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Journal articles on the topic 'Vitamin D binding protein'

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Published: 4 June 2021

Last updated: 8 February 2022

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1

COOKE, NANCY E., ALESSANDRA MURGIA, and JAMES F. McLEOD. "Vitamin D-Binding Protein." Annals of the New York Academy of Sciences 538, no. 1 Steroid-Prote (September 1988): 49–59. http://dx.doi.org/10.1111/j.1749-6632.1988.tb48849.x.

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2

Xie, Zhongjian, Arthur C. Santora, Sue A. Shapses, and Xiangbing Wang. "Vitamin D Binding Protein and Vitamin D Levels." International Journal of Endocrinology 2014 (2014): 1–2. http://dx.doi.org/10.1155/2014/638263.

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3

Qin, Rundong, Renbin Huang, Wanyi Fu, MuLin Feng, and Jing Li. "Sputum vitamin D binding protein." Annals of Allergy, Asthma & Immunology 125, no. 3 (September 2020): 350–52. http://dx.doi.org/10.1016/j.anai.2020.06.005.

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4

Delanghe, Joris R., Reinhart Speeckaert, and Marijn M. Speeckaert. "Behind the scenes of vitamin D binding protein: More than vitamin D binding." Best Practice & Research Clinical Endocrinology & Metabolism 29, no. 5 (October 2015): 773–86. http://dx.doi.org/10.1016/j.beem.2015.06.006.

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5

Blakeley, Matthew, Agata Sobczyńska-Malefora, and Guy Carpenter. "The Origins of Salivary Vitamin A, Vitamin B12 and Vitamin D-Binding Proteins." Nutrients 12, no. 12 (December 16, 2020): 3838. http://dx.doi.org/10.3390/nu12123838.

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Vitamin A- (retinol), vitamin B12- (haptocorrin) and vitamin D-binding proteins are the major circulatory transporters of their respective ligands; they are also constituents of the salivary proteome, the origins of which, remain unclear. The aim of this study was to explore how these proteins enter saliva and their relationship (if any) with vitamin status. Firstly, the three vitamin-binding proteins were quantified in resting whole mouth saliva and chewing-stimulated saliva from healthy donors (n = 10) to determine if they enter the mouth by salivary secretion or from the circulation. Secondly paired whole mouth saliva and serum samples were analysed from healthy donors (n = 14) to determine the relationships between the vitamin-binding proteins and vitamin status. Salivary output of all three vitamin-binding proteins studied increased when secretion was stimulated, suggesting they are secreted by the salivary glands. Whilst retinol-binding protein and haptocorrin were secreted by all major salivary glands, vitamin D-binding protein was restricted to the mucus glands. Salivary vitamin-binding protein concentrations were not found to be indicative of systemic vitamin status.

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6

Ferrero, Simone, David J. Gillott, Paola Anserini, Valentino Remorgida, Karen M. Price, Nicola Ragni, and Jurgis G. Grudzinskas. "Vitamin D Binding Protein in Endometriosis." Journal of the Society for Gynecologic Investigation 12, no. 4 (May 2005): 272–77. http://dx.doi.org/10.1016/j.jsgi.2005.01.027.

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7

COOKE, NANCY E., and JOHN G. HADDAD. "Vitamin D Binding Protein (Gc-Globulin)*." Endocrine Reviews 10, no. 3 (August 1989): 294–307. http://dx.doi.org/10.1210/edrv-10-3-294.

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8

Allewaert, Katrien, Hugo Van Baelen, and Roger Bouillon. "Vitamin D-binding protein in pisces." Steroids 52, no. 4 (October 1988): 357–58. http://dx.doi.org/10.1016/0039-128x(88)90145-6.

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9

Bhan, Ishir. "Vitamin D Binding Protein and Bone Health." International Journal of Endocrinology 2014 (2014): 1–5. http://dx.doi.org/10.1155/2014/561214.

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Vitamin D binding protein (DBP) is the major carrier protein of 25-hydroxyvitamin D (25(OH) D) in the circulation, where it may serve roles in maintaining stable levels during times of decreased 25(OH) availability and in regulating delivery of 25(OH) D to target tissues. Several genetic polymorphisms of DBP have been described that lead to phenotypic changes in the protein that may affect affinity, activity, and concentration. These polymorphisms have been linked with alterations in bone density in several populations. One of the mechanisms by which DBP may alter bone health involves regulating vitamin D bioavailability. DBP-bound vitamin is thought to be relatively unavailable to target tissues, and thus alterations in DBP levels or affinity could lead to changes in vitamin D bioactivity. As a result, functional vitamin D status may differ greatly between individuals with similar total 25(OH) D levels. Additionally, DBP may have independent roles on macrophage and osteoclast activation. This review will summarize recent findings about DBP with respect to measures of bone density and health.

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10

Anic, Gabriella M., Stephanie J. Weinstein, Alison M. Mondul, Satu Männistö, and Demetrius Albanes. "Serum vitamin D, vitamin D binding protein, and lung cancer survival." Lung Cancer 86, no. 3 (December 2014): 297–303. http://dx.doi.org/10.1016/j.lungcan.2014.10.008.

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11

Persson, Louise J. P., Marianne Aanerud, Pieter S. Hiemstra, Annika E. Michelsen, Thor Ueland, Jon A. Hardie, Pål Aukrust, Per S. Bakke, and Tomas M. L. Eagan. "Vitamin D, Vitamin D Binding Protein, and Longitudinal Outcomes in COPD." PLOS ONE 10, no. 3 (March 24, 2015): e0121622. http://dx.doi.org/10.1371/journal.pone.0121622.

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12

Powe, Camille E., Ellen W. Seely, Sarosh Rana, Ishir Bhan, Jeffrey Ecker, S. Ananth Karumanchi, and Ravi Thadhani. "First Trimester Vitamin D, Vitamin D Binding Protein, and Subsequent Preeclampsia." Hypertension 56, no. 4 (October 2010): 758–63. http://dx.doi.org/10.1161/hypertensionaha.110.158238.

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13

Bouillon, R., A. Verstuyf, J. Zhao, B. K. Tan, and H. VanBaelen. "Nonhypercalcemic Vitamin D Analogs: Interactions with the Vitamin D-Binding Protein." Hormone Research 45, no. 3-5 (1996): 117–21. http://dx.doi.org/10.1159/000184773.

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14

Altinova, Alev Eroglu, Cigdem Ozkan, Mujde Akturk, Ozlem Gulbahar, Muhittin Yalcin, Nuri Cakir, and Fusun Balos Toruner. "Vitamin D-binding protein and free vitamin D concentrations in acromegaly." Endocrine 52, no. 2 (November 7, 2015): 374–79. http://dx.doi.org/10.1007/s12020-015-0789-1.

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15

Calvo, Miguel, and JoséM Ena. "Relations between vitamin D and fatty acid binding properties of vitamin D-binding protein." Biochemical and Biophysical Research Communications 163, no. 1 (August 1989): 14–17. http://dx.doi.org/10.1016/0006-291x(89)92091-3.

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16

Duchow, Elizabeth G., Nancy E. Cooke, Jeremy Seeman, Lori A. Plum, and Hector F. DeLuca. "Vitamin D binding protein is required to utilize skin-generated vitamin D." Proceedings of the National Academy of Sciences 116, no. 49 (November 20, 2019): 24527–32. http://dx.doi.org/10.1073/pnas.1915442116.

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Vitamin D is produced in the skin following exposure to sunlight. Ultraviolet (UV) B (UVB, 280–310 nm) results in isomerization of 7-dehydrocholesterol to previtamin D that spontaneously isomerizes to vitamin D. This pool of skin-derived vitamin D is the major source of vitamin D for animals. However, the mechanisms by which it becomes available remain undefined. It has been assumed that cutaneous vitamin D is transported into the circulation by vitamin D binding protein (DBP), but experimental evidence is lacking. To determine whether cutaneous vitamin D is transported by DBP, we utilized DBP−/− mice that were made vitamin D-deficient. These animals lack measurable 25(OH)D in blood and are hypocalcemic. As controls, DBP+/+ animals were vitamin D depleted and made equally hypocalcemic. UV irradiation of DBP+/+ animals restored serum calcium and serum 25(OH)D while the same treatment of DBP−/− animals failed to show either a serum calcium or 25(OH)D response despite having normal vitamin D production in skin. Intravenous injection of small amounts of recombinant DBP to the vitamin D-deficient DBP−/− mice restored the response to UV light. These results demonstrate a requirement for DBP to utilize cutaneously produced vitamin D.

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17

Ray, R. "Molecular Recognition in Vitamin D-Binding Protein." Experimental Biology and Medicine 212, no. 4 (September 1, 1996): 305–12. http://dx.doi.org/10.3181/00379727-212-44020.

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18

Speeckaert, Marijn M., Reinhart Speeckaert, and Joris R. Delanghe. "Vitamin D binding protein in COVID-19." Clinical Medicine 20, no. 5 (September 2020): e136.2-e137. http://dx.doi.org/10.7861/clinmed.let.20.5.2.

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19

Gomme, Peter T., and Joseph Bertolini. "Therapeutic potential of vitamin D-binding protein." Trends in Biotechnology 22, no. 7 (July 2004): 340–45. http://dx.doi.org/10.1016/j.tibtech.2004.05.001.

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20

Haughton, M. A., and R. S. Mason. "Immunonephelometric Assay of Vitamin D-Binding Protein." Clinical Chemistry 38, no. 9 (September 1, 1992): 1796–801. http://dx.doi.org/10.1093/clinchem/38.9.1796.

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Abstract An automated immunonephelometric assay was developed to measure vitamin D-binding protein (DBP) in serum. The assay is described for the Behring Nephelometer System, which uses rabbit anti-DBP antiserum and purified human DBP. The detection limit is 0.05 g/L (0.86 mumol/L), and the working range is less than or equal to 1.60 g/L (27.59 mumol/L). Intra- and interassay CVs of 2.0% and 2.8-3.8% compare favorably with alternative methods. When results were compared with those from a immunoradiometric assay, the correlation coefficient was 0.976 (P less than 0.001), and the regression equation [y = 0.866 +/- 0.085x + 0.05 (Syx = 0.042, n = 42)] identified a negative bias. Analysis indicated that both methods appeared to contribute equally to the bias. Although the assay was relatively free from analytical interference, falsely increased values were noted in severely lipemic specimens and in frozen specimens. Interference may be minimized by inclusion of Supplementary Precipitation reagent in a modified assay protocol. The range of concentrations expected in clinical samples was established from normal subjects [0.32-0.46 g/L (5.52-7.93 mumol/L), n = 28], pregnant subjects [0.51-0.70 g/L (8.79-12.07 mumol/L), n = 13], and subjects with liver diseases [0.12-0.33 g/L (2.07-5.69 mumol/L), n = 18].

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21

Chen, Hong, Bing Hu, Elizabeth A. Allegretto, and John S. Adams. "The Vitamin D Response Element-binding Protein." Journal of Biological Chemistry 275, no. 45 (August 17, 2000): 35557–64. http://dx.doi.org/10.1074/jbc.m007117200.

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22

Fang, Yue, Joyce B. J. van Meurs, Pascal Arp, Johannes P. T. van Leeuwen, Albert Hofman, Huibert A. P. Pols, and André G. Uitterlinden. "Vitamin D Binding Protein Genotype and Osteoporosis." Calcified Tissue International 85, no. 2 (June 2, 2009): 85–93. http://dx.doi.org/10.1007/s00223-009-9251-9.

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23

Morgan, Samantha, Ryan Rowe, Amy Kirkham, and David Hanks. "Vitamin D Binding Protein Isoforms and Vitamin D Levels in Diabetes Patients." American Society for Clinical Laboratory Science 29, no. 3 (July 2016): 152–57. http://dx.doi.org/10.29074/ascls.29.3.152.

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24

Berg, Isaac, Corrine Hanson, Harlan Sayles, Debra Romberger, Amy Nelson, Jane Meza, Bruce Miller, et al. "Vitamin D, vitamin D binding protein, lung function and structure in COPD." Respiratory Medicine 107, no. 10 (October 2013): 1578–88. http://dx.doi.org/10.1016/j.rmed.2013.05.010.

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25

Al-Daghri, Nasser M., Abdul Khader Mohammed, Ihtisham Bukhari, Maryam Rikli, Saba Abdi, Mohammed Ghouse Ahmed Ansari, Shaun Sabico, et al. "Efficacy of vitamin D supplementation according to vitamin D-binding protein polymorphisms." Nutrition 63-64 (July 2019): 148–54. http://dx.doi.org/10.1016/j.nut.2019.02.003.

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26

Newton, Danforth A., John E. Baatz, Mark S. Kindy, Sebastiano Gattoni-Celli, Judy R. Shary, Bruce W. Hollis, and Carol L. Wagner. "Vitamin D binding protein polymorphisms significantly impact vitamin D status in children." Pediatric Research 86, no. 5 (February 2, 2019): 662–69. http://dx.doi.org/10.1038/s41390-019-0322-y.

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27

Anic, Gabriella M., Stephanie J. Weinstein, Alison M. Mondul, Satu Männistö, and Demetrius Albanes. "Serum Vitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer." PLoS ONE 9, no. 7 (July 18, 2014): e102966. http://dx.doi.org/10.1371/journal.pone.0102966.

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28

Merchant, Reshma A., R. M. van Dam, L. W. L. Tan, M. Y. Lim, J. L. Low, and J. E. Morley. "Vitamin D Binding Protein and Vitamin D Levels in Multi-Ethnic Population." Journal of nutrition, health & aging 22, no. 9 (October 16, 2018): 1060–65. http://dx.doi.org/10.1007/s12603-018-1114-5.

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29

Powe, Camille E., Catherine Ricciardi, Anders H. Berg, Delger Erdenesanaa, Gina Collerone, Elizabeth Ankers, Julia Wenger, S. Ananth Karumanchi, Ravi Thadhani, and Ishir Bhan. "Vitamin D–binding protein modifies the vitamin D–bone mineral density relationship." Journal of Bone and Mineral Research 26, no. 7 (June 21, 2011): 1609–16. http://dx.doi.org/10.1002/jbmr.387.

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30

Wookey, Alice F., Tejasvy Chollangi, Hannah E. J. Yong, Bill Kalionis, Shaun P. Brennecke, Padma Murthi, and Harry M. Georgiou. "Placental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction." Journal of Pregnancy 2017 (2017): 1–5. http://dx.doi.org/10.1155/2017/5120267.

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Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restriction-associated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestation-matched subjects with fetal growth restriction (FGR). FGR subjects were further subdivided as idiopathic (n=9) and nonidiopathic (n=9). Vitamin D-binding protein and 25(OH) vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR,p<0.05, Student’st-test) that were strongly associated with idiopathic fetal growth restriction (p<0.01, Kruskal-Wallis), whereas levels of vitamin D-binding protein were not associated with placental 25(OH) vitamin D stores (p=0.295, Pearson’s correlation). As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease.

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31

Miller, Matthew S., Adam J. Rudinsky, Brett G. Klamer, Dennis J. Chew, and Valerie J. Parker. "Association between vitamin D metabolites, vitamin D binding protein, and proteinuria in dogs." Journal of Veterinary Internal Medicine 34, no. 6 (October 7, 2020): 2468–77. http://dx.doi.org/10.1111/jvim.15912.

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32

Ganz, Ariel B., Heyjun Park, Olga V. Malysheva, and Marie A. Caudill. "Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women." FASEB Journal 32, no. 4 (January 5, 2018): 2012–20. http://dx.doi.org/10.1096/fj.201700992r.

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33

Mondul, Alison M., Stephanie J. Weinstein, Kristin A. Moy, Satu Männistö, and Demetrius Albanes. "Vitamin D-binding protein, circulating vitamin D and risk of renal cell carcinoma." International Journal of Cancer 134, no. 11 (January 30, 2014): 2699–706. http://dx.doi.org/10.1002/ijc.28596.

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34

Powe, Camille E., Catherine Ricciardi, Anders H. Berg, Delger Erdenesanaa, Gina Collerone, Elizabeth Ankers, Julia Wenger, S. Ananth Karumanchi, Ravi Thadhani, and Ishir Bhan. "Erratum: Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship." Journal of Bone and Mineral Research 27, no. 6 (May 17, 2012): 1438. http://dx.doi.org/10.1002/jbmr.1653.

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35

Speeckaert, Marijn M., Griet L. Glorieux, Raymond Vanholder, Wim Van Biesen, Youri E. Taes, Frédéric Clement, Charline Wehlou, and Joris R. Delanghe. "Vitamin D Binding Protein and the Need for Vitamin D in Hemodialysis Patients." Journal of Renal Nutrition 18, no. 5 (September 2008): 400–407. http://dx.doi.org/10.1053/j.jrn.2008.04.013.

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36

Bratke, K., A. Wendt, K. Garbe, M. Kuepper, P. Julius, M. Lommatzsch, and J. C. Virchow. "Vitamin D binding protein and vitamin D in human allergen-induced endobronchial inflammation." Clinical & Experimental Immunology 177, no. 1 (June 9, 2014): 366–72. http://dx.doi.org/10.1111/cei.12346.

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37

Kissmeyer, A. M., I. S. Mathiasen, S. Latini, and L. Binderup. "Pharmacokinetic studies of vitamin D analogues: relationship to vitamin D binding protein (DBP)." Endocrine 3, no. 4 (April 1995): 263–66. http://dx.doi.org/10.1007/bf03021403.

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38

Speeckaert, M. M., R. Speeckaert, and J. R. Delanghe. "Vitamin D and Vitamin D binding protein: the inseparable duo in COVID-19." Journal of Endocrinological Investigation 44, no. 10 (April 11, 2021): 2323–24. http://dx.doi.org/10.1007/s40618-021-01573-w.

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39

Faniyi, Aduragbemi A., Sebastian T. Lugg, Sian E. Faustini, Craig Webster, Joanne E. Duffy, Martin Hewison, Adrian Shields, Peter Nightingale, Alex G. Richter, and David R. Thickett. "Genetic polymorphisms, vitamin D binding protein and vitamin D deficiency in COVID-19." European Respiratory Journal 57, no. 5 (April 22, 2021): 2100653. http://dx.doi.org/10.1183/13993003.00653-2021.

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40

Speeckaert, Marijn M., Reinhart Speeckaert, and Joris R. Delanghe. "Genetic polymorphisms, vitamin D binding protein and vitamin D deficiency in COVID-19." European Respiratory Journal 57, no. 5 (February 4, 2021): 2004638. http://dx.doi.org/10.1183/13993003.04638-2020.

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41

Dueland, S., R. Blomhoff, and J. I. Pedersen. "Uptake and degradation of vitamin D binding protein and vitamin D binding protein–actin complex in vivo in the rat." Biochemical Journal 267, no. 3 (May 1, 1990): 721–25. http://dx.doi.org/10.1042/bj2670721.

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We have labelled the rat vitamin D binding protein (DBP), DBP-actin and rat albumin with 125I-tyramine-cellobiose (125I-TC). In contrast with traditional 125I-labelling techniques where degraded radioactive metabolites are released into plasma, the 125I-TC moiety is trapped intracellularly in the tissues, where the degradation of the labelled proteins takes place. By using this labelling method, the catabolism of proteins can be studied in vivo. In this study we have used this labelling technique to compare the tissue uptake and degradation of DBP, DBP-actin and albumin in the rat. DBP-actin was cleared from plasma at a considerably faster rate than DBP. After intravenous injection of labelled DBP-actin complex, 48% of the radioactive dose was recovered in the liver after 30 min, compared with 14% when labelled DBP was administered. Only small amounts of DBP-actin complex were recovered in the kidneys. In contrast with the results obtained with DBP-actin complex, liver and kidneys contributed about equally in the uptake and degradation of DBP determined 24 h after the injection. When labelled DBP was compared with labelled albumin, the amount of radioactivity taken up by the liver and kidneys by 24 h after the injection was 2 and 5 times higher respectively. In conclusion, liver and kidneys are the major organs for catabolism of DBP in the rat. Furthermore, binding of actin to DBP enhances the clearance of DBP from circulation as well as its uptake by the liver.

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42

Newnham, M., R. Carter, L. Sapey, R. A. Stockley, and A. M. Wood. "P115 Vitamin D binding protein in COPD exacerbations." Thorax 65, Suppl 4 (November 16, 2010): A126. http://dx.doi.org/10.1136/thx.2010.150987.16.

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43

Fu, Lei, Chad R. Borges, Douglas S. Rehder, Betty Y. L. Wong, Rashida Williams, Thomas O. Carpenter, and David E. C. Cole. "Characterization of additional vitamin D binding protein variants." Journal of Steroid Biochemistry and Molecular Biology 159 (May 2016): 54–59. http://dx.doi.org/10.1016/j.jsbmb.2016.02.022.

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44

Chun, Rene F. "New perspectives on the vitamin D binding protein." Cell Biochemistry and Function 30, no. 6 (April 23, 2012): 445–56. http://dx.doi.org/10.1002/cbf.2835.

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45

Speeckaert, Marijn M., Marc L. De Buyzere, and Joris R. Delanghe. "Vitamin D binding protein polymorphism and COVID‐19." Journal of Medical Virology 93, no. 2 (September 28, 2020): 705–7. http://dx.doi.org/10.1002/jmv.26508.

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46

Pierce, E. A., M. C. Dame, R. Bouillon, H. Van Baelen, and H. F. DeLuca. "Monoclonal antibodies to human vitamin D-binding protein." Proceedings of the National Academy of Sciences 82, no. 24 (December 1, 1985): 8429–33. http://dx.doi.org/10.1073/pnas.82.24.8429.

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47

Auconi, P., R. Biagini, P. Colarizi, R. Luciano, V. L. Pascali, D. Rastelli, and G. Tortorolo. "Vitamin D-binding protein in the perinatal period." European Journal of Pediatrics 144, no. 3 (September 1985): 228–29. http://dx.doi.org/10.1007/bf00451946.

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48

van Seters, Arnoud P., and Abraham J. Moolenaar. "Mitotane increases the blood levels of hormone-binding proteins." Acta Endocrinologica 124, no. 5 (May 1991): 526–33. http://dx.doi.org/10.1530/acta.0.1240526.

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Abstract. In 3 patients with adrenocortical carcinoma the effects of long-term mitotane therapy on the serum levels of three hormone-binding globulins and vitamin D-binding protein were studied. Within the first month of treatment cortisol-binding globulin increased two to three times, in close correlation with sex hormone-binding globulin. The rises in thyroxine-binding globulin and vitamin D-binding protein were considerably less. Elevated cortisol-binding protein appeared to be associated with increased binding of cortisol, whereas the binding of thyroxine and vitamin D remained below normal. Binding proteins returned to normal in 2 patients within a year after mitotane discontinuation. This phenomenon of hormone-binding protein enhancement invalidates the use of total serum hormone levels to monitor the effects of mitotane on endocrine function and could provide an explanation for the increased cortisol substitution requirement during mitotane therapy.

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49

Colston, K., N. J. Williams, and H. J. Cleeve. "Studies on vitamin D binding protein in the nephrotic syndrome." Clinical Chemistry 31, no. 5 (May 1, 1985): 718–21. http://dx.doi.org/10.1093/clinchem/31.5.718.

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Abstract We studied the properties of vitamin D binding protein in plasma and urine from nine patients with nephrotic syndrome. Samples were incubated with 25-[3H]hydroxyvitamin D3, after which we determined binding capacity and apparent dissociation constants. Binding capacity was markedly less in plasma from patients with nephrotic syndrome than that from normal subjects, but binding affinity was unchanged. Specific binding of 25-hydroxy[3H]vitamin D3 could be demonstrated in urine from all the nephrotic patients, and sucrose density-gradient analysis of these urines revealed a single binding peak with sedimentation characteristics similar to those of vitamin D binding protein in plasma.

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50

Powe, Camille E., Michele K. Evans, Julia Wenger, Alan B. Zonderman, Anders H. Berg, Michael Nalls, Hector Tamez, et al. "Vitamin D–Binding Protein and Vitamin D Status of Black Americans and White Americans." New England Journal of Medicine 369, no. 21 (November 21, 2013): 1991–2000. http://dx.doi.org/10.1056/nejmoa1306357.

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