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1.
  • Backmark, Anna, 1979, et al. (author)
  • Affinity tags can reduce merohedral twinning of membrane protein crystals
  • 2008
  • In: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047 .- 0907-4449. ; D64, s. 1183-1186
  • Journal article (peer-reviewed)abstract
    • This work presents a comparison of the crystal packing of three eukaryotic membrane proteins: human aquaporin 1, human aquaporin 5 and a spinach plasma membrane aquaporin. All were purified from expression constructs both with and without affinity tags. With the exception of tagged aquaporin 1, all constructs yielded crystals. Two significant effects of the affinity tags were observed: crystals containing a tag typically diffracted to lower resolution than those from constructs encoding the protein sequence alone and constructs without a tag frequently produced crystals that suffered from merohedral twinning. Twinning is a challenging crystallographic problem that can seriously hinder solution of the structure. Thus, for integral membrane proteins, the addition of an affinity tag may help to disrupt the approximate symmetry of the protein and thereby reduce or avoid merohedral twinning.
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2.
  • Beers, Timothy C., et al. (author)
  • Broadband UBVRCIC photometry of horizontal-branch and metal-poor candidates from the HK and Hamburg/ESO surveys. I.
  • 2007
  • In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 168:1, s. 128-139
  • Journal article (peer-reviewed)abstract
    • We report broadband UBV and/or BVRCIC CCD photometry for a total of 1857 stars in the thick-disk and halo populations of the Galaxy. The majority of our targets were selected as candidate field horizontal-branch or other A-type stars (FHB/ A, N = 576), or candidate low-metallicity stars (N = 1221), from the HK and Hamburg/ESO objective-prism surveys. Similar data for a small number of additional stars from other samples are also reported. These data are being used for several purposes. In the case of the FHB/ A candidates they are used to accurately separate the lower gravity FHB stars from various higher gravity A-type stars, a subsample that includes the so-called blue metal poor stars, halo and thick-disk blue stragglers, main-sequence A-type dwarfs, and Am and Ap stars. These data are also being used to derive photometric distance estimates to high-velocity hydrogen clouds in the Galaxy and for improved measurements of the mass of the Galaxy. Photometric data for the metal-poor candidates are being used to refine estimates of stellar metallicity for objects with available medium-resolution spectroscopy, to obtain distance estimates for kinematic analyses, and to establish initial estimates of effective temperature for analysis of high-resolution spectroscopy of the stars for which this information now exists.
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3.
  • Benrick, Anna, 1979, et al. (author)
  • A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population.
  • 2008
  • In: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 146:1-3, s. 189-96
  • Journal article (peer-reviewed)abstract
    • Inflammation is a key component in the development of atherosclerosis, and myocardial infarction (MI); therefore we investigated the association between an interleukin-6 signal transducer (IL6ST)/gp130 polymorphism, gp130 function and risk of MI. Structural modeling suggested that a non-conservative single nucleotide polymorphism in the gp130, Gly148Arg, can change the stability and functional properties of the molecule. In vitro studies were done with BAF/3 cells lacking endogenous gp130. Cells stably transfected with the gp130 148Arg variant proliferated less and showed slightly lower STAT-3 phosphorylation in response to gp130 stimulation as compared to cells transfected with gp130 148Gly. In a prospectively followed hypertensive cohort we identified 167 patients who suffered a MI during the study and compared them to matched controls (mean age 57 years, 73% males, n=482). Carriers of the 148Arg variant (f(Arg)=0.12) of the gp130 receptor had decreased odds ratio for MI in univariate analysis (0.56, 95% CI 0.34-0.91, p=0.02). In conclusion, a genetically determined structural variant of the IL-6 receptor subunit gp130 is, independently of other known risk factors, associated with decreased risk of MI. The variant is also associated with decreased IL-6 responsiveness and could lead to a configuration change in the gp130 receptor.
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4.
  • Eriksson, Anna-Lena, 1971, et al. (author)
  • The COMT val158met polymorphism is associated with prevalent fractures in Swedish men.
  • 2008
  • In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
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5.
  • Furmark, Tomas, et al. (author)
  • Guided and unguided self-help for social anxiety disorder : randomised controlled trial
  • 2009
  • In: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 195:5, s. 440-447
  • Journal article (peer-reviewed)abstract
    • Background Internet-delivered self-help programmes with added guidance have shown efficacy in social anxiety disorder, unguided self-help has been insufficiently studied. Aims To evaluate the efficacy of guided and unguided self-help social anxiety disorder. Method Participants followed a cognitive-behavioural self-help programme in the form of either pure bibliotherapy or an internet-based treatment with therapist guidance and online group discussions. A subsequent trial was conducted to evaluate treatment specificity. Participants (n=235) were randomised to one of three conditions in the first trial, or one of four conditions in the second. Results Pure bibliotherapy and the internet-based treatment were better than waiting list on measures of social anxiety, general anxiety, depression and quality of life. The internet-based therapy had the highest effect sizes, but directly comparable effects were noted for bibliotherapy augmented with online group discussions. Gains were well maintained a year later. Conclusions Unguided self-help through bibliotherapy can produce enduring improvement for individuals with social anxiety disorder.
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6.
  • Janson, Staffan, 1945-, et al. (author)
  • Äldre i Värmland : Om hälsa, levnadsvanor och livssituation 2006
  • 2007
  • Book (other academic/artistic)abstract
    • Landstinget har i samarbete med Karlstads universitet gjort flera befolkningsundersökningar i Värmland och publicerat rapporter om både den vuxna befolkningens och barns hälsa, senast med rapporten Värmlänningarnas Liv och Hälsa 2004. Någon befolkningsstudie av de äldres hälsa och livsvillkor har dock inte gjorts tidigare.Efter tre års förarbeten och samråd mellan landstinget, Värmlands kommuner och flera institutioner vid Karlstads universitet genomfördes den föreliggande studien av de äldres hälsa under senhösten 2006, i form av en omfattande postenkät. Urvalet utgjordes av 2500 slumpmässigt uttagna kvinnor och män som var 80 år eller äldre. Svarsfrekvensen var 60 procent, vilket får betraktas som mycket bra med tanke på att cirka 15 procent i denna åldersgrupp lever i särskilda boenden.Studien avspeglar således hälsan och livsvillkoren för de äldre. Överlag visar det sig att de äldre mår bra och har stor kapacitet att fungera som aktiva samhällsmedborgare. Samtidigt är det många som har kroniska besvär, med värk, syn- och hörselnedsättning, inkontinensbesvär etc. Det föreligger också en klar social gradient, där särskilt äldre kvinnor med arbetarbakgrund har både mer sjukdom och större ekonomiska problem än de övriga.
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7.
  • Lindhagen, Elin, et al. (author)
  • Significant cytotoxic activity in vitro of the EGFR tyrosine kinase inhibitor gefitinib in acute myeloblastic leukaemia.
  • 2008
  • In: Eur J Haematol. - : Wiley. - 1600-0609 .- 0902-4441. ; 81:5, s. 344-353
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES:Gefitinib inhibits epidermal growth factor receptor (EGFR) signalling, but may also act by non-EGFR dependent mechanisms. We have investigated the activity of gefitinib in haematological tumour cells, in particular acute myeloblastic leukaemia (AML).METHODS:Cytotoxic activity of gefitinib, alone or in combination with standard anti-leukaemic drugs, was assessed by the short-term fluorometric microculture cytotoxicity assay in tumour cells from 117 patients representing five haematological and five non-haematological malignancies. In AML, the EGFR status was analysed by immunochemistry. Gefitinib-induced apoptosis was investigated in a subset of AML samples, as well as in the leukaemia cell line MV-4-11, using a multiparametric high content screening assay. To confirm activation of caspase-3 in cells treated with gefitinib, a blocking test was carried out in which MV4-11 cells were pretreated with the specific caspase inhibitor DEVD-FMK.RESULTS:Gefitinib showed highest cytotoxic activity in AML (n = 19) with many samples being sensitive at concentrations achievable in clinical practice (<10 microM), and no difference between previously untreated and relapsed patients. No correlation between the activity of gefitinib and standard antileukaemic drugs (cytarabine, doxorubicin, etoposide) was observed. Combining gefitinib with these drugs resulted in mainly additive or synergistic (etoposide) effects, with no evidence of sequence dependency. The AML cells did not express the EGFR. Gefitinib induced apoptosis, which was at least partly mediated by activation of the caspase-3 pathway.CONCLUSION:In vitro, gefitinib has significant cytotoxic activity in AML by inducing apoptosis through non-EGFR dependent pathways.
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8.
  • Maripuu, Linda, et al. (author)
  • Dynamics of the immune response against extracellular products of group A streptococci during infection
  • 2007
  • In: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 14:1, s. 44-51
  • Journal article (peer-reviewed)abstract
    • The immune response against the infecting group A streptococcus (GAS) extracellular products (EP) was determined in acute- and convalescent-phase sera from 75 patients with different clinical manifestations of GAS infection. All EP elicited a high proliferative response in human peripheral blood mononuclear cells. In patients with bacteremia, low neutralization in acute-phase sera was associated with development of streptococcal toxic shock syndrome. Lack of neutralization in acute-phase sera was more common in patients infected with the T1emm1 serotype. The majority of patients did not develop the ability to neutralize the mitogenic activity of their infecting isolate despite a significant increase in enzyme-linked immunosorbent assay titer in early convalescent-phase sera. In patients with the ability to neutralize GAS EP, the immune response remained high over at least 3 years. In contrast, the neutralization capacity conferred by intravenous immunoglobulin and/or plasma treatment disappeared within 3 months.
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9.
  • Mellström, Dan, et al. (author)
  • Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men : MrOS Sweden
  • 2006
  • In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 21:4, s. 529-535
  • Journal article (peer-reviewed)abstract
    • The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
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10.
  • Mellström, Dan, 1945, et al. (author)
  • Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.
  • 2006
  • In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 21:4, s. 529-35
  • Journal article (peer-reviewed)abstract
    • The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
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11.
  • Möllsten, Anna, et al. (author)
  • The effect of polymorphisms in the renin-angiotensin-aldosterone system on diabetic nephropathy risk
  • 2008
  • In: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 22:6, s. 377-383
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES:The risk of diabetic nephropathy (DN) can be increased by elevated intraglomerular pressure and glomerular filtration rate, leading to glomerular damage. This can be controlled by the renin-angiotensin-aldosterone (RAA) system, which has an important function regulating both systemic and intrarenal blood pressure. Smoking increases the risk of DN, but not all diabetic patients who smoke develop DN. There is a possibility that smoking has different effects depending on the different genotypes of the individual. We investigated the association of DN with seven polymorphisms in the RAA system and their possible interaction with smoking.SUBJECTS AND METHODS:In the present case-control study, type 1 diabetic patients with diabetes duration > or =20 years, without albuminuria and without antihypertensive treatment (n=197), were included as controls. An albumin excretion rate (AER) of 20-200 microg/min (n=73) was considered as incipient DN, and an AER >200 microg/min was considered as overt DN (n=48). Smoking habits were obtained from questionnaires.RESULTS:Homozygosity for the A allele, of the angiotensin II type 1 receptor (AGTR1) A1166C polymorphism, was associated with increased risk of overt DN (OR=3.04; 99% CI=1.02-9.06), independently of the other associated variables: age, duration of diabetes, ever smoking, HbA1c, and sex. The effect of the AA genotype was enhanced to a four times risk increase among ever-smoking patients. Two alleles of the microsatellite marker adjacent to the angiotensinogen gene were less common among nephropathy cases than among controls, but this was not significant when controlling for the same variables as above.CONCLUSIONS:The risk of having overt DN was increased in patients homozygous for the A1166 allele, and smoking seemed to enhance the effect of the AGTR1 genotype.
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12.
  • Strandberg, Louise, 1981, et al. (author)
  • IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS Study Sweden.
  • 2008
  • In: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381 .- 1930-739X. ; 16:3, s. 710-3
  • Journal article (peer-reviewed)abstract
    • There is growing evidence that immune functions are linked to the regulation of body fat. Our studies of knockout mice indicate that both endogenous interleukin (IL)-6 and IL-1 can suppress mature-onset obesity. We now investigated whether four common polymorphisms of the IL6 and IL1 systems are associated with the fat mass measured with dual-energy X-ray absorptiometry (DXA) in elderly men (n = 3,014). The study subjects were from the Swedish part of the MrOS multicenter population study and 69-81 years of age. The IL6 -174 G>C (Minor allele frequency (MAF) = 48%) gene promoter polymorphism was associated with the primary outcome total fat mass (P = 0.006) and regional fat masses, but not with lean body mass. The IL1B -31T>C (MAF = 34%) polymorphism was also associated with total fat (P = 0.007) and regional fat masses, but not lean body mass. The IL-1 receptor antagonist (IL-1ra) gene (IL1RN) +2018 T>C (MAF = 27%) polymorphism (in linkage disequilibrium (LD) with a well-studied variable number tandem repeat of 86 base pair (bp)) and IL1B +3953 C>T (MAF = 26%) polymorphism were not associated with total fat mass. In conclusion, the IL-1 and IL-6 systems, shown to suppress mature-onset obesity in experimental animals, contain gene polymorphisms that are associated with fat, but not lean, mass in elderly men.
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14.
  • Tillfors, Maria, 1963-, et al. (author)
  • Treating university students with social phobia and public speaking fears : Internet delivered self-help with or without live group exposure sessions
  • 2008
  • In: Depression and anxiety (Print). - : Hindawi Limited. - 1091-4269 .- 1520-6394. ; 25:8, s. 708-717
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: This study investigated the efficacy of an Internet-based self-help program with minimal therapist contact via e-mail for Swedish university students with social phobia and public speaking fears. The main objective was to test if the Internet-based self-help program would be more effective if five live group exposure sessions were added. METHODS: Thirty-eight students meeting the diagnostic and statistical manual of mental disorders, 4th edition criteria for social phobia were randomized into two different treatment groups: Internet delivered cognitive behavior therapy combined with five group exposure sessions (ICBT+ exp) or the Internet program alone (ICBT). RESULTS: Results were analyzed on an intention-to-treat basis. Both treatment groups showed significant improvement from pre- to post-test, and from pre-test to 1-year follow-up, on all measured dimensions (social anxiety, general anxiety, depression levels, and quality of life). For both the groups, the average within-group effect sizes for the primary social anxiety scales, expressed as Cohen's d, were comparable to those seen in traditionally administered cognitive behavioral therapy both at post-test and at 1- year follow-up. CONCLUSIONS: The results suggest that the Internet-based self-help program on its own is efficient in the treatment of university students with social phobia. Adding group exposure sessions did not improve the outcome significantly.
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15.
  • Uhlén, Mathias, et al. (author)
  • A human protein atlas for normal and cancer tissues based on antibody proteomics
  • 2005
  • In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
  • Journal article (peer-reviewed)abstract
    • Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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16.
  • Undén, Anna-Lena, et al. (author)
  • Gender Differences in Self-Rated Health, Quality of Life, Quality of Care, and Matebolic Control in Patients with Diabetes
  • 2008
  • In: Gender Medicine. - : Elsevier BV. - 1550-8579 .- 1878-7398. ; 5:2, s. 162-180
  • Journal article (peer-reviewed)abstract
    • Background: Because the projected increase in the number of diabetic patients is expected to strain the capabilities of health care providers worldwide, we are challenged to find ways of reducing the burden of diabetes. Maintaining and improving health-related quality of life (QoL) for diabetic patients may be viewed as public health goals.Objective: The aim of this cross-sectional study was to compare different aspects of health, QoL, and quality of care (QoC) between men and women with diabetes as a basis for planning and managing diabees care.Methods: All patients in 2 age groups (aged 20–30 years [younger age group] and aged 50–60 years [middle-aged group]) who were registered with the Department of Endocrinology, Metabolism, and Diabetes at Karolinska University Hospital, Stockholm, Sweden, in October 2004, were recruited for a survey. Questions were included about self-rated health (SRH), QoL, QoC, diabetes-related worries, occupational status, physical activity level, living arrangements, and educational background. Glycosylated hemoglobin (HbA1c) values were obtained from medical records.Results: Of the 223 eligible patients (109 men, 114 women) in the younger age group, 49 men and 74 women responded to the questionnaire; of the 300 eligible patients (170 men, 130 women) in the middle-aged group, 120 men and 93 women responded. Middle-aged women rated their mental well-being and QoL as worse compared with men (P < 0.001 and P < 0.05, respectively). In both age groups, women reported more diabetes-related worries and less ability to cope (P < 0.05 for the younger age group and P < 0.001 for the middle-aged group for both variables), thus the differences were more marked for middleaged women. Although there were no gender differences in metabolic control, middle-aged women reported less satisfaction with diabetes care (P < 0.001). Higher HbA1c was related to worse SRH in both men and women when analyzing the age groups together (P < 0.05). This association was most prominent in young women, in whom having more diabetes-related worries was also related to higher HbA1c (P < 0.01).Conclusion: In this study, women with diabetes appeared to have worse QoL and mental well-being compared with men with diabetes. Therefore, identifying strategies to improve SRH and QoL among diabetic patients, especially among women, is of great importance.
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17.
  • Vikerfors, Anna, et al. (author)
  • Severe group A streptococcal infections in Uppsala County, Sweden : clinical and molecular characterization of a case cluster from 2006 to 2007
  • 2009
  • In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 41:11-12, s. 823-830
  • Journal article (peer-reviewed)abstract
    • This study describes a recent cluster of 30 patients (median age 52 years) with serious group A streptococcal (GAS) infections in Uppsala County, Sweden, from December 2006 to May 2007. Patients hospitalized with a severe GAS infection, i.e. cases with either invasive GAS (iGAS) disease or patients with a positive non-sterile site culture/rapid antigen test for GAS and clinically considered as having a critical disease, were included in the study. Common clinical presentations were skin and soft tissue infections (53%) and pneumonia (17%). Eight patients (27%) were diagnosed with streptococcal toxic shock syndrome. In 40% of the cases no relevant underlying disease was reported. Among the 16 patients with soft tissue infections, the upper chest, neck or upper arm area was frequently affected and the infection was associated with severe pain. Among the 20 collected isolates, the T1/emm1 type dominated (80%). The majority (86%) of 7 analysed acute sera lacked neutralizing activity against superantigens produced by the patients' own infecting isolate. The study underscores the association between T1/emm1 and outbreaks of serious GAS infections. This highlights the importance of surveillance for prompt identification of more aggressive isolates in the community, thereby increasing awareness among healthcare professionals of these life-threatening infections.
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18.
  • Abelson, Anna-Karin, et al. (author)
  • STAT4 Associates with SLE through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk
  • 2009
  • In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 68:11, s. 1746-1753
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To confirm and define the genetic association of STAT4 and systemic lupus erythematosus, investigate the possibility of correlations with differential splicing and/or expression levels, and genetic interaction with IRF5. METHODS: 30 tag SNPs were genotyped in an independent set of Spanish cases and controls. SNPs surviving correction for multiple tests were genotyped in 5 new sets of cases and controls for replication. STAT4 cDNA was analyzed by 5'-RACE PCR and sequencing. Expression levels were measured by quantitative PCR. RESULTS: In the fine-mapping, four SNPs were significant after correction for multiple testing, with rs3821236 and rs3024866 as the strongest signals, followed by the previously associated rs7574865, and by rs1467199. Association was replicated in all cohorts. After conditional regression analyses, two major independent signals represented by SNPs rs3821236 and rs7574865, remained significant across the sets. These SNPs belong to separate haplotype blocks. High levels of STAT4 expression correlated with SNPs rs3821236, rs3024866 (both in the same haplotype block) and rs7574865 but not with other SNPs. We also detected transcription of alternative tissue-specific exons 1, indicating presence of tissue-specific promoters of potential importance in the expression of STAT4. No interaction with associated SNPs of IRF5 was observed using regression analysis. CONCLUSIONS: These data confirm STAT4 as a susceptibility gene for SLE and suggest the presence of at least two functional variants affecting levels of STAT4. Our results also indicate that both genes STAT4 and IRF5 act additively to increase risk for SLE.
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21.
  • Ahlstrand, Elisabeth, et al. (author)
  • Erfarna lärares engagemang : livsberättelser som retrospektiv reflektion
  • 2008. - 1
  • In: Läraren i blickpunkten<em> </em>. - Stockholm : Lärarförbundets Förlag. - 9789197659895 - 9197659894 ; , s. 189-205
  • Book chapter (other academic/artistic)abstract
    • Lärares arbete är komplext och kan beskrivas på olika sätt beroende på vilken utgångspunkt man väljer. I takt med att det ställs allt högre krav på lärare att utgå från en vetenskaplig bas i arbetet, behövs också fler redskap och begrepp för att förstå och förklara läraryrket. Hur ser arbetsprocesserna ut? Vad formar yrket? Vilka insatser kan göras för att förbättra verksamheten? Den här antologin presenterar femton sätt att se på lärares liv och arbete med hjälp av olika teoretiska perspektiv.Boken vänder sig till lärare och blivande lärare samt till alla som är intresserade av kunskapsutvecklingen kring lärares arbete.
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22.
  • Albertsson, Anna-Karin, et al. (author)
  • PLUS Borås : Om professionsutveckling och dokumentation
  • 2009
  • Conference paper (other academic/artistic)abstract
    • PLUS betyder Projekt för Läsutveckling, Utvärdering och Samverkan. Det handlar om lässtimulerande arbete bland barn från nyfödd upp till 16 år och omfattar alltså alla barn- och skolbibliotekarier i Borås. Folkbiblioteken i Borås består av Stadsbiblioteket och nio kommundelsbibliotek. I kommundelarna är skol- och folkbiblioteken samorganiserade eller i nära samverkan. Samtliga högstadieskolor och flera låg- och mellanstadieskolor har fackutbildade bibliotekarier. Alla folkbiblioteksenheter har barnbibliotekarietjänster. Stadsbiblioteket ansvarar för att barnbibliotekarier och skolbibliotekarier träffas regelbundet i sina respektive nätverk. Läsfrämjande arbete bedrivs på alla bibliotek, drygt trettio personer arbetar med det på varsitt håll. Det finns mycket kunskap och gedigen erfarenhet men tid för reflektion och bollande med idéer för inspiration och metodikutveckling är mycket begränsad. Idéer till projektets innehåll baseras i strävan att knyta alla bibliotekarier som arbetar med språk- och läsutvecklingen till en gemensam bas och därmed skapa förutsättningar för ett utvecklingsarbete i hela kommunen.
  •  
23.
  • Andersen, Henrik Rasmus, et al. (author)
  • Estrogenic personal care products in a greywater reuse system
  • 2007
  • In: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 56:12, s. 45-49
  • Journal article (peer-reviewed)abstract
    • The occurrence and fate of parabens in a greywater system was assessed. The potential for removal of residual paraben concentrations in effluent greywater with chlorine dioxide was also investigated. The influent to the greywater plant was characterised by considerable variation, with concentrations from below the detection limit to 40 μg/L and the five commonly used parabens in consumer products were frequently detected. After the biological treatment only two paraben were detected with concentration from 65–120 ng/L. Chlorine dioxide treatment of the biologically treated effluent with dosages down to 0.75 mg/L resulted in more than 97% reduction of all parabens. Formation of the by-product chloroform was insignificant from the chlorine dioxide treatment.
  •  
24.
  • Andersen, Niels S., et al. (author)
  • Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
  • 2009
  • In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
  • Journal article (peer-reviewed)abstract
    • Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
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25.
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