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Gustafson, Elisabet K.
Alternative names
Publications (10 of 13) Show all publications
Gustafson, E. K., Larsson, T. & Danielson, J. (2019). Controlled outcome of Hirschsprung's disease beyond adolescence: a single center experience. Pediatric surgery international (Print), 35(2), 181-185
Open this publication in new window or tab >>Controlled outcome of Hirschsprung's disease beyond adolescence: a single center experience
2019 (English)In: Pediatric surgery international (Print), ISSN 0179-0358, E-ISSN 1437-9813, Vol. 35, no 2, p. 181-185Article in journal (Refereed) Published
Abstract [en]

PurposeThe aim of this study was to assess the function and quality of life of Hirschsprung's Disease (HD) beyond adolescence and relate it to matched controls.MethodsAll 203 patients diagnosed with HD at our department from 1961 to 1995 were identified. 21 had died, 43 had unclear diagnosis and 16 could not be traced. The remaining 123 patients were sent bowel function and SF-36 quality of life questionnaires. 69 patients (mean age 37.8, range 22-58, 13 female) responded and were matched with 138 age and sex-matched controls.ResultsFunction: HD-patients had significantly higher number of bowel movements per week, higher incidence of soiling, urgency, permanent stomas, use of laxatives, enemas and loperamide. HD-patients also scored significantly lower in their satisfaction with their bowel function. There was, however, no significant difference in Miller Incontinence score.QOL: HD-patients reported a significantly higher incidence of negative impact by their bowel function on daily life, social interaction and ability to go on vacation. There were no significant differences in SF-36-scores.ConclusionsBowel function has a lifelong negative impact on the lives of patients with HD. This strongly indicates a need for structured follow-up beyond adolescence.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Hirschsprung's disease, Aganglionosis, Long-term, Bowel function, Quality of life
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-376730 (URN)10.1007/s00383-018-4391-5 (DOI)000456316100002 ()30460379 (PubMedID)
Funder
Fredrik och Ingrid Thurings Stiftelse
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved
Ogasawara, H., Teramura, Y., Imura, T., Inagaki, A., Saito, Y., Matsumura, M., . . . Goto, M. (2018). The Optimization of the Hepatocyte Surface Modification Procedures in Terms of Heparin and Apyrase for Improving Hepatocyte Engraftment. Paper presented at 14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA. Transplantation, 102, S727-S727
Open this publication in new window or tab >>The Optimization of the Hepatocyte Surface Modification Procedures in Terms of Heparin and Apyrase for Improving Hepatocyte Engraftment
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2018 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 102, p. S727-S727Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-368383 (URN)10.1097/01.tp.0000543706.60801.e9 (DOI)000444541201427 ()
Conference
14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Teramura, Y., Asif, S., Nilsson Ekdahl, K., Gustafson, E. K. & Nilsson, B. (2017). Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures. ACS Applied Materials and Interfaces, 9(1), 244-254
Open this publication in new window or tab >>Cell Adhesion Induced Using Surface Modification with Cell-Penetrating Peptide-Conjugated Poly(ethylene glycol)-Lipid: A New Cell Glue for 3D Cell-Based Structures
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2017 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 1, p. 244-254Article in journal (Refereed) Published
Abstract [en]

We synthesized a novel material, cell-penetrating peptide-conjugated poly(ethylene glycol)-lipid (CPP-PEG-lipid), that can induce the adhesion of floating cells. Firm cell adhesion with spreading could be induced by cell surface modification with the CPP-PEG-lipids. Cell adhesion was induced by CPPs but not by any other cationic short peptides we tested. Here, we demonstrated adherence using the floating cell line CCRF-CEM as well as primary human T cells, B cells, erythrocytes, and hepatocytes. As compared to cells grown in suspension, adherent cells were more rapidly induced to attach to substrates with the cell-surface modification. The critical factor for attachment was localization of CPPs at the cell membrane by PEG-lipids with PEG > 20 kDa. These cationic CPPs on PEG chains were able to interact with substrate surfaces such as polystyrene (PS) surfaces, glass surfaces, and PS microfibers that are negatively charged, inducing firm cell adhesion and cell spreading. Also, as opposed to normal cationic peptides that interact strongly with cell membranes, CPPs were less interactive with the cell surfaces because of their cell-penetrating property, making them more available for adhering cells to the substrate surface. No effects on cell viability or cell proliferation were observed after the induction of cell adhesion. With this technique, cells could be easily immobilized onto PS microfibers, an important step in fabricating 3D cell-based structures. Cells immobilized onto 3D PS microfibers were alive, and human hepatocytes showed normal production of urea and albumin on the microfibers. This method is novel in inducing firm cell adhesion via a one-step treatment.

Keywords
3D structure, cell adhesion, cell surface modification, cell-penetrating peptide (CPP), poly(ethylene glycol)-conjugated phospholipid (PEG−lipid)
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-373991 (URN)10.1021/acsami.6b14584 (DOI)000392037400031 ()27976850 (PubMedID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2019-01-17 Created: 2019-01-17 Last updated: 2019-01-24Bibliographically approved
Gustafson, E., Asif, S., Kozarcanin, H., Meurling, S., Ekdahl, K. N. & Nilsson, B. (2017). Control of IBMIR induced by fresh and cryopreserved hepatocytes by low molecular weight dextran sulfate. Cell Transplantation, 26(1), 71-81
Open this publication in new window or tab >>Control of IBMIR induced by fresh and cryopreserved hepatocytes by low molecular weight dextran sulfate
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2017 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 26, no 1, p. 71-81Article in journal (Refereed) Published
Abstract [en]

Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 mu g/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

Keywords
Innate immunity, IBMIR, Thromboinflammation, Hepatocyte transplantation, Low molecular weight dextran sulfate (LMW-DS)
National Category
Other Medical Sciences
Identifiers
urn:nbn:se:uu:diva-286868 (URN)10.3727/096368916X692609 (DOI)000392785000007 ()
Note

The manuscript of this article is part of the thesis Thromboinflammation: in a Model of Hepatocyte Transplantation http://uu.diva-portal.org/smash/record.jsf?pid=diva2:922111

Available from: 2016-04-22 Created: 2016-04-22 Last updated: 2019-01-21Bibliographically approved
Angsten, G., Gustafson, E., Dahl, N. & Christofferson, R. H. (2017). Resolution of infantile intestinal pseudo-obstruction in a boy. Journal of Osteoporosis and Physical Activity, 24, 28-34
Open this publication in new window or tab >>Resolution of infantile intestinal pseudo-obstruction in a boy
2017 (English)In: Journal of Osteoporosis and Physical Activity, ISSN 2052-3211, E-ISSN 2213-5766, Vol. 24, p. 28-34Article in journal (Refereed) Published
Abstract [en]

A term boy with spontaneous passage of meconium exhibited episodes of abdominal distension and diarrhea. Due to failure to thrive and suspicion of Hischsprung's disease he was referred to our university hospital at five months of age. Rectal biopsies were normal. Laparotomy revealed dilation of the small bowel and colon without any mechanical obstruction. Full thickness bowel biopsies were taken and a loop ileostomy was constructed. Histopathology revealed fibrosing myopathy, Cajal cell hypertrophy, and neuronal degeneration in both the large and small bowel. The small bowel showed mastocytosis without inflammation. A central venous catheter was placed for vascular access, replaced three times and later switched to a subcutaneous venous port. Catheters were locked after use with vancomycin-heparin and later taurolidine. The individually tailored home parenteral nutrition contained unsaturated fatty acid lipids to reduce cholestasis. Initial insufficient growth was improved after correction of partial parenteral nutrition based on a metabolic balance study. The ileostomy was revised once and finally taken down at 11 years of age following one year without parenteral support. At follow-up at 13 years of age he has episodes of moderate abdominal pain and has entered puberty and reports a high quality of life. (C) 2017 The Authors. Published by Elsevier Inc.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Child, Intestinal pseudo-obstruction, Home parenteral nutrition, Unsaturated fatty acid parenteral nutrition, Taurolidine, Outcome
National Category
Pediatrics
Identifiers
urn:nbn:se:uu:diva-335647 (URN)10.1016/j.epsc.2017.06.007 (DOI)000409098900008 ()
Available from: 2017-12-08 Created: 2017-12-08 Last updated: 2017-12-08Bibliographically approved
Nilsson Ekdahl, K., Teramura, Y., Hamad, O. A., Asif, S., Dührkop, C., Fromell, K., . . . Nilsson, B. (2016). Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation. Immunological Reviews, 274(1), 245-269
Open this publication in new window or tab >>Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation
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2016 (English)In: Immunological Reviews, ISSN 0105-2896, E-ISSN 1600-065X, Vol. 274, no 1, p. 245-269Article in journal (Refereed) Published
Abstract [en]

Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.

Keywords
coagulation, complement system, contact activation/kallikrein system, innate immunity, platelets, thromboinflammation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-373992 (URN)10.1111/imr.12471 (DOI)000387059600017 ()27782319 (PubMedID)
Funder
Swedish Research Council, 2013‐65X‐05647‐34‐4EU, FP7, Seventh Framework Programme, 602699The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Novo Nordisk
Available from: 2019-01-17 Created: 2019-01-17 Last updated: 2019-01-21Bibliographically approved
Asif, S., Ekdahl, K. N., Fromell, K., Gustafson, E., Barbu, A., Le Bland, K., . . . Teramura, Y. (2016). Heparinization of cell surfaces with short pepetide-conjugated PEG-lipid regulates thromboinflammation in thransplantation of human MSCs and hepatocytes. Acta Biomaterialia, 35, 194-205
Open this publication in new window or tab >>Heparinization of cell surfaces with short pepetide-conjugated PEG-lipid regulates thromboinflammation in thransplantation of human MSCs and hepatocytes
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2016 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed) Published
Abstract [en]

Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival.

Keywords
Cell surface modification; Heparinization; Thromboinflammation; MSCs; Hepatocyte; Polyethylene glycol-conjugated phospholipid (PEG-lipid)
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-279420 (URN)10.1016/j.actbio.2016.02.018 (DOI)000375162200018 ()26876877 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2019-01-24Bibliographically approved
Donoso, F., Kassa, A.-M., Gustafson, E. K., Meurling, S. & Engstrand Lilja, H. (2016). Outcome and management in infants with esophageal atresia: a single centre observational study. Journal of Pediatric Surgery, 51(9), 1421-1425
Open this publication in new window or tab >>Outcome and management in infants with esophageal atresia: a single centre observational study
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2016 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 51, no 9, p. 1421-1425Article in journal (Refereed) Published
Abstract [en]

Background/Purpose: A successful outcome in the repair of esophageal atresia (EA) is associated with a high quality pediatric surgical centre, however there are several controversies regarding the optimal management. The aim of this study was to investigate the outcome and management EA in a single pediatric surgical centre.

Methods: Medical records of infants with repaired EA from 1994 to 2013 were reviewed.

Results: 129 infants were included. Median follow-up was 5.3 (range 0.1-21) years. Overall survival was 94.6%, incidences of anastomotic leakage 7.0%, recurrent fistula 4.6% and anastomotic stricture 53.5% (36.2% within first year). In long gap EA (n = 13), delayed primary anastomosis was performed in 9 (69.2%), gastric tube in 3 (23.1%) and gastric transposition in one (7.7%) infants. The incidences of anastomotic leakage and stricture in long gap EA were, 23.1% and 69.2%, respectively. Peroperative tracheobronchoscopy and postoperative esophagography were implemented as a routine during the study-period, but chest drains were routinely abandoned.

Conclusion: The outcome in this study is fully comparable with recent international reports showing a low mortality but a significant morbidity, especially considering anastomotic strictures and LGEA. Multicenter EA registry with long-term follow up may help to establish best management of EA.

National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-304712 (URN)10.1016/j.jpedsurg.2016.03.010 (DOI)000382243300005 ()27114309 (PubMedID)
Available from: 2016-10-07 Created: 2016-10-07 Last updated: 2019-06-11Bibliographically approved
Gustafson, E. (2016). Thromboinflammation: in a Model of Hepatocyte Transplantation. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Thromboinflammation: in a Model of Hepatocyte Transplantation
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hepatocyte transplantation is an attractive method for the treatment of metabolic liver disease and acute liver failure. The clinical application of this method has been hampered by a large initial loss of transplanted cells.

This thesis has identified and characterized an instant blood-mediated inflammatory reaction (IBMIR), which is a thromboinflammatory response from the innate immunity that may partly explain the observed loss of cells. In vitro perifusion experiments were performed and established that hepatocytes in contact with blood activate the complement and coagulation systems and induce clot formation in conjunction with the recruitment of neutrophils.  Within an hour, the hepatocytes were surrounded by platelets and entrapped in a clot infiltrated by neutrophils. Furthermore, hepatocytes expressed tissue factor (TF), and the reactions were shown to be initiated through the TF pathway. Monitoring of hepatocyte transplantation in vivo revealed activation of the same parameters as were noted in vitro.

For the first time, von Willebrand factor (vWF) was identified on the hepatocyte surface, being demonstrated by flow cytometry and confocal microscopy. mRNA for vWF was also confirmed in hepatocytes. Complex formation between platelets and hepatocytes was also identified. Addition of antibodies targeting the binding site for vWF on the platelets reduced the complex formation.

Two different strategies, systemic and local intervention, were applied to diminish the thromboinflammation elicited from the hepatocytes in contact with ABO-matched blood. Systemic inhibition with LMW-DS, in a clinically applicable dose, was found to be superior in controlling the IBMIR in vitro when compared to heparin. Cryopreserved hepatocytes elicited the IBMIR to the same extent as did fresh hepatocytes, and the IBMIR was equally well controlled with LMW-DS in both cryopreserved and fresh cells.

Hepatocytes were coated with two layers of immobilized heparin in an attempt to protect the cells from the IBMIR. In vitro perifusion experiments showed heparinized hepatocytes triggered a significantly lower degree of IBMIR.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. p. 75
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 123
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-286869 (URN)978-91-554-9592-3 (ISBN)
Public defence
2016-06-10, Rosénsalen, Akademiska Barnsjukhuset Ing 95/96, Uppsala, 10:00 (Swedish)
Opponent
Supervisors
Available from: 2016-05-20 Created: 2016-04-22 Last updated: 2018-01-10Bibliographically approved
Klar, J., Raykova, D., Gustafson, E., Tóthová, I., Ameur, A., Wanders, A. & Dahl, N. (2015). Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution. European Journal of Human Genetics, 23(12), 1679-1683
Open this publication in new window or tab >>Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution
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2015 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 23, no 12, p. 1679-1683Article in journal (Refereed) Published
Abstract [en]

Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin γ-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.

National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-244419 (URN)10.1038/ejhg.2015.49 (DOI)000365129700015 ()25782675 (PubMedID)
Funder
Swedish Research Council, K2013-66X-10829-20-3
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2015-03-03 Created: 2015-02-16 Last updated: 2017-12-04Bibliographically approved
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