance and satisfaction with performance of the five occupations they find the most important to change in everyday life.
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16.
  • Gunnarsson, A Birgitta, 1958, et al. (författare)
  • Outcomes of the Tree Theme Method versus regular occupational therapy: A longitudinal follow-up
  • 2022
  • Ingår i: Australian Occupational Therapy Journal. - : Wiley. - 0045-0766 .- 1440-1630.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Depression and anxiety disorders affect individuals' everyday lives, and treatments that can help them to perform everyday occupations are needed. Occupational therapy for this group has been evaluated from a short-term perspective but not from a long-term perspective; further research is thus warranted. The aim of the study was to investigate the longitudinal outcomes of the Tree Theme Method (TTM) compared with care as usual, provided by occupational therapists, in terms of everyday occupations, psychological symptoms, and health-related aspects. Methods This randomised controlled trial comprised a follow-up 3 and 12 months after an intervention. A total of 118 participants (19-64 years) with depression or anxiety disorders and problems with everyday occupations completed the base line questionnaires, 100 completed the follow-up at 3 months, and 84 completed the follow-up at 12 months. Imputations of missing data were performed using the last observation, and parametric analysis was used. Results Both groups showed significant improvements (P value <= 0.01) in everyday occupations, psychological symptoms and health-related aspects after 3 and 12 months. No significant differences were found between the groups. Conclusion This study contributes with knowledge about the outcomes of occupational therapy for clients living with depression and anxiety disorders. Both TTM and care as usual lead to significant improvements over time concerning everyday occupations, psychological symptoms, and health-related aspects. The fact that both occupational therapy methods were associated with improvements for clients with depression and anxiety supports client-centredness in enabling an occupational therapist to choose the method best suited for the individual.
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18.
  • Gunnarsson, Birgitta, 1958-, et al. (författare)
  • Effectiveness of the Tree Theme Method® (TTM) versus regular occupational therapy : a longitudinal follow-up
  • 2021
  • Konferensbidrag (refereegranskat)abstract
    • Background: There is need for interventions for people with depression and anxiety, not only focusing on psychological symptoms, but also how to cope with everyday life. The TTM involves that individuals during five sessions, paint and tell their life story. The focus is on everyday occupations, and finally, they create a picture of their future goals. In this study, the TTM was compared to regular occupational therapy.Objective: The aim of this study was to evaluate the TTM compared to regular occupational therapy regarding everyday occupations, psychological symptoms and health in people with depression and/or anxiety disorders.Methods: 118 clients, 18-65 years, diagnosed with depression or anxiety in primary care and mental health care were randomized to the TTM or regular occupational therapy. Before and after treatment as well as 3 and 12 months afterwards they answered self-assessment questionnaires. Parametric statistical analysis was used.Results: There were continued positive significant outcomes of everyday occupations, psychological symptoms and health shown in both groups; 3 months as well as 12 months after completed treatment. No significant differences were found between the groups.Conclusions: The TTM can contribute to an increased number of interventions for people suffering from depression and anxiety.
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19.
  • Gunnarsson, Birgitta, 1958-, et al. (författare)
  • Treatment of depression and/or anxiety - outcomes of a randomised controlled trial of the tree theme method® versus regular occupational therapy
  • 2018
  • Ingår i: BMC psychology. - : Springer Science and Business Media LLC. - 2050-7283. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Depression and anxiety disorders are a major concern in western countries, and because these often have a negative affect on everyday life interventions based on activities in everyday life are needed. The Tree Theme Method® (TTM) is a client-centred occupational therapy intervention designed to increase the ability to cope with, and to enhance satisfaction with, everyday life, both at home and at work. The aim of this study was to compare the short term outcomes of the TTM intervention with regular occupational therapy treatment for people with depression and/or anxiety disorders. Methods: This randomised controlled trial included patients from three counties in Sweden. Men and women with depression and/or anxiety disorders, ages 18 to 65, were randomised to either TTM or regular occupational therapy. Assessment data were collected at baseline and the follow-up directly after completing the intervention. Non-parametric and parametric statistical methods were used. Results: The questionnaires were answered by 118 patients at baseline and by 107 patients after completing the intervention. No significant differences in short term outcomes were found between the groups. Both groups showed positive significant outcomes regarding almost all aspects of activities in everyday life, psychological symptoms, and health-related and intervention-related aspects. Conclusions: Despite the lack of differences between the groups, the positive outcomes regarding activities in everyday life, psychological symptoms, and health-related aspects after completing the intervention indicates the need for further research on the long-term perspective of TTM compared to regular occupational therapy.
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22.
  • Hall, Anders, et al. (författare)
  • Structural basis for the biological specificity of cystatin C. Identification of leucine 9 in the N-terminal binding region as a selectivity-conferring residue in the inhibition of mammalian cysteine peptidases
  • 1995
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 270:10, s. 5115-5121
  • Tidskriftsartikel (refereegranskat)abstract
    • The structural basis for the biological specificity of human cystatin C has been investigated. Cystatin C and other inhibitors belonging to family 2 of the cystatin superfamily interact reversibly with target peptidases, seemingly by independent affinity contributions from a wedge-shaped binding region built from two loop-forming inhibitor segments and a binding region corresponding to the N-terminal segment of the inhibitor. Human cystatin C variants with Gly substitutions for residues Arg-8, Leu-9, and/or Val-10 of the N-terminal binding region, and/or the evolutionarily conserved Trp-106 in the wedge-shaped binding region, were produced by site-directed mutagenesis and Escherichia coli expression. A total of 10 variants were isolated, structurally verified, and compared to wild-type cystatin C with respect to inhibition of the mammalian cysteine peptidases, cathepsins B, H, L, and S. Varying contributions from the N-terminal binding region and the wedge-shaped binding region to cystatin C affinity for the four target peptidases were observed. Interactions from the side chains of residues in the N-terminal binding region and Trp-106 are jointly responsible for the major part of cystatin C affinity for cathepsin L and are also of considerable importance for cathepsin B and H affinity. In contrast, for cathepsin S inhibition these interactions are of lesser significance, as reflected by a Ki value of 10(-8) M for the cystatin C variant devoid of Arg-8, Leu-9, Val-10, and Trp-106 side chains. The side chain of Val-10 is responsible for most of the affinity contribution from the N-terminal binding region, for all four enzymes. The contribution of the Arg-8 side chain is minor, but significant for cystatin C interaction with cathepsin B. The Leu-9 side chain confers selectivity to the inhibition of the target peptidases; it contributes to cathepsin B and L affinity by factors of 200 and 50, respectively, to cathepsin S binding by a factor of 5 only, and results in a 10-fold decreased affinity between cystatin C and cathepsin H.
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23.
  • Hedin, Katarina, et al. (författare)
  • A population-based study of different antibiotic prescribing in different areas
  • 2006
  • Ingår i: British Journal of General Practice. - London, UK : Royal College of General Practitioners. - 0960-1643 .- 1478-5242. ; 56:530, s. 680-685
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Respiratory tract infections are the most common reason for antibiotic prescription in Sweden as in other countries. The prescription rates vary markedly in different countries, counties and municipalities. The reasons for these variations in prescription rate are not obvious. Aim: To find possible explanations for different antibiotic prescription rates in children. Design of study Prospective population based study. Setting All child health clinics in four municipalities in Sweden which, according to official statistics, had high antibiotic prescription rates, and all child health clinics in three municipalities which had low antibiotic prescription rates. Method: During one month, parents recorded all infectious symptoms, physician consultations and antibiotic treatments, from 848 18-month-old children in a log book. The parents also answered a questionnaire about socioeconomic factors and concern about infectious diseases. Results: Antibiotics were prescribed to 11.6% of the children in the high prescription area and 4.7% in the low prescription area during the study month (crude odds ratio [OR] = 2.67; 95% confidence interval [CI] = 1.45 to 4.93). After multiple logistic regression analyses taking account of socioeconomic factors, concern about infectious illness, number of symptom days and physician consultations, differences in antibiotic prescription rates remained (adjusted OR = 2.61; 95% CI = 1.14 to 5.98). The variable that impacted most on antibiotic prescription rates, although it was not relevant to the geographical differences, was a high level of concern about infectious illness in the family. Conclusions: The differences in antibiotic prescription rates could not be explained by socioeconomic factors, concern about infectious illness, number of symptom days and physician consultations. The differences may be attributable to different prescription behaviour.
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24.
  • Hedin, Katarina, et al. (författare)
  • Infection prevention at day-care centres: Feasibility and possible effects of intervention
  • 2006
  • Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 24:1, s. 44-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study the effect of an educationally oriented intervention programme, with the recommendations from the National Board of Health and Welfare as a base. Design. A prospective intervention study. Setting. Six day-care centres in Vaxjo, Sweden. Three centres comprised the intervention group and three constituted the control group. Subjects and main outcome measures. The parents and personnel completed a questionnaire on their views concerning information about infectious diseases. During a nine-month period, parents of all children reported every episode of absence, the number of days absent, the cause of absence, and any contact with doctors or prescription of antibiotics. Results. The guidelines were implementable in routine child day-care. Parents found regular information valuable and felt better informed about infectious diseases. Multilevel analyses showed no statistically significant results of the intervention. "Infection-prone'' children had more sickness absence, doctor's consultations, and antibiotic prescriptions than those not "infection-prone''. Conclusion. It is possible to implement an educationally oriented intervention programme directed against infectious diseases in child day-care. No significant effect of the intervention was found, which is why a larger intervention study is needed.
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25.
  • Hedin, Katarina, et al. (författare)
  • Infectious morbidity in 18-month-old children with and without older siblings
  • 2010
  • Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 27:5, s. 507-512
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Infections are the most commonly reported health problems in children. Younger age and day care outside the home are two factors of importance for infectious morbidity. The influence of siblings on infectious symptoms is not clear. OBJECTIVES: To compare families with one child and families with more than one child in terms of reported infectious symptoms, physician consultations and antibiotic prescriptions. METHODS: A prospective population-based survey was performed. During 1 month, all infectious symptoms, physician consultations and antibiotic prescriptions for 18-month-old children were noted by the parents. The 789 families also answered questions about socio-economic factors, numbers of siblings in the family and type of day care. RESULTS: No difference in number of symptom days was found between children with and without older siblings. Neither could we find any significance in terms of having older siblings in relation to physician consultations and antibiotic prescriptions. CONCLUSIONS: The results of our study indicate that having older siblings not was important in relation to number of symptoms days, physician consultations or antibiotic prescriptions for 18-month-old children in Sweden today. Changes in social activities and attitudes towards antibiotic prescription may explain our different findings as compared with previous Swedish studies and studies from other countries.
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26.
  • Hedin, Katarina, et al. (författare)
  • Physician consultation and antibiotic prescription in Swedish infants : population-based comparison of group daycare and home care.
  • 2007
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 96:7, s. 1059-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Daycare infants have more infectious episodes, see a physician more often, and are prescribed antibiotics more often than home care infants. Aim: To compare physician consultations and antibiotic prescription in daycare children and home care children taking number of symptom days, sociodemographic factors, concern about infectious illness and antibiotic knowledge into account. Methods: For a cohort of Swedish 18-month-old children all infectious symptoms, physician consultation and antibiotic prescriptions were registered during 1 month. Results: 561 infants with daycare outside the home and 278 with daycare at home were included. Of the daycare infants, 23.2% saw a physician and 11.4% were prescribed antibiotics, as compared with 10.8% physician consultations and 5.0% antibiotic prescription for the home care infants. For daycare infants the crude odds ratio for physician consultation were 2.49 (1.63–3.82) and for antibiotic prescription 2.43 (1.34–4.41) compared with home care infants. However, these differences were no longer statistically significant when background data, concern about infectious illness and reported symptoms were taken into account. Conclusion: When background data, concern about infectious illness and reported infectious symptoms were taken into account daycare infants saw a physician and was prescribed antibiotics in the same way as home care infants.
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27.
  • Huh, C, et al. (författare)
  • Decreased metastatic spread in mice homozygous for a null allele of the cystatin C protease inhibitor gene
  • 1999
  • Ingår i: Molecular Pathology. - 1366-8714. ; 52:6, s. 332-340
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Increased or altered activities of cysteine proteases have been implicated in serious human disorders such as cancer, rheumatoid arthritis, sepsis, and osteoporosis. To improve the current knowledge of the regulatory role of a major mammalian cysteine protease inhibitor, cystatin C, in such disease processes, a cystatin C deficient mouse was generated and characterized. METHODS: The mouse cystatin C gene was inactivated by insertion of a bacterial neo gene through homologous recombination in 129/Sv embryonic stem cells. Embryonic stem cell clones were injected into C57BL/6J blastocysts followed by injection of the blastocysts into pseudopregnant female mice. F1 offspring with agouti coat colour after mating of chimaeric males with C57BL/6J females were examined by DNA analysis, and mice carrying the targeted mutation were intercrossed to obtain homozygous cystatin C deficient (CysC-/-) mice. To study the role of cysteine proteases and their inhibitors in metastasis, the spread of B16-F10 melanoma cells in CysC-/- and wild-type mice was compared. Analysis of the formation of remote metastases was carried out by intravenous injection of beta-galactosidase transfected B16-F10 cells and subsequent determination of cancer cell colonies in the lungs. RESULTS: Cystatin C deficient mice were fertile and showed no gross pathological abnormality up to 6 months of age. Compared with wild-type mice, seven times fewer large metastatic colonies were counted by means of a dissecting microscope in CysC-/- mice two weeks after tail vein injection of B16-F10 cells. At all of eight time points from 15 minutes to two weeks after intravenous injection of tumour cells, the CysC-/- mice had significantly fewer lung metastases. The observed differences were smaller when beta-galactosidase transfected cells were used to allow counting of small colonies. Subcutaneous and intracerebral tumour growth was not different in the CysC-/- mice. CONCLUSIONS: Cystatin C concentrations in vivo might influence metastasis in some tissues. The decreased metastatic spread of B16-F10 cells in CysC-/- mice is the result of both reduced seeding and reduced growth of tumour cells in their lungs.
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28.
  • Håkansson, Anders, et al. (författare)
  • Forskningstræning for alle læger - også uden for universitetssygehusene
  • 2003
  • Ingår i: Ugeskrift for Læger. - 0041-5782. ; 165:36, s. 3423-3423
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: General practitioners are often interested in doing research but are hampered by lack of time and research training. Interpreting the results of others can also be difficult. For this reason a course in basic research methods for GPs was started in Sweden in 1989. It was originally aimed at GPs but was later extended to hospital physicians as well. The course is given regionally and at present is held in six different locations in southern Sweden as well as in Hillerod, Denmark. The aim of this study is to evaluate the course as part of a research project to recommend changes to the courses in accordance with the course evaluations. MATERIALS AND METHODS: The course consists of theory (lectures/seminars six hours a month) and practice (project work) over a period of 18 months. Questionnaires were mailed to the 112 physicians who, starting in 1997 and 1999, completed the course. Eighty-five percent responded to the questionnaire, which asked if the course goals were relevant and if they thought they had achieved them. RESULTS: The most frequent reasons given for attending the course were a desire to learn how to read scientific articles critically and how to carry out one's own research projects. Two thirds of the participants thought that the theoretical lectures and project work had supplemented each other well. Most of the participants thought that the goals were very relevant but fewer--between 57% and 77%--felt those goals had been achieved. DISCUSSION: The course provides important empirical information with regard to future specialist training in Denmark. The plan is for all physicians to have research training--amounting to a total of 60 days--with lectures in research methodology and tutored research projects. The Danish College of General Practitioners has planned research training in accordance with the experience from these courses.
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29.
  • Håkansson, Cecilia, et al. (författare)
  • Estimating Distributional Effects of Environmental Policy in Swedish Coastal Environments : A Walk along different Socio-economic Dimensions
  • 2016
  • Ingår i: Journal of Environmental Economics and Policy. - : Taylor & Francis. - 2160-6544 .- 2160-6552. ; 5:1, s. 49-78
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper studies distributional effects of environmental policies in Swedish coastal environments, in monetary and environmental quality terms, for different dimensions: income, gender, age, non-users vs. users, distance, familiarity, and origin (if people have a Swedish background or not). The study area is widely used for different recreational activities and has a mix of different visitors. The data come from a choice experiment study. The results indicate that latent class modelling can be used to identify how monetary preferences vary between different groups of respondents, and largely confirm the limited existing knowledge from the previous research on distributional effects of environmental policies. However, the previous literature on distributional effects related to background is very limited, making it hard to draw comparisons. The results in our paper also show that the distributional effects differ depending on the environmental amenity. These results are of policy relevance since coastal environments are important for people's well-being and associated with positive health effects.
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30.
  • Håkansson, Cecilia, et al. (författare)
  • Estimating distributional effects of environmental policy in Swedish coastal environments : A walk along different socio-economic dimensions
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This paper studies distributional effects of environmental policies in Swedish coastal environments, in monetary and environmental quality terms, for different socio-economic groups. The study area is widely used for different recreational activities and has a mix of different visitors. Data comes from a choice experiment study. Some results confirm limited existing knowledge from previous research, although the ethnical dimension to a certain extent contradicts conventional perceptions. Based on previous research from other countries, the hypothesis would be that native Swedes would benefit more from environmental improvements than respondents with a non-Swedish background. Interestingly results differ, depending on the environmental amenity. For example, respondents with a non-Swedish origin benefit more, both in monetary and environmental quality terms, from reduced noise and littering compared to respondents with a Swedish origin. Also, independent of ethnical background, people use the area in a similar manner.
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31.
  • Håkansson, Katarina (författare)
  • Cystatin C functions in vitro and in vivo. Studies on target enzyme inhibition by cystatin C variants and cystatin C deficient mice.
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cystatin C variants with Arg8, Leu9 and/or Val10 replaced by Gly residues were produced by site-directed mutagenesis and E. coli expression. Their interactions with the target proteases, cathepsin B, L, H and S, were studied in vitro in order to provide basic structure-function information of use in the design of specific inhibitors for therapeutic use. Val10 was shown to be the most contributing residue in the N-terminal region in binding of all enzymes. By replacing Leu9 with a Gly residue a more specific inhibitor was obtained. Substitution of Gly for Trp106 in the second hairpin loop of cystatin C demonstrated a general importance of this region in binding to all enzymes. Studies on mouse and rat cystatin C were performed in order to clarify the normal physiological role of cystatin C in vivo. Mouse and rat cystatin C were produced, isolated and characterised. Quantitation of cystatin C demonstrated high overall similarities in distribution patterns in human, mouse and rat tissues and the inhibitory properties of the species variants were also alike. Rat and mouse cystatin C were observed to have slightly higher affinity for cathepsin B than human cystatin C, which could be explained by amino acid substitutions in the N-terminal segment and the first hairpin loop of the enzyme-interacting inhibitor surface. Mouse and rat were concluded to serve as relevant experimental animals for studies of cystatin C. Cystatin C deficient mice were generated. Injected melanoma cells were demonstrated to form fewer metastatic lung colonies in such mice than in wildtype mice. To allow an investigation of the mechanism leading to amyloid fibril formation in patients suffering from hereditary cystatin C amyloid agiopathy (HCCAA), vectors for homologous recombination were constructed to introduce the human wildtype and L68Q-cystatin C genes in the mouse genome. These constructs were functional in embryonic stem cells and should, therefore, be useful for the generation of gene targeted mice strains to accomplish an animal model for detailed studies of HCCAA.
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32.
  • Håkansson, Katarina, et al. (författare)
  • Degradation of acetonitrile through a sequence of microbial processes
  • 2005
  • Ingår i: Water Research. - 0043-1354 .- 1879-2448. ; , s. 648-654-
  • Tidskriftsartikel (refereegranskat)abstract
    • Degradation of nitrogen containing organic compounds often leads to formation of ammonium and low molecular weight organic compounds. The study is focuseed on degradtion of acetonitrile in a sequence of stirred biofilm reactors, where degradation of acetonitrile to acetic acid and ammonia takes place in the first two reactors. A large fraction of the acetic acid is also degraded in these reactors. The subsequent two reactors were introduced in order to take care of the ammonia, while a fifth reactor was a polishing step before the water was released to the recipient. From earlier studies it is known that the rate of acetonitrile degradation is approximately 80 g acetonitrile/(m3 reactor h). This means that the reactors involved in remval of the nitrogen component needs to be far larger than those dealing with degradation of the more complex molecules.
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33.
  • Håkansson, Katarina (författare)
  • Evaluation of MRI as a diagnostic method in biliary tract conditions
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The diagnostic value of modern fast pulse sequences and breath-hold technique was evaluated in a prospective study of patients with suspected biliary diseases. The cost-effectiveness of MRI compared to ultrasound was calculated. Characteristics of acute cholecystitis and cholangitis were evaluated, the appearance of bile in MRCP with reference to its chemical and physical properties was studied, as well as MRI appearance after cholecystectomy with and without postoperative abdominal complications. The sensitivity and specificity to diagnose acute cholecystitis was 88% and 89% for MRI and 65% and 89% for US. The sensitivity of US, MRI and ERCP for correct diagnosis in jaundiced or not jaundiced patients was 53, 93 and 89% and 50, 100, and 70%, respectively. MRI is superior to US giving correct diagnosis in patients with right upper quadrant abdominal pain or to diagnose biliary tract conditions. Screening with US and supplemental MRI in non-diagnostic cases was estimated to cost 80% of the total amount compared to examining with MRI only. Relaxation rates 1/T1 and 1/T2 of gallbladder bile in vitro showed large inter-individual variation but a consistent linear relationship was found. The relaxation rates increased with increasing amounts of substances in the bile. No single chemical parameter showed dominating influence on relaxation rates. Occasionally bile shows very high relaxation rates leading to unsuccessful MRCP. Early MR findings following cholecystectomy consist normally of only subtle changes, mainly in the gallbladder fossa. A postoperative surgical complication is unlikely if MRI fails to show a fluid collection. Acute cholangitis has multiple findings on MRI, biliary ductal dilatation was the most consistent finding and inflammatory changes were observed in 50% of patients. MRI has the potential to confirm the diagnosis acute cholangitis and exclude alternative diagnosis especially in older patients where the clinical symptoms may be vague. MRI is a reliable method providing high quality images performed with a minimum of inconvenience for the patient. In the future the non-invasive MRI will play a greater role as the primary imaging technique to provide maximum clinical utility when the MRI system will be even more easy to manage, faster, more cost-efficient and, compared with CT, MRI has a significant advantage since no ionizing radiation is involved.
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34.
  • Håkansson, Katarina, et al. (författare)
  • Mouse and rat cystatin C: Escherichia coli production, characterization and tissue distribution
  • 1996
  • Ingår i: Comparative Biochemistry and Physiology - Part B: Biochemistry & Molecular Biology. - : Elsevier BV. - 1879-1107 .- 1096-4959. ; 114:3, s. 303-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant mouse (Mus musculus) and rat (Rattus norvegicus) cystatin C were produced by expression in Escherichia coli, isolated and functionally characterized. The mouse and rat inhibitors were both fully active in titrations of papain. Determination of equilibrium constants for dissociation (Ki) for their complexes with the target proteinase, cathepsin B, produced values not largely different from that for human cystatin C (Ki 0.07-0.13 nM). Rabbit antisera against mouse and rat cystatin C were produced and used for improved affinity purification of the recombinant inhibitors. Affinity purified immunoglobulins isolated from the antiserum against mouse cystatin C were used for construction of a sensitive enzyme-linked immunosorbent assay. The assay was used to demonstrate a high degree of immunological cross-reactivity between mouse and rat cystatin C and could be used for cystatin C quantification in mouse and rat tissue homogenates. All tissues analyzed contained cystatin C, with a relative content very similar to that of human tissues. For all species, brain tissue contained the highest cystatin C amounts and liver the lowest, whereas kidney, spleen and muscle tissues were intermediate in content. In the mouse, a notable high cystatin C content in parotid gland tissue was observed. The high degree of similarity in distribution pattern and functional properties for mouse, rat and human cystatin C indicates that a murine model should be relevant for studies of the human disease, hereditary cystatin C amyloid angiopathy.
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35.
  • Håkansson, Katarina, et al. (författare)
  • Process and system integration aspects of biomass torrefaction
  • 2010
  • Ingår i: 18th European Biomass Conference and Exhibition: Proceedings.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The pre-treatment method torrefaction has been shown to significantly improve biomass fuel characteristics such as energy density, moisture content, milling energy, feeding and hydrophobic properties. These improvements establish torrefaction as a key process in facilitating an expanding market for biomass raw materials. Most of the previous work has focused on evaluating and optimizing the torrefaction process alone. However, to fully explore the maximum energy/exergy and cost efficiency of biomass torrefaction, the entire fuel supply chain and site specific systems must be considered; including logistics, scale and integration with other processes. The present work in progress aims to develop a model that incorporates optimization of the biomass supply chain and process integration systems together with the torrefaction process in order to avoid sub-optimization.
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36.
  • Håkansson, Katarina, et al. (författare)
  • Torrefaction and Gasification of Hydrolysis Residue
  • 2008
  • Ingår i: 16th European Biomass Conference and Exhibition: Proceedings.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • When producing ethanol from lignocellulosic material using hydrolysis combined with fermentation, a large amount of residue consisting of mainly lignin is generated. A significant amount of energy is retained in this residue which may be utilised as a measure for the process to become economically viable. One possibility is as fuel in a gasification process for synthesis gas production, improving the fuel yield and the overall plant efficiency. Furthermore, the pre-treatment method torrefaction has been shown to significantly improve biomass fuel characteristics such as energy density, moisture content, feeding and hydrophobic properties, as well as significantly facilitate particle size reduction. Therefore, the process chain from hydrolysis residue to synthesis gas was investigated and demonstrated in the present work through bench-scale experiments in a batch torrefaction reactor and a bubbling fluidised bed gasifier. The results from the torrefaction work confirmed the improved fuel characteristics and the effects of process variables were evaluated by factorial designed experiments. The torrefaction residence time was identified as the most influential variable. The results from reactivity tests and gasification experiments indicate that hydrolysis residue and corresponding torrefied residue are suitable for synthesis gas production, with some improved feedstock handling characteristics for the latter.
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37.
  • Håkansson, Mikael, 1957, et al. (författare)
  • Copper(I) complexes with conjugated dienes
  • 2000
  • Ingår i: Journal of Organometallic Chemistry. - 0022-328X. ; 602:1-2, s. 5-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Three copper(I) complexes containing conjugated dienes and one containing the acetylenic analogue of isoprene, 2-methyl-1-butene-3-yne (isopropenylacetylene), have been prepared and characterised by means of crystal-structure determination. Direct reaction between isoprene (2-methylbutadiene) and copper(I) trifluoromethylsulfonate, using triphenylphosphine as a stabilising ligand, results in [Cu-2(PPh3)(2)(mu-(H2C=CHC(CH3)=CH2))(O3SCF3)(2)] (1), whereas reaction between copper(I) chloride and isopropenylacetylene, dimethylbutadiene, and trans-1,3-pentadiene yields the labile compounds [Cu2Cl2 (mu-(H2C=CHC(CH3)=CH))] (2), [Cu2Cl2 (mu-(H2C=C(CH3)C(CH3)-CH2))] (3) and [Cu2Cl2(mu-(trans-H2C=CHCH=CH(CH3))] (4), respectively. All four compounds are polymeric. Thus, the organic ligands bridge two copper(I) centres via the alkene or alkyne bonds, the conjugated dienes all assuming the s-trans conformation. Further bridging is effected by the trifluoromethylsulfonate ligands in 1 and by the chloride ligands in 2, 3 and 4. In 1, copper(I) has distorted tetrahedral geometry, whereas in 2, 3 and 4, copper(I) exhibits tetrahedral or trigonal pyramidal geometry with the C=C/C=C linkage in the trigonal plane and an apical Cu-Cl bond. The nearly planar carbon skeleton of isoprene in 1 bonds to two copper(I) atoms from opposite faces of the diene. The Cu-C distances range from 2.085(6) to 2.220(6) Angstrom [C(CH3)] and the C=C bond lengths are 1.360(8) and 1.353(8) Angstrom. Trifluoromethylsulfonate ligands bridge adjacent [Cu-2(PPh3)(2)(mu-(H2C=CHC(CH3)-CH2))(O3SCF3)(2)] units leading to the formation of chains, containing internal chair-shaped Cu2S2O4 rings alternating with isoprene ligands, with peripheral triphenylphosphine ligands. The carbon skeleton of the isopropenylacetylene ligand in 2 and those of dimethylbutadiene in 3 and of trans-1,3-pentadiene in 4 are also approximately planar, but, unlike the situation in 1, in compounds 2-4, two copper(I) atoms are coordinated by C=C/C=C from the same face of the ligand. In 2, Cu-C distances range from 2.005(11) to 2.158(9) Angstrom [C(CH3)] and the C=C and C=C bond lengths are 1.373(13) and 1.200(14) Angstrom, respectively. In 3, Cu-C distances range from 2.06(1) to 2.17(1) Angstrom [C(CH3)] and both C=C bonds are 1.35(1) Angstrom. Dimeric [Cu2Cl2(mu-(H2C=CHC(CH3)=CH))](2) and [Cu2Cl2(mu-(H2C=C(CH3)C(CH3)=(CH2))] units are linked by long Cu-Cl bonds leading to the formation of chains with peripheral isopropenylacetylene (2) and dimethylbutadiene (3) ligands. The crystal structure of 4 could be determined only with low precision, but can be described in terms of copper(I) chloride layers with peripheral trans-1,3-pentadiene ligands. Shifts in the infrared absorptions on coordination of the conjugated dienes (including butadiene and cis-1,3-pentadiene) to copper(I) are discussed in the light of the crystal structures of 2-4.
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38.
  • Håkansson, Stellan, et al. (författare)
  • Group B streptococcal carriage in Sweden : a national study on risk factors for mother and infant colonisation
  • 2008
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - Stockholm : Wiley. - 0001-6349 .- 1600-0412. ; 87:1, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. To study group B streptococcus (GBS) colonisation in parturients and infants in relation to obstetric outcome and to define serotypes and antibiotic resistance in GBS isolates acquired. Methods. A population-based, national cohort of parturients and their infants was investigated. During 1 calendar week in 2005 all women giving birth (n=1,754) were requested to participate in the study. Results. A total of 1,569 mother/infant pairs with obstetric and bacteriological data were obtained. Maternal carriage rate was 25.4% (95% confidence interval (CI): 23.3-27.6). In GBS-positive mothers with vaginal delivery and no intrapartum antibiotics, the infant colonisation rate was 68%. Some 30% of infants were colonised after acute caesarean section, and 0% were colonised after an elective procedure. Duration of transport of maternal recto/vaginal swabs of more than 1 day impeded culture sensitivity. Infant mMales were more frequently colonised than females (76.9 versus 59.8%, odds ratio (OR): 2.16; 95% CI: 1.27-3.70), as were infants born after rupture of membranes ≥24 h (p =0.039). Gestational age, birth weight and duration of labor did not significantly influence infant colonisation. Some 30% of parturients with at least one risk factor for neonatal disease received intrapartum antibiotics. The most common GBS serotypes were type III and V. Some 5% of the isolates were resistant to clindamycin and erythromycin, respectively. Conclusions. Maternal GBS prevalence and infant transfer rate were high in Sweden. Males were more frequently colonised than females. The sensitivity of maternal cultures decreased with the duration of sample transport. Clindamycin resistance was scarce. The use of intrapartum antibiotics was limited in parturients with obstetric risk factors for early onset group B streptococcal disease.
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39.
  • Håkansson, Stellan, et al. (författare)
  • Real-time PCR-assay in the delivery suite for determination of group B streptococcal colonization in a setting with risk-based antibiotic prophylaxis
  • 2014
  • Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 27:4, s. 328-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Intrapartum antibiotic prophylaxis (IAP) reduces the incidence of neonatal early onset group B streptococcal infections. The present study investigated if an automated PCR-assay, used bedside by the labor ward personnel was manageable and could decrease the use of IAP in a setting with a risk-based IAP strategy. Methods: The study comprises two phases. Phase 1 was a multicenter, randomized, controlled trial. Women with selected risk-factors were allocated either to PCR-IAP (prophylaxis given if positive or indeterminate) or IAP. A vaginal/rectal swab and superficial swabs from the neonate for conventional culture were also obtained. Phase 2 was non-randomized, assessing an improved version of the assay. Results: Phase 1 included 112 women in the PCR-IAP group and 117 in the IAP group. Excluding indeterminate results, the assay showed a sensitivity of 89% and a specificity of 90%. In 44 % of the PCR assays the result was indeterminate. The use of IAP was lower in the PCR group (53 versus 92%). Phase 2 included 94 women. The proportion of indeterminate results was reduced (15%). The GBS colonization rate was 31%. Conclusion: The PCR assay, in the hands of labor ward personnel, can be useful for selection of women to which IAP should be offered.
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40.
  • Ilinca, Andreea, et al. (författare)
  • MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
  • 2021
  • Ingår i: Neurology: Genetics. - 2376-7839. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke.Methods: We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses.Results: Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease.Conclusions: Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
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41.
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42.
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43.
  • Lyckegaard, E., et al. (författare)
  • Budesonide in Crohn's disease: Findings of a compassionate-use program
  • 2007
  • Ingår i: Hepato-Gastroenterology. - 0172-6390. ; 54:79, s. 2024-2027
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Budesonide controlled-release (CR) capsules are effective for inducing remission of Crohn's disease (CD) and are associated with fewer side effects than conventional corticosteroids. A compassionate-use program was implemented in countries where this treatment was unavailable. This paper reports the findings of this program. Methodology: Physicians were allowed to apply to AstraZeneca for a supply of budesonide CR capsules primarily for patients with CD who had experienced unacceptable side effects from conventional steroids or were unresponsive to other drugs. Physicians were requested to record adverse events (AEs) and patient response (1 = 'moderate'; 2 = 'well'; 3,very well'). Results: Four thousand and ninety-two patients were enrolled. There were 232 AE reports involving 326 different symptoms. There were 138 serious AEs (mainly gastrointestinal), and four deaths. Ten serious AEs were considered related to budesonide (no deaths). Budesonide was discontinued as a result of AEs in 147 patients (75 due to serious AEs, mainly gastrointestinal). Efficacy data were obtained from 1188 patients, with 943 (79%) responding 'well' or,very well'. In the subgroups of patients that were young, elderly, or had unsuccessfully received immunosuppressants previously, the mean patient response score was > 2. Conclusions: In a normal clinical setting, budesonide CR capsules were well tolerated by patients with ileocecal CD.
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44.
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45.
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46.
  • Pirttila, T J, et al. (författare)
  • Cystatin C modulates neurodegeneration and neurogenesis following status epilepticus in mouse
  • 2005
  • Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 20:2, s. 241-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Brain damaging insults cause alterations in neuronal networks that trigger epileptogenesis, and eventually lead to the appearance of spontaneous seizures. The present experiments were designed to study the cellular expression and functions of a cysteine proteinase inhibitor, cystatin C, whose gene expression is previously shown to be upregulated in the rat hippocampus during status epilepticus (SE)induced epileptogenesis. The present data showed that the expression of cystatin C protein increased in the mouse hippocampus 7 days following SE and localized mainly to astrocytes and microglia. Acute neuronal death in the hippocampus at 24 h after SE was reduced in cystatin C-/- mice. Also, the basal level of neurogenesis in the subgranular layer of dentate gyros was decreased in cystatin C-/- mice compared to wildtype littermates. Interestingly, migration of newly born neurons within the granule cell layer was attenuated in cystatin C-/- mice. These data demonstrate that cystatin C has a role in neuronal death and neurogenesis during SE-induced network reorganization.
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47.
  • Thiesen, Susanne, et al. (författare)
  • The protease inhibitor cystatin C downregulates the release of IL-β and TNF-α in lipopolysaccharide activated monocytes
  • 2016
  • Ingår i: Journal of Leukocyte Biology. - 0741-5400. ; 100:4, s. 811-822
  • Tidskriftsartikel (refereegranskat)abstract
    • Human cystatin C, a member of the cysteine proteinaseinhibitory family, is produced by all nucleated cells and has important roles in regulating natural immunity. Nematode homologs to human cystatin C have been shown to have anti-inflammatory effects on monocytes and to reduce colitis in mice. In Crohn’s disease, pathogenic activated monocytes help drive inflammatory processes via the release of proinflammatory cytokines and chemokines. In particular, tumor necrosis factora-producing inflammatory monocytes have a central role in the intestinal inflammation in patients with Crohn’s disease. We investigated the potential of human cystatin C to regulate pathogenic activated monocytes and its potential as an Immunomodulator in Crohn’s disease.We found that cystatin C significantly decreased the lipopolysaccharide-stimulated release and expression of interleukin-1b and tumor necrosis factor-α in monocyte and peripheral blood mononuclear cell cultures from healthy donors, whereas interleukin-6 and interleukin-8 levels were unchanged. A similar reduction of interleukin-1b and tumor necrosis factor-α was also seen in peripheral bloodmononuclear cell cultures from patientswith Crohn’s disease, and in particular, tumor necrosis factor-α was reduced in supernatants from lamina propria cell cultures from patients with Crohn’s disease. Further investigation revealed that cystatin C was internalized by monocytes via an active endocytic process, decreased phosphorylation of the mitogen-αctivated protein kinase pathway extracellular signal-regulated kinase-1/2, and altered surface marker expression. The ability of cystatin C to modulate the cytokine expression of monocytes, together with its protease-inhibitory function, indicates that modulation of the local cystatin C expression could be an option in future Crohn’s disease therapy.
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48.
  • Wagman, Petra, et al. (författare)
  • Associations between occupational performance, occupational satisfaction, quality of life and occupational balance in people with depression and/or anxiety
  • 2021
  • Konferensbidrag (refereegranskat)abstract
    • Background: Anxiety and depressive disorders are common in western societies and related to occupational problems.Objective: To describe occupational balance in people with anxiety and/or depression and associations with higher occupational balance.Methods: Clients (20 men and 98 women), aged 18 to 65 years were recruited from outpatient mental health care or primary health care. They had a diagnosis of anxiety and/or depression as well as occupational problems.The participants answered questionnaires about occupational balance, occupational performance, satisfaction with occupational performance, quality of life, and psychological problems.Results: The participants rated generally low occupational balance. However, the level of occupational balance differed depending on their self-rated level of anxiety and depression; quality of life; occupational performance; and satisfaction with the occupational performance.High occupational balance was, in a logistic regression, associated with high satisfaction with occupational performance, high quality of life, and low level of depression.Conclusion: The results indicate that satisfaction with occupational performance is a relevant aspect in relation to occupational balance in clients with anxiety and depression.
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49.
  • Wagman, Petra, et al. (författare)
  • Factors associated with higher occupational balance in people with anxiety and/or depression who require occupational therapy treatment
  • 2021
  • Ingår i: Scandinavian Journal of Occupational Therapy. - : Taylor & Francis. - 1103-8128 .- 1651-2014. ; 28:6, s. 426-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Anxiety and depressive disorders are associated with problems with everyday occupations, including difficulties achieving occupational balance. The aim of this cross-sectional study was to describe occupational balance in people suffering from anxiety and/or depression and the factors that are associated with better self-rated occupational balance. Material: One hundred and eighteen participants were recruited from outpatient mental health care and primary health care. The participants were 18-65 years, had a diagnosis of anxiety and/or depression, and had problems in everyday occupations. They answered questionnaires on occupational balance, psychological symptoms, quality of life and everyday occupations. Results: A generally low rating of occupational balance was found; however, the scores differed depending on the participants' degree of anxiety and depression, their quality of life, their occupational performance and satisfaction with their occupational performance. Logistic regression analyses revealed that high quality of life, high satisfaction with occupational performance and low level of depression were associated to occupational balance. Conclusion: The results indicate that enhanced satisfaction with life and with performance of everyday occupations are relevant factors for achieving occupational balance in clients diagnosed with anxiety and/or depression.
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50.
  • Wagman, Petra, et al. (författare)
  • Quality of life, sense of coherence and occupational balance one year after an occupational therapy intervention for people with depression and anxiety disorders
  • 2023
  • Ingår i: Work. - : IOS Press. - 1051-9815 .- 1875-9270. ; 76:2, s. 561-568
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Quality of life (QOL), sense of coherence (SOC) and occupational balance (OB) have been found to increase after rehabilitation among people living with depression and anxiety. However, these aspects have not been investigated over time in participants with different paid work situations, such as being on sick leave or not. OBJECTIVE: To describe and compare the self-rated QOL, SOC and OB after participation in occupational therapy in three groups of people with depression and anxiety disorders based on their work situation during the study period: continuous sick leave, return to work and continuous work. METHODS: Forty-seven women and seven men, 19-60 years old with depression and anxiety were followed over time. They completed questionnaires on QOL, SOC and OB on four occasions. Data were analyzed with non-parametric statistics. RESULTS: No statistically significant differences between the groups were identified. All groups improved in at least one of the studied areas over time: the sick leave group in OB; the return-to-work group in QOL and OB; and the Work group in QOL and SOC. CONCLUSION: The results indicate variations in QOL, SOC and OB between people with different work situations over time after occupational therapy. Studies with larger samples are, however, warranted.
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