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CLA Has a Useful Effect on Bone Markers in Patients with Rheumatoid Arthritis

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Lipids

Abstract

Rheumatoid arthritis is a systemic, chronic disease which may increase the risk of osteoporosis. This study was carried out in order to examine the effect of conjugated linoleic acid (CLA) on bone markers in rheumatoid arthritis disease which is the most common autoimmune disease. The present study is a randomized double-blind clinical trial. Subjects included 52 patients with active rheumatoid arthritis who were divided into two groups. Group I received standard treatment plus 2 daily 1.25 g capsules (Containing about 2 g of 9-cis 11-trans isomer and 10-cis 12-trans isomer in ratio of 50 −50 CLA in glycerinated form), Group II received standard treatment plus 2 Placebo 1.25 g capsules containing sunflower oil with high oleic acid. Telopeptides C, osteocalcin, and MMP3 were analyzed by ELISA method, PGE2 was done by competitive enzymatic immunoassay method, and IGF-1 was analyzed by the IRMA method based on the sandwich method and ALK-P of bone. Before and after the intervention, the questionnaires about general information, nutrition assessment and medical history were filled out by the subjects. Nutritional assessment was done by a 24-h record questionnaire for the three-day diet. The results were analyzed using SPSS software (version 18). Findings: There was no significant difference between the groups in enzyme activity of ALK-P of bone, PGE2 and MMP3 variables. However, differences between the two groups in terms of activity of telopeptides C, Osteocalcin, and IGF1 were significant (P < 0.05). CLA has a potentially beneficial effect on bone markers in patients with rheumatoid arthritis. Therefore, in order to study the effect of CLA on bone health in patients with RA and all patients with autoimmune and bone diseases more studies with longer duration and evaluation of bone mass density are required.

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Abbreviations

ACR:

American College of Rheumatology

ALK-P:

Alkaline phosphatase

BMD:

Bone mass density

BMI:

Body mass index

BMP:

Bone morphogenic proteins

CLA:

Conjugated linoleic acid

FA:

Fatty acid

IGF1:

Insulin-like growth factor 1

MMP3:

Matrix metalloproteinase 3

PGE2 :

Prostaglandine E2

PPARγ:

Peroxisome proliferator activated receptor gamma

RA:

Rheumatoid Arthritis

References

  1. Smolen JS, Aletaha D (2010) The assessment of disease activity in rheumatoid arthritis. Clin Exp Rheumatol 28(3 Suppl 59):S18–S27

    PubMed  Google Scholar 

  2. Goronzy JJ, Shao L, Weyand CM (2010) Immune aging and rheumatoid arthritis. Rheum Dis Clin N Am 36(2):297–310

    Article  Google Scholar 

  3. Mikuls TR (2003) Co-morbidity in rheumatoid arthritis. Best Pract Res Clin Rheumatol 17:729–752

    Article  PubMed  Google Scholar 

  4. Turhanoğlu AD, Güler H, Yönden Z, Aslan F, Mansuroglu A, Ozer C (2011) The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis. Rheumatol Int 31(7):911–914

    Article  CAS  PubMed  Google Scholar 

  5. Gomez FE, Kaufer-Horwitz M (2012) Medical nutrition therapy for rheumatic disease. In: Mahan LK, Escott-Stump S, Raymond J (eds) Krause’s food and nutrition care process, 13th edn. Elsevier, Missouri, pp 901–922

    Google Scholar 

  6. Silva RR, Rodrigues LBO, Lisboa MD, Silva Pereira MM, de Souza SO (2014) Conjugated linoleic acid (CLA): a review. Int J Appl Sci Technol 4(2):154–170

    Google Scholar 

  7. Yang B, Chen H, Stanton C, Ross R, Zhang HQ, Chen Y, Chen (2015) Review of the roles of conjugated linoleic acid in health and disease. J Funct Foods 15(3):14–25

    Google Scholar 

  8. Aryaeian N, Shahram F, Djalali M, Eshragian MR, Djazayeri A, Sarrafnejad A, Salimzadeh A, Naderi N, Maryam C (2009) Effect of conjugated linoleic acids, vitamin E and their combination on the clinical outcome of Iranian adults with active rheumatoid arthritis. Int J Rheumat Diseases 12(1):20–28

    Article  Google Scholar 

  9. Aryaeian N, Shahram F, Djalali M, Eshragian MR, Djazayeri A, Sarrafnejad A, Naderi N, Chamari M, Fatehi F, Zarei M (2008) Effect of conjugated linoleic acid, vitamin E and their combination on lipid profiles and blood pressure of Iranian adults with active rheumatoid arthritis. Vasc Health Risk Manag 4(6):1423–1432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Aryaeian N, Djalali M, Shahram F, Djazayery A, Eshragian MR (2014) Effect of conjugated linoleic acid, vitamin E, alone or combined on immunity and inflammatory parameters in adults with active rheumatoid arthritis: a randomized controlled trial. Int J Prev Med 5(12):1567–1577

    PubMed  PubMed Central  Google Scholar 

  11. Corl BA, Dm Barbanano, Bauman DE (2003) cis-9,trans-11 CLA derived endogenously from trans-11 18:1 reduces cancer risk in rats. J Nutr 133:2893–2900

    CAS  PubMed  Google Scholar 

  12. Park Y, Pariza MW (2001) Lipoxygenase inhibitors inhibit heparin-releasable lipoprotein lipase activity in 3T3-L1 adipocytes and enhance body fat reduction in mice by conjugated linoleic acid. Biochim Biophys Acta 1534:27–33

    Article  CAS  PubMed  Google Scholar 

  13. Shen CL, Dunn DM, Henry JH, Li Y, Watkins BA (2004) Decreased production of inflammatory mediators in human osteoarthritic chondrocytes by conjugated linoleic acids. Lipids 39:161–166

    CAS  PubMed  Google Scholar 

  14. Pariza MW, Park Y, Cook ME (2001) The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 40:283–298

    Article  CAS  PubMed  Google Scholar 

  15. Pariza MW, Park Y, Xu X, Ntambi J, Kang K (2000) Speculation on the mechanisms of action of conjugated linoleic acid. Proc Soc Exp Biol Med 223(1):8–13

    Article  CAS  PubMed  Google Scholar 

  16. Banu J, Bhattacharya A, Rahman M, Fernandes G (2008) Beneficial effects of conjugated linoleic acid and exercise on bone of middle-aged female mice. J Bone Miner Metab 26:436–445

    Article  CAS  PubMed  Google Scholar 

  17. Lunogo D, Bergamo P, Rossi M (2003) Effects of conjugated linoleic acid on growth and cytokine expression. Immonol Lett 90:195–201

    Article  CAS  Google Scholar 

  18. Doyle L, Jewell C, Mullen A, Nugent AP, Roche HM, Cashman KD (2005) Effect of dietary supplementation with conjugated linoleic acid on markers of calcium and bone metabolism in healthy adult men. Eur J Clin Nutr 59:432–440

    Article  CAS  PubMed  Google Scholar 

  19. Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada AL (2002) Effects of conjugated linoleic acid supplementation during resistance training on body composition, bone density, strength, and selected hematological markers. J Strength Cond Res 16:325–334

    PubMed  Google Scholar 

  20. Gaullier JM, Halse J, Hoye K, Kristiansen K, Fagertun H, Vik H, Gudmundsen O (2004) Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans. Am J Clin Nutr 79:1118–1125

    CAS  PubMed  Google Scholar 

  21. Banu J, Bhattacharya A, Rahman M, O’Shea M, Fernandes G (2006) Effects of conjugated linoleic acid and exercise on bone mass in young male Balb/C mice. Lipids Health Disease 5(7):1–9

    Google Scholar 

  22. Kelly O, Cusack S, Jewell C, Cashman KD (2003) The effect of polyunsaturated fatty acids, including conjugated linoleic acid, on calcium absorption and bone metabolism and composition in young growing rats. Br J Nutr 90:743–750

    Article  CAS  PubMed  Google Scholar 

  23. Jewell C, Cusack S, Cashman KD (2005) The effect of conjugated linoleic acid on transepithelial calcium transport and mediators of paracellular permeability in human intestinal-like caco-2 cells. Prostaglandins Leukot Essent Fat Acids 72:163–171

    Article  CAS  Google Scholar 

  24. Jewell C, Cashman KD (2003) The effect of conjugated linoleic acid and medium-chain fatty acids on transepithelial calcium transport in human intestinal-like caco-2 cells. Br J Nutr 89:639–647

    Article  CAS  PubMed  Google Scholar 

  25. Roche HM, Terres AM, Black IB, Gibney MJ, Kelleher D (2001) Fatty acids and epithelial permeability: effect of conjugated linoleic acid in caco-2 cells. Gut 48:797–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Watkins BA, Li Y, Lippman HE, Reinwald S, Seifert MF (2004) A test of Ockham’s razor: implications of conjugated linoleic acid in bone biology. Am J Clin Nutr 79:1175S–1185S

    CAS  PubMed  Google Scholar 

  27. Dorizo N, Ficoneri C, Riccioni G, Conti P, Theoharides TC, Bollea MR (2003) Conjugated linoleic acid: a functional food. Int J Immunopathol 16:215–220

    Google Scholar 

  28. Rahman MM, Bhattacharya A, Fernandes G (2006) Conjugated linoleic acid inhibits osteoclast differentiation of RAW264.7 cells by modulating RANKL signaling. J Lipid Res 47:1739–1748

    Article  CAS  PubMed  Google Scholar 

  29. Yu Y, Correll PH, Vanden Heuvel JP (2002) Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPARgamma-dependent mechanism. Biochim Biophys Acta 1581:89–99

    Article  CAS  PubMed  Google Scholar 

  30. Iwakiri Y, Sampson DA, Allen KG (2002) Suppression of cyclooxygenase-2 and inducible nitric oxide synthase expression by conjugated linoleic acid in murine macrophages. Prostaglandins Leukot Essent Fatty Acids 67:435–443

    Article  CAS  PubMed  Google Scholar 

  31. Watkins BA, Shen CL, McMurtry JP, Xu H, Bain SD, Allen KG, Seifert MF (1997) Dietary lipids modulate bone prostaglandin E2 Production, insulin-like growth factor-I concentration and formation rate in chicks. J Nutr 127(6):1084–1191

    CAS  PubMed  Google Scholar 

  32. Ostrowska E, Suster D, Muralitharan M, Cross RF, Leury BJ, Bauman DE, Dunshea FR (2003) Conjugated linoleic acid decreases fat accretion in pigs: evaluation by dual-energy X-ray absorptiometry. Br J Nutr 89:219–229

    Article  CAS  PubMed  Google Scholar 

  33. Kelly O, Cashman KD (2004) The effect of conjugated linoleic acid on calcium absorption and bone metabolism and composition in adult ovariectomised rats. Prostaglandins Leukot Essent Fat Acids 71:295–301

    Article  CAS  Google Scholar 

  34. Whigham LD, Higbee A, Bjorling DE, Park Y, Pariza MW, Cook ME (2002) Decreased antigen-induced eicosanoid release in conjugated linoleic acid-fed guinea pigs. Am J Physiol Regul Integr Comp Physiol 282:R1104–R1112

    Article  CAS  PubMed  Google Scholar 

  35. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS (1998) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324

    Article  Google Scholar 

  36. Scott DL, Saraux A (2004) Biologic markers in the diagnosis and assessment of outcome in rheumatoid arthritis; In: Rose BD (ed), 13th ed: 1

  37. Li Y, Watkins BA (1998) Conjugated linoleic acids alter bone fatty acid composition and redox vivo prostaglandin E2 biosynthesis in rats fed n-6 or n-3 fatty acids. Lipids 33(4):417–425

    Article  CAS  PubMed  Google Scholar 

  38. Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW (1997) Effect of conjugated linoleic acid on body composition in mice. Lipids 32:853–858

    Article  CAS  PubMed  Google Scholar 

  39. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW (1999) Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids 34:243–248

    Article  CAS  PubMed  Google Scholar 

  40. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW (1999) Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34:235–241

    Article  CAS  PubMed  Google Scholar 

  41. Platt ID, El-Sohemy A (2009) Regulation of osteoblast and adipocyte differentiation from human mesenchymal stem cells by conjugated linoleic acid. J Nutr Biochem 20:956–964

    Article  CAS  PubMed  Google Scholar 

  42. Platt I, Leticia G, El-Sohemy R (2007) Isomer-specific effects of conjugated linoleic acid on mineralized bone nodule formation from human osteoblast-like cells. Exp Biol Med 232(2):246–252

    CAS  Google Scholar 

  43. DeGuire JR, Mak IL, Lavery P, Agellon S, Wykes LJ, Weiler HA (2014) Orchidectomy-induced alterations in volumetric bone density, cortical porosity and strength of femur are attenuated by dietary conjugated linoleic acid in aged guinea pigs. Bone 73:1342–1350

    Google Scholar 

  44. Yang M, Cook ME, Seifert DM, Grahn M (1999) Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids. JBMR 14(7):1153–1161

    Article  Google Scholar 

  45. Shen AL, Dunn DM, Henry JH, Li Y, Watkins BA (2004) Decreased production of inflammatory mediators in human osteoarthritic chondrocytes by conjugated linoleic acids. Lipids 39(2):161–166

    CAS  PubMed  Google Scholar 

  46. Turek JJ, Li Y, Schoenlein IA, Allen KGD, Watkins BA (1998) Modulation of macrophage cytokine production by conjugated linoleic acids is influenced by the dietary n-6: N-3 fatty acid ratio. J Nutr Biochem 9:258–266

    Article  CAS  Google Scholar 

  47. Kreider RB, Ferreira MP, Greenwood M, Wilson M, Almada AL (2002) Effects of conjugated linoleic acid supplementation during resistance-training on body composition, bone density, strength, and selected hematological markers. J Strength Cond Res 3:325–334

    Google Scholar 

  48. Gaullier JM, Halse J, Hoye K (2005) Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy. Over weight humans. J Nutr 135:778–784

    CAS  PubMed  Google Scholar 

  49. Brownbill RA, Petrsian M, Illich JZ (2005) Association between dietary conjugated linoleic acid and bone mineral density in postmenopausal women. J Am Coll Nutr 24:177–181

    Article  CAS  PubMed  Google Scholar 

  50. Watkins BA, Feng S, Strom AK, DeVitt AA, Yu L, Li Y (2003) Conjugated linoleic acids alter the fatty acid composition and physical properties of egg yolk and albumen. J Agric Food Chem 51:6870–6876

    Article  CAS  PubMed  Google Scholar 

  51. Kang K, Liu W, Albright KJ, Park Y, Pariza MW (2003) trans -10, cis-12 CLA inhibits differentiation of 3T3-L1 adipocytes and decreases PPAR gamma expression. Biochem Biophys Res Commun 303:795–799

    Article  CAS  PubMed  Google Scholar 

  52. kim J, Park Y, Lee SH, Park Y (2013) trans-10, cis-12 conjugated linoleic acid promotes bone formation by inhibiting adipogenesis by peroxisome proliferator activated receptor-γ-dependent mechanisms and by directly enhancing osteoblastogenesis from bone marrow mesenchymal stem cells. J Nutr Biochem 24:672–679

    Article  CAS  PubMed  Google Scholar 

  53. Kang K, Pariza MW (2001) trans-10, cis-12-conjugated linoleic acid reduces leptin secretion from 3T3-L1 adipocytes. Biochem Biophys Res Commun 287:377–382

    Article  CAS  PubMed  Google Scholar 

  54. Medina EA, Horn WF, Keim NL (2000) Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids 35:783–788

    Article  CAS  PubMed  Google Scholar 

  55. Yamasaki M, Mansho K, Ogino Y, Kasai M, Tachibana H, Yamada K (2000) Acute reduction of serum leptin level by dietary conjugated linoleic acid in Sprague-Dawley rats. J Nutr Biochem 11:467–471

    Article  CAS  PubMed  Google Scholar 

  56. Halade GV, Rahman MM, Williams PJ, Fernandes G (2001) Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice. J Nutr Biochem 22(5):459–469

    Article  CAS  Google Scholar 

  57. Mallamaci F, Tripepi G, Zoccali C (2005) Leptin in end stage renal disease: a link between fat mass, bone and the cardiovascular system. J Nephrol 18:464–468

    CAS  PubMed  Google Scholar 

  58. Ducy P, Amling M, Takeda S, Preimel M, Schiling AF, Beil FT, Shen J, Vincon C, Rueger GM, Karesnty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100(2):197–207

    Article  CAS  PubMed  Google Scholar 

  59. Rahman SM, Wang Y-M, Han S-Y (2007) Effects of short-term administration of conjugated linoleic acid on lipid metabolism in white and brown adipose tissues of starved/refed Otsuka Long-Evans Tokushima fatty rats. Food Res Int 34:515–520

    Article  Google Scholar 

  60. Ochoa JJ, Farquharson AJ, Grant I, Moffat LE, Hey SD, Wahle KW (2004) Conjugated linoleic acids decrease prostate cancer cell proliferation: different molecular mechanisms for cis -9, trans-11 and trans-10, cis-12 isomers. Carcinogenesis 19:142–150

    Google Scholar 

  61. Miyaura C, Inada M, Matsumoto C, Ohshiba T, Uozumi N, Shimizu T, Ito A (2003) An essential role of cytosolic phospholipase A2alpha in prostaglandin E2-mediated bone resorption associated with inflammation. J Exp Med 197:1303–1310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bassaganya-Riera J, Hontecillas R, Beitz DC (2002) Colonic anti-inflammatory mechanisms of conjugated linoleic acid. Clin Nutr 21:451–459

    Article  CAS  PubMed  Google Scholar 

  63. Jaudszus A, Foerster M, Kroegel C, Wolf I, Jahreis G (2005) cis-9, trans-11-CLA exerts anti-inflammatory effects in human bronchial epithelial cells and eosinophils: comparison to trans-10, cis-12-CLA and to linoleic acid. Biochim Biophys Acta 173:111–118

    Article  CAS  Google Scholar 

  64. Whigham LD, Cook EB, Stahl JL, Saban R, Bjorling DE, Pariza MW, Cook ME (2001) CLA reduces antigen-induced histamine and PGE2 release from sensitized guinea pig tracheae. Am J Physiol Regul Integr Comp Physiol 280:R908–R912

    CAS  PubMed  Google Scholar 

  65. Watkins BA, Li Y, Allen KG, Hoffmann WE, Seifert MF (2000) Dietary ratio of (n-6)/(n-3) polyunsaturated fatty acids alters the fatty acid composition of bone compartments and biomarkers of bone formation in rats. J Nutr 130:2274–2284

    CAS  PubMed  Google Scholar 

  66. Li Y, Seifert MF, Ney DM, Grahn M, Grant AL, Allen KG, Watkins BA (1999) Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n6) or (n3) fatty acids. J Bone Miner Res 14:1153–1162

    Article  CAS  PubMed  Google Scholar 

  67. Hur SJ, Park Y (2007) Effect of conjugated linoleic acid on bone formation and rheumatoid arthritis. Eur J Pharmacol 568:16–24

    Article  CAS  PubMed  Google Scholar 

  68. Maciel FM, Sarrazin P, Morisset S, Lora M, Patry C, Dumais R, deBrum-Fernandes AJ (1997) Induction of cyclooxygenase-2 by parathyroid hormone in human osteoblasts in culture. J Rheumatol 24:2429–2435

    CAS  PubMed  Google Scholar 

  69. Deguire JR, Makarem N, Vanstone CA, Morin S, Duque G, Weiler HA (2012) Conjugated linoleic acid is related to bone mineral density but does not affect parathyroid hormone in men. Nutr Res 32(12):911–920

    Article  CAS  PubMed  Google Scholar 

  70. Brownbill Rhonda A, Petrosian Mary, Ilich Jasminka Z (2005) Association between dietary conjugated linoleic acid and bone mineral density in postmenopausal women. Am Coll Nutr 24(3):177–181

    Article  CAS  Google Scholar 

  71. Park Y, Kim J, Scrimgeour AG, Condlin ML, Kim D, Park Y (2013) Conjugated linoleic acid and calcium co-supplementation improves bone health in ovariectomised mice. Food Chem 140:280–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rahman MM, Fernandes G, Williams P (2014) Conjugated linoleic acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis. Lipids 49(3):211–224

    Article  CAS  PubMed  Google Scholar 

  73. Kim J, Park Y, Park Y (2014) trans-10, cis-12 CLA promotes osteoblastogenesis via SMAD mediated mechanism in bone marrow mesenchymal stem cells. J Funct Foods 1(8):367–376

    Article  CAS  Google Scholar 

  74. Houseman M, Potter C, Marshall N, Lakey R, Cawston T, Griffiths L, Young-Min S, Isaacs JD (2012) Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up. Arthritis Res Ther 14:R30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was funded by a research grant from the Research Deputy of Tehran University of Medical Sciences (with Proposal No. 24528). We are thankful for the kind cooperation of Lipid Nutrition Company (Netherlands) for providing CLA capsules as Clarinol G-80 and its placebo for this research.

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Correspondence to M. Djalali.

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None of the authors report conflicting interests.

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The study was funded by the Iran University of Medical Sciences. This study was conducted independently from the funders. The funders were not involved in the study design, data collection and analysis, interpretation of the data or in the writing of the report or its submission for publication.

Ethical approval

The study was approved by the respective research ethics committees and medicinal regulatory agencies in each country (No IRCT201207109472N4). Informed written consent was obtained from the patient before recruitment.

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DP affirms that the manuscript is an honest, accurate, and transparent account of the study; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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Aryaeian, N., Shahram, F. & Djalali, M. CLA Has a Useful Effect on Bone Markers in Patients with Rheumatoid Arthritis. Lipids 51, 1397–1405 (2016). https://doi.org/10.1007/s11745-016-4201-6

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