| 1. |
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| 2. |
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| 3. |
- Bonagas, Nadilly, et al.
(author)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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In: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Journal article (peer-reviewed)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 4. |
- Hognert, Helena, 1973, et al.
(author)
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Acute effects of transdermal 17beta-estradiol on hemostatic variables after 24-hour treatment.
- 2002
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In: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. - 1076-0296. ; 8:3, s. 239-43
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the acute effects of transdermal 17beta-estradiol (Estraderm) on plasma levels of coagulatory and fibrinolytic factors in postmenopausal normotensive and hypertensive women. Eleven normotensive and 13 hypertensive women were included in this placebo-controlled crossover study. In a randomized order each subject was treated with a patch of 100 microg 17beta-estradiol or placebo for 24 hours. Serum levels of tissue type plasminogen activator (tPA) activity, plasminogen activator inhibitor-I (PAI-1) activity, tPA antigen, PAI-I antigen, FVII, FX, and fibrinogen were assayed after both treatments. There was no significant difference in serum levels of hemostatic variables after treatment with estrogen compared to levels after placebo treatment in either of the groups. Nor was there any measurable difference when comparing hypertensive and normotensive subjects.
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| 5. |
- Höjer, Ingrid, 1953, et al.
(author)
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Recognition of education and schooling in case files for children and young people placed in out-of-home care
- 2018
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In: Children and youth services review. - : Elsevier BV. - 0190-7409. ; 93, s. 135-142
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Journal article (peer-reviewed)abstract
- © 2018 Elsevier Ltd The aim of the article is to describe and discuss how issues related to schooling and educational achievement are recognized and addressed in social services case files for children and young people placed in out-of-home care (OHC) in the city of Gothenburg, Sweden. Four cohorts were included in the study: children born 1967, 1977, 1987 and 1992. 40 case files were selected from each cohort (38 from the 1977 cohort), in total 158 cases. The analyses were made through a counting of rows related to schooling and education in the documents. Results were then processed in the statistical program SPSS. The results show that the level of recognition of schooling/education was low, and that it was more frequent when the child/young person had behaviour problems and/or was placed in residential care. Little attention was paid to changes of schools. On a positive note, there was an increased attention to education and schooling for the two latter cohorts (1987, 1992), and the involvement of children, young people and parents was also more visible. To conclude, the acknowledgement of schooling and education that should be present in all placements in OHC was not generally visible in the documents in the case files, although the level of attention had increased. The message for practice is that this issue need more attention on several levels: better planning for the transition between old and new school, a developed cooperation between social services, foster/residential care and schools and a pro-active approach from social services concerning education and schooling.
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| 6. |
- Andersson, Claes R., et al.
(author)
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Quantitative Chemogenomics : Machine-Learning Models of Protein-Ligand Interaction
- 2011
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In: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 11:15, s. 1978-1993
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Research review (peer-reviewed)abstract
- Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed.
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| 7. |
- Axelsson, Viktoria, et al.
(author)
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Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells.
- 2006
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In: Biochem Biophys Res Commun. - 0006-291X. ; 345:3, s. 1068-74
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Journal article (peer-reviewed)abstract
- In this study, a significant increase by 50% in intracellular free calcium concentration ([Ca(2+)](i)) was observed in differentiated human neuroblastoma (SH-SY5Y) cells after exposure to 0.25microM of the fungal metabolite gliotoxin for 72h. Further, the involvement of caspases and calpains was demonstrated to underlie the gliotoxin-induced cytotoxic and neurite degenerative effects. The caspase inhibitor Z-VAD-fmk almost completely reduced the neurite degeneration from 40% degeneration of neurites to 5% as compared to control. Inhibition of calpains with calpeptin significantly attenuated gliotoxin-induced cytotoxicity, determined as reduction in total cellular protein content, from 43% to 14% as compared to control cells. Western blot analyses of alphaII-spectrin breakdown fragments confirmed activity of the proteases, and that alphaII-spectrin was cleaved by caspases in gliotoxin-exposed cells. These results show that calpains and caspases have a role in the toxicity of gliotoxin in differentiated SH-SY5Y cells and that the process may be Ca(2+)-mediated.
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| 8. |
- Berg, Lisa, et al.
(author)
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Health risk behaviours among migrants by duration of residence : protocol for a systematic review and meta-analysis
- 2020
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In: BMJ Open. - : BMJ. - 2044-6055. ; 10:10
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Research review (peer-reviewed)abstract
- Introduction International migrants’ health has often been found to deteriorate in new countries, partly due to changes in health risk behaviours such as alcohol consumption, tobacco use, physical inactivity, and poor dietary habits. However, limited efforts have been made to comprehensively evaluate the extent to which migrants adopt unhealthy risk behaviours with longer duration of residence. This systematic review and meta-analysis will summarise evidence on international migrants’ behavioural patterns by duration of residence in multiple country contexts.Methods and analysis PubMed/MEDLINE, Web of Science and ProQuest databases will be searched for quantitative or mixed-method observational studies published in peer-reviewed scientific journals between 1 January 2000 and 31 December 2019. Studies comparing foreign-born individuals by duration of residence will be included. Information on study characteristics, descriptive statistics and measures of effect will be extracted. All included studies will be quality assessed using a modified Newcastle-Ottawa scale. The review will include narrative synthesis and, if sufficient and comparable data are available, random effects meta-analyses. The review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Ethics and dissemination Ethical approval is not required since previously published information from peer-reviewed studies will be assessed. The results of this review will be published in peer-reviewed journals and presented at scientific conferences. Other forms of dissemination will include communication to broader audiences using well-established channels, including through university-based press releases. Progress will be regularly updated on the International Prospective Register of Systematic Reviews to ensure full transparency.
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| 9. |
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| 10. |
- Brandin, Lisa, 1974, et al.
(author)
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Effects of estrogen plus progesterone on hemodynamic and vascular reactivity in hypertensive postmenopausal women.
- 2010
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In: Blood pressure. - : Informa UK Limited. - 1651-1999 .- 0803-7051. ; 19:3, s. 156-63
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Journal article (peer-reviewed)abstract
- AIMS: To investigate the medium-term effects of estrogen plus progesterone therapy (EPT) on vascular reactivity, endothelial function and hemodynamic responses in 20 hypertensive postmenopausal women. METHODS: This randomized, double-blind, cross-over, placebo-controlled study investigates the effect of 6 months of EPT (conjugated equine estrogen plus medroxyprogesterone). Blood pressure (office and ambulatory), heart rate and heart rate variability (HRV) were measured at baseline and following EPT/placebo treatment. In eight women, we used a wire-myograph to assess endothelial function and contractile response of subcutaneous arteries to transmural nerve stimulation (TNS) and exogenous noradrenaline. RESULTS: EPT decreased vascular reactivity to cumulative TNS compared with baseline (p<0.01) and placebo (p<0.05). Moreover, EPT diminished sensitivity to exogenous noradrenaline (p<0.05). Although EPT reinforced response to acetylcholine, we observed no difference in maximal relaxation induced by substance P or acetylcholine. EPT did not affect ambulatory blood pressure, heart rate or HRV. CONCLUSIONS: Oral combined medium-term EPT reduces adrenergic reactivity in subcutaneous arteries from treated hypertensive postmenopausal women. EPT might act postjunctionally at the adrenergic vascular receptor level. In the present study, EPT neither reduces sympathetic activity nor increases vagal tone, and thus does not support an effect on the central hemodynamic system.
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| 11. |
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| 12. |
- Bybrant, M. C., et al.
(author)
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Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
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Journal article (peer-reviewed)abstract
- Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
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| 13. |
- Bäckvall, Helena, et al.
(author)
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Genetic tumor archeology : microdissection and genetic heterogeneity in squamous and basal cell carcinoma
- 2005
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In: Mutation research. - : Elsevier BV. - 0027-5107 .- 1873-135X. ; 571:02-jan, s. 65-79
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Research review (peer-reviewed)abstract
- Carcinogenesis is a multi-step series of somatic genetic events. The complexity of this multi-hit process makes it difficult to determine each single event and the definitive outcome of such events. To investigate the genetic alterations in cancer-related genes, sensitive and reliable detection methods are of major importance for generating relevant results. Another critical issue is the quality of starting material which largely affects the outcome of the analysis. Microdissection of cells defined under the microscope ensures a selection of representative material for subsequent genetic analysis. Skin cancer provides an advantageous model for studying the development of cancer. Detectable lesions occur early during tumor progression, facilitating molecular analysis of the cell populations from both preneoplastic and neoplastic lesions. Alterations of the p53 tumor suppressor gene are very common in non-melanoma skin cancer, and dysregulation of p53 pathways appear to be an early event in the tumor development. A high frequency of epidermal p53 clones has been detected in chronically sun-exposed skin. The abundance of clones containing p53 mutated keratinocytes adjacent to basal cell (BCC) and squamous cell carcinoma (SCC) suggests a role in human skin carcinogenesis. Studies using p53 mutations as a clonality marker have suggested a direct link between actinic keratosis, SCC in situ and invasive SCC. Microdissection-based studies have also shown that different parts of individual BCC tumors can share a common p53 mutation yet differ with respect to additional alterations within the p53 gene, consistent with subclonal development within tumors. Here, we present examples of using well-defined cell populations, including single cells, from complex tissue in combination with molecular tools to reveal features involved in skin carcinogenesis.
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| 14. |
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| 15. |
- Clemedson, Cecilia, et al.
(author)
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Development of an in vitro test battery for the estimation of acute human systemic toxicity : An outline of the EDIT project. Evaluation-guided Development of New In Vitro Test Batteries
- 2002
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In: ATLA (Alternatives to Laboratory Animals). - 0261-1929. ; 30:3, s. 313-321
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Journal article (peer-reviewed)abstract
- The aim of the Evaluation-guided Development of new In Vitro Test Batteries (EDIT) multicentre programme is to establish and validate in vitro tests relevant to toxicokinetics and for organ-specific toxicity, to be incorporated into optimal test batteries for the estimation of human acute systemic toxicity. The scientific basis of EDIT is the good prediction of human acute toxicity obtained with three human cell line tests (R(2) = 0.77), in the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. However, the results from the MEIC study indicated that at least two other types of in vitro test ought to be added to the existing test battery to improve the prediction of human acute systemic toxicity - to determine key kinetic events (such as biotransformation and passage through biological barriers), and to predict crucial organ-specific mechanisms not covered by the tests in the MEIC battery. The EDIT programme will be a case-by-case project, but the establishment and validation of new tests will be carried through by a common, step-wise procedure. The Scientific Committee of the EDIT programme defines the need for a specific set of toxicity or toxicokinetic data. Laboratories are then invited to perform the defined tests in order to provide the "missing" data for the EDIT reference chemicals. The results obtained will be evaluated against the MEMO (the MEIC Monograph programme) database, i.e. against human acute systemic lethal and toxicity data. The aim of the round-table discussions at the 19th Scandinavian Society for Cell Toxicology (SSCT) workshop, held in Ringsted, Denmark on 6-9 September 2001, was to identify which tests are the most important for inclusion in the MEIC battery, i.e. which types of tests the EDIT programme should focus on. It was proposed that it is important to include in vitro methods for various kinetic events, such as biotransformation, absorption in the gut, passage across the blood-brain barrier, distribution volumes, protein binding, and renal clearance/accumulation. Models for target organ toxicity were also discussed. Because several of the outlier chemicals (paracetamol, digoxin, malathion, nicotine, paraquat, atropine and potassium cyanide) in the MEIC in vivo-in vitro evaluation have a neurotoxic potential, it was proposed that the development within the EDIT target organ programme should initially be focused on the nervous system.
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| 16. |
- Collen, Anna-Clara, 1970, et al.
(author)
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Cardiac structure and function is related to current blood pressure rather than to previous hypertensive pregnancy
- 2015
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In: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 29:11, s. 702-704
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Journal article (peer-reviewed)abstract
- One-hundred five women were examined with echocardiography and ambulatory blood pressure measurements 40 years post partum to evaluate the effect of former hypertensive pregnancies versus current blood pressure on cardiac structure and function. Hypertensive pregnancies did not have an adverse effect on the heart, but current minor elevation in blood pressure had a negative impact on the myocardium. The increased prevalence of hypertension following hypertensive pregnancies may be a crucial factor regarding the increased risk for cardiovascular disease shown in affected women.
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| 17. |
- Collen, Anna-Clara, 1970, et al.
(author)
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Cardiovascular and metabolic characteristics 40 years after hypertensive pregnancies: a long-term follow-up study of mothers.
- 2013
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In: Journal of hypertension. - 1473-5598. ; 31:4, s. 758-765
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Journal article (peer-reviewed)abstract
- OBJECTIVES:: Maternal cardiovascular morbidity is increased after hypertensive pregnancies (HTP). The pathways from complicated pregnancies to future cardiovascular disease are complex. The aim of the present study was to test the hypothesis that different cardiovascular mechanisms are changed in women who experienced HTP four decades earlier in comparison to women with normotensive pregnancies. METHODS:: One hundred and five women (50 with hypertensive and 55 with normal pregnancies) were examined with anthropometric measurements; office blood pressure, ambulatory blood pressure and central blood pressure, pulse wave velocity, augmentation index, intimal-media thickness, echocardiography and laboratory measurements. In addition another 204 women were followed-up by a questionnaire regarding their pregnancy 40 years ago, as well as their present health status and medications. RESULTS:: Women with HTP had more often diagnosed hypertension when compared with women with normal pregnancies (50 vs. 31%, respectively; P=0.046), but the groups did not differ in any blood pressure levels. HTP were associated with higher pulse wave velocity (8.8m/s vs. 7.8m/s, P=0.021), and higher levels of P-glucose (5.7mmol/l vs. 5.2mmol/l, P=0.022), P-HbA1c (4.4% vs. 4.2%, P=0.010) and noradrenaline (2.45mmol/l vs. 2.11mmol/l, P=0.040) when compared with normotensive pregnancies. Women followed up with a questionnaire reported deteriorated cardiovascular health compared to women attending the clinical investigations of the study. CONCLUSION:: HTP are associated with impairment in vascular function and metabolic status 40 years postpartum despite well controlled blood pressure levels.
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| 18. |
- Collen, Anna-Clara, 1970, et al.
(author)
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Cardiovascular response to stress and perceived stress is not altered 40 years after hypertensive pregnancies
- 2015
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In: Hypertension in Pregnancy. - : Informa UK Limited. - 1064-1955 .- 1525-6065. ; 34:1, s. 116-124
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Journal article (peer-reviewed)abstract
- Objective: Women experiencing hypertensive pregnancies have an increased risk for cardiovascular disease. Whether stress increase the risk is unknown. The objective was to test if cardiovascular response to stress and/or perceived stress differed in relation to blood pressure status during pregnancy 40 years earlier. Methods: Cardiovascular response was examined with mental stress test, and perceived stress was evaluated with a questionnaire in 105 women. Results: Resting heart rate was higher, and pulse reactivity was lower in women with previous hypertensive pregnancies. Neither blood pressure nor perceived stress differed. Conclusion: Response to physical or psychological stress is not affected many years after pregnancy.
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| 19. |
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| 20. |
- Dahlgren, Madelene, et al.
(author)
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T Follicular Helper, but Not Th1, Cell Differentiation in the Absence of Conventional Dendritic Cells
- 2015
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 194:11, s. 5187-5199
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Journal article (peer-reviewed)abstract
- Development of long-lived humoral immunity is dependent on CXCR5-expressing T follicular helper (Tfh) cells, which develop concomitantly to effector Th cells that support cellular immunity. Conventional dendritic cells (cDCs) are critical APCs for initial priming of naive CD4(+) T cells but, importantly, also provide accessory signals that govern effector Th cell commitment. To define the accessory role of cDCs during the concurrent development of Tfh and effector Th1 cells, we performed high-dose Ag immunization in conjunction with the Th1-biased adjuvant polyinosinic: polycytidylic acid (pI:C). In the absence of cDCs, pI: C failed to induce Th1 cell commitment and IgG2c production. However, cDC depletion did not impair Tfh cell differentiation or germinal center formation, and long-lived IgG1 responses of unaltered affinity developed in mice lacking cDCs at the time point for immunization. Thus, cDCs are required for the pI: C-driven Th1 cell fate commitment but have no crucial accessory function in relation to Tfh cell differentiation.
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| 21. |
- Danielsson, Helena, et al.
(author)
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Förstudie F-gaser : Identifiering av delar i den svenska beräkningsmodellen där förbättringspotential finns
- 2016
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Reports (other academic/artistic)abstract
- Projektets syfte är att hitta möjliga vägar att förbättra den svenska beräkningsmodellen för emissioner av F-gaser. Genom att jämföra den svenska rapporteringen med andra jämförbara länders har delar identifierats i Sveriges rapportering som särskilt viktiga att se över, verifiera eller korrigera. Detta gäller framför allt uppdelning av emissioner av F-gaser från kommersiell, industriell och stationär kyla som idag rapporteras sammanslaget. Det är också viktigt att läckagefaktorerna ses över för dessa koder. Även för kyltransporter och mobil luftkonditionering bör läckagefaktorer ses över och verifieras eller eventuellt korrigeras, för mobil luftkonditionering framför allt för senare år. Mängder F-gaser i importerade produkter bör utredas vidare för att i ett första steg få en uppfattning om storleksordningen. Detta gäller bland annat F-gaser i importerade vägfordon, arbetsmaskiner, tåg och båtar. Slutligen finns anledning att undersöka hur stora mängder SF6 som används som spårgas, som elektrisk isolergas vid sterilisering med elektronstrålning av medicinsk utrustning samt förekomst i läkemedel.
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| 22. |
- de Peppo, Giuseppe Maria, et al.
(author)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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In: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Journal article (peer-reviewed)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role inthe osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenicdifferentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 23. |
- de Peppo, Giuseppe Maria, 1981, et al.
(author)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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In: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
-
Journal article (peer-reviewed)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 24. |
- Ehrenberg, Angelica, et al.
(author)
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Accounting for strain variations and resistance mutations in the characterization of hepatitis C NS3 protease inhibitors
- 2014
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In: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 29:6, s. 868-876
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Journal article (peer-reviewed)abstract
- Context: Natural strain variation and rapid resistance development makes development of broad spectrum hepatitis C virus (HCV) drugs very challenging and evaluation of inhibitor selectivity and resistance must account for differences in the catalytic properties of enzyme variants.Objective: To understand how to study selectivity and relationships between efficacy and genotype or resistant mutants for NS3 protease inhibitors.Materials and methods: The catalytic properties of NS3 protease from genotypes 1a, 1b and 3a, and their sensitivities to four structurally and mechanistically different NS3 protease inhibitors have been analysed under different experimental conditions.Results: The optimisation of buffer conditions for each protease variant enabled the comparison of their catalytic properties and sensitivities to the inhibitors. All inhibitors were most effective against genotype 1a protease, with VX-950 having the broadest selectivity.Discussion and conclusion: A new strategy for evaluation of inhibitors relevant for the discovery of broad spectrum HCV drugs was established.
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| 25. |
- Eklund, Kajsa, 1952, et al.
(author)
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Long term outcome of frailty and ADL following "Continuum of care for frail elderly persons"
- 2012
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In: The Gerontologist. 2012 GSA Annual Scientific Meeting Abstracts. - 0016-9013 .- 1758-5341. ; 52:S1
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Conference paper (other academic/artistic)abstract
- The current trend in Western societies facing a growing proportion of older people is to support frail older persons to remain in their homes as long as possible, so-called ageing in place. Older persons comprise a group whose reserve of strength is decreasing, and whose activity and participation levels will deteriorate with increasing frailty, often leading to dependence in daily activities. Frail older persons need integrated care from different caregivers at different care levels with multi-professional competences. An intervention study for frail community-dwelling older people was designed, creating a continuum of care from the hospital through and back to their own homes. Objectives were to evaluate its effects on activities of daily living (ADL) and frailty up to one year. The study design was a RCT with participants randomized to either the intervention or a control group with follow-ups at three-, six- and 12 months. The study group includes 161 older people who sought care at the emergency department at Mölndal hospital, Sweden, and discharged to their own homes. Inclusion criteria were age 80 and older or 65 to 79 with at least one chronic disease and dependent in ADL. Frailty was measured as a sum of eight core frailty indicators and ADL with the ADL staircase. The analyses were made on the basis of the intention-to-treat principle. At both three- and twelve-month follow-up the intervention group had a higher OR in improved number of ADL managed independently. There were no significant differences between the groups regarding frailty.
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| 26. |
- Eklund, Kajsa, 1952, et al.
(author)
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One-year outcome of frailty indicators and activities of daily living following the randomised controlled trial; "Continuum of care for frail older people"
- 2013
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In: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 13
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Journal article (peer-reviewed)abstract
- Background: The intervention; "Continuum of Care for Frail Older People", was designed to create an integrated continuum of care from the hospital emergency department through the hospital and back to the older person's own home. The aim of this study is to evaluate the effects of the intervention on functional ability in terms of activities of daily living (ADL). Methods: The study is a non-blinded controlled trial with participants randomised to either the intervention group or a control group with follow-ups at three-, six- and 12 months. The intervention involved collaboration between a nurse with geriatric competence at the emergency department, the hospital wards and a multi-professional team for care and rehabilitation of the older people in the municipality with a case manager as the hub. Older people who sought care at the emergency department at Sahlgrenska University Hospital/Molndal and who were discharged to their own homes in the municipality of Molndal, Sweden were asked to participate. Inclusion criteria were age 80 and older or 65 to 79 with at least one chronic disease and dependent in at least one ADL. Analyses were made on the basis of the intention-to-treat principle. Outcome measures were ADL independence and eight frailty indicators. These were analysed, using Chi-square and odds ratio (OR). Results: A total of 161 participated in the study, 76 persons allocated to the control group and 85 to the intervention group were analysed throughout the study. There were no significant differences between the groups with regards to change in frailty compared to baseline at any follow-up. At both the three-and twelve-month follow-ups the intervention group had doubled their odds for improved ADL independence compared to the control (OR 2.37, 95% CI; 1.20 - 4.68) and (2.04, 95% CI; 1.03 - 4.06) respectively. At six months the intervention group had halved their odds for decreased ADL independence (OR 0.52, 95% CI; 0.27 - 0.98) compared to the control group. Conclusions: The intervention has the potential to reduce dependency in ADLs, a valuable benefit both for the individual and for society.
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| 27. |
- Engström, Katarina, 1956, et al.
(author)
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The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
- 2006
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In: The American journal of pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 168:5, s. 1642-53
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Journal article (peer-reviewed)abstract
- Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.
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| 28. |
- Enocsson, Helena, et al.
(author)
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Soluble Urokinase Plasminogen Activator Receptor (suPAR) Independently Predicts Severity and Length of Hospitalisation in Patients With COVID-19
- 2021
-
In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
-
Journal article (peer-reviewed)abstract
- Background: Efficient healthcare based on prognostic variables in hospitalised patients with COVID-19 could reduce the risk of complications and death. Recently, soluble urokinase Plasminogen Activator Receptor (suPAR) was shown to predict respiratory failure, kidney injury, and clinical outcome in patients with SARS-CoV-2 infection. The aim of this study was to investigate the value of suPAR as a prognostic tool, in comparison with other variables, regarding disease severity and length of hospital stay in patients with COVID-19.Patients and Methods: Individuals hospitalised with COVID-19 (40 males, 20 females; median age 57.5 years) with a median symptom duration of 10 days and matched, healthy controls (n = 30) were included. Admission levels of suPAR were measured in serum by enzyme-linked immunosorbent assay. Blood cell counts, C-reactive protein (CRP) levels, lactate dehydrogenase (LDH), plasma creatinine and estimated glomerular filtration rates were analysed and oxygen demand, level of care and length of hospitalisation recorded.Results: Patients had significantly higher suPAR levels compared to controls (P < 0.001). Levels were higher in severely/critically (median 6.6 ng/mL) compared with moderately ill patients (median 5.0 ng/mL; P = 0.002). In addition, suPAR levels correlated with length of hospitalisation (rho = 0.35; P = 0.006). Besides suPAR, LDH, CRP, neutrophil count, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratio, body mass index and chronic renal failure were discriminators of COVID-19 severity and/or predictors of length of hospitalisation.Conclusion: Admission levels of suPAR were higher in patients who developed severe/critical COVID-19 and associated with length of hospital stay. In addition, we showed that suPAR functioned as an independent predictor of COVID-19 disease severity.
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| 29. |
- Filipsson, Helena L., 1973, et al.
(author)
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Seasonal study of delta O-18 and delta C-13 in living (stained) benthic foraminifera from two Swedish fjords
- 2004
-
In: Marine Micropaleontology. - : Elsevier BV. - 0377-8398. ; 53:1-2, s. 159-172
-
Journal article (peer-reviewed)abstract
- In a previous 16-month seasonal study on living (stained) benthic foraminifera from two fjords on the Swedish west coast, it was reported that foraminifera proliferated in response to phytodetritus input; the strongest response came from the opportunistic species Stainforthia fusiformis. In this study, our objective was to find out if that phytodetritus input resulted in a change in the carbon isotopic composition of the foraminiferal tests. We also wanted to examine if variations in salinity and temperature (due to seasonality or deep-water exchanges) were reflected in the delta(18)O values. From S. fusiformis that were obtained from the Havstens Fjord (20 m) and the Gullmar Fjord (119 m) during the 16-month study, we developed a time series of delta(18)O and delta(13)C. After the spring blooms in the Havstens and the Gullmar Fjord, decreases of about 0.2parts per thousand to 0.3parts per thousand in the foraminiferal delta(13)C values were noted; in the Gullmar Fjord after the autumn blooms, decreases of the same order were also noted. Comparing the Havstens and the Gullmar Fjord, we found a 1parts per thousand difference in both delta(13)C and delta(18)O; we attribute this to hydrographic differences between the two fjords. Using calculated values of delta(18)O, together with the measured ones, we noticed that S. fusiformis in the Gullmar Fjord seems to calcify close to equilibrium with respect to the oxygen isotopes. During autumn, water temperatures were relatively high in the Havstens Fjord, and foraminiferal abundance in the fjord was also high after a phytodetritus input; but, the measured delta(18)O values do not reflect these higher temperatures. This apparently contradictory combination of results might be explained by a varying delta(18)O composition of the water during the year, which counterbalances the temperature effect. (C) 2004 Published by Elsevier B.V.
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| 30. |
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| 31. |
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| 32. |
- Fritz, Helena, et al.
(author)
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The Axl-Regulating Tumor Suppressor miR-34a Is Increased in ccRCC but Does Not Correlate with Axl mRNA or Axl Protein Levels.
- 2015
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
-
Journal article (peer-reviewed)abstract
- High expression of the receptor tyrosine kinase Axl is associated with poor prognosis in patients with Renal Cell Carcinoma (RCC), the most common malignancy of the kidney. The miR-34a has been shown to directly regulate Axl in cancer cells. The miR-34a is a mediator of p53-dependent tumor suppression, and low expression of miR-34a has been associated with worse prognosis in several cancers. Our aim was to elucidate whether miR-34a or the other members of the miR-34 family (miR-34b/c) regulate Axl in RCC.
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| 33. |
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| 34. |
- Girhammar, Ulf Arne, 1948-, et al.
(author)
-
Stabilisering och bjälklag kritiska för höghus i trä
- 2011
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In: Husbyggaren. - Stockholm : Svenska Byggingenjörers Riksförbund. - 0018-7968. ; 53:1, s. 16-21
-
Journal article (pop. science, debate, etc.)abstract
- INDUSTRI- OCH KONTORSBYGGANDE Stabilisering och bjälklagsutformning är kritiska moment vid byggandet av flervåningshus i trä. Bjälklagen måste bland annat klara stora spännvidder. Nu finns en nyutvecklad plastisk metod som ska säkra horisontalstabilisering.
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| 35. |
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| 36. |
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| 37. |
- Golubinskaya, Veronika, 1974, et al.
(author)
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Bestrophin-3 Expression in a Subpopulation of Astrocytes in the Neonatal Brain After Hypoxic-Ischemic Injury
- 2019
-
In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
-
Journal article (peer-reviewed)abstract
- Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min. Endoplasmic reticulum stress was induced by thapsigargin treatment in primary culture of mouse brain astrocytes. We also investigated expression of bestrophin-3 protein in a sample of human neonatal brain tissue. Bestrophin-3 protein expression was detected with immunohistochemical methods and western blot; mRNA expression and splicing were analyzed by RT-PCR. HI induced a brain tissue infarct and a pronounced increase in the endoplasmic reticulum-associated marker CHOP. Three days after HI a population of astrocytes co-expressed bestrophin-3 and nestin in a penumbra-like area of the injured hemisphere. However, total levels of Bestrophin-3 protein in mouse cortex were reduced after injury. Mouse astrocytes in primary culture also expressed bestrophin-3 protein, the amount of which was reduced by endoplasmic reticulum stress. Bestrophin-3 protein was detected in astrocytes in the hippocampal region of the human neonatal brain which had patchy white matter gliosis and neuronal loss in the Sommer's sector of the Ammon's horn (CA1). Analysis of bestrophin-3 mRNA in mouse brain with and without injury showed the presence of two truncated spliced variants, but no full-length mRNA. Total amount of bestrophin-3 mRNA increased after HI, but showed only minor injury-related change. However, the splice variants of bestrophin-3 mRNA were differentially regulated after HI depending on the presence of tissue injury. Our results show that bestrophin-3 is expressed in neonatal mouse brain after injury and in the human neonatal brain with pathology. In mouse brain bestrophin-3 protein is upregulated in a specific astrocyte population after injury and is co-expressed with nestin. Splice variants of bestrophin-3 mRNA respond differently to HI, which might indicate their different roles in tissue injury.
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| 38. |
- Golubinskaya, Veronika, 1974, et al.
(author)
-
Bestrophin-3 is differently expressed in normal and injured mouse glomerular podocytes.
- 2015
-
In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 214:4, s. 481-496
-
Journal article (peer-reviewed)abstract
- Bestrophins are putative calcium-activated chloride channels. Recently cell-protective functions for Bestrophin-3 (Best3) were proposed. Best3 exists in different splice variants. We have here examined expression, alternative splicing and localization of Best3 in mouse podocytes under normal conditions and during endoplasmic reticulum (ER) stress.
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| 39. |
- Gundale, Michael, et al.
(author)
-
The sensitivity of nitrogen fixation by a feathermoss-cyanobacteria association to litter and moisture variability in young and old boreal forests
- 2009
-
In: Canadian Journal of Forest Research. - 0045-5067 .- 1208-6037. ; 39, s. 2542-2549
-
Journal article (peer-reviewed)abstract
- We conducted a pair of experiments to assess whether nitrogen (N) fixation by a feathermoss-cyanobacteria association was sensitive to moisture availability and quality of litter inputs, and whether sensitivity to these factors differed between young and old forests. In our first greenhouse experiment, we experimentally varied the frequency of water addition to Pleurozium schreberi (Brid.) Mitt. collected from young and old forest sites. This experiment revealed that the extreme drought treatment reduced N fixation capacity (measured via acetylene reduction), whereas daily watering increased N fixation capacity. The experiment also demonstrated that sensitivity to moisture variability was greater in old forests than in young forests. In a second greenhouse experiment, we repeatedly applied litter extracts from six common boreal species, Pinus sylvestris L., Picea abies (L.) Karst., Betula pubescens Ehrh., Vaccinium myrtillus L., Vaccinium vitis-idaea L., and Empetrum hermaphroditum Lange ex Hagerup. After 43 days, we found no significant effects of litter or litter by stand age interaction on N fixation capacity of P. schreberi, whereas stand age remained a significant factor. These experiments suggest that the N fixation capacity of the P. schreberi - cyanobacteria association is relatively resistant to short-term variation of litter as an environmental driver but that precipitation extremes in old forests may significantly alter the N fixation capacity of the association.
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| 40. |
- Gupta, Dhanu, et al.
(author)
-
Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
- 2021
-
In: Nature Biomedical Engineering. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 2157-846X.
-
Journal article (peer-reviewed)abstract
- Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.
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| 41. |
- Gustafsson, Anna, et al.
(author)
-
Gas6-Axl signaling in presence of Sunitinib is enhanced, diversified and sustained in renal tumor cells, resulting in tumor-progressive advantages
- 2017
-
In: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 355:1, s. 47-56
-
Journal article (peer-reviewed)abstract
- Clear Cell Renal Cell Carcinoma (CCRCC) is a lethal cancer with bad prognosis due to development of chemoresistance and recurrence of more aggressive tumors. Investigation of Gas6-mediated Axl signaling in CCRCC and endothelial cells reveals a Sunitinib resistant Gas6-Axl signaling that is sustained and enhanced and specifically triggers downstream AKT and PRAS40 activation in an intensified manner. Gas6-induced Axl signaling in presence of Sunitinib is also diversified displaying onset of Axl-dependent EGFR and METR activation and activation of classical MAPK pathways. Gas6+Sunitinib-adapted CCRCC cells present increased viability and decreased apoptosis and enhanced production of the multi-tumorigenic Osteopontin (OPN) and of one of its activator matrix metalloproteinase-7. Axl activity is necessary for CCRCC cell sphere formation and the ability of the cells to attach after non-adhesive growth. In addition, Gas6+Sunitinib-adapted CCRCC cells displayed enhanced migration and sphere formation, both mechanisms being Axl and OPN dependent. Altogether, this suggests that Sunitinib while targeting endothelial cells and tumor angiogenesis, simultaneously provides protumorigenic effects due to a constitutively, intensified and divergent Gas6-Axl system. Implications: Gas6-mediated Axl signaling, which is enhanced and diversified in the presence of Sunitinib possibly contributes to acquired chemoresistance, recurrence of aggressive disease and metastasis of CCRCC tumors. Therefore, combinatorial Axl-targeted therapy might be beneficial for CCRCC patients intended for Sunitinib treatment.
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| 42. |
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| 43. |
- Gustafsson Asting, Annika, et al.
(author)
-
COX-2 Gene Expression in Colon Cancer Tissue related to Regulating Factors and Promoter Methylation Status
- 2011
-
In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
-
Journal article (peer-reviewed)abstract
- Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.
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| 44. |
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| 45. |
- Gustafsson, Dan, et al.
(author)
-
Tissue zinc levels in a child with hypercalprotectinaemia and hyperzincaemia : a case report and a review of the literature
- 2012
-
In: Scandinavian Journal of Clinical and Laboratory Investigation. - London, United Kingdom : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 72:1, s. 34-38
-
Research review (peer-reviewed)abstract
- Background: A girl suffering from a rare syndrome of unknown aetiology, termed hypercalprotectinaemia, was evaluated for tissue zinc status, because calprotectin is a protein which chelates Zn at multiple binding-sites, which might have affected the distribution of Zn in her body.Methods: Measurement of serum, urine, hair and nail zinc (Zn) concentration, complemented with measurement of total Zn in ultrafiltrates of plasma.Results: Her serum Zn concentration was 105-133 mu mol/L. Zn levels in her hair (102 mu g/g), nail (90 mu g/g) and urine (3-12 mu mol/L; 20-80 mu g/dL) were all at the lower end of the reference intervals described in the sparse literature. Zn concentrations in ultrafiltrates of plasma were below the detection limit (<100 nmol/L). Thus, the elevated serum Zn did not translate into a similarly increased level of Zn in any of the tissues tested, nor in free Zn concentrations. Instead it appeared to be a result of Zn being chelated to binder proteins, most probably calprotectin.Conclusion: Her grossly elevated serum calprotectin concentration is probably able to raise circulating total Zn concentrations without raising ionized concentrations, but this Zn remains confined to the circulating blood as well as to excreted body fluids, particularly faeces.
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| 46. |
- Gustafsson, Erik, et al.
(author)
-
Invasive Staphylococcus aureus strains are highly variable in PFGE patterns, agr group and exoprotein production
- 2009
-
In: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 41:8, s. 577-583
-
Journal article (peer-reviewed)abstract
- In the present study, we have investigated 37 invasive Staphylococcus aureus strains (collected between 1997 and 2005) from 33 human episodes of septicaemia causing either endocarditis or vertebral osteomyelitis. All S. aureus strains were typed using pulsed field gel electrophoresis (PFGE), and most strains belonged to any of 4 different PFGE clusters. There was no correlation between any of the PFGE clusters with site of infection. All strains showed highly different expression patterns of extracellular proteins, i.e. we found a vast variation in the number of proteins and amount of individual proteins expressed by the different strains. There was no correlation between any cluster of exoprotein patterns with endocarditis or with vertebral osteomyelitis. We did not find any correlation between agr group and endocarditis, as previously reported. On the other hand, a correlation between some of the PFGE clusters with a certain agr group was found. Known risk factors for S. aureus infections were observed in a majority of the patients.
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| 47. |
- Gustafsson (Emilsson), Sara, Biträdande professor, 1974-, et al.
(author)
-
Lokal implementering av Agenda 2030 och Globala målen : en kort översikt av regioners och kommuners erfarenheter, möjligheter och utmaningar
- 2018
-
Reports (other academic/artistic)abstract
- Med Agenda 2030 och FN:s 17 Globala mål för hållbar utveckling initierades en ny era för det globala hållbarhetsarbetet med tydligt fokus på målstyrning, där samverkan och integration är nyckelbegrepp. Globala målen skulle kunna bidra till ett mer proaktivt och allomfattande hållbarhetsarbete genom att arbetet bättre operationaliseras och integreras i såväl internationella, nationella, regionala som lokala policyer och strategier. Men det kan också finnas en risk att denna nya globala Agenda kan leda till det bara är retoriken och inramningen som ändras och inte praktiken. Hur man ska gå tillväga på regional och lokal nivå för att implementera Globala målen finns inte särskilt tydligt beskrivet i Agenda 2030. Det pågår dock mycket aktivitet kopplat till de globala målen på såväl regional som lokal nivå, vilket betyder att erfarenhetsbanken för implementering av de globala målen växer för varje dag.Regioner och kommuner är institutioner som står för kontinuitet och långsiktighet i det lokala och regionala hållbarhetsarbetet. Då flera av målen är av mellankommunal och kommunal art skulle de regionala och lokala nivåerna kunna utgöra eller bidra till plattformar och ha samordnande roller för strategisk samverkan kring hållbarhetsfrågor i allmänhet och de globala målen i synnerhet.Det finns redan ett utvecklat hållbarhetsarbete inom kommuner och regioner. Därför är det viktigt att reflektera över hur det kan förhållas till de Globala målen för undersöka hur de kan integreras i processerna istället för att bli separata projekt. Det är även viktigt att reflektera över redan existerande samverkansformer och arenor. De globala målen skulle kunna ses som ett instrument för att samordna den flora av hållbarhetsinitiativ som redan finns i de regionala och kommunala kontexterna, vilket skulle kunna bidra till att man ökar verkningsfullheten i det existerande hållbarhetsarbetet och ”levlar” (höjer) hållbarhetsprestandan till nästa nivå.Den här rapporten, som är en förstudie, är den första inom forskningsprojektet ”Förbättrad regional och lokalhållbarhetsprestanda genom integrering av FN:s globala hållbarhetsmål (LETS[1]). Projektet fyller en viktig funktion i att samla, sammanställa, analysera och kommunicera erfarenheter och därmed bidra med ny kunskap och inspiration till tillvägagångssätt för regioner och kommuner som står i begrepp att integrera de globala målen. Syftet med den här studien, som är en förstudie till LETS, och den här rapporten är inte att var heltäckande och allomfattande, utan den fyller främst funktionen att utgöra underlag för de kommande etapperna i forskningsprojektet LETS vad gäller tex. urval av djupstudieobjekt, litteratursökning etc. Den ger en översiktlig bild av kunskapsläget våren 2018 med utgångspunkt från forskningsfrågorna i forskningsprojektet LETS. Syftet med att sammanställa det här underlaget i en rapport fyller förhoppningsvis en funktion som inspiration till de kommuner och regioner som idag är i eller ska påbörja processen att implementera Globala målen.Studien baseras på dels en genomgång av vetenskaplig litteratur och andra rapporter och dels en övergripande intervjustudie med miljö/hållbarhetsstrateger (eller motsvarande) i 15 kommuner och 4 regioner i Sverige. Medan litteraturstudien har ett internationellt perspektiv är intervjustudien mer fokuserad till svenska förhållanden (vilket också är fokus för forskningsprojektet LETS).I litteraturundersökningen har vi även gått tillbaka till tidigare globala initiativ, som Agenda 21 och Milleniemålen, för att reflektera över vilka lärdomar som kan dras från dessa processer och hur det kan utnyttjas i arbetet med de Globala målen.De globala målen har beskrivits i en rad olika publikationer under de senaste åren, men är först nyligen dessa har börjat ge exempel på hur målen omsatts i praktik, vilket ju inte är särskilt överraskande. Utifrån de artiklar och rapporter vi studerat för den här rapporten har vi valt ut ett antal teman, utifrån forskningsprojektets övergripande syfte och frågeställningar. Rapporten ger bland annat exempel på de utmaningar och möjligheter med regional och lokal implementering som vi identifierat i litteraturen. Många av både möjligheterna och utmaningarna som litteraturen beskriver handlar om samverkan och det tvärsektoriella arbetssättet. Den inneboende komplexiteten hos de Globala målen seglar upp som en av utmaningarna, och detta kopplat till hur En av utmaningarna, som nämns på flera ställen i litteraturen är Globala målens inneboende komplexitet och svårigheten att anpassa målen och indikatorerna till lokal nivå. Andra utmaningar som identifierats är svårigheten att samla intressenter med rätt kunskap och engagemang. Vidare diskuteras data som en utmaning och då handlar det om tillgång till data och tillgång till tillförlitliga data. Samordning kunskap är andra aspekter som pekas ut som utmaningar. Bland de möjligheter som vi identifierat i litteraturgenomgången. När det gäller utmaningar handlar det mycket om att hållbarhetsarbetet kan få ett uppsving, att det kan underlätta beslutsfattande, öka resurseffektivitet samt underlätta för kunskapsbyggande. Vidare nämns att detta gemensamma ramverk skulle kunna underlätta för att visualisera och jämföra hållbarhetsarbetet mellan olika organisationer samt att det kn underlätta för samarbete kring dessa frågor eftersom man pratar samma hållbarhetsspråk.Det finns även ett stort antal vetenskapliga artiklar och olika rapporter som beskriver olika slags verktyg som ska stötta och underlätta för implementeringen av Globala målen. Det finns verktyg som ger stöd till såväl inventering som mätning och uppföljning. Men det finns också verktyg för att underlätta samverkan mellan olika aktörer.Utifrån de intervjuer vi gjort för den här studien kan vi konstatera att många kommuner och regioner är i uppstartsfasen av att implementera Global målen. Det handlar i stor utsträckning om att integrera målen i strategier och att förankra och kommunicera. Utifrån intervjuerna kan vi utläsa att den främsta potentialen som kommunerna och regionerna i den här studien ser med Globala målen handlar om att få struktur och stöd i sina processer för hållbar utveckling. En annan potential är att få ett gemensamt hållbarhetsspråk som fungerar över organisationsgränser och nationsgränser. De hinder som kommunerna och regionerna upplever är framförallt koppade till svårigheten att konkretisera Globala målen och att omsätta dem i lokal praktik i kärnverksamheten. En annan utmaning som flera nämnde var svårigheten att mäta och följa upp arbetet med målen.Trots att vi har identifierat en mängd utmaningar, både genom litteraturgenomgången och i de intervjuer vi gjort för den här studien, ser vi också att det finns en tilltro till och en potential i att implementera Globala målen i regioner och kommuner. Genom att utgå från redan existerande hållbarhetsarbete, identifiera vad som redan görs och hur det kan stärkas upp genom tydligare koppling till Globala målen skulle de kunna underlätta för ett mer sammanhållet och systematiskt hållbarhetsarbete internt i organisationerna men även för samverkan kring dessa frågor med andra aktörer. Tid är en viktig resurs i detta sammanhang och därför behöver det avsättas tid för att jobba med dessa frågor i organisationerna och man måste låta arbetet ta tid. 2030 är inte långt borta, men hållbarhetsarbetet i kommunerna och regionerna behöver ett längre perspektiv än så.
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| 48. |
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| 49. |
- Gustafsson, Helena, et al.
(author)
-
Depression and subsequent risk of Parkinson disease : A nationwide cohort study
- 2015
-
In: Neurology. - 0028-3878 .- 1526-632X. ; 84:24, s. 2422-2429
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the long-term risk of Parkinson disease (PD) after depression and evaluate potential confounding by shared susceptibility to the 2 diagnoses.METHODS: The nationwide study cohort included 140,688 cases of depression, matched 1:3 using a nested case-control design to evaluate temporal aspects of study parameters (total, n = 562,631). Potential familial coaggregation of the 2 diagnoses was investigated in a subcohort of 540,811 sibling pairs. Associations were investigated using multivariable adjusted statistical models.RESULTS: During a median follow-up period of 6.8 (range, 0-26.0) years, 3,260 individuals in the cohort were diagnosed with PD. The multivariable adjusted odds ratio (OR) for PD was 3.2 (95% confidence interval [CI], 2.5-4.1) within the first year of depression, decreasing to 1.5 (95% CI, 1.1-2.0) after 15 to 25 years. Among participants with depression, recurrent hospitalization was an independent risk factor for PD (OR, 1.4; 95% CI, 1.1-1.9 for ≥5 vs 1 hospitalization). In family analyses, siblings' depression was not significantly associated with PD risk in index persons (OR, 1.1; 95% CI, 0.9-1.4).CONCLUSIONS: The time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for coaggregation among siblings all indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than 2 decades, depression may be a very early prodromal symptom of PD, or a causal risk factor.
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| 50. |
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