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Ramstedt, Madeleine
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Santos, D. E. S., Li, D., Ramstedt, M., Gautrot, J. E. & Soares, T. A. (2019). Conformational Dynamics and Responsiveness of Weak and Strong Polyelectrolyte Brushes: Atomistic Simulations of Poly(dimethyl aminoethyl methacrylate) and Poly(2-(methacryloyloxy)ethyl trimethylammonium chloride). Langmuir, 35(14), 5037-5049
Öppna denna publikation i ny flik eller fönster >>Conformational Dynamics and Responsiveness of Weak and Strong Polyelectrolyte Brushes: Atomistic Simulations of Poly(dimethyl aminoethyl methacrylate) and Poly(2-(methacryloyloxy)ethyl trimethylammonium chloride)
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2019 (Engelska)Ingår i: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 35, nr 14, s. 5037-5049Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The complex solution behavior of polymer brushes is key to control their properties, including for biomedical applications and catalysis. The swelling behavior of poly(dimethyl aminoethyl methacrylate) (PDMAEMA) and poly(2-(methacryloyloxy)ethyl trimethylammonium chloride) (PMETAC) in response to changes in pH, solvent, and salt types has been investigated using atomistic molecular dynamics simulations. PDMAEMA and PMETAC have been selected as canonical models for weak and strong polyelectrolytes whose complex conformational behavior is particularly challenging for the development and validation of atomistic models. The GROMOS-derived atomic parameters reproduce the experimental swelling coefficients obtained from ellipsometry measurements for brushes of 5–15 nm thickness. The present atomistic models capture the protonated morphology of PDMAEMA, the swollen and collapsed conformations of PDMAEMA and PMETAC in good and bad solvents, and the salt-selective response of PMETAC. The modular nature of the molecular models allows for the simple extension of atomic parameters to a variety of polymers or copolymers.

Ort, förlag, år, upplaga, sidor
Washington: American Chemical Society (ACS), 2019
Nationell ämneskategori
Materialkemi Polymerkemi Teoretisk kemi Fysikalisk kemi
Identifikatorer
urn:nbn:se:umu:diva-158041 (URN)10.1021/acs.langmuir.8b04268 (DOI)30869897 (PubMedID)
Tillgänglig från: 2019-04-11 Skapad: 2019-04-11 Senast uppdaterad: 2019-06-13Bibliografiskt granskad
Ramstedt, M., Ribeiro, I. A. C., Bujdakova, H., Mergulhão, F. J. M., Jordao, L., Thomsen, P., . . . Sjollema, J. (2019). Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations. Paper presented at 2019/05/16. Macromolecular Bioscience, 19(5), Article ID 1800384.
Öppna denna publikation i ny flik eller fönster >>Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations
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2019 (Engelska)Ingår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 19, nr 5, artikel-id 1800384Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

In Europe, the mean incidence of urinary tract infections in intensive care units is 1.1 per 1000 patient‐days. Of these cases, catheter‐associated urinary tract infections (CAUTI) account for 98%. In total, CAUTI in hospitals is estimated to give additional health‐care costs of £1–2.5 billion in the United Kingdom alone. This is in sharp contrast to the low cost of urinary catheters and emphasizes the need for innovative products that reduce the incidence rate of CAUTI. Ureteral stents and other urinary‐tract devices suffer similar problems. Antimicrobial strategies are being developed, however, the evaluation of their efficacy is very challenging. This review aims to provide considerations and recommendations covering all relevant aspects of antimicrobial material testing, including surface characterization, biocompatibility, cytotoxicity, in vitro and in vivo tests, microbial strain selection, and hydrodynamic conditions, all in the perspective of complying to the complex pathology of device‐associated urinary tract infection. The recommendations should be on the basis of standard assays to be developed which would enable comparisons of results obtained in different research labs both in industry and in academia, as well as provide industry and academia with tools to assess the antimicrobial properties for urinary tract devices in a reliable way.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2019
Nyckelord
antimicrobial, device-associated urinary tract infections, in vitro, in vivo, material testing
Nationell ämneskategori
Biomaterialvetenskap
Identifikatorer
urn:nbn:se:umu:diva-159033 (URN)10.1002/mabi.201800384 (DOI)000471340300003 ()30884146 (PubMedID)
Konferens
2019/05/16
Tillgänglig från: 2019-05-16 Skapad: 2019-05-16 Senast uppdaterad: 2019-07-09Bibliografiskt granskad
Bjarnsholt, T., Buhlin, K., Dufrêne, Y. F., Gomelsky, M., Moroni, A., Ramstedt, M., . . . Römling, U. (2018). Biofilm formation – what we can learn from recent developments. Paper presented at 2018/09/30. Journal of Internal Medicine, 284(4), 332-345
Öppna denna publikation i ny flik eller fönster >>Biofilm formation – what we can learn from recent developments
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2018 (Engelska)Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 284, nr 4, s. 332-345Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.

Ort, förlag, år, upplaga, sidor
Wiley-Blackwell, 2018
Nyckelord
antimicrobial strategies, biofilm formation, cyclic di-nucleotide second messengers, extracellular matrix, underlying diseases
Nationell ämneskategori
Annan kemi
Identifikatorer
urn:nbn:se:umu:diva-152180 (URN)10.1111/joim.12782 (DOI)
Konferens
2018/09/30
Tillgänglig från: 2018-10-01 Skapad: 2018-10-01 Senast uppdaterad: 2018-10-05Bibliografiskt granskad
Rzhepishevska, O. I., Limanska, N., Galkin, M., Lacoma, A., Lundquist, M., Sokol, D., . . . Ramstedt, M. (2018). Characterization of clinically relevant model bacterial strains of Pseudomonas aeruginosa for anti-biofilm testing of materials. Acta Biomaterialia, 76, 99-107
Öppna denna publikation i ny flik eller fönster >>Characterization of clinically relevant model bacterial strains of Pseudomonas aeruginosa for anti-biofilm testing of materials
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2018 (Engelska)Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 76, s. 99-107Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

There is a great interest in developing novel anti-biofilm materials in order to decrease medical device-associated bacterial infections causing morbidity and high healthcare costs. However, the testing of novel materials is often done using bacterial lab strains that may not exhibit the same phenotype as clinically relevant strains infecting medical devices. Furthermore, no consensus of strain selection exists in the field, making results very difficult to compare between studies. In this work, 19 clinical isolates of Pseudomonas aeruginosa originating from intubated patients in an intensive care unit have been characterized and compared to the lab reference strain PAO1 and a rmlC lipopolysaccharide mutant of PAO1. The adhesion and biofilm formation was monitored, as well as cell properties such as hydrophobicity, zeta potential and motility. Two groups of isolates were observed: one with high adhesion to polymer surfaces and one with low adhesion (the latter including PAO1). Furthermore, detailed biofilm assays in a flow system were performed using five characteristic isolates from the two groups. Confocal microscopy showed that the adhesion and biofilm formation of four of these five strains could be reduced dramatically on zwitterionic surface coatings. However, one isolate with pronounced swarming colonized and formed biofilm also on the antifouling surface. We demonstrate that the biofilm properties of clinical isolates can differ greatly from that of a standard lab strain and propose two clinical model strains for testing of materials designed for prevention of biofilm formation in the respiratory tract. The methodology used could beneficially be applied for screening of other collections of pathogens to identify suitable model strains for in vitro biofilm testing.

Statement of Significance: Medical-device associated infections present a great challenge in health care. Therefore, much research is undertaken to prevent bacterial colonization of new types of biomaterials. The work described here characterizes, tests and presents a number of clinically relevant bacterial model strains for assessing biofilm formation by Pseudomonas aeruginosa. Such model strains are of importance as they may provide better predictability of lab testing protocols with respect to how well materials would perform in an infection situation in a patient. Furthermore, this study uses the strains to test the performance of polymer surfaces designed to repel bacterial adhesion and it is shown that the biofilm formation for four out of the five tested bacterial strains was reduced.

Ort, förlag, år, upplaga, sidor
Elsevier, 2018
Nyckelord
Clinical isolates, Pseudomonas aeruginosa, Antifouling, Model strain, Surface chemistry
Nationell ämneskategori
Annan kemi
Identifikatorer
urn:nbn:se:umu:diva-150151 (URN)10.1016/j.actbio.2018.06.019 (DOI)000442055600010 ()29902594 (PubMedID)2-s2.0-8504885706 (Scopus ID)
Forskningsfinansiär
Stiftelsen Olle Engkvist Byggmästare, 2014/660
Tillgänglig från: 2018-07-11 Skapad: 2018-07-11 Senast uppdaterad: 2018-09-10Bibliografiskt granskad
Hakobyan, S., Rzhepishevska, O., Barbero, D. R. & Ramstedt, M. (2018). Functionalization of zwitterionic polymer brushes, do they remain antifouling?. Surface and Interface Analysis, 50(11), 1001-1006
Öppna denna publikation i ny flik eller fönster >>Functionalization of zwitterionic polymer brushes, do they remain antifouling?
2018 (Engelska)Ingår i: Surface and Interface Analysis, ISSN 0142-2421, E-ISSN 1096-9918, Vol. 50, nr 11, s. 1001-1006Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Polymer brushes are surface coatings that can be tailored in many ways to suit specific demands including reduction of protein and bacterial fouling of biomaterials. Previously, we reported that antifouling poly (2-(methacryloxy)ethyl)dimethyl-3-sulphopropyl ammonium hydroxide) brushes dramatically reduced formation of bacterial biofilm. We hypothesized that: (1) this brush could be efficiently functionalized with a small molecule (2-oxo-2-[N-(2,4,6-trihydroxybenzylidene)-hydrazino]-acetamide, ME0163, hydrazone) and that (2) the antifouling property would remain also after functionalization. Diblock co-polymer brushes of 2-(methacryloxy)ethyl)dimethyl-3-sulphopropyl ammonium hydroxide and poly (glycidyl methacrylate) were formed by surface-initiated atom transfer radical polymerization (SI-ATRP), and the ME0163 hydrazone was covalently bound to the surface via a ring-opening reaction. Functionalization of the surfaces was followed by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and UV-Vis spectroscopy. The influence of temperature, reaction time, and reagent concentrations on the immobilization process was investigated. Surfaces with high degree of functionalization could be made in this way. However, the functionalization rendered the surface more hydrophobic, and the antifouling property of the brush was lost, thus, disproving the second of our starting hypotheses but corroborating the first.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2018
Nationell ämneskategori
Kemi
Identifikatorer
urn:nbn:se:umu:diva-143891 (URN)10.1002/sia.6376 (DOI)000448889600005 ()
Forskningsfinansiär
Vetenskapsrådet, 2011-3504KempestiftelsernaStiftelsen Olle Engkvist Byggmästare, 2014/660
Anmärkning

SIA-17-0337.R1

Tillgänglig från: 2018-01-12 Skapad: 2018-01-12 Senast uppdaterad: 2018-11-22Bibliografiskt granskad
Sjollema, J., Zaat, S. A. .., Fontaine, V., Ramstedt, M., Luginbuehl, R., Thevissen, K., . . . Busscher, H. J. (2018). In vitro methods for the evaluation of antimicrobial surface designs. Acta Biomaterialia, 70, 12-24
Öppna denna publikation i ny flik eller fönster >>In vitro methods for the evaluation of antimicrobial surface designs
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2018 (Engelska)Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 70, s. 12-24Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Bacterial adhesion and subsequent biofilm formation on biomedical implants and devices are a major cause of their failure. As systemic antibiotic treatment is often ineffective, there is an urgent need for antimicrobial biomaterials and coatings. The term “antimicrobial” can encompass different mechanisms of action (here termed “antimicrobial surface designs”), such as antimicrobial-releasing, contact-killing or non-adhesivity. Biomaterials equipped with antimicrobial surface designs based on different mechanisms of action require different in vitro evaluation methods. Available industrial standard evaluation tests do not address the specific mechanisms of different antimicrobial surface designs and have therefore been modified over the past years, adding to the myriad of methods available in the literature to evaluate antimicrobial surface designs. The aim of this review is to categorize fourteen presently available methods including industrial standard tests for the in vitro evaluation of antimicrobial surface designs according to their suitability with respect to their antimicrobial mechanism of action. There is no single method or industrial test that allows to distinguish antimicrobial designs according to all three mechanisms identified here. However, critical consideration of each method clearly relates the different methods to a specific mechanism of antimicrobial action. It is anticipated that use of the provided table with the fourteen methods will avoid the use of wrong methods for evaluating new antimicrobial designs and therewith facilitate translation of novel antimicrobial biomaterials and coatings to clinical use. The need for more and better updated industrial standard tests is emphasized. Statement of Significance European COST-action TD1305, IPROMEDAI aims to provide better understanding of mechanisms of antimicrobial surface designs of biomaterial implants and devices. Current industrial evaluation standard tests do not sufficiently account for different, advanced antimicrobial surface designs, yet are urgently needed to obtain convincing in vitro data for approval of animal experiments and clinical trials. This review aims to provide an innovative and clear guide to choose appropriate evaluation methods for three distinctly different mechanisms of antimicrobial design: (1) antimicrobial-releasing, (2) contact-killing and (3) non-adhesivity. Use of antimicrobial evaluation methods and definition of industrial standard tests, tailored toward the antimicrobial mechanism of the design, as identified here, fulfill a missing link in the translation of novel antimicrobial surface designs to clinical use.

Nyckelord
Biofilm, Biomaterial-associated infection, Antimicrobial-releasing, Contact-killing, Non-adhesive
Nationell ämneskategori
Annan kemi Biomedicinsk laboratorievetenskap/teknologi
Identifikatorer
urn:nbn:se:umu:diva-146283 (URN)10.1016/j.actbio.2018.02.001 (DOI)
Tillgänglig från: 2018-04-03 Skapad: 2018-04-03 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Kong, D., Megone, W., Nguyen, K. D. Q., Di Cio, S., Ramstedt, M. & Gautrot, J. E. (2018). Protein nanosheet mechanics controls cell adhesion and expansion on low-viscosity liquids [Letter to the editor]. Nano letters (Print), 18(3), 1946-1951
Öppna denna publikation i ny flik eller fönster >>Protein nanosheet mechanics controls cell adhesion and expansion on low-viscosity liquids
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2018 (Engelska)Ingår i: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 18, nr 3, s. 1946-1951Artikel i tidskrift, Letter (Refereegranskat) Published
Abstract [en]

Adherent cell culture typically requires cell spreading at the surface of solid substrates to sustain the formation of stable focal adhesions and assembly of a contractile cytoskeleton. However, a few reports have demonstrated that cell culture is possible on liquid substrates such as silicone and fluorinated oils, even displaying very low viscosities (0.77 cSt). Such behavior is surprising as low viscosity liquids are thought to relax much too fast (<ms) to enable the stabilization of focal adhesions (with lifetimes on the order of minutes to hours). Here we show that cell spreading and proliferation at the surface of low viscosity liquids are enabled by the self-assembly of mechanically strong protein nanosheets at these interfaces. We propose that this phenomenon results from the denaturation of globular proteins, such as albumin, in combination with the coupling of surfactant molecules to the resulting protein nanosheets. We use interfacial rheology and atomic force microscopy indentation to characterize the mechanical properties of protein nanosheets and associated liquid–liquid interfaces. We identify a direct relationship between interfacial mechanics and the association of surfactant molecules with proteins and polymers assembled at liquid–liquid interfaces. In addition, our data indicate that cells primarily sense in-plane mechanical properties of interfaces, rather than relying on surface tension to sustain spreading, as in the spreading of water striders. These findings demonstrate that bulk and nanoscale mechanical properties may be designed independently, to provide structure and regulate cell phenotype, therefore calling for a paradigm shift for the design of biomaterials in regenerative medicine.

Ort, förlag, år, upplaga, sidor
Washington: American Chemical Society (ACS), 2018
Nyckelord
cell adhesion, interfacial mechanics, liquid−liquid interface, nanosheets, Protein self-assembly
Nationell ämneskategori
Annan kemi
Identifikatorer
urn:nbn:se:umu:diva-145890 (URN)10.1021/acs.nanolett.7b05339 (DOI)000427910600054 ()
Tillgänglig från: 2018-03-20 Skapad: 2018-03-20 Senast uppdaterad: 2018-08-07Bibliografiskt granskad
Shchukarev, A. & Ramstedt, M. (2017). Cryo-XPS: probing intact interfaces in nature and life. Surface and Interface Analysis, 49(4), 349-356
Öppna denna publikation i ny flik eller fönster >>Cryo-XPS: probing intact interfaces in nature and life
2017 (Engelska)Ingår i: Surface and Interface Analysis, ISSN 0142-2421, E-ISSN 1096-9918, Vol. 49, nr 4, s. 349-356Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Experimental studies of solid–aqueous solution interfaces are of great importance for reaching a better chemical understanding ofinterfacial phenomena at the molecular level. This perspective article presents a recently developed approach for investigation ofintact interfaces, based on fast freezing of centrifuged wet pastes followed by traditional XPS measurements at liquid nitrogentemperatures. Sample preparation and handling protocols, applicable to any suspension or gel, are discussed in detail. For mineralsuspensions, cryogenic XPS is an important complement to traditional analyses of supernatant solutions and dry solids that iscapable of revealing novel insights of the electrical double layer in terms of structure and composition. It can be used to studychanges in the biochemistry of bacterial cell walls as influenced by external stimuli, and interfacial features related tobiocompatibility of implant materials. Herein we review how the technique has been applied to minerals in electrolyte solutions,intact bacterial surfaces, and biomaterial interfaces in biologically relevant media, and highlight some future requirements fordevelopment of interface analysis methodologies.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2017
Nyckelord
cryogenic XPS, solid–aqueous solution interface, electrical double layer, cell wall composition
Nationell ämneskategori
Kemi
Identifikatorer
urn:nbn:se:umu:diva-128825 (URN)10.1002/sia.6025 (DOI)000397496800016 ()
Tillgänglig från: 2016-12-15 Skapad: 2016-12-15 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ferreira, M., Rzhepishevska, O., Grenho, L., Malheiros, D., Gonçalves, L., Almeida, A. J., . . . Bettencourt, A. (2017). Levofloxacin-loaded bone cement delivery system: highly effective against intracellular bacteria and Staphylococcus aureus biofilms. International Journal of Pharmaceutics, 532(1), 241-248
Öppna denna publikation i ny flik eller fönster >>Levofloxacin-loaded bone cement delivery system: highly effective against intracellular bacteria and Staphylococcus aureus biofilms
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2017 (Engelska)Ingår i: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 532, nr 1, s. 241-248Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Staphylococcus aureus is a major pathogen in bone associated infections due to its ability to adhere and form biofilms on bone and/or implants. Moreover, recrudescent and chronic infections have been associated with S. aureus capacity to invade and persist within osteoblast cells. With the growing need of novel therapeutic tools, this research aimed to evaluate some important key biological properties of a novel carrier system composed of acrylic bone cement (polymethylmethacrylate – PMMA), loaded with a release modulator (lactose) and an antibiotic (levofloxacin).

Levofloxacin-loaded bone cement (BC) exhibited antimicrobial effects against planktonic and biofilm forms of S. aureus (evaluated by a flow chamber system). Moreover, novel BC formulation showed high anti-bacterial intraosteoblast activity. This fact led to the conclusion that levofloxacin released from BC matrices could penetrate the cell membrane of osteoblasts and be active against S. aureus strains in the intracellular environment. Furthermore, levofloxacin-BC formulations showed no significant in vitro cytotoxicity and no allergic potential (measured by the in vivo chorioallantoic membrane assay). Our results indicate that levofloxacin-loaded BC has potential as a local antibiotic delivery system for treating S. aureus associated bone infections.

Ort, förlag, år, upplaga, sidor
Elsevier, 2017
Nyckelord
Bone-infection, Fluoroquinolone-delivery-system, Flow-chamber system, Osteoblast-infection-model, Biocompatibility
Nationell ämneskategori
Kemi Läkemedelskemi
Identifikatorer
urn:nbn:se:umu:diva-139506 (URN)10.1016/j.ijpharm.2017.08.089 (DOI)000413669700025 ()
Tillgänglig från: 2017-09-15 Skapad: 2017-09-15 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ramstedt, M. (2017). Polymer Brushes and Microorganisms. In: Omar Azzaroni and Igal Szleifer (Ed.), Polymer and Biopolymer Brushes: for Materials Science and Biotechnology: (pp. 515-552). John Wiley & Sons
Öppna denna publikation i ny flik eller fönster >>Polymer Brushes and Microorganisms
2017 (Engelska)Ingår i: Polymer and Biopolymer Brushes: for Materials Science and Biotechnology / [ed] Omar Azzaroni and Igal Szleifer, John Wiley & Sons, 2017, s. 515-552Kapitel i bok, del av antologi (Övrigt vetenskapligt)
Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2017
Nationell ämneskategori
Kemi
Identifikatorer
urn:nbn:se:umu:diva-144050 (URN)
Tillgänglig från: 2018-01-19 Skapad: 2018-01-19 Senast uppdaterad: 2018-06-09
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