| 1. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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| 2. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
- Adliene, Diana, et al.
(författare)
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Assessment of the environmental contamination with long-lived radionuclides around an operating RBMK reactor station
- 2006
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Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X. ; 90:1, s. 68-77
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Tidskriftsartikel (refereegranskat)abstract
- The presence of man-made gamma emitting radionuclides in the region within 32 km radius of the Ignalina NPP/Lithuania has been investigated during the period 2001-2004, prior to the closure of the first 4 the two operating RBMK 1500-type reactors. Gamma spectrometric measurements of various terrestrial and aquatic plants as well as of soil samples showed moderate environmental contamination with the fission product Cs-137 and with the neutron activation products Co-60 and Mn-54. Traces of the activation products Zn-65 and Ag-110m were found in the nearest vicinity of the NPP. Activity concentrations were inhomogeneously distributed in the area of interest. Moss and algae samples showed the highest uptake of radionuclides. In addition to the gamma spectrometric measurements, the levels of C-14 were determined in the same bio-indicator samples using accelerator mass spectrometry. (c) 2006 Elsevier Ltd. All rights reserved.
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| 4. |
- Ahrland, Åsa, et al.
(författare)
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Forntiden i parker
- 1999
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Ingår i: Bebyggelsehistorisk tidskrift. - : Föreningen Bebyggelsehistorisk tidskrift. - 0349-2834 .- 2002-3812. ; :37, s. 7-32
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Ahrland, Åsa, 1961-
(författare)
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Under arbetsledighetens stunder
- 2000
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Ingår i: Kulturmiljövård. - Stockholm : Riksantikvarieämbetet. - 1100-4800. ; :2, s. 36-40
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Industrialismens genombrott innebar en av de största förändringarna i samhället någonsin. Människors liv förändrades i grunden och deras tid kom att indelas i arbete, fritid och vila. De offentliga parkernas betydelse för stadsborna betonades ofta under 1800-talet. Frågan är vilken roll parker och trädgårdar fick vid fabrikerna.
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| 6. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 7. |
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| 8. |
- Aulchenko, Yurii S, et al.
(författare)
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Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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| 9. |
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| 10. |
- Beraki, Åsa, et al.
(författare)
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Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes : results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS)
- 2014
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Ingår i: Diabetes Research and Clinical Practice. - Clare, Ireland : Elsevier. - 0168-8227 .- 1872-8227. ; 105:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes.Methods: Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7-18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA.Results: Mean HbA1c level was higher in the least physically active groups (PA0: 8.8% +/- 1.5 (72 +/- 16 mmol/mol)) than in the most physically active groups (PA4: 7.7% +/- 1.0 (60 +/- 11 mmol/mol)) (p < 0.001). An inverse dose-response association was found between PA and HbA1c (beta: -0.30, 95%CI: -0.34 to -0.26, p < 0.001). This association was found in both sexes and all age groups, apart from girls aged 7-10 years. Multiple regression analysis revealed that the relationship remained significant (beta: -0.21, 95% CI: -0.25 to -0.18, p < 0.001) when adjusted for possible confounding factors.Conclusions: Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment.
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| 11. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 12. |
- Berntsen, S., et al.
(författare)
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A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities
- 2021
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 27:5, s. 801-847
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. OBJECTIVE AND RATIONALE: The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. SEARCH METHODS: Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. OUTCOMES: The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. WIDER IMPLICATIONS: This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.
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| 13. |
- Boström, Madelene, et al.
(författare)
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Nursing patients suffering from trauma : critical care nurses narrate their experiences
- 2012
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Ingår i: International Journal of Orthopaedic and Trauma Nursing. - : Elsevier BV. - 1878-1241 .- 1878-1292. ; 16:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe critical care nurses' experiences of nursing patients suffering from trauma. Eight critical care nurses were interviewed. Qualitative thematic content analysis was applied to the data and resulted in one theme; 'Needing to feel in control and part of a team', with six categories; 'different ways of dealing with uncertainty', 'feelings of responsibility and security', 'wanting to relieve the pain', 'supporting the relatives', 'suppressing one's own feelings', and 'reflecting over one's work'. The findings show the importance of preparation for caring for a patient suffering from trauma. Standardized care of the patient according to Advanced Trauma Life Support was described as a good basis, but for the quality of care to be good this always had to be complemented with personal nursing care for the patient and care for their relatives. This study contributes knowledge about meeting critically ill patients suffering from trauma and suggestions about how to cope with thoughts that might arise after a serious situation in nursing care
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| 14. |
- Carlsson, Anders, 1980-
(författare)
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Role of mast cells and probiotics in the regulation of intestinal barrier function
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicles. The epithelium covering the Peyer’s patches is called follicle-associated epithelium and is specialized in antigen sampling and uptake. The special epithelium enables presentation of luminal antigen to immune cells in the underlying follicle.Persistent life stress and stressful life events affect the course of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) through largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immune-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis and Crohns disease. Vasoactive intestinal polypeptide (VIP) and corticotropin-releasing factor have been implicated as important mediators of stress-induced abnormalities in intestinal mucosal functions in animal models. Both of these mediators have been reported to regulate bowel ion secretion in humans during stress and uptake of horseradish peroxidase in rodents. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated.The aim of this thesis was to elucidate whether mast cells play an important role in intestinal barrier function during stress and inflammation. Moreover, we wanted to determine whether probiotics can ameliorate the mucosal barrier integrity during stress and inflammation.To study the function of mast cells we conducted in vitro experiments on cell lines and ex vivo experiments in Ussing chambers on mouse, rat and human intestinal tissue. The Ussing chamber technique measures electrophysiological properties of the tissue and also gives the possibility to study transcellular and paracellular passage of markers and bacteria. Immunohistology and confocal microscopy have been used to identify mast cells and receptors of interest.Our results show that stress affects the follicle-associated epithelium barrier by mechanisms involving VIP and mast cells. These findings were corroborated by the localization of VIP receptors on mucosal mast cells. Furthermore, pretreatment with probiotics was effective in protecting the gut against stress-induced intestinal barrier dysfunction and mucosal inflammation. This protection appeared to involve a mast cell and peroxisome proliferatoractivated receptor-γ dependent mechanism.
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| 15. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 16. |
- Dahlin, Mats, et al.
(författare)
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Internet-delivered acceptance-based behaviour therapy for generalized anxiety disorder : A randomized controlled trial
- 2016
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Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 77, s. 86-95
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Tidskriftsartikel (refereegranskat)abstract
- Generalized anxiety disorder (GAD) is a disabling condition which can be treated with cognitive behaviour therapy (CBT). The present study tested the effects of therapist-guided internet-delivered acceptance-based behaviour therapy on symptoms of GAD and quality of life. An audio CD with acceptance and mindfulness exercises and a separate workbook were also included in the treatment. Participants diagnosed with GAD (N = 103) were randomly allocated to immediate therapist-guided internet-delivered acceptance-based behaviour therapy or to a waiting-list control condition. A six month follow-up was also included. Results using hierarchical linear modelling showed moderate to large effects on symptoms of GAD (Cohen's d = 0.70 to 0.98), moderate effects on depressive symptoms (Cohen's d = 0.51 to 0.56), and no effect on quality of life. Follow-up data showed maintained effects. While there was a 20% dropout rate, sensitivity analyses showed that dropouts did not differ in their degree of change during treatment. To conclude, our study suggests that internet-delivered acceptance-based behaviour therapy can be effective in reducing the symptoms of GAD.
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| 17. |
- Demirkan, Ayse, et al.
(författare)
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Genetic architecture of circulating lipid levels
- 2011
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:7, s. 813-819
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Tidskriftsartikel (refereegranskat)abstract
- Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
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| 18. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 19. |
- Eksell, Jörgen, et al.
(författare)
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Att kombinera intervju med observation
- 2014
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Ingår i: Kvalitativa metoder i strategisk kommunikation. - 9789144096582 ; , s. 93-109
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Bokkapitel (refereegranskat)
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| 20. |
- Ganna, Andrea, et al.
(författare)
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Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease
- 2014
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:12, s. e1004801-
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
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| 21. |
- Gao, Chuansi, et al.
(författare)
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Using a walkway with adjustable inclination to measure and assess slip and fall risks
- 2014
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Ingår i: Proceedings of CIB W099 International Conference Achieving Sustainable Construction Health and Safety. - 9789176230053 ; , s. 118-124
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Konferensbidrag (refereegranskat)abstract
- Fall is the most common cause of serious work related accidents. Falls and related injuries not only cause suffering for individuals, but also means a high economic burden to industries and society. The objective of the study was to use a walkway with in-built force plate, adjustable inclination and surface to assess how risks of slips and falls vary due to inclination and friction of the walkway surface. A walkway was designed with adjustable slopes between 0 to 30 degrees. Subject walking tests were performed on dry and wet steel sheet surfaces in two walking directions (uphill and downhill) at three inclination angles (0, 5 and 10 degrees). 3D ground reaction forces while walking were recorded using the force plate. Required coefficient of friction (RCOF) was derived to determine slip and fall risks. The main finding of this study is that the RCOF during heel strike when walking downwards on the steel plate surface increases linearly as the inclination increases. The results contribute to the understanding of slipping and falling mechanisms and the prevention of slipping and falling accidents. When ramps or sloped surfaces are used in workplaces, slip resistance between footwear and the sloped surfaces should be improved.
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| 22. |
- Hagbom, Marie, et al.
(författare)
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Neurotrophic Factors Protect the Intestinal Barrier from Rotavirus Insult in Mice
- 2020
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Ingår i: mBio. - : AMER SOC MICROBIOLOGY. - 2161-2129 .- 2150-7511. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Increased intestinal permeability has been proposed as a mechanism of rotavirus-induced diarrhea. Studies with humans and mice have, however, shown that rotavirus leaves intestinal permeability unaffected or even reduced during diarrhea, in contrast to most bacterial infections. Gastrointestinal permeability is regulated by the vagus nerve and the enteric nervous system, which is composed of neurons and enteric glial cells (EGCs). We investigated whether the vagus nerve, serotonin (5-HT), EGCs, and neurotropic factors contribute to maintaining gut barrier homeostasis during rotavirus infection. Using subdiaphragmatic vagotomized and 5-HT3 receptor knockout mice, we found that the unaffected epithelial barrier during rotavirus infection is independent of the vagus nerve but dependent on 5-HT signaling through enteric intrinsic 5-HT3 receptors. Immunofluorescence analysis showed that rotavirus-infected enterocytes were in close contact with EGCs and enteric neurons and that the glial cell-derived neurotrophic factor (GDNF) was strongly upregulated in enterocytes of infected mice. Moreover, rotavirus and 5-HT activated EGCs (P < 0.001). Using Ussing chambers, we found that GDNF and S-nitrosoglutathione (GSNO) led to denser epithelial barriers in small intestinal resections from noninfected mice (P < 0.01) and humans (P < 0.001) and that permeability was unaffected in rotavirus-infected mice. GSNO made the epithelial barrier denser in Caco-2 cells by increasing the expression of the tight junction protein zona occludens 1 (P < 0.001), resulting in reduced passage of fluorescein isothiocyanate dextran (P < 0.05) in rotavirus-infected monolayers. This is the first report to show that neurotropic factors contribute to maintaining the gut epithelial barrier during viral insult. IMPORTANCE Human and mouse studies have shown that rotavirus infection is associated with low inflammation and unaffected intestinal barrier at the time of diarrhea, properties different from most bacterial and inflammatory diseases of the gut. We showed by in vitro, ex vivo, and in vivo experiments that neurotrophic factors and 5-HT have barrier protective properties during rotavirus insult. These observations advance our understanding of how the gut barrier is protected against rotavirus and suggest that rotavirus affects the gut barrier differently from bacteria. This is the first report to show that neurotrophic factors contribute to maintain the gut epithelial barrier during viral insult.
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| 23. |
- Hammarberg, Anders, et al.
(författare)
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Medberoende bör inte bli en diagnos
- 2018
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Ingår i: Alkohol & Narkotika. ; 2018-09-29
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 24. |
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| 25. |
- Harrysson, Lars, et al.
(författare)
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Student Centred Learning in a Flexible Blended Mode Environment
- 2009
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Konferensbidrag (refereegranskat)abstract
- The Faculty of Sciences at Lund University has developed online courses to enhance physical as well as virtual exchange and promote joint delivery of courses among partner universities. The purpose is to increase the flexibility of studies within joint programmes. As part of the development of a blended mode course we have included an online research tool, “Global Research Gateway”.
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| 26. |
- Holm, Åsa, et al.
(författare)
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Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation : correlation with impaired translocation of PKCα and defective phagosome maturation
- 2001
-
Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 3:7, s. 439-447
-
Tidskriftsartikel (refereegranskat)abstract
- Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes. The repeating disaccharide–phosphate units of LPG are crucial for promastigote survival inside macrophages and establishment of infection. LPG has a number of effects on the host cell, including inhibition of PKC activity, inhibition of nitric oxide production and altered expression of cytokines. LPG also inhibits phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin. In the present study, we have characterized the dynamics of F-actin during the phagocytosis of L. donovani promastigotes in J774 macrophages. We observed that F-actin accumulated progressively around phagosomes containing wild-type L. donovani promastigotes during the first hour of phagocytosis. Using LPG-defective mutants and yeast particles coated with purified LPG, we obtained evidence that this effect could be attributed to the repeating units of LPG. LPG also disturbed cortical actin turnover during phagocytosis. The LPG-dependent accumulation of periphagosomal F-actin correlated with an impaired recruitment of the lysosomal marker LAMP1 and PKCα to the phagosome. Accumulation of periphagosomal F-actin during phagocytosis of L. donovani promastigotes may contribute to the inhibition of phagosomal maturation by physically preventing vesicular trafficking to and from the phagosome.
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| 27. |
- Holm, Åsa, et al.
(författare)
-
Lipid rafts are required for the effects of Leishmania donovani lipophosphoglycan on periphagosomal F-actin and phagosomal maturation
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lipophosphoglycan (LPG) is the major surface glycoconjugate on Leishmania donovani promastigotes, and is cmcial for pro mastigote survival following phagocytosis by macrophages. LPG consists of a chain of repeating phosphodisaccharides anchored to the parasite membrane by a lysophosphatidylinositol lipid anchor with an unusually long saturated fatty acid residue. During phagocytosis, LPG transfers from the parasite surface to the plasma membrane of the host macrophage. The presence of LPG alters the biophysical properties of the host cell membrane and the signaling capacity of the macrophage. LPG induces accumulation ofF-actin around the phagosome, and inhibits phagosome maturation. The effects of LPG on the host ce!l include inhibition of PKCα, a PKC isoenzyme involved in F-actin tumover.The biophysical properties of the LPG lipid anchor suggest that it partitions into caveolae or lipid rafts, which are cholesterol-rich plasma membrane microdomains central for signal transduction. Since PKCa is enriched in caveolae/lipid rafts in other cell types, we investigated if lipid rafts constitute a platform for the interaction of LPG and PKCα. We found that the plasma membrane of human monocyte-derived macrophages were rich in lipid rafts, but did not contain caveolae. LPG colocalized with lipid raft markers after interaction with WT L. donovani promastigotes. The presence of LPG inhibited the translocation of PKCα to the plasma membrane. Destruction of lipid rafts by cholesterol depletion lead to a complete eradication of LPG's effects on periphagosomal F-actin and phagosomal maturation. We also found that cholesterol depletion reduced uptake of WT L. donovani promastigotes, while uptake of an LPG-defective mutant was not affected.We conclude that LPG partitions to lipid rafts in the plasma membrane of human macrophages and inhibits the translocation of PKCα to the membrane. The presence of lipid rafts is a prerequisite for LPG to exert its effects on host cell actin and phagosomal maturation.
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| 28. |
- Holm, Åsa, 1969-, et al.
(författare)
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Mechanical manipulation of polymorphonuclear leukocyte plasma membranes with optical tweezers causes influx of extracellular calcium through membrane channels
- 1999
-
Ingår i: Medical and Biological Engineering and Computing. - 0140-0118 .- 1741-0444. ; 37:3, s. 410-412
-
Tidskriftsartikel (refereegranskat)abstract
- Optical tweezers are used mechanically to manipulate the plasma membrane of polymophonuclear leukocytes attached to the bottom of a glass manipulation chamber. The laser trapping beam is dragged across the membrane of cells in calcium-containing and calcium-depleted extracellular medium. This treatment causes a significant rise in the intracellular calcium concentration compared with controls, in cells in calcium-containing medium (239.8±49.0% against 75.4±16.4%, respectively), but not in cells in calcium-depeleted medium (69.1±9.6% against 83.4±18.5%, respectively), indicating that the calcium rise is caused by an influx of calcium from the environment. The rise in calcium concentration is blocked (23.5±7.1% against 17.1±4.1%, respectively) by the addition of lansoprazole, indicating that the influx is not due to unspecific membrane damage caused by the mechanical manipulation of the cell. It can therefore be concluded that mechanical manipulation of the neutrophil membrane, in the piconewton force range exerted by the optical tweezer, does not damage the plasma membrane but stimulates a mechanically inducible, membrane channel-mediated influx of extracellular calcium.
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| 29. |
- Holm, Åsa, et al.
(författare)
-
Protein C α regulates phagocytosis actin dynamics and phagosomal maturation in macrophages
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Promastigotes of the protozoan parasite Leishmania donovani cause an accumulation of periphagosomal F-actin instead of the normal decrease seen with other prey [1]. This accumulation is dependent on promastigote lipophosphoglycan (LPG), which has several detrimental effects on the cell including inhibition of PKCα activity.To directly address the role of PKCα and LPG for actin remodeling in macrophages, we investigated F-actin dynamics in RAW 264.7 macrophages overexpressing a dominant-negative mutant of PKCα (DN PKCα). We found that DN PKCα-overexpressing cells displayed increased levels of cortical F-actin and decreased phagocytic capacity, which was augmented when the cells were subjected to LPG-coated prey. The DN PKCα-overexpressing cells also showed defective breakdown of periphagosomal F-actin and inhibition of phagosomal maturation. The level of periphagosomal F-actin was similar to that of controls subjected to LPG-coated prey. Our results show that PKCα regulates phagocytosis and F-actin turnover in macrophages, and that PKCα-dependent breakdown of periphagosomal F-actin is required for normal phagosomal maturation.
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| 30. |
- Holm, Åsa, et al.
(författare)
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Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages
- 2003
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 302:4, s. 653-658
-
Tidskriftsartikel (refereegranskat)abstract
- Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the dissassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKCα. To investigate a possible connection between PKCα and LPG’s effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PKCα (DN PKCα). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKCα-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKCα is involved in F-actin turnover in macrophages and that PKCα-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKCα by LPG.
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| 31. |
- Högdahl, Elisabeth, et al.
(författare)
-
Jämställt Övre
- 2016
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten behandlar metodutveckling och resultat av forskningsprojektet "Ett jämställt Övre" som bedrevs av Trelleborgs kommun i samverkan med Nyréns arkitektkontor och Lunds universitet. Projektet finansierades av Boverket.
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| 32. |
- Jennbacken, Karin, et al.
(författare)
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Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells
- 2019
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:23
-
Tidskriftsartikel (refereegranskat)abstract
- Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naive cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair.
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| 33. |
- Jeuthe, Julius, et al.
(författare)
-
Semi-Automated 3D Segmentation of Pelvic Region Bones in CT Volumes for the Annotation of Machine Learning Datasets
- 2021
-
Ingår i: Radiation Protection Dosimetry. - : Oxford University Press. - 0144-8420 .- 1742-3406. ; 195:3-4, s. 172-176
-
Tidskriftsartikel (refereegranskat)abstract
- Automatic segmentation of bones in computed tomography (CT) images is used for instance in beam hardening correction algorithms where it improves the accuracy of resulting CT numbers. Of special interest are pelvic bones, which—because of their strong attenuation—affect the accuracy of brachytherapy in this region. This work evaluated the performance of the JJ2016 algorithm with the performance of MK2014v2 and JS2018 algorithms; all these algorithms were developed by authors. Visual comparison, and, in the latter case, also Dice similarity coefficients derived from the ground truth were used. It was found that the 3D-based JJ2016 performed better than the 2D-based MK2014v2, mainly because of the more accurate hole filling that benefitted from information in adjacent slices. The neural network-based JS2018 outperformed both traditional algorithms. It was, however, limited to the resolution of 1283 owing to the limited amount of memory in the graphical processing unit (GPU).
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| 34. |
- Johansson, Åsa, et al.
(författare)
-
Endothelial cell signalling supports pancreatic beta cellfunction in the rat
- 2009
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 52:11, s. 2385-2394
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The proximity of endothelial cells andbeta cells in islets by necessity means that they are exposedto each other’s products. Whereas islet endothelial cellsrequire signals from beta cells to function properly,endothelin-1, thrombospondin-1 and laminins, amongothers, have been identified as endothelial-derived molecules,although their full effects on beta cells have not beenexplored. We tested the hypothesis that islet endothelialderivedproducts affect beta cell function.Methods Endothelial cells from rat islets were proliferatedand purified. Endothelium-conditioned culture medium(ECCM) was obtained by maintaining the endothelial cellsin culture medium. Islet function was evaluated followingexposure of cultured islets to standard culture medium orECCM. Changes in mRNA levels for key beta cellmetabolic enzymes were also measured in islets afterECCM exposure.Results Glucose-stimulated insulin release and islet insulincontent were markedly enhanced by exposure to ECCM.This was at least partly explained by improved mitochondrialfunction, as assessed by glucose oxidation and anupregulation of the mitochondrial gene for glycerol-3-phosphate dehydrogenase (mGpdh [also known as Gpd2]),combined with upregulation of the rate-limiting enzyme inthe glycolysis, glucokinase, in the islets. The intracellulardegradation of insulin was also decreased in the islets. Isletendothelial cells produced laminins, and the positive effectsof islet endothelial cells were prevented by addition of aneutralising antibody to the β1-chain of laminin. Additionof exogenous laminin stimulated islet function.Conclusions/interpretation This study provides proof ofprinciple that endothelial cells can affect the function of betacells in their vicinity and that this is at least partially mediatedby laminins.
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| 35. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
-
Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 36. |
- Kastensson, Åsa
(författare)
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Managing Product Innovation in the Automotive Industry : in light of the environmental challenge
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A company’s ability to introduce new products is a key success factor for sustaining a competitive advantage. Increasing environmental concerns are an even stronger incentive to innovate. Environmental regulations will exert immense pressure on manufacturing industries, which will increase in the future, enabling a more sustainable world for coming generations. Facing the automotive industry, an aggravating circumstance is, however, that the industry is deeply affected by the paradigm grounded in mass production, a dominant design and incremental development. A common view in the innovation literature is that large, established firms usually experience difficulty fostering radical innovations. Taking on the environmental challenge, it is argued that companies lack the methods, tools and processes to scan markets and to find opportunities beyond their existing businesses. Further challenges fostering radical innovations are the conflicting demands to explore new opportunities in parallel with daily business. The aim of this thesis is to explore the prerequisites embracing innovations in terms of what hinders and enables the development and implementation of new technologies in future products. The research question is answered through qualitative studies at Saab Automobile, Volvo Cars and the lightweight project SåNätt. I also draw upon my experience working in the automotive industry for many years. The empirical studies revealed different approaches to develop radical innovations. While one of the companies focused on radical development of new concepts aiming to build a supplier structure for collaboration, the other company’s focus was on incremental development of technical solutions to be implemented in a shorter time horizon. However both companies were stuck in the paradigm where the first focused on more explorative projects and through significant interest in technology and a more informal way of working, they managed to bypass several parts in the paradigm. The other company was managing the projects through a formal process governed by strategic plans and a strong implementation focus and was more deeply committed to its infrastructure for body manufacturing thus hindering more radical changes. The thesis shows that some inertias in the paradigm can indeed be challenged, but it also shows that in order to succeed in an environmentally driven transition, the paradigm dominating the automotive industry has to be questioned.
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| 37. |
- Keita, Åsa, 1973-, et al.
(författare)
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Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn's disease
- 2008
-
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 215:2, s. 135-144
-
Tidskriftsartikel (refereegranskat)abstract
- In Crohn's disease (CD), inflammation is driven by luminal commensal micro-organisms, however, mechanisms of early phases of inflammation need further clarification. The earliest observable lesions of recurrent CD are microscopic erosions at the specialized follicle-associated epithelium (FAE), which lines the Peyer's patches. Therefore, our aim was to investigate the mucosal barrier to non-pathogenic bacteria in FAE of CD. The FAE of macroscopically normal ileum from patients with longstanding CD, ulcerative colitis, and controls was studied in Ussing chambers regarding electrophysiology and permeability to 51Cr-EDTA, horseradish peroxidase, and non-pathogenic E. coli strains. Transepithelial passage routes and uptake into dendritic cells were studied by confocal and electron microscopy. FAE of CD showed increased numbers of adherent bacteria, after E. coli exposure in Ussing chambers, as well as spontaneously in non-exposed archival surgical tissues. Further, we found increased uptake of fluorescent E. coli K-12 and HB101 across FAE of CD, but not in ulcerative colitis. Microscopy demonstrated intercellular and transcellular uptake of E. coli in CD, but only transcellular in controls. FAE exposed to E. coli demonstrated changes in conductance and 51Cr-EDTA permeability, suggesting that bacteria affected the paracellular pathway in CD mucosa. Following bacterial uptake, CD mucosa also demonstrated an increased percentage of E. coli co-localizing with dendritic cells, and augmented tissue release of TNF-α. Our data present novel insights into the pathophysiology of CD by demonstrating a previously unrecognized defect of FAE barrier to bacteria in ileal CD, leading to increased load of commensal bacteria to the inductive sites of mucosal immunity. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 38. |
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| 39. |
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| 40. |
- Kristensson Ekwall, Anna, et al.
(författare)
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Dizzy - Why Not Take a Walk? Low Level Physical Activity Improves Quality of Life among Elderly with Dizziness
- 2009
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Ingår i: GERONTOLOGY. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 55:6, s. 652-659
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Dizziness is a very common complaint. The frequency of dizziness increases with age. It affects quality of life negatively for older persons in several ways. Objectives: This study intended to investigate which variables (physical activity, loneliness, health complaints, need of help for daily living and falls) differed between those with and without dizziness and also to investigate which factors affected quality of life among older persons with dizziness. Method: An age-stratified, randomised sample of senior citizens-aged 75 or older - living in the south of Sweden (n = 4,360) answered a questionnaire concerning demographic data, social network, health complaints and diseases, feelings of loneliness, quality of life (Short Form 12), frequency of falls and activities. Results: Dizziness was associated with an increased risk of falling. Falls in the last 3 months were reported in 31% of the subjects with dizziness compared to 15% among those without (p andlt; 0.001). Dizziness also correlated with depression, with 42.5% feeling depressed among the elderly reporting dizziness as compared with 13.2%. Exercise, both light (i.e. go for a walk) or heavy (i.e. work in the garden), correlated with reduced risk of low quality of life among older, dizzy persons, both mental (light exercise OR 0.58; heavy OR 0.48) and physical (light OR 0.62; heavy OR 0.21). The proportion of dizzy persons doing light exercise was 75.6% versus 87.4% among the not dizzy (p andlt; 0.001). Exercise reduces the risk of falling and the risk of being depressed, and increases quality of life. Conclusion: Even light exercise seems beneficial both for improving quality of life and to decrease the risk of falling, which in turn will lower the mortality rate. Older persons reporting dizziness should be encouraged and perhaps helped to exercise. If one could increase physical activity among the elderly, it would reduce the number of falls, diminish medical costs, suffering for the individual, and be of paramount medicosocial importance for society.
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| 41. |
- Kristensson Hallström, Inger, et al.
(författare)
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eHealth as an Aid for Facilitating and Supporting Self-Management in Families with Long-Term Childhood Illness; Development, Evaluation, and Implementation in Clinical Practice
- 2023
-
Ingår i: Clinical Health Promotion - Research and Best Practice for patients, staff and community. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction eHealth, defined by WHO as: “the transfer of health resources and healthcare by electronic means” are expected to increase communication between healthcare providers and patients and increase accessibility and patient participation in healthcare. The aim of this research programme is to: 1) develop a sustainable multidisciplinary environment for advancing, evaluating, and implementing models of eHealth to promote self-management for children and their families, and 2) increase the present knowledge of clinical and economic cost-effectiveness of eHealth as an aid for supporting self-management in families with long-term childhood illness. Method The research is performed in Sweden, Denmark, and Ethiopia and organized in three research domains: eHealth to enable and promote self-management in advanced paediatric care, eHealth for early diagnosis and treatment in paediatric care, and Co-Creation of multidisciplinary knowledge for the translation of eHealth in practice. The research follows a framework for developing and evaluating complex interventions in healthcare. Through participatory design family members and care providers participate throughout the research process. Quantitative and qualitative data as well as health economics are collected in six clinical areas. Five general areas are run transversal. Results and conclusion Evidence-based best practices in developing and evaluating eHealth in paediatric healthcare will be suggested. As implementation is part of the programme, cost-effective eHealth directly benefiting families and healthcare services will be guaranteed.
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| 42. |
- Lerm, Maria, 1973-, et al.
(författare)
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Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal maturation
- 2006
-
Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 74:5, s. 2613-2618
-
Tidskriftsartikel (refereegranskat)abstract
- Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase Cα. The present study shows that functional Cdc42 and Rac1 are required for the formation of F-actin around L. donovani phagosomes. Moreover, we present data showing that phagosomes containing LPG-defective L. donovani, which is unable to induce F-actin accumulation, display both elevated levels of periphagosomal F-actin and impaired phagosomal maturation in macrophages with permanently active forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to build up a protective coat of F-actin around its phagosome to prevent phagosomal maturation. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
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| 43. |
- Lerm, Maria, et al.
(författare)
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Rac1 and Cdc42 are involved in the periphagosomal F-actin accumulation and inhibition of phagosomal maturation caused by Leishmania donovani lipophosphoglycan
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The intracellular parasite Leishmania donovani survives inside macrophage phagosomes by inhibiting phagosornal maturation. Its main surface glycoconjugate, lipophosphoglycan (LPG), is crucial for survival and essential for the build-up of a coat of F-actin surrounding the phagosome. Previous studies have shown that inhibition of PKCα by LPG is partly responsible for the elevated levels of F-actin around the phagosome (1, 2). This study shows that simultaneous inhibition of Cdc42 and Rac1, members of the Rho family of small GTPases, prevented the accumulation of F-actin around L. donovani containing phagosomes in murine macrophages. Moreover, an LPG-defective L. donovani mutant normally not capable of accumulating F-actin around it's phagosome, displayed elevated amounts of periphagosomal F-actin in cells pre-treated with permanently active forms of Cdc42 and Rac. The lysosomal marker LAMP1 did not translocate normally to phagosomes in these cells, indicating defective phagosomal maturation. We conclude that Cdc42 and Rac are activated by L. donovani in an LPG-dependent manner, and that this activation contributes to the accumulation of periphagosomal F-actin around L. donovani phagosomes. Our results also indicate a direct link between the build-up of periphagosomal F-actinand inhibition of phagosomal mahuation.
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| 44. |
- Lidén, Åsa, 1975-
(författare)
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Integrin αVβ3-Directed Contraction by Connective Tissue Cells : Role in Control of Interstitial Fluid Pressure and Modulation by Bacterial Proteins
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis aimed at studying mechanisms involved in control of tissue fluid homeostasis during inflammation.The interstitial fluid pressure (PIF) is of importance for control of tissue fluid balance. A lowering of PIF in vivo will result in a transport of fluid from the circulation into the tissue, leading to edema. Loose connective tissues that surround blood vessels have an intrinsic ability to take up fluid and swell. The connective tissue cells exert a tension on the fibrous network of the tissues, thereby preventing the tissues from swelling. Under normal homeostasis, the interactions between the cells and the fibrous network are mediated by β1 integrins. Connective tissue cells are in this way actively controlling PIF.Here we show a previously unrecognized function for the integrin αVβ3, namely in the control of PIF. During inflammation the β1 integrin function is disturbed and the connective tissue cells release their tension on the fibrous network resulting in a lowering of PIF. Such a lowering can be restored by platelet-derived growth factor (PDGF) -BB. We demonstrated that PDGF-BB restored PIF through a mechanism that was dependent on integrin αVβ3. This was shown by the inability of PDGF-BB to restore a lowered PIF in the presence of anti-integrin β3 IgG or a peptide inhibitor of integrin αVβ3. PDGF-BB was in addition unable to normalize a lowered PIF in β3 null mice. Furthermore, we demonstrated that extracellular proteins from Streptococcus equi modulated αVβ3-mediated collagen gel contraction. Because of the established concordance between collagen gel contraction in vitro and control of PIF in vivo, a potential role for these proteins in control of tissue fluid homeostasis during inflammation could be assumed. Sepsis and septic shock are severe, and sometimes lethal, conditions. Knowledge of how bacterial components influence PIF and the mechanisms for tissue fluid control during inflammatory reactions is likely to be of clinical importance in treating sepsis and septic shock.
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| 45. |
- Lindberg, Åsa, et al.
(författare)
-
Yrsel
- 2010
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Ingår i: Äldres hälsa och ohälsa. - Lund : Studentlitteratur AB. - 9789144053530 ; , s. 245-258
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Yrsel är vanligt hos äldre personer och påverkar deras liv negativt. Rädsla, oro och depression är vanligt hos äldre med yrsel. Yrsel är ofta ett tecken på balansstörningar, vilket är en vanlig orsak till fallolyckor och död. Genom att minska yrseln hos äldre skulle antalet fallolyckor också kunna minskas. Fysisk aktivitet minskar risken för yrsel och förbättrar därmed livskvaliteten.
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| 46. |
- Ling Lundström, Maria, et al.
(författare)
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Faecal biomarkers for diagnosis and prediction of disease course in treatment-naïve patients with IBD.
- 2024
-
Ingår i: Alimentary Pharmacology and Therapeutics. - 0269-2813 .- 1365-2036.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD).AIM: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD.METHODS: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression.RESULTS: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006).CONCLUSIONS: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.
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| 47. |
- Ling Lundström, Maria, et al.
(författare)
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Fecal Biomarkers of Neutrophil and Eosinophil Origin Reflect the Response to Biological Therapy and Corticosteroids in Patients With Inflammatory Bowel Disease
- 2023
-
Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fecal calprotectin (FC) is anoninvasive tool for examining response to biologics in inflammatory boweldisease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown.Methods: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated.Results: In patients achieving clinical remission (n = 27), a decrease in levels of FC (P = 0.005), MPO (P < 0.001), HNL (P < 0.001), and EDN (P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO (P = 0.01) and HNL (P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL (P = 0.01) and EDN (P < 0.001) at baseline, compared with patients without corticosteroids.Discussion: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.
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| 48. |
- Magnusson, Jenny, et al.
(författare)
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Improving information literacy instruction through reflection
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Improving information literacy instruction through reflection! Keywords: teaching, reflection, improvement Reflective teaching is highlighted as a way to become a reflective practitioner; to learn and improve practice through reflection. The value of reflection in improving teaching is well documented. Research concludes that while reflective teaching may present some difficulties, its benefits lead to a teacher's success in the classroom (Goodsett, 2014). This poster aims to illustrate how Malmö University library works with reflective teaching as a way to improve quality and evaluate our information literacy instruction. There are many different methods of reflective teaching. We chose to focus on a model based on self-reflecting through a reflective teaching form. The model is based on setting aside time to reflect on what happened during the session, identifying problems and development areas and reflections of what you would do differently next time. What we did was to develop an assessment form, inspired by Radcliff et al (2007), for us librarians to fill out and save after each information literacy instruction session. The assessment form consists of questions that we have identified as important to reflect on to be able to improve our teaching. For example, one of the questions encourages us to think of ways to make the students more active and involved. We have experienced that using the form helps us to take this minimal extra time to reflect and it also helps us formalize, structure, save and share our reflections. In addition to filling out the forms individually, we have used our reflections to discuss our thoughts with colleagues and learned from each other. We have also shared our reflections with teachers at the university that we collaborate with. Right now we are evaluating the use of the assessment form. In the poster we will share our results, experiences and what we have learned from working with reflective teaching. References: Goodsett, M. (2014). Reflective Teaching: Improving Library Instruction Through Self-Reflection, Southeastern Librarian, 62(3), ss. 12-15. Radcliff, C J. (2007). A practical guide to information literacy assessment for academic librarians. Westport, Conn.: Libraries Unlimited.
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| 49. |
- Magnusson, Maria, 1961-, et al.
(författare)
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ACCURACY OF CT NUMBERS OBTAINED BY DIRA AND MONOENERGETIC PLUS ALGORITHMS IN DUAL-ENERGY COMPUTED TOMOGRAPHY
- 2021
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press. - 0144-8420 .- 1742-3406. ; 195:3-4, s. 212-217
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Tidskriftsartikel (refereegranskat)abstract
- Dual-energy computed tomography (CT) can be used in radiotherapy treatment planning for the calculation of absorbed dose distributions. The aim of this work is to evaluate whether there is room for improvement in the accuracy of the Monoenergetic Plus algorithm by Siemens Healthineers. A Siemens SOMATOM Force scanner was used to scan a cylindrical polymethyl methacrylate phantom with four rod-inserts made of different materials. Images were reconstructed using ADMIRE and processed with Monoenergetic Plus. The resulting CT numbers were compared with tabulated values and values simulated by the proof-of-a-concept algorithm DIRA developed by the authors. Both the Monoenergetic Plus and DIRA algorithms performed well; the accuracy of attenuation coefficients was better than about ±1% at the energy of 70 keV. Compared with DIRA, the worse performance of Monoenergetic Plus was caused by its (i) two-material decomposition to iodine and water and (ii) imperfect suppression of the beam hardening artifact in ADMIRE.
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| 50. |
- Magnusson, Maria, et al.
(författare)
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DIRA-3D-a model-based iterative algorithm for accurate dual-energy dual-source 3D helical CT
- 2019
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Ingår i: Biomedical Engineering & Physics Express. - : IOP PUBLISHING LTD. - 2057-1976. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative dual-energy computed tomography may improve the accuracy of treatment planning in radiation therapy. Of special interest are algorithms that can estimate material composition of the imaged object. One example of such an algorithm is the 2D model-based iterative reconstruction algorithm DIRA. The aim of this work is to extend this algorithm to 3D so that it can be used with cone-beams and helical scanning. In the new algorithm, the parallel FBP method was replaced with the approximate 3D FBP-based PI-method. Its performance was tested using a mathematical phantom consisting of six ellipsoids. The algorithm substantially reduced the beam-hardening artefact and the artefacts caused by approximate reconstruction after six iterations. Compared to Alvarez-Macovskis base material decomposition, DIRA-3D does not require geometrically consistent projections and hence can be used in dual-source CT scanners. Also, it can use several tissue-specific material bases at the same time to represent the imaged object.
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