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  • Backmark, Anna, et al. (författare)
  • Affinity tags can reduce merohedral twinning of membrane protein crystals
  • 2008
  • Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - : John Wiley and Sons. - 1399-0047 .- 0907-4449. ; D64, s. 1183-1186
  • Tidskriftsartikel (refereegranskat)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.
  • Bengtsson, D., et al. (författare)
  • Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide
  • 2015
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 100:4, s. 1689-1698
  • Tidskriftsartikel (refereegranskat)abstract
    • Context/Objective: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited. Design and Setting: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas. Main Outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry. Results: Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. Conclusions: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
  • Gallo, Valentina, et al. (författare)
  • Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study
  • 2016
  • Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 31:3, s. 255-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected through standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33 % less likely to die from ALS compared to those inactive: HR = 0.67 (95 % CI 0.42-1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased-not increased like in case-control studies-risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity.
  • Holst, Anna, et al. (författare)
  • Cost-effectiveness analysis of internet-mediated cognitive behavioural therapy for depression in the primary care setting : results based on a controlled trial
  • 2018
  • Ingår i: BMJ Open. - 2044-6055 .- 2044-6055. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To perform a cost-effectiveness analysis of a randomised controlled trial of internet-mediated cognitive behavioural therapy (ICBT) compared with treatment as usual (Tall) for patients with mild to moderate depression in the Swedish primary care setting. In particular, the objective was to assess from a healthcare and societal perspective the incremental cost-effectiveness ratio (ICER) of ICBT versus TaU at 12 months follow-up. Design A cost-effectiveness analysis alongside a pragmatic effectiveness trial. Setting Sixteen primary care centres (PCCs) in south-west Sweden. Participants Ninety patients diagnosed with mild to moderate depression at the PCCs. Main outcome measure ICERs calculated as (Cost(ICBT)-Cost(TaU))/(Health outcome(ICBT)-Health outcome(TaU))=Delta Cost/Delta Health outcomes, the health outcomes being changes in the Beck Depression Inventory-II (BDI-II) score and quality-adjusted life-years (QALYs). Results The total cost per patient for ICBT was 4044 Swedish kronor (SEK) ((sic)426) (healthcare perspective) and SEK47679 ((sic)5028) (societal perspective). The total cost per patient for TaU was SEK4434 ((sic)468) and SEK50 343 ((sic)5308). In both groups, the largest cost was associated with productivity loss. The differences in cost per patient were not statistically significant. The mean reduction in BDI-ll score was 13.4 and 13.8 units in the ICBT and Tall groups, respectively. The mean QALYs per patient was 0.74 and 0.79 in the ICBT and TaU groups, respectively. The differences in BDI-11 score reduction and mean QALYs were not statistically significant. The uncertainty of the study estimates when assessed by bootstrapping indicated that no firm conclusion could be drawn as to whether ICBT treatment compared with Tall was the most cost-effective use of resources. Conclusions ICBT was regarded to be as cost-effective as TaU as costs, health outcomes and cost-effectiveness were similar for ICBT and TaU, both from a healthcare and societal perspective.
  • Johansson, B., et al. (författare)
  • Health-related quality of life and distress in cancer patients: results from a large randomised study
  • 2008
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 1532-1827 .- 0007-0920. ; 99:12, s. 1975-1983
  • Konferensbidrag (refereegranskat)abstract
    • To compare the effectiveness of individual support, group rehabilitation and a combination of the two in improving health-related quality of life (HRQOL) and psychological well-being in cancer patients during 24 months after diagnosis, as compared with standard care (SC). Furthermore, to compare the study sample and a random sample of the Swedish population with regard to HRQOL. A total of 481 consecutive patients, newly diagnosed with cancer, were randomly assigned to one of the four alternatives. Data on HRQOL and psychological well-being were collected at baseline and after 3, 6, 12 and 24 months. The interventions did not improve HRQOL or psychological well-being, as compared with SC. At 3 months, the study sample reported an HRQOL comparable with the normal population. Many cancer patients are able to manage their cancer-related concerns with the support available from SC. However, it is reasonable to assume that the findings suffer from a lack of data from especially vulnerable patients and a possible Hawthorne effect. It cannot be concluded that cancer patients have no need for additional psychosocial interventions. Future projects should include screening and target interventions for those at risk for significant and prolonged psychological distress.
  • Wikberg, Carl, et al. (författare)
  • Comparison Between the Montgomery-Asberg Depression Rating Scale–Self and the Beck Depression Inventory II in Primary Care
  • 2015
  • Ingår i: The Primary Care Companion for CNS Disorders. - 0160-6689 .- 1555-2101 .- 2155-7772. ; 17:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Montgomery-Asberg Depression Rating Scale–Self (MADRS-S) and the Beck Depression Inventory II (BDI-II) are commonly used self-assessment instruments for screening and diagnosis of depression. The BDI-II has 21 items and the MADRS-S has 9 items. These instruments have been tested with psychiatric inpatients but not in outpatient primary care, where most patients with symptoms of depression initially seek treatment. The purpose of this study was to compare these 2 instruments in the primary care setting. Method: Data were collected from 2 primary care randomized controlled trials that were performed from 2010 to 2013 in Sweden: the Primary Care Self-Assessment MADRS-S Study and Primary Care Internet-Based Cognitive Behavioral Therapy Study. There were 146 patients (73 patients each from both trials) who had newly diagnosed mild or moderate depression (per DSM-IV recommendations) and who had assessment with both the MADRS-S and BDI-II at primary care centers. Comparability and reliability of the instruments were estimated by Pearson product moment correlation and Cronbach α. Results: A good correlation was observed between the 2 instruments: 0.66 and 0.62 in the 2 study cohorts. The reliability within the 2 study cohorts was good for both MADRS-S (Cronbach α: 0.76 for both cohorts) and BDI-II items (Cronbach α: 0.88 and 0.85). Conclusions: The 2 instruments showed good comparability and reliability for low, middle, and high total depression scores. The MADRS-S may be used as a rapid, easily administered, and inexpensive tool in primary care and has results comparable to the BDI-II in all domains.
  • Altman, Maria, et al. (författare)
  • Prolonged second stage of labor is associated with low Apgar score
  • 2015
  • Ingår i: European Journal of Epidemiology. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. ; 30:11, s. 1209-1215
  • Tidskriftsartikel (refereegranskat)abstract
    • There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 minutes. All nulliparous women (n= 32 796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 minutes <7 and <4. We found that the overall rates of 5 minute Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 hour from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 minutes generally increased with length of second stage of labor: 1-<2 hours: OR 1.78 (95% CI 1.19-2.66); 2- <3 hours: OR 1.66 (1.05-2.62); 3-<4 hours: OR 2.08 (1.29-3.35); and ≥4 hours: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 minute Apgar score.
  • Andersson, Maria L. E., et al. (författare)
  • Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis
  • 2013
  • Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Currently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease. Methods: In all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change <= 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by >= 5.8. Results: The group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels. The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression. Conclusion: Increasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.
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