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| 2. |
- Falck, Anna-Karin, et al.
(författare)
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Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods: Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results: DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63-2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions: The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.
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| 3. |
- Antoniou, Antonis C., et al.
(författare)
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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
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Tidskriftsartikel (refereegranskat)abstract
- Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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| 4. |
- Armulik, Annika, et al.
(författare)
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Pericytes regulate the blood-brain barrier
- 2010
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Ingår i: NATURE. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 468:7323, s. 557-U231
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Bengtsson, Eva, et al.
(författare)
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The leucine-rich repeat protein PRELP binds fibroblast cell surface proteoglycans and enhances focal adhesion formation.
- 2016
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Ingår i: The Biochemical journal. - 1470-8728. ; 473:9, s. 1153-1164
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Tidskriftsartikel (refereegranskat)abstract
- PRELP is a member of the leucine-rich repeat family of extracellular matrix proteins in connective tissue. In contrast to other members of the family, the amino-terminal domain of PRELP has a high content of proline and positively charged amino acids. This domain has previously been shown to bind chondrocytes and to inhibit osteoclast differentiation. Here we show that PRELP mediates cell adhesion by binding to cell surface glycosaminoglycans. Thus, rat skin fibroblasts bound to full-length PRELP and to the amino-terminal part of PRELP alone, but not to truncated PRELP lacking the positively charged amino-terminal region. Cell attachment to PRELP was inhibited by addition of soluble heparin or heparan sulfate, by blocking sulfation of the fibroblasts, or by treating the cells with a combination of chondroitinase and heparinase. Using affinity chromatography, we identified syndecan-1, syndecan-4 and glypican-1 as cell surface proteoglycans binding to the amino-terminal part of PRELP. Finally, we show that the amino-terminal domain of PRELP in combination with the integrin-binding domain of fibronectin, but neither of the fragments alone, induced fibroblast focal adhesion formation. These findings provide support for a role of the amino-terminal region of PRELP as an important regulator of cell adhesion and behavior, which may be of importance in pathological conditions.
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| 6. |
- Berg, Gita, 1982-, et al.
(författare)
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Sustainable Home Economics Teacher Education in Pandemic Times : Experiences from Swedish Universities
- 2022
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Konferensbidrag (refereegranskat)abstract
- One aspect of the Sustainable Development Goals is quality education. Not only should education work in favor of sustainable development on a global level; quality education needs to be sustainable in the sense that it provides opportunities for students’ learning in relation to the subject taught. The school subject Home Economics (HE) is often described as having cooking as a core feature. Consequently, HE-teacher education commonly includes practical cooking as a central part of the content. During the outbreak of the Covid-19 pandemic, educational preconditions suddenly changed, and possibilities for undertaking cooking on campus became limited. In this study, we investigate HE-teacher educators’ experiences of adjusting practical cooking activities during the covid-19 pandemic. The aim is twofold: first, to highlight how the pandemic situation has been tackled in Swedish HE-teacher education. Second, to contribute to the understanding of practical cooking as a part of sustainable HE-teacher education.In Sweden, there are four universities that offer HE-teacher education. Educators from these four universities were interviewed digitally in focus groups in two rounds. The first round was held in October 2020, the second in April/May 2021. The interviews followed a semi-structured design, and questions were asked about what the pandemic had meant for practical cooking activities in terms of problems, solutions and insights for the future. The interviews are analyzed using thematic analysis, and preliminary results show e.g. how educators used digital solutions, making the education accessible despite new restrictions. These solutions did not necessarily affect students’ possibilities to achieve formally stated learning goals, but there was a hesitation concerning whether tacit and situated aspects of learning was lost when physical encounters did not take place. In short, the results evoke new insights regarding what constitutes sustainable education for HE-teachers of today.
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| 7. |
- Black, Rebecca Mae, et al.
(författare)
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Tissue catabolism and donor-specific dexamethasone response in a human osteochondral model of post-traumatic osteoarthritis
- 2022
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Post-traumatic osteoarthritis (PTOA) does not currently have clinical prognostic biomarkers or disease-modifying drugs, though promising candidates such as dexamethasone (Dex) exist. Many challenges in studying and treating this disease stem from tissue interactions that complicate understanding of drug effects. We present an ex vivo human osteochondral model of PTOA to investigate disease effects on cartilage and bone homeostasis and discover biomarkers for disease progression and drug efficacy. Methods: Human osteochondral explants were harvested from normal (Collins grade 0–1) ankle talocrural joints of human donors (2 female, 5 male, ages 23–70). After pre-equilibration, osteochondral explants were treated with a single-impact mechanical injury and TNF-α, IL-6, and sIL-6R ± 100 nM Dex for 21 days and media collected every 2–3 days. Chondrocyte viability, tissue DNA content, and glycosaminoglycan (sGAG) percent loss to the media were assayed and compared to untreated controls using a linear mixed effects model. Mass spectrometry analysis was performed for both cartilage tissue and pooled culture medium, and the statistical significance of protein abundance changes was determined with the R package limma and empirical Bayes statistics. Partial least squares regression analyses of sGAG loss and Dex attenuation of sGAG loss against proteomic data were performed. Results: Injury and cytokine treatment caused an increase in the release of matrix components, proteases, pro-inflammatory factors, and intracellular proteins, while tissue lost intracellular metabolic proteins, which was mitigated with the addition of Dex. Dex maintained chondrocyte viability and reduced sGAG loss caused by injury and cytokine treatment by 2/3 overall, with donor-specific differences in the sGAG attenuation effect. Biomarkers of bone metabolism had mixed effects, and collagen II synthesis was suppressed with both disease and Dex treatment by 2- to 5-fold. Semitryptic peptides associated with increased sGAG loss were identified. Pro-inflammatory humoral proteins and apolipoproteins were associated with lower Dex responses. Conclusions: Catabolic effects on cartilage tissue caused by injury and cytokine treatment were reduced with the addition of Dex in this osteochondral PTOA model. This study presents potential peptide biomarkers of early PTOA progression and Dex efficacy that can help identify and treat patients at risk of PTOA.
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| 8. |
- Boersma, Katja, et al.
(författare)
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Stability and change in burnout profiles over time : A prospective study in the working population
- 2009
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Ingår i: Work & Stress. - London : Taylor & Francis. - 0267-8373 .- 1464-5335. ; 23:3, s. 264-283
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Tidskriftsartikel (refereegranskat)abstract
- This is a prospective study on the development of burnout in the general Swedish working population from a person-oriented perspective. A large random sample of the general working population (N=1118) was cluster analyzed, using scores on the subscales of the Maslach Burnout Inventory at baseline and at 1-year follow-up. The individual and structural stability of the configurations over time, as well as accompanying changes on work-related and mental health variables were investigated. The results show the occurrence of several different configurations of burnout variables. Scoring patterns with high exhaustion and cynicism reflected burnout; those with a high level of professional efficacy reflected engagement; there were also scoring patterns characterized by only one of the dimensions in the relative absence of others. These patterns show structural, as well as individual stability over time. The risk factors for development of burnout or engagement from clusters with only one burnout characteristic varied according to the cluster. These results give new insights, indicating that the road to burnout may be different for subgroups of different burnout profiles, and that these subgroups may potentially have different risk factors associated with the development of burnout. This is of importance for the development of early interventions.
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| 9. |
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| 10. |
- Brouwers, Lisa, et al.
(författare)
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Den ljusnande framtid är vård : delresultat från LEV-projektet
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- År 2050 väntas andelen äldre i befolkningen öka från dagens 17 procent till 25 procent. Befolkningen åldras, hälsan förbättras och livslängden ökar. Det är en positiv utveckling som samhället måste anpassas till. Därför har en arbetsgrupp inom Socialdepartementet med en unik modell simulerat hur 300 000 individer åldras fram till 2050 och hur det väntas påverka hälsa, sjuklighet och dödlighet samt det framtida behovet av vård och omsorg. Simuleringarna visar att det är möjligt att kombinera åtgärder för att möta den åldrande befolkningens ökande behov av vård och omsorg om 10-15 år. Men det krävs ett målmedvetet arbete med att förbättra hälsa och funktionsförmåga, öka tillgängligheten, få en effektiv vård och omsorg som tillämpar dagens kunskap och tänker nytt forska och utveckla.
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