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| 12. |
- Alkaissi, Hammoudi, et al.
(författare)
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Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development
- 2018
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic autoimmune rheumatic disorders (SARD) represent important causes of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Mercury-induced autoimmunity (HgIA) in mice is an established model to study the mechanisms of the development of antinuclear antibodies (ANA), which is a hallmark in the diagnosis of SARD. A.SW mice with HgIA show a significantly higher titer of antinucleolar antibodies (ANoA) than the B10.S mice, although both share the same MHC class II (H-2). We applied a genome-wide association study (GWAS) to their Hg-exposed F2 offspring to investigate the non-MHC genes involved in the development of ANoA. Quantitative trait locus (QTL) analysis showed a peak logarithm of odds ratio (LOD) score of 3.05 on chromosome 3. Microsatellites were used for haplotyping, and fine mapping was conducted with next generation sequencing. The candidate genes Bank1 (B-cell scaffold protein with ankyrin repeats 1) and Nfkbl (nuclear factor kappa B subunit 1) were identified by additional QTL analysis. Expression of the Bank1 and Nfkb1 genes and their downstream target genes involved in the intracellular pathway (Tlr9,II6, Tnf) was investigated in mercury-exposed A.SW and B10.S mice by real-time PCR. Bank1 showed significantly lower gene expression in the A.SW strain after Hg-exposure, whereas the B10.S strain showed no significant difference. Nfkb1, Tlr9, II6 and Tnf had significantly higher gene expression in the A.SW strain after Hg-exposure, while the B10.S strain showed no difference. This study supports the roles of Bank1 (produced mainly in B-cells) and Nfkbl (produced in most immune cells) as key regulators of ANoA development in HgIA.
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| 13. |
- Almblad, Ann-Charlotte, 1965-, et al.
(författare)
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From skepticism to assurance and control : Implementation of a patient safety system at a pediatric hospital in Sweden
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of evidence-based practice among healthcare professionals directly correlates to better outcomes for patients and higher professional satisfaction. Translating knowledge in practice and mobilizing evidence-based clinical care remains a continuing challenge in healthcare systems across the world.Purpose: To describe experiences from the implementation of an Early Detection and Treatment Program for Children (EDT-C) among health care professionals at a pediatric hospital in Sweden.Design and Methods: Sixteen individual interviews were conducted with physicians, nurses and nurse assistants, which of five were instructors. Data were analyzed with qualitative content analysis.Results: An overarching theme was created: From uncertainty and skepticism towards assurance and control. The theme was based on the content of eight categories: An innovation suitable for clinical practice, Differing conditions for change, Lack of organizational slack, Complex situations, A pragmatic implementation strategy, Delegated responsibility, Experiences of control and Successful implementation.Conclusions: Successful implementation was achieved when initial skepticism among staff was changed into acceptance and using EDT-C had become routine in their daily work. Inter-professional education including material from authentic patient cases promotes knowledge about different professions and can strengthen teamwork. EDT-C with evidenced-based material adapted to the context can give healthcare professionals a structured and objective tool with which to assess and treat patients, giving them a sense of control and assurance.
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| 16. |
- Anandavadivelan, Poorna, et al.
(författare)
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Profiles of patient and tumour characteristics in relation to health-related quality of life after oesophageal cancer surgery
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Strong deterioration in health-related quality of life (HRQOL) is a major concern in a sub-group of long-term oesophageal cancer survivors. This study aimed to identify potential clustering of patients and tumour variables that predicts such deterioration. Patient and tumour variables were collected in a prospective cohort of patients who underwent surgery for oesophageal cancer in Sweden 2001–2005. Latent cluster analysis identified statistically significant clustering of these variables. Multivariable logistic regression adjusted for age, BMI, tumour stage and marital status was used to determine odds ratios (ORs) with 95% confidence intervals (CIs) between patient profiles and HRQOL at 3 and 5 years from surgery. Among 155 included patients at 3 years, three patient profiles were identified: 1) ‘reference profile’ (males, younger age, employed, upper secondary education, co-habitating, urban dwellers, adenocarcinoma and advanced tumour stage) (n = 47;30%), 2) ‘adenocarcinoma profile’ (middle age, unemployed/retired, males, low education, co-habitating, adenocarcinoma, advanced tumour stage, tumour in lower oesophagus/cardia, and co-morbidities (n = 79;51%), and 3) ‘squamous-cell carcinoma profile’ (unemployed/retired, middle-age, males, low BMI, urban dwellers, squamous-cell carcinoma, tumour in upper/middle oesophagus (n = 29;19%). These profiles did not differ regarding most HRQOL measures. Exceptions were the squamous-cell carcinoma profile, reporting more constipation (OR = 5.69; 95%CI: 1.34–24.28) and trouble swallowing saliva (OR = 4.87; 95%CI: 1.04–22.78) and the adenocarcinoma profile reporting more dyspnoea (OR = 2.60; 95%CI: 1.00–6.77) and constipation (OR = 3.31; 95%CI: 1.00–10.97) compared to the reference profile. Three distinct patient profiles were identified but these could not explain the substantial deterioration in HRQOL observed in the sub-sample of survivors.
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| 17. |
- Ander, Malin, et al.
(författare)
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Exploration of psychological distress experienced by survivors of adolescent cancer reporting a need for psychological support
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective In this qualitative study, we aimed to provide an in-depth exploration of cancer-related psychological distress experienced by young survivors of cancer during adolescence reporting a need for psychological support.MethodsTwo individual interviews were held with ten young survivors of cancer diagnosed in adolescence. The interviews were audio-recorded and transcribed verbatim. Analysis followed the guidelines for inductive qualitative manifest content analysis.ResultsThe survivors described distress experienced during and after the end of treatment. Five categories comprising 14 subcategories were generated. The categories included: A tough treatment, Marked and hindered, Not feeling good enough, Struggling with the fragility of life, and finally, An ongoing battle with emotions.Conclusion Young survivors of adolescent cancer reporting a need for psychological support described feeling physically, socially, and mentally marked by the cancer experience. They struggled with powerlessness, insecurity, social disconnection, loneliness, and feelings of being unimportant and a failure, and had difficulties understanding and managing their experiences. These concerns should be addressed in psychological treatments for the population irrespective of which approach or model is used to understand survivors’ difficulties. A transdiagnostic approach targeting processes that underpin different manifestations of distress may be effective.
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| 20. |
- Anh, Nhi, et al.
(författare)
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High-resolution detection of chromosomal rearrangements in leukemias through mate pair whole genome sequencing
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- The detection of recurrent somatic chromosomal rearrangements is standard of care for most leukemia types. Even though karyotype analysis-a low-resolution genome-wide chromosome analysis-is still the gold standard, it often needs to be complemented with other methods to increase resolution. To evaluate the feasibility and applicability of mate pair whole genome sequencing (MP-WGS) to detect structural chromosomal rearrangements in the diagnostic setting, we sequenced ten bone marrow samples from leukemia patients with recurrent rearrangements. Samples were selected based on cytogenetic and FISH results at leukemia diagnosis to include common rearrangements of prognostic relevance. Using MP-WGS and in-house bioinformatic analysis all sought rearrangements were successfully detected. In addition, unexpected complexity or additional, previously undetected rearrangements was unraveled in three samples. Finally, the MP-WGS analysis pinpointed the location of chromosome junctions at high resolution and we were able to identify the exact exons involved in the resulting fusion genes in all samples and the specific junction at the nucleotide level in half of the samples. The results show that our approach combines the screening character from karyotype analysis with the specificity and resolution of cytogenetic and molecular methods. As a result of the straightforward analysis and high-resolution detection of clinically relevant rearrangements, we conclude that MP-WGS is a feasible method for routine leukemia diagnostics of structural chromosomal rearrangements.
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