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Forslund, Tony
Publications (10 of 18) Show all publications
Tapsas, D., Fälth-Magnusson, K., Högberg, L., Forslund, T., Sundqvist, T. & Hollén, E. (2014). Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet. Scandinavian Journal of Gastroenterology, 49(11), 1311-1317
Open this publication in new window or tab >>Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet
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2014 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 11, p. 1311-1317Article in journal (Refereed) Published
Abstract [en]

Objective. Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. Materials and Methods. Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. Results. Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 mu M. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, less than 1400 mu M, while 29.8% demonstrated high levels, that is, greater than 1400 mu M. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. Conclusion. The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
Keywords
celiac disease; gluten-free diet; oats; urinary nitrite/nitrate
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113064 (URN)10.3109/00365521.2014.946081 (DOI)000345603400006 ()25263796 (PubMedID)
Note

Funding Agencies|Medical Research Council of Southeast Sweden; County Council of Ostergotland; Swedish Research Council

Available from: 2015-01-09 Created: 2015-01-08 Last updated: 2017-12-05
Högberg, L., Webb, C., Fälth-Magnusson, K., Forslund, T., Magnusson, K.-E., Danielsson, L., . . . Sundqvist, T. (2011). Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine. ACTA PAEDIATRICA, 100(7), 1023-1027
Open this publication in new window or tab >>Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine
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2011 (English)In: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 100, no 7, p. 1023-1027Article in journal (Refereed) Published
Abstract [en]

Aim: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. Methods: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. Results: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p andlt; 0.001). Conclusion: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd, 2011
Keywords
Coeliac disease, Nitric oxide, Screening, Urinary nitrite, nitrate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69187 (URN)10.1111/j.1651-2227.2011.02186.x (DOI)000291224200031 ()
Available from: 2011-06-17 Created: 2011-06-17 Last updated: 2011-06-17
Schön, T., Idh, J., Westman, A., Elias, D., Abate, E., Diro, E., . . . Sundqvist, T. (2011). Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis - A randomised trial. Tuberculosis, 91(5), 370-377
Open this publication in new window or tab >>Effects of a food supplement rich in arginine in patients with smear positive pulmonary tuberculosis - A randomised trial
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2011 (English)In: Tuberculosis, ISSN 1472-9792, E-ISSN 1873-281X, Vol. 91, no 5, p. 370-377Article in journal (Refereed) Published
Abstract [en]

In tuberculosis (TB), the production of nitric oxide (NO) is confirmed but its importance in host defense is debated. Our aim was to investigate whether a food supplement rich in arginine could enhance clinical improvement in TB patients by increased NO production. Smear positive TB patients from Gondar, Ethiopia (n = 180) were randomized to a food supplementation rich in arginine (peanuts, equivalent to 1 g of arginine/day) or with a low arginine content (wheat crackers, locally called daboqolo) during four weeks. The primary outcome was cure rate according to the WHO classification and secondary outcomes were sputum smear conversion, weight gain, sedimentation rate, reduction of cough and chest X-ray improvement as well as levels of NO in urine (uNO) or exhaled air (eNO) at two months. There was no effect of the intervention on the primary outcome (OR 1.44, 95% CI: 0.69-3.0, p = 0.39) or secondary outcomes. In the subgroup analysis according to HIV status, peanut supplemented HIV+/TB patients showed increased cure rate (83.8% (31/37) vs 53.1% (17/32), p andlt; 0.01). A low baseline eNO (andlt; 10 ppb) in HIV+/TB patients was associated with a decreased cure rate. We conclude that nutritional supplementation with a food supplement rich in arginine did not have any overall clinical effect. In the subgroup of HIV positive TB patients, it significantly increased the cure rate and as an additional finding in this subgroup, low initial levels of NO in exhaled air were associated with a poor clinical outcome but this needs to be confirmed in further studies.

Place, publisher, year, edition, pages
Elsevier, 2011
Keywords
Nitric oxide, Arginine, Nutritional supplementation, Tuberculosis, Interleukin 10
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71556 (URN)10.1016/j.tube.2011.06.002 (DOI)000295462300004 ()
Note
Funding Agencies|Swedish Heart and Lung Foundation||Swedish SAREC/SIDA foundation||Swedish Research Council||Available from: 2011-10-21 Created: 2011-10-21 Last updated: 2017-12-08Bibliographically approved
Särndahl, E., Bergström, I., Nijm, J., Forslund, T., Perretti, M. & Jonasson, L. (2010). Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease. Metabolism: Clinical and Experimental, 59(3), 443-440
Open this publication in new window or tab >>Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
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2010 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 59, no 3, p. 443-440Article in journal (Refereed) Published
Abstract [en]

Background: A dysregulated cortisol response in patients with stable coronary artery disease (CAD) is related to systemic inflammatory activity. Moreover, a dysfunctional activation status of neutrophils in CAD has been discussed. The anti-inflammatory actions of glucocorticoids are mediated by annexin-1 (ANXA1), a protein mainly expressed by innate immune cells. An altered expression of glucocorticoid receptors (GR) and ANXA1 has been associated with glucocorticoid resistance.

Methods and Results: Salivary cortisol levels were measured in the morning and evening during 3 consecutive days in 30 CAD patients and 30 healthy individuals. The neutrophil expression of GR and ANXA1 was determined by flow cytometry. The effect of exogenous ANXA1 was determined in neutrophil stimulation assays. The patients showed a flattened diurnal cortisol pattern compared to healthy subjects, involving higher levels in the evening. The neutrophil expression of GRtotal and GRα, as well as the ratio of GRα:GRβ expression was significantly decreased in patients, whereas the GRβ expression did not differ compared to controls. The neutrophil expression of ANXA1 was significantly increased in patients. Ex vivo, ANXA1 suppressed LTB4-induced ROS production in neutrophils from patients, but not from controls. On the other hand, ANXA1 impaired the LTB4-induced up-regulation of β2-integrins in both patients and controls.

Conclusion: CAD patients displayed a more flattened diurnal cortisol rhythm caused by higher cortisol levels in the evening compared to healthy subjects. Our findings indicate a chronic overactivation of the hypothalamic-pituitary-adrenal (HPA) axis but give no conclusive evidence for glucocorticoid resistance, as assessed by the neutrophil expression of GR and ANXA1. The data rather point towards an increased anti-inflammatory potential in neutrophils from patients with stable CAD.

Keywords
Coronary artery disease, cortisol, neutrophil, glucocorticoid receptor, annexin-1
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-17247 (URN)10.1016/j.metabol.2009.07.044 (DOI)000276761800021 ()
Note
Original Publication: Eva Särndahl, Ida Bergström, Johnny Nijm, Tony Forslund, Mauro Perretti and Lena Jonasson, Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease, 2010, Metabolism: Clinical and Experimental, (59), 3, 443-440. http://dx.doi.org/10.1016/j.metabol.2009.07.044 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2017-12-13
Devenney, I., Norrman, G., Forslund, T., Fälth-Magnusson, K. & Sundqvist, T. (2010). Urinary nitric oxide excretion in infants with eczema. Pediatric Allergy and Immunology, 21(1), e229-e234
Open this publication in new window or tab >>Urinary nitric oxide excretion in infants with eczema
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2010 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 21, no 1, p. e229-e234Article in journal (Refereed) Published
Abstract [en]

Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.

Keywords
paediatric • eczema • clinical immunology • nitric oxide
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13932 (URN)10.1111/j.1399-3038.2009.00892.x (DOI)000276186200019 ()19725898 (PubMedID)
Note

Tidigare titel: Nitric oxide urinary products in infants with eczema This is the authors’ version of the following article: which has been published in final form at:Irene Devenney, Gunilla Norrman, Tony Forslund, Karin Fälth-Magnusson and Tommy Sundqvist, Urinary nitric oxide excretion in infants with eczema., 2010, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, (21), 1, E229-E234which has been published in final form at: http://dx.doi.org/10.1111/j.1399-3038.2009.00892.xCopyright: Wiley-Blackwell

Available from: 2006-09-05 Created: 2006-09-05 Last updated: 2017-12-13
Idh, J., Westman, A., Elias, D., Moges, F., Getachew, A., Gelaw, A., . . . Schön, T. (2008). Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection. BMC Infectious Diseases, 8(146)
Open this publication in new window or tab >>Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection
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2008 (English)In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 8, no 146Article in journal (Refereed) Published
Abstract [en]

Background: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO).

Methods: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia.

Results: The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate.

Conclusion: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16238 (URN)10.1186/1471-2334-8-146 (DOI)
Note
Original Publication: Jonna Idh, Anna Westman, Daniel Elias, Feleke Moges, Assefa Getachew, Aschalew Gelaw, Tommy Sundqvist, Tony Forslund, Addis Alemu, Belete Ayele, Ermias Diro, Endalkachew Melese, Yared Wondmikun, Sven Britton, Olle Stendahl and Thomas Schoen, Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection, 2008, BMC INFECTIOUS DISEASES, (8), 146. http://dx.doi.org/10.1186/1471-2334-8-146 Publisher: BioMed Central http://www.biomedcentral.com/Available from: 2009-01-16 Created: 2009-01-09 Last updated: 2017-12-14Bibliographically approved
Cedergren, J., Forslund, T., Sundqvist, T. & Skogh, T. (2007). Intracellular oxidative activation in synovial fluid neutrophils from patients with rheumatoid arthritis but not from other arthritis patients. Journal of Rheumatology, 34(11), 2162-2170
Open this publication in new window or tab >>Intracellular oxidative activation in synovial fluid neutrophils from patients with rheumatoid arthritis but not from other arthritis patients
2007 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 34, no 11, p. 2162-2170Article in journal (Refereed) Published
Abstract [en]

Objective: To compare total and intracellular oxidative activation of blood and synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and other arthritides with blood donor neutrophils.

Methods: Peripheral blood and SF samples were obtained from 26 gonarthritis patients (13 RA, 13 non-RA) attending the rheumatology unit for therapeutic joint aspiration. Isolated neutrophils were stimulated by a formylated tripeptide (fMLF) or by microbeads coated with collagen-I. Formation of superoxide-anion-derived reactive oxygen species (ROS) was studied by luminol-enhanced chemiluminescence. Paired samples of blood and SF neutrophils from patients with active arthritis were compared with blood neutrophils from patients in remission and from 47 healthy blood donors.

Results: SF neutrophils from patients with RA, but not from non-RA patients, showed high baseline intracellular ROS production. Blood neutrophils from arthritis patients in remission existed in a primed state as revealed by more rapid oxidative response after collagen-bead challenge and a more pronounced response after fMLF stimulation compared to healthy blood donors. Blood neutrophils from RA patients with ongoing gonarthritis, however, did not differ from healthy blood donors concerning oxidative activation, whereas blood neutrophils from non-RA patients with gonarthritis showed a significantly lower peak ROS production.

Conclusions: A novel finding with pathogenetic implications in our study is that SF neutrophils from patients with RA, but not other arthritides, are activated and produce ROS intracellularly. This implies that synovial neutrophils in RA are engaged in the processing of endocytosed material.

Keywords
Neutrophils, Arthritis, Reactive oxygen species, Superoxide anion
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14585 (URN)
Available from: 2007-08-27 Created: 2007-08-27 Last updated: 2017-12-13
Cedergren, J., Forslund, T., Sundqvist, T. & Skogh, T. (2007). Oxidative activation of human neutrophils by type-1-collagen-coated particles is influenced by nitric oxide production and modulated by endogenous arginase. Journal of Leukocyte Biology
Open this publication in new window or tab >>Oxidative activation of human neutrophils by type-1-collagen-coated particles is influenced by nitric oxide production and modulated by endogenous arginase
2007 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673Article in journal (Refereed) Submitted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14588 (URN)
Available from: 2007-08-27 Created: 2007-08-27 Last updated: 2017-12-13
Abdalla, H., Forslund, T., Schön, T., Stendahl, O. & Sundqvist, T. (2006). Effects of CNI-1493 on human granulocyte functions. Immunobiology, 211(3), 191-197
Open this publication in new window or tab >>Effects of CNI-1493 on human granulocyte functions
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2006 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 211, no 3, p. 191-197Article in journal (Refereed) Published
Abstract [en]

During acute bacterial infections such as sepsis and meningitis, activation of inflammatory mediators such as nitric oxide (NO) plays a crucial role in both pathogenesis and host defense. We have previously reported that CNI-1493, a macrophage deactivator, reduced mortality in infant rats infected with Haemophilus influenzae type b (Hib) with associated decrease in the number of granulocytes in the infected tissue. The aim of the present study was to investigate how CNI-1493 affects granulocytes and macrophages in vitro. Murine macrophages (RAW 264.7) pre-incubated with CNI-1493 prior to activation with lipopolysaccharide (LPS)/interferon gamma (IFNγ) had decreased NO production measured as NO2/NO3 levels and reduction in inducible NO-synthase (iNOS) expression. Reactive oxygen species (ROS) production was increased in formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated granulocytes following CNI-1493 treatment, whereas F-actin content, motility and chemotaxis were decreased under the same conditions. The effects of CNI-1493 on both NO production in LPS/IFNγ-activated macrophages and ROS production, F-actin content, motility and chemotaxis in granulocytes, may contribute to the reduced inflammatory response and increased survival in Hib-infected animals treated with CNI-1493.

Keywords
CNI-1493, Granulocytes, iNOS, Macrophages, ROS
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-50239 (URN)10.1016/j.imbio.2005.09.006 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
Petersson, C., Forsberg, M., Aspholm, M., Olfat, F. O., Forslund, T., Borén, T. & Magnusson, K.-E. (2006). Helicobacter pylori sabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein. Medical Microbiology and Immmunology, 195(4), 195-206
Open this publication in new window or tab >>Helicobacter pylori sabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein
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2006 (English)In: Medical Microbiology and Immmunology, ISSN 0300-8584, E-ISSN 1432-1831, Vol. 195, no 4, p. 195-206Article in journal (Refereed) Published
Abstract [en]

The human pathogen Helicobacter pylori expresses two dominant adhesins; the Lewis b blood group antigen binding adhesin, BabA, and the sialic acid-binding adhesin, SabA. These adhesins recognize specific carbohydrate moieties of the gastric epithelium, i.e. the Lewis b antigen, Leb, and the sialyl-Lewis x antigen, sLex, respectively, which promote infection and inflammatory processes in the gastroduodenal tract. To assess the contribution of each of BabA, SabA and the neutrophil activating protein (HP-NAP) in a local inflammation, we investigated the traits of H. pylori mutants in their capacity to interact with and stimulate human neutrophils. We thence found that the SabA adhesin was not only the key inducer of oxidative metabolism (Unemo et al. J Biol Chem 280:15390–15397, 2005), but also essential in phagocytosis induction, as evaluated by flow cytometry, fluorescence microscopy and luminol-enhanced chemiluminescence. The napA deletion resulted in enhanced generation of reactive oxygen species and impaired adherence to the host cells. In conclusion, the SabA adhesin stimulates human neutrophils through selectin-mimicry. Interestingly, HP-NAP modulates the oxidative burst, which could tune the impact of the H. pylori infection for establishment of balanced and chronic inflammation of the gastric mucosa.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-38156 (URN)10.1007/s00430-006-0018-x (DOI)42125 (Local ID)42125 (Archive number)42125 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
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