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Bergquist, Maria
Publications (10 of 16) Show all publications
Bergquist, M., Hastbacka, J., Glaumann, C., Fredén, F., Huss, F. & Lipcsey, M. (2019). The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome. Burns, 45(2), 354-363
Open this publication in new window or tab >>The time-course of the inflammatory response to major burn injury and its relation to organ failure and outcome
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2019 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, no 2, p. 354-363Article in journal (Refereed) Published
Abstract [en]

Burn injury causes major inflammatory activation and cytokine release, however, the temporal resolution of the acute and sub-acute inflammatory response has not yet been fully delineated. To this end, we have quantified 20 inflammatory mediators in plasma from 44 adult patients 0-21 days after burn injury and related the time course of these mediators to % total body surface area (TBSA) burned, clinical parameters, organ failure and outcome. Of the cytokines analyzed in these patients, interleukin 6 (IL-6), IL-8, IL-10 and monocyte chemoattractant protein 1 (MCP-1) correlated to the size of the injury at 24-48h after burn injury. In our study, the concentration of IL-10 had prognostic value in patients with burn injury both measured at admission and at 24-48h after injury. However, simple demographic data such as age, % burned TBSA, inhalation injury and their combination, the Baux score and modified Baux score, outperform most of the cytokines, with the exception of IL-8 and MCP1 levels on admission, in predicting death.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Cytokines, Burns, Mortality, Multiple organ failure, Severity of illness index
National Category
Anesthesiology and Intensive Care Surgery
Identifiers
urn:nbn:se:uu:diva-380482 (URN)10.1016/j.burns.2018.09.001 (DOI)000461044900012 ()30274808 (PubMedID)
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-15Bibliographically approved
Bergquist, M., Huss, F., Hästbacka, J., Lindholm, C., Martijn, C., Rylander, C., . . . Fredén, F. (2016). Glucocorticoid receptor expression and binding capacity in patients with burn injury. Acta Anaesthesiologica Scandinavica, 60(2), 213-221
Open this publication in new window or tab >>Glucocorticoid receptor expression and binding capacity in patients with burn injury
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2016 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 2, p. 213-221Article in journal (Refereed) Published
Abstract [en]

Background

Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center.

Methods

Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry.

Results

GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (< 0.05).

Conclusions

GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-229116 (URN)10.1111/aas.12604 (DOI)000368139700009 ()
Funder
Swedish Research Council, 5315
Available from: 2014-07-31 Created: 2014-07-31 Last updated: 2018-01-11
Bergquist, M., Lindholm, C., Strinnholm, M., Hedenstierna, G. & Rylander, C. (2015). Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock. Intensive care medicine experimental, 3(1), Article ID 23.
Open this publication in new window or tab >>Impairment of neutrophilic glucocorticoid receptor function in patients treated with steroids for septic shock
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2015 (English)In: Intensive care medicine experimental, ISSN 2197-425X, Vol. 3, no 1, article id 23Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Glucocorticoid (GC) treatment has variable effect in sepsis. This may be explained by decreased expression or function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in patients during and after sepsis.

METHODS: In this prospective, non-interventional clinical study, peripheral blood and clinical data were collected from 20 adult patients at five timepoints during sepsis and 5-13 months after recovery. GR expression and binding capacity were assessed by flow cytometry.

RESULTS: GR expression was higher in T lymphocytes from patients with septic shock compared to healthy subjects (p = 0.01). While there was no difference in GR expression between GC-treated and non-treated patients, GR binding capacity was lower in GC-treated patients at admission compared to healthy subjects (p ≤ 0.03). After the acute inflammation inflammatory phase, GR binding capacity was still lower in neutrophils of GC-treated patients, compared to healthy subjects (p = 0.01). On admission, GR binding capacity in T lymphocytes and neutrophils was inversely correlated with noradrenaline dose and lactate (p ≤ 0.03).

CONCLUSIONS: Our data suggest that GR expression is increased in T lymphocytes during septic shock regardless of GC treatment, while GR binding capacity is decreased in neutrophils in GC-treated patients. As neutrophils are the predominant circulating leucocyte in septic shock, their decreased GR binding capacity may impede the response to exogenous or endogenous glucocorticoids.

National Category
Medical and Health Sciences
Research subject
Biochemistry; Anaesthesiology and Intensive Care; Physiology
Identifiers
urn:nbn:se:uu:diva-264213 (URN)10.1186/s40635-015-0059-9 (DOI)26215823 (PubMedID)
Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2015-10-09Bibliographically approved
Borges, J. B., Costa, E. L. V., Bergquist, M., Lucchetta, L., Widström, C., Maripuu, E., . . . Hedenstierna, G. (2015). Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung. Critical Care Medicine, 43(5), E123-E132
Open this publication in new window or tab >>Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung
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2015 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 43, no 5, p. E123-E132Article in journal (Refereed) Published
Abstract [en]

Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

Keywords
[F-18]fluoro-2-deoxy-D-glucose, acute pulmonary inflammation, acute respiratory distress syndrome, mechanical ventilation, positron emission tomography, ventilator-induced lung injury
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-252977 (URN)10.1097/CCM.0000000000000926 (DOI)000353061000001 ()25746507 (PubMedID)
Available from: 2015-05-19 Created: 2015-05-18 Last updated: 2018-11-12Bibliographically approved
Hastbacka, J., Fredén, F., Hult, M., Bergquist, M., Wilkman, E., Vuola, J., . . . Huss, F. (2015). Matrix Metalloproteinases-8 and-9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study. PLoS ONE, 10(5), Article ID e0125918.
Open this publication in new window or tab >>Matrix Metalloproteinases-8 and-9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0125918Article in journal (Refereed) Published
Abstract [en]

Introduction Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Results Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.

National Category
Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:uu:diva-256129 (URN)10.1371/journal.pone.0125918 (DOI)000354049700096 ()25945788 (PubMedID)
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2017-12-04Bibliographically approved
Trachsel, S., Hambraeus-Jonzon, K., Bergquist, M., Martijn, C., Chen, L. & Hedenstierna, G. (2015). No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist. Journal of applied physiology, 118(6), 768-775
Open this publication in new window or tab >>No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist
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2015 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 118, no 6, p. 768-775Article in journal (Refereed) Published
Abstract [en]

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and non-response is common. A better understanding of the mechanisms by which INO acts, may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, non-ventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsis-like condition (infusion of endotoxin) were blunted by INO 40ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (ET-A/ET-B) in atelectatic lung regions. INO caused a shift in blood flow away from atelectatic lung regions in the endotoxemic piglets, but not during ET receptor antagonism. We conclude that INO in short term experiments, in addition to causing selective pulmonary vasodilation in ventilated lung regions, also increases the ET-A/ET-B mRNA expression ratio in lung tissue. This might augment the vasoconstriction in atelectatic lung regions, enhancing the redistribution of pulmonary blood flow to ventilated lung regions which are reached by INO. Such vasoconstriction may be an important additional factor explaining the effect of INO.

National Category
Clinical Medicine Physiology
Identifiers
urn:nbn:se:uu:diva-243210 (URN)10.1152/japplphysiol.00591.2014 (DOI)000350985100014 ()25549764 (PubMedID)
Available from: 2015-02-05 Created: 2015-02-05 Last updated: 2018-01-11Bibliographically approved
Bergquist, M., Jonasson, S., Hjoberg, J., Hedenstierna, G. & Hanrieder, J. (2014). Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma. BMC Pulmonary Medicine, 14, 110
Open this publication in new window or tab >>Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma
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2014 (English)In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 14, p. 110-Article in journal (Refereed) Published
Abstract [en]

Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL). Methods: BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex T assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts. Results: Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex T analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation. Conclusion: Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes.

Keywords
Asthma, Bronchoalveolar lavage, Endotoxin, Inflammation, Ovalbumin, Proteomics, Mass spectrometry
National Category
Clinical Medicine Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-232074 (URN)10.1186/1471-2466-14-110 (DOI)000340642000001 ()
Available from: 2014-09-13 Created: 2014-09-12 Last updated: 2017-12-05Bibliographically approved
Bergquist, M., Jirholt, P., Nurkkala, M., Rylander, C., Hedenstierna, G. & Lindholm, C. (2014). Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock. Journal of Infection, 69(2), 113-122
Open this publication in new window or tab >>Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock
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2014 (English)In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 69, no 2, p. 113-122Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome.

METHODS: Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied.

RESULTS: Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration.

CONCLUSION: The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.

National Category
Infectious Medicine
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-223346 (URN)10.1016/j.jinf.2014.03.011 (DOI)000339751500002 ()24657243 (PubMedID)
Available from: 2014-04-17 Created: 2014-04-17 Last updated: 2017-12-05Bibliographically approved
Molnar, M., Bergquist, M., Larsson, A., Wiklund, L. & Lennmyr, F. (2014). Hyperglycaemia increases S100β after short experimental cardiac arrest. Acta Anaesthesiologica Scandinavica, 58(1), 106-113
Open this publication in new window or tab >>Hyperglycaemia increases S100β after short experimental cardiac arrest
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2014 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 1, p. 106-113Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Hyperglycaemia is associated with aggravated ischaemic brain injury. The main objective of this study was to investigate the effects on cerebral perfusion of 5 min of cardiac arrest during hyperglycaemia and normoglycaemia.

METHODS:

Twenty triple-breed pigs (weight: 22-29 kg) were randomised and clamped at blood glucose levels of 8.5-10 mM [high (H)] or 4-5.5 mM [normal (N)] and thereafter subjected to alternating current-induced 5 min-cardiac arrest followed by 8 min of cardiopulmonary resuscitation and direct current shock to restore spontaneous circulation.

RESULTS:

Haemodynamics, laser Doppler measurements and regional venous oxygen saturation (HbO2 ) were monitored, and biochemical markers in blood [S100β, interleukin (IL)-6 and tumour necrosis factor (TNF)] quantified throughout an observation period of 3 h. The haemodynamics and physiological measurements were similar in the two groups. S100β increased over the experiment in the H compared with the N group (P < 0.05). IL-6 and TNF levels increased across the experiment, but no differences were seen between the groups.

CONCLUSIONS:

The enhanced S100β response is compatible with increased cerebral injury by hyperglycaemic compared with normoglycaemic 5 min of cardiac arrest and resuscitation. The inflammatory cytokines were similar between groups.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-210633 (URN)10.1111/aas.12209 (DOI)000328156800014 ()24117011 (PubMedID)
Available from: 2013-11-12 Created: 2013-11-12 Last updated: 2017-12-06Bibliographically approved
Nilsson, M., Hambraeus-Jonzon, K., Alving, K., Wiklund, P., Bergquist, M. & Fredén, F. (2013). Distant effects of nitric oxide inhalation in lavage induced lung injury in anaesthetised pigs. Acta Anaesthesiologica Scandinavica, 57(3), 326-333
Open this publication in new window or tab >>Distant effects of nitric oxide inhalation in lavage induced lung injury in anaesthetised pigs
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2013 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 3, p. 326-333Article in journal (Refereed) Published
Abstract [en]

Background Inhalation of nitric oxide (INO) exerts both local and distanteffects. INO in healthy pigs causes down-regulation of endogenous nitric oxide(NO) production and vasoconstriction in lung regions not reached by INO, especially in hypoxic regions, which augments hypoxic pulmonary vasoconstriction. In contrast, in pigs with endotoxemia-induced lung injury, INO causes increased NO production in lung regions not reached by INO. The aim ofthis study was to investigate whether INO exerts distant effects in surfactant-depleted lungs. Methods Twelve pigs were anaesthetised, and the left lower lobe (LLL) was separately ventilated. Lavage injury was induced in all lung regions, except the LLL. In six pigs, 40 ppm INO was given to the LLL (INO group), and theeffects on endogenous NO production and blood flow in the lavage-injured lungregions were studied. Six pigs served as a control group. NO concentration inexhaled air (ENO), NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. Results The calcium (Ca2+)-dependent NOS activity was lower (P<0.05) in the lavage-injured lung regions in the INO group than in the control group. There were no measurable differences between the groups for Ca2+-independent NOS activity, cGMP, ENO, or regional pulmonary blood flow. Conclusions Regional INO did not increase endogenous NO production in lavage-injured lung regions not directly reached by INO, but instead down-regulated the constitutive calcium-dependent nitric oxide synthase activity, indicating that NO may inhibit its own synthesis.

Keywords
Nitric oxide, Nitric oxide synthase, Lavage induced lung injury, pulmonary blood flow, exhaled nitric oxide, cyclic guanosine monophosphate
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-157085 (URN)10.1111/aas.12030 (DOI)000314652400009 ()
Available from: 2011-08-15 Created: 2011-08-15 Last updated: 2017-12-08Bibliographically approved
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