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Sökning: WFRF:(Simonsen Anne)

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1.
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2.
  • Blauenfeldt, Rolf Ankerlund, et al. (författare)
  • Remote Ischemic Conditioning for Acute Stroke : The RESIST Randomized Clinical Trial
  • 2023
  • Ingår i: JAMA. - 0098-7484. ; 330:13, s. 1236-1246
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P =.67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P =.68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.
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3.
  • Hörder, Helena M, et al. (författare)
  • Home as a health promotion setting for older adults
  • 2014
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 42:Suppl 15, s. 36-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The number and the proportion of older persons is growing in the Nordic Countries. The growth in the older population has a clear impact on the care system for older persons. One trend is to prioritise home care instead of care in institutions. Another trend is to emphasise preventive and health promotion care. As official guidelines in the Nordic countries state that home is the best place to grow old, it is essential that older persons keep their health and functional capacity in order to be able to live at home for as long as possible. As current policy emphasises living at home, home care, preventive work and health promotion it becomes essential to study the home as a health promotion setting. Objective: The aim of this study was to reach a new understanding of home as a health promotion setting for older persons. Study design: The method used was a literature reflection and analysis with a hermeneutical approach. Results: The results show that with increasing age the home environment becomes a crucial determinant for independence. The home environment supports the self as people age; it has associations with the past, can provide proximity to family, and a sense of being a part of neighbourhood life. Conclusions: Only by taking into consideration the meaning of home and the resources of the individual older person can home function as a true health promoting setting. If health personnel focus solely on risk prevention, they can neglect the perspectives of the older person, resulting in dis-empowerment not health promotion.
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4.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Nivestam, Anna, et al. (författare)
  • Health promotion in ageing research in a Nordic context: : A scoping review of doctoral theses
  • 2023
  • Konferensbidrag (refereegranskat)abstract
    • Background: This scoping review is conducted by the ‘healthy ageing’ research group which is part of the Nordic Health Promotion Research Network. Aim: The overall aim is to explore how ageing research under the label ‘health promotion’ is undertaken in a Nordic context. Method: A scoping review method is used where different data bases in Denmark, Finland, Norway, and Sweden were searched for theses published between the years 2011 and 2021. Findings: The preliminary results show that both qualitative and quantitative methods were used. Data was collected mainly from healthy older-home dwelling persons. Theoretical perspectives varied and were sometimes absent. This also applied to definitions of health promotion. The number of thesis published differed between the Nordic countries. Conclusion: To conclude, doctoral theses within the field of healthy ageing research must be more specific about the meaning and use of the concept of Health Promotion. The use of a health promotive theoretical perspectives could help develop a solid theoretical foundation that could guide healthy ageing research.
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6.
  • Ahrensbøll-Friis, Ulrik, et al. (författare)
  • Allergic contact dermatitis from dyes used in the temple of spectacles
  • 2022
  • Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:1, s. 25-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We observed an increasing number of patients who presented with facial or retro-auricular dermatitis after skin contact with plastic spectacles or plastic covered temples. Objectives: To identify the allergens in plastic spectacles that may cause allergic contact dermatitis. Methods: All patients with suspected allergic contact dermatitis to eyewear were tested with Solvent Orange 60 (SO60), four additionally with Solvent Yellow 14 (SY14), and five with scrapings from their own spectacles. In one case, a chemical analysis of the spectacles was performed to uncover the causative allergen. Results: Three patients were allergic to SO60, two patients to SY14, and two patients were allergic to both SO60 and SY14. Conclusion: Patients with suspected allergic contact dermatitis from spectacles should be tested with SO60 and SY14, and based on findings from previous reports, also with Solvent Red 179.
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7.
  • Carlsson, Sven R, et al. (författare)
  • Membrane dynamics in autophagosome biogenesis
  • 2015
  • Ingår i: Journal of Cell Science. - : The Company of Biologists LTD. - 0021-9533 .- 1477-9137. ; 128:2, s. 193-205
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Bilayered phospholipid membranes are vital to the organization of the living cell. Based on fundamental principles of polarity, membranes create borders allowing defined spaces to be encapsulated. This compartmentalization is a prerequisite for the complex functional design of the eukaryotic cell, yielding localities that can differ in composition and operation. During macroautophagy, cytoplasmic components become enclosed by a growing double bilayered membrane, which upon closure creates a separate compartment, the autophagosome. The autophagosome is then primed for fusion with endosomal and lysosomal compartments, leading to degradation of the captured material. A large number of proteins have been found to be essential for autophagy, but little is known about the specific lipids that constitute the autophagic membranes and the membrane modeling events that are responsible for regulation of autophagosome shape and size. In this Commentary, we review the recent progress in our understanding of the membrane shaping and remodeling events that are required at different steps of the autophagy pathway.
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8.
  • Carlsson, Sven R, 1952-, et al. (författare)
  • Recycling endosomes and autophagy
  • 2015
  • Ingår i: Cell Technology (Saibou Kougaku). - Tokyo : Gakken Medical Shujunsha Co.. ; 34:2, s. 138-142
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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9.
  • Corkery, Dale, et al. (författare)
  • Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy
  • 2021
  • Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Autophagy plays an essential role in the defense against manymicrobial pathogens as a regulator of both innate and adaptive immunity. Some pathogens have evolved sophisticated mechanisms that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered Vibrio cholerae cytotoxin, motility-associatedkilling factor A (MakA). pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 (herein referring to MAP1LC3B) lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex, required for LC3 lipidation at the membranous aggregate, resulted in an inhibition of both canonical autophagy and autophagy-related processes, including the unconventional secretion of interleukin-1β (IL-1β). These findings identify a novel mechanismof host autophagy modulation and immune modulation employed by V. cholerae during bacterial infection.
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10.
  • Durgan, Joanne, et al. (författare)
  • Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine
  • 2021
  • Ingår i: Molecular Cell. - : Elsevier. - 1097-2765 .- 1097-4164. ; 81:9, s. 2031-2040
  • Tidskriftsartikel (refereegranskat)abstract
    • Autophagy is a fundamental catabolic process that uses a unique post-translational modification, the conjugation of ATG8 protein to phosphatidylethanolamine (PE). ATG8 lipidation also occurs during non-canonical autophagy, a parallel pathway involving conjugation of ATG8 to single membranes (CASM) at endolysosomal compartments, with key functions in immunity, vision, and neurobiology. It is widely assumed that CASM involves the same conjugation of ATG8 to PE, but this has not been formally tested. Here, we discover that all ATG8s can also undergo alternative lipidation to phosphatidylserine (PS) during CASM, induced pharmacologically, by LC3-associated phagocytosis or influenza A virus infection, in mammalian cells. Importantly, ATG8-PS and ATG8-PE adducts are differentially delipidated by the ATG4 family and bear different cellular dynamics, indicating significant molecular distinctions. These results provide important insights into autophagy signaling, revealing an alternative form of the hallmark ATG8 lipidation event. Furthermore, ATG8-PS provides a specific “molecular signature” for the non-canonical autophagy pathway.
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11.
  • Eriksson, Andrea, et al. (författare)
  • How is health promotion research undertaken in a Nordic context? : A scoping review on doctoral dissertations from 2008-2018
  • 2020
  • Ingår i: Socialmedicinsk Tidskrift. - 0037-833X. ; 97:3, s. 488-502
  • Tidskriftsartikel (refereegranskat)abstract
    • This scoping review was commenced as a collaboration within the NordicHealth Promotion Research Network (NHPRN). The overall aim was to explore how research under the label ‘health promotion’ was undertaken in a Nordic context. The search for dissertations published in Denmark, Finland, Iceland, Norway and Sweden was limited to the years 2008 to 2018. Manual searches of university websites, as well as different databases in the Nordic countries, were required for collecting dissertations from all universities. The collection of dissertations was more difficult than expected. There were 56 published PhD dissertations from 6 universities in Denmark, 51 from 8 universities in Finland, 0 from Iceland, 53 from 7 universities in Norway and 193 from 22 universities in Sweden. Almost half of the analysed dissertations combined qualitative and quantitative methods. About one-third of the dissertations had a settings approach, followed by a societal approach and individual approach. Finland and Sweden presented more intervention studies than the other countries. A majority of the intervention studies included individual lifestyle issues. Based on the analysis of the research approaches, more dissertations embracing societal perspectives and broader determinants of health may be recommended for future Nordic dissertations.
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13.
  • Giovannucci, Tatiana A., et al. (författare)
  • Identification of a novel compound that simultaneously impairs the ubiquitin-proteasome system and autophagy
  • 2022
  • Ingår i: Autophagy. - : Taylor & Francis. - 1554-8627 .- 1554-8635. ; 18:7, s. 1486-1502
  • Tidskriftsartikel (refereegranskat)abstract
    • The ubiquitin-proteasome system (UPS) and macroautophagy/autophagy are the main proteolytic systems in eukaryotic cells for preserving protein homeostasis, i.e., proteostasis. By facilitating the timely destruction of aberrant proteins, these complementary pathways keep the intracellular environment free of inherently toxic protein aggregates. Chemical interference with the UPS or autophagy has emerged as a viable strategy for therapeutically targeting malignant cells which, owing to their hyperactive state, heavily rely on the sanitizing activity of these proteolytic systems. Here, we report on the discovery of CBK79, a novel compound that impairs both protein degradation by the UPS and autophagy. While CBK79 was identified in a high-content screen for drug-like molecules that inhibit the UPS, subsequent analysis revealed that this compound also compromises autophagic degradation of long-lived proteins. We show that CBK79 induces non-canonical lipidation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) that requires ATG16L1 but is independent of the ULK1 (unc-51 like autophagy activating kinase 1) and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes. Thermal preconditioning of cells prevented CBK79-induced UPS impairment but failed to restore autophagy, indicating that activation of stress responses does not allow cells to bypass the inhibitory effect of CBK79 on autophagy. The identification of a small molecule that simultaneously impairs the two main proteolytic systems for protein quality control provides a starting point for the development of a novel class of proteostasis-targeting drugs.
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14.
  • Gravningen, Kirsten, et al. (författare)
  • Multilocus Sequence Typing of Genital Chlamydia trachomatis in Norway Reveals Multiple New Sequence Types and a Large Genetic Diversity
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e34452-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Chlamydia trachomatis incidence rate in Finnmark, the most northern and sparsely populated county in Norway, has been twice the national average. This population based cross-sectional study among Finnmark high school students had the following aims: i) to examine distribution of multilocus sequence types (STs) of C. trachomatis in a previously unmapped area, ii) to compare chlamydia genetic diversity in Finnmark with that of two urban regions, and iii) to compare discriminatory capacity of multilocus sequence typing (MLST) with conventional ompA sequencing in a large number of chlamydia specimens. Methodology: ompA sequencing and a high-resolution MLST system based on PCR amplification and DNA sequencing of five highly variable genetic regions were used. Eighty chlamydia specimens from adolescents aged 15-20 years in Finnmark were collected in five high schools (n = 60) and from routine clinical samples in the laboratory (n = 20). These were compared to routine clinical samples from adolescents in Tromso (n = 80) and Trondheim (n = 88), capitals of North and Central Norway, respectively. Principal Findings: ompA sequencing detected 11 genotypes in 248 specimens from all three areas. MLST displayed 50 STs providing a five-fold higher resolution. Two-thirds of all STs were novel. The common ompA E/Bour genotype comprised 46% and resolved into 24 different STs. MLST identified the Swedish new variant of C. trachomatis not discriminated by ompA sequencing. Simpson's discriminatory index (D) was 0.93 for MLST, while a corrected D-c was 0.97. There were no statistically significant differences in ST genetic diversity between geographic areas. Finnmark had an atypical genovar distribution with G being predominant. This was mainly due to expansion of specific STs of which the novel ST161 was unique for Finnmark. Conclusions/Significance: MLST revealed multiple new STs and a larger genetic diversity in comparison to ompA sequencing and proved to be a useful tool in molecular epidemiology of chlamydia infections.
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15.
  • Holland, Petter, et al. (författare)
  • HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1-and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes. We propose that HS1BP3 regulates autophagy by modulating the PA content of the ATG16L1-positive autophagosome precursor membranes through PLD1 activity and localization. Our findings provide key insights into how autophagosome formation is regulated by a novel negative-feedback mechanism on membrane lipids.
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16.
  • Kaur, Namrita, et al. (författare)
  • TECPR1 is activated by damage-induced sphingomyelin exposure to mediate noncanonical autophagy
  • 2023
  • Ingår i: EMBO Journal. - : EMBO Press. - 0261-4189 .- 1460-2075. ; 42:17
  • Tidskriftsartikel (refereegranskat)abstract
    • Cells use noncanonical autophagy, also called conjugation of ATG8 to single membranes (CASM), to label damaged intracellular compartments with ubiquitin-like ATG8 family proteins in order to signal danger caused by pathogens or toxic compounds. CASM relies on E3 complexes to sense membrane damage, but so far, only the mechanism to activate ATG16L1-containing E3 complexes, associated with proton gradient loss, has been described. Here, we show that TECPR1-containing E3 complexes are key mediators of CASM in cells treated with a variety of pharmacological drugs, including clinically relevant nanoparticles, transfection reagents, antihistamines, lysosomotropic compounds, and detergents. Interestingly, TECPR1 retains E3 activity when ATG16L1 CASM activity is obstructed by the Salmonella Typhimurium pathogenicity factor SopF. Mechanistically, TECPR1 is recruited by damage-induced sphingomyelin (SM) exposure using two DysF domains, resulting in its activation and ATG8 lipidation. In vitro assays using purified human TECPR1-ATG5-ATG12 complex show direct activation of its E3 activity by SM, whereas SM has no effect on ATG16L1-ATG5-ATG12. We conclude that TECPR1 is a key activator of CASM downstream of SM exposure.
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17.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
  • 2008
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
  • Forskningsöversikt (refereegranskat)abstract
    • Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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18.
  • Knævelsrud, Helene, et al. (författare)
  • Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation
  • 2013
  • Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 202:2, s. 331-349
  • Tidskriftsartikel (refereegranskat)abstract
    • The membrane remodeling events required for autophagosome biogenesis are still poorly understood. Because PX domain proteins mediate membrane remodeling and trafficking, we conducted an imaging-based siRNA screen for autophagosome formation targeting human PX proteins. The PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation, and its Drosophila melanogaster homologue SH3PX1 was found to be required for efficient autophagosome formation in the larval fat body. We show that SNX18 is required for recruitment of Atg16L1-positive recycling endosomes to a perinuclear area and for delivery of Atg16L1- and LC3-positive membranes to autophagosome precursors. We identify a direct interaction of SNX18 with LC3 and show that the pro-autophagic activity of SNX18 depends on its membrane binding and tubulation capacity. We also show that the function of SNX18 in membrane tubulation and autophagy is negatively regulated by phosphorylation of S233. We conclude that SNX18 promotes autophagosome formation by virtue of its ability to remodel membranes and provide membrane to forming autophagosomes.
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19.
  • Knævelsrud, Helene, et al. (författare)
  • SNX18 tubulates recycling endosomes for autophagosome biogenesis
  • 2013
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 9:10, s. 1639-1641
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of membrane remodeling and phosphoinositide-binding proteins in autophagy remains elusive. PX domain proteins bind phosphoinositides and participate in membrane remodeling and trafficking events and we therefore hypothesized that one or several PX domain proteins are involved in autophagy. Indeed, the PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation using an image-based siRNA screen. We show that SNX18 interacts with ATG16L1 and LC3, and functions downstream of ATG14 and the class III PtdIns3K complex in autophagosome formation. SNX18 facilitates recruitment of ATG16L1 to perinuclear recycling endosomes, and its overexpression leads to tubulation of ATG16L1- and LC3-positive membranes. We propose that SNX18 promotes LC3 lipidation and tubulation of recycling endosomes to provide membrane for phagophore expansion.
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20.
  • Knævelsrud, Helene, et al. (författare)
  • The membrane-remodeling PX-BAR protein SNX18 is required for autophagy
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Autophagy is a catabolic pathway targeting cytoplasmic material for lysosomal degradation,thereby protecting cells from accumulation of toxic components and enabling cells to survivescarce nutrient supplies. Macroautophagy is characterized by the sequestration of cytoplasmicmaterial into double-membrane vesicles, but the membrane remodeling events required forformation of autophagic vesicles are still not completely understood. However, the class IIIphosphatidylinositol 3-kinase (PI3K)/Vps34 complex and phosphatidylinositol-3-phosphate(PI3P) are of core importance to induction of autophagy. Since PX domain containingproteins are known to bind PI3P and other phosphoinositides and mediate membraneremodeling and trafficking events, we performed an imaging-based siRNA screen targetingPX domain proteins using formation of GFP-LC3 positive autophagosomes as a read-out.The PX-BAR protein SNX18 was found to strongly inhibit autophagosome formation. In linewith this, overexpression of SNX18 increased LC3 lipidation and GFP-LC3 spot formationand we demonstrate that membrane binding of SNX18 is required for efficientautophagosome formation. Moreover, SNX18 colocalizes and interacts with the autophagyassociatedproteins LC3 and TBK1. Our study identified the PX-BAR protein SNX18 to beinvolved in membrane events required for autophagosome formation.
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21.
  • Koponen, Anne M., et al. (författare)
  • Health-care climate, perceived self-care competence, and glycemic control among patients with type 2 diabetes in primary care
  • 2015
  • Ingår i: Health Psychology Open. - : Sage Publications. - 2055-1029. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • This study showed, in line with self-determination theory, that glycemic control among patients with type 2 diabetes (n=2866) was strongly associated with perceived self-care competence, which in turn was associated with autonomous motivation and autonomy-supportive health-care climate. These associations remained after adjusting for the effect of important life-context factors. Autonomous motivation partially mediated the effect of health-care climate on perceived competence, which fully mediated the effect of autonomous motivation on glycemic control. The results of the study emphasize health-care personnel's important role in supporting patients' autonomous motivation and perceived self-care competence.
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22.
  • Koponen, Anne M., et al. (författare)
  • How to promote fruits, vegetables, and berries intake among patients with type 2 diabetes in primary care? : A self-determination theory perspective
  • 2019
  • Ingår i: Health Psychology Open. - : Sage Publications. - 2055-1029. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The results of this study showed the importance of autonomous motivation for healthy eating. Autonomous motivation and female gender were the determinants most strongly associated with fruits, vegetables, and berries intake among patients with type 2 diabetes. Other determinants of fruits, vegetables, and berries intake were high education, high social support, high age, and a strong sense of coherence. Autonomous motivation and self-care competence mediated the effect of perceived autonomy support from a physician on fruits, vegetables, and berries intake. Thus, physicians can promote patients’ fruits, vegetables, and berries intake by supporting their autonomous motivation and self-care competence. The results are in line with self-determination theory.
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23.
  • Koponen, Anne M., et al. (författare)
  • Success in increasing physical activity (PA) among patients with type 2 diabetes : a self-determination theory perspective
  • 2018
  • Ingår i: Health Psychology and Behavioral Medicine. - : Taylor & Francis. - 2164-2850. ; 6:1, s. 104-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Increased physical activity (PA) is crucial for achieving and maintaining glycemic control and is beneficial for overall well-being of patients with type 2 diabetes as well. Despite that, many patients fail to make changes in their exercise behavior. Self-determination theory (SDT) addresses this problem and suggests that perceived autonomy support, autonomous motivation and self-care competence play a key role in the process of health behavior change. This study investigated the impact of these three factors on success in increasing PA among patients with type 2 diabetes but considered also the role of other important life-context factors, such as mental health, stress and social support. The effect of these other factors may outweigh the effect of SDT constructs; however, previous studies based on SDT have largely overlooked them. Methods: This cross-sectional mail survey was carried out in 2011. Out of 2866 respondents, those who had been over 2 years in care in their present and principal primary care health center and had during the past two years tried to increase PA either with or without success (n = 1256, mean age 63 years, 52% men), were included in this study. Logistic regression and mediation analyses were the main methods used in the data analysis. Results: Autonomous motivation predicted success in increasing PA even after controlling for the effect of other important life-context factors. Other predictors of success were felt energy, good perceived health, younger age and less social support. Autonomous motivation mediated the effect of perceived autonomy support from a doctor on success in increasing PA. Conclusion: The results were in line with SDT showing the importance of autonomous motivation for success in increasing PA. Doctor-patient relationships and lifestyle interventions should focus on promoting self-motivated reasons for health behavior change.
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24.
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25.
  • Lystad, Aif Hakon, et al. (författare)
  • Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes
  • 2019
  • Ingår i: Nature Cell Biology. - : NATURE PUBLISHING GROUP. - 1465-7392 .- 1476-4679. ; 21:3, s. 372-383
  • Tidskriftsartikel (refereegranskat)abstract
    • Covalent modification of LC3 and GABARAP proteins to phosphatidylethanolamine in the double-membrane phagophore is a key event in the early phase of macroautophagy, but can also occur on single-membrane structures. In both cases this involves transfer of LC3/GABARAP from ATG3 to phosphatidylethanolamine at the target membrane. Here we have purified the full-length human ATG12-5-ATG16L1 complex and show its essential role in LC3B/GABARAP lipidation in vitro. We have identified two functionally distinct membrane-binding regions in ATG16L1. An N-terminal membrane-binding amphipathic helix is required for LC3B lipidation under all conditions tested. By contrast, the C-terminal membrane-binding region is dispensable for canonical autophagy but essential for VPS34-independent LC3B lipidation at perturbed endosomes. We further show that the ATG16L1 C-terminus can compensate for WIPI2 depletion to sustain lipidation during starvation. This C-terminal membrane-binding region is present only in the beta-isoform of ATG16L1, showing that ATG16L1 isoforms mechanistically distinguish between different LC3B lipidation mechanisms under different cellular conditions.
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26.
  • Lystad, Alf Håkon, et al. (författare)
  • Toward the function of mammalian ATG12-ATG5-ATG16L1 complex in autophagy and related processes
  • 2019
  • Ingår i: Autophagy. - : Taylor & Francis Group. - 1554-8627 .- 1554-8635. ; 15:8, s. 1485-1486
  • Tidskriftsartikel (refereegranskat)abstract
    • The machinery that decorates autophagic membranes with lipid-conjugated LC3/GABARAP is not yet fully understood. We recently reported the purification of the full-length ATG12-ATG5-ATG16L1 complex, and in reconstitution experiments with purified ATG7, ATG3, and LC3/GABARAP in vitro, together with rescue experiments in knockout cells, important aspects of the complete lipidation reaction were revealed. Hitherto unobserved membrane-binding regions in ATG16L1 were found, contributing to properties that explain the crucial role of this protein in membrane targeting and LC3/GABARAP lipidation in macroautophagy/autophagy and other related processes.
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27.
  • Reijs, Babette L R, et al. (författare)
  • The Central Biobank and Virtual Biobank of BIOMARKAPD: A Resource for Studies on Neurodegenerative Diseases.
  • 2015
  • Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer's disease (AD) and Parkinson's disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized pre-analytical procedures and stored at Integrated BioBank of Luxembourg. The virtual biobank provides an overview of available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), vascular dementia, multiple system atrophy, progressive supranuclear palsy, PD, PD with dementia, and dementia with Lewy bodies. The virtual biobank contains information on over 8,600 subjects with varying diagnoses from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual biobank.
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28.
  • Roswall, Nina, et al. (författare)
  • Long-term exposure to traffic noise and risk of incident colon cancer : A pooled study of eleven Nordic cohorts
  • 2023
  • Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 224
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundColon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this.ObjectivesThe objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons.MethodsWe identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data.ResultsDuring follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99–1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98–1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure.DiscussionA prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.
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29.
  • Schultz, Sebastian (författare)
  • Studies on Islet Amyloid Polypeptide Aggregation : From Model Organism to Molecular Mechanisms
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The proper folding of a protein into its defined three--‐dimensional structure is one of the many fundamental challenges a cell encounters. A number of tightly controlled pathways have evolved to assist in the proper folding of a protein, but also to aid in the removal of misfolded proteins. Despite the presence of these pathways accumulation of misfolded proteins can still occur. Amyloid deposits consist of misfolded proteins with a characteristic highly ordered fibrillar structure that will exert affinity for the amyloid dye Congo red and has a unique X-ray diffraction pattern. Currently 27 different proteins have been identified as amyloid forming proteins in human, however the exact role of amyloid in the pathogenesis of the connected disease is most often unclear.Islet amyloid is made up of the beta cell derived hormone islet amyloid polypeptide (IAPP) and is associated with the development of type 2 diabetes. Propagation of IAPP-fibrils is believed to be one important cause of the pancreatic beta cell death detected in patients with type 2 diabetes. IAPP is a naturally occurring polypeptide hormone stored and secreted together with insulin. IAPP and insulin arise from posttranslational processing of their biological inactive precursors proIAPP and proinsulin. In addition to human, cat and monkey IAPP will form amyloid deposits in conditions resembling human type 2 diabetes. However, IAPP from mouse and rat do not form amyloid as a result of the differences in amino acid sequence.My main research goal was to establish a unique model system suitable to study the effects of proIAPP and IAPP aggregation. I selected Drosophila melanogaster due to its many suitable characteristics as a model organism and its superior genetic toolbox. I have demonstrated that over--‐expression of hproIAPP and hIAPP in the central nervous system (CNS) results in aggregate formation in the brain and neighbouring fat body. Consistent with previous studies, expression of mIAPP does not result in the formation of aggregates. To investigate the intracellular effects of hproIAPP and hIAPP aggregation on a specific population of neurons, we targeted the expression of these peptides specifically to 16 neurons in the brain, the pdf- neurons. These pdf-neurons are divided into 2 clusters of 8 cells per brain hemisphere. First I showed that expression of aggregation prone hIAPP and hproIAPP resulted in significant death of the 8 cells, whereas expression of mIAPP had no such effect. In efforts to pinpoint the mechanisms behind the observed cell death I demonstrated that hproIAPP and hIAPP both pass the ERs quality control for protein folding and that the initiated cell death does not occur through classical apoptosis. Instead, selective autophagy is activated by hIAPP and hproIAPP. This activation counteracts the usually neuro-protective effects of autophagy and contributes to cell death. Strikingly, I also showed that Aâ, the amyloid protein implicated in Alzheimer’s disease, does not exhibit any intracellular toxicity when expressed in pdf-cells. This supports the existence of separate toxic pathways for different amyloid proteins.
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30.
  • Simonsen, Nina, et al. (författare)
  • Empowerment among adult patients with type 2 diabetes : age differentials in relation to person-centred primary care, community resources, social support and other life-contextual circumstances
  • 2021
  • Ingår i: BMC Public Health. - : Springer Nature. - 1471-2458. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rising prevalence of type 2 diabetes (T2D), also among younger adults, constitutes a growing public health challenge. According to the person-centred Chronic Care Model, proactive care and self-management support in combination with community resources enhance quality of healthcare and health outcomes for patients with T2D. However, research is scarce concerning the importance of person-centred care and community resources for such outcomes as empowerment, and the relative impact of various patient support sources for empowerment is not known. Moreover, little is known about the association of age with these variables in this patient-group. This study, carried out among patients with T2D, examined in three age-groups (27–54, 55–64 and 65–75 years) whether person-centred care and diabetes-related social support, including community support and possibilities to influence community health issues, are associated with patient empowerment, when considering possible confounding factors, such as other quality of care indicators and psychosocial wellbeing. We also explored age differentials in empowerment and in the proposed correlates of empowerment. Method: Individuals from a register-based sample with T2D participated in a cross-sectional survey (participation 56%, n = 2866). Data were analysed by descriptive statistics and multivariate logistic regression analyses. Results: Respondents in the youngest age-group were more likely to have low empowerment scores, less continuity of care, and lower wellbeing than the other age-groups, and to perceive less social support, but a higher level of person-centred care than the oldest group. Community support, including possibilities to influence community health issues, was independently and consistently associated with high empowerment in all three age-groups, as was person-centred care in the two older age-groups. Community support was the social support variable with the strongest association with empowerment across age-groups. Moreover, vitality was positively and diabetes-related distress negatively associated with high empowerment in all age-groups, whereas continuity of care, i.e. having a family/regular nurse, was independently associated in the youngest age-group only. Conclusion: Person-centred care and community support, including possibilities to influence community health issues, supports empowerment among adults with T2D. Findings suggest that age is related to most correlates of empowerment, and that younger adults with T2D have specific healthcare needs.
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31.
  • Simonsen, Nina, et al. (författare)
  • Patients' assessment of chronic illness care : a validation study among patients with type 2 diabetes in Finland
  • 2018
  • Ingår i: BMC Health Services Research. - : BioMed Central. - 1472-6963. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To meet the challenges of the rising prevalence of chronic diseases, such as type 2 diabetes, new approaches to healthcare delivery have been initiated; among these the influential Chronic Care Model (CCM). Valid instruments are needed to evaluate the public health impact of these frameworks in different countries. The Patient Assessment of Chronic Illness Care (PACIC) is a 20-item quality of care measure that, from the perspective of the patient, measures the extent to which care is congruent with the CCM. The aim of this study was to evaluate the psychometric properties of the Finnish translation of the PACIC questionnaire, in terms of validity and reliability, in a large register-based sample of patients with type 2 diabetes.Method: The PACIC items were translated into Finnish in a standardized forward-backward procedure, followed by a cross-sectional survey among patients with type 2 diabetes (response rate 56%; n = 2866). We assessed the Finnish version of the PACIC scale for the following psychometric properties: content validity, internal consistency reliability, convergent and construct validity. We also present descriptive data on total scale as well as predetermined subscale levels.Results: The item-response on the PACIC scale was high with only small numbers of missing data (0.5-1.1%). Ceiling effects were low (0.3-5.3%) whereas floor effects were over 20% for two of the predetermined subscales (problem solving and follow-up/coordination). The total PACIC scale showed a reasonable distribution and excellent internal consistency (alpha 0.94) while the internal consistency of the subscales were at least acceptable (0.74-0.86). The principal component analysis identified a two-or three-factor solution instead of the proposed five-dimensional. In other respects, the PACIC scale showed the hypothesized relationships with quality of care and outcome measures, thus demonstrating convergent and construct validity.Conclusion: A Finnish version of the PACIC scale is now validated in the primary care setting among patients with type 2 diabetes. The findings suggest comparable psychometric properties of the Finnish scale as of the original English instrument and earlier translations, and reasonable levels of validity and reliability.
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32.
  • So, Rina, et al. (författare)
  • Long-term exposure to air pollution and liver cancer incidence in six European cohorts
  • 2021
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:11, s. 1887-1897
  • Tidskriftsartikel (refereegranskat)abstract
    • Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the Effects of low-level air pollution: A study in Europe (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2), particulate matter with diameter <2.5 mu m (PM2.5), black carbon (BC), warm-season ozone (O-3), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 mu g/m(3)), PM2.5 (1.12, 0.92-1.36 per 5 mu g/m(3)), and BC (1.15, 1.00-1.33 per 0.5 10(-5)/m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5. Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2. Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.
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33.
  • Sorensen, Anne, et al. (författare)
  • Changes in human fetal oxygenation during maternal hyperoxia as estimated by BOLD MRI
  • 2013
  • Ingår i: Prenatal Diagnosis. - : Wiley. - 1097-0223 .- 0197-3851. ; 33:2, s. 141-145
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Changes in blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) signal are closely related to changes in fetal oxygenation. In this study, we aimed to investigate the changes in human fetal oxygenation during maternal hyperoxia by using the non-invasive BOLD MRI technique. Method Eight healthy pregnant women in gestational week 28 to 34 were included. With the use of a facial oxygen mask, we induced maternal hyperoxia and measured changes in the BOLD MRI signal of selected fetal organs. Results In a number of fetal organs, the BOLD MRI signal increased significantly (P<0.01) during maternal hyperoxia (mean change in %+/- SEM): liver (14.3 +/- 3.7%), spleen (15.2 +/- 3.5%) and kidney (6.2 +/- 1.8%) as well as the placenta (6.5 +/- 1.6%). In the fetal brain, however, the BOLD MRI signal remained constant (0.3 +/- 0.2%). Conclusion During maternal hyperoxia, we demonstrated an increased oxygenation in a number of human fetal organs by using the non-invasive BOLD technique. The oxygenation of the fetal brain remained constant, thus a reversed' brain sparing mechanism could be considered in healthy fetuses subjected to hyperoxia. (c) 2012 John Wiley & Sons, Ltd.
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34.
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35.
  • Søreng, Kristiane, et al. (författare)
  • SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting Dynamin-2
  • 2018
  • Ingår i: EMBO Reports. - : John Wiley & Sons. - 1469-221X .- 1469-3178. ; 19:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Trafficking of mammalian ATG9A between the Golgi apparatus, endosomes and peripheral ATG9A compartments is important for autophagosome biogenesis. Here, we show that the membrane remodelling protein SNX18, previously identified as a positive regulator of autophagy, regulates ATG9A trafficking from recycling endosomes. ATG9A is recruited to SNX18-induced tubules generated from recycling endosomes and accumulates in juxtanuclear recycling endosomes in cells lacking SNX18. Binding of SNX18 to Dynamin-2 is important for ATG9A trafficking from recycling endosomes and for formation of ATG16L1- and WIPI2-positive autophagosome precursor membranes. We propose a model where upon autophagy induction, SNX18 recruits Dynamin-2 to induce budding of ATG9A and ATG16L1 containing membranes from recycling endosomes that traffic to sites of autophagosome formation.
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36.
  • Thacher, Jesse D., et al. (författare)
  • Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts
  • 2023
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence.Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution.Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise.Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before conclusions regarding noise as a risk factor for breast cancer can be made.
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37.
  • von Thiele Schwarz, Ulrica, 1975-, et al. (författare)
  • How to design, implement and evaluate organizational interventions for maximum impact : the Sigtuna Principles
  • 2021
  • Ingår i: European Journal of Work and Organizational Psychology. - Abingdon : Routledge. - 1359-432X .- 1464-0643. ; 30:3, s. 415-427
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on organizational interventions needs to meet the objectives of both researchers and participating organizations. This duality means that real-world impact has to be considered throughout the research process, simultaneously addressing both scientific rigour and practical relevance. This discussion paper aims to offer a set of principles, grounded in knowledge from various disciplines that can guide researchers in designing, implementing, and evaluating organizational interventions. Inspired by Mode 2 knowledge production, the principles were developed through a transdisciplinary, participatory and iterative process where practitioners and academics were invited to develop, refine and validate the principles. The process resulted in 10 principles: 1) Ensure active engagement and participation among key stakeholders; 2) Understand the situation (starting points and objectives); 3) Align the intervention with existing organizational objectives; 4) Explicate the program logic; 5) Prioritize intervention activities based on effort-gain balance; 6) Work with existing practices, processes, and mindsets; 7) Iteratively observe, reflect, and adapt; 8) Develop organizational learning capabilities; 9) Evaluate the interaction between intervention, process, and context; and 10) Transfer knowledge beyond the specific organization. The principles suggest how the design, implementation, and evaluation of organizational interventions can be researched in a way that maximizes both practical and scientific impact. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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38.
  • Wackström, Nanna, et al. (författare)
  • Does chronic pain hinder physical activity among older adults with type 2 diabetes?
  • 2020
  • Ingår i: Health Psychology and Behavioral Medicine. - : Taylor & Francis. - 2164-2850. ; 8:1, s. 362-382
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Physical activity (PA) is a key component in management of type 2 diabetes (T2D). Pain might be a barrier to PA especially among older adults with T2D, but surprisingly few studies have investigated the association between chronic pain and PA. Our aim was to evaluate the prevalence of chronic pain among older adults with T2D and to examine the association between chronic pain and PA while taking important life-contextual factors into account. Methods: Data of this register-based, cross-sectional study were collected in a survey among adults with T2D (n=2866). In the current study, only respondents aged 65–75 years were included (response rate 63%, n=1386). Data were analysed by means of descriptive statistics and multivariate logistic regression analysis. Results: In total, 64% reported chronic pain. In specific groups, e.g. women and those who were obese, the prevalence was even higher. Among respondents experiencing chronic pain, frequent pain among women and severe pain among both genders were independently associated with decreased likelihood of being physically active. Moreover, the likelihood of being physically active decreased with higher age and BMI, whereas it increased with higher autonomous motivation and feelings of energy. Among physically active respondents suffering from chronic pain, neither intensity nor frequency of pain explained engagement in exercise (as compared with incidental PA). Instead, men were more likely to exercise regularly as were those with good perceived health and higher autonomous motivation. Conclusions: The prevalence of chronic pain is high among older adults with T2D. This study shows that among those suffering from chronic pain, severe pain is independently and inversely associated with being physically active, as is frequent pain, but only among women. Moreover, the findings show the importance of autonomous motivation and health variables for both incidental PA and exercise among older adults with T2D experiencing chronic pain. 
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