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Serum NPY and BNDF response to a behavioral stressor in alcohol-dependent and healthy control participants

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Abstract

Rationale

Neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) have been implicated in both the stress response and alcohol addiction. However, few studies have assessed the NPY and BDNF response to stress in alcohol-dependent participants and the concurrent measure of NPY and BDNF has not been reported in human participants.

Objective

The purpose of this study was to concurrently assess serum NPY and BDNF, as well as adrenocorticotropin (ACTH) and cortisol, in control and race- and aged-matched abstinent alcohol-dependent participants in response to a stress-inducing public-speaking task.

Methods

Basal and post-stress serum values of NPY and BDNF, as well as ACTH and cortisol, were assessed in 14 abstinent alcohol-dependent and ten healthy control male participants.

Results

Basal measures were stable over short periods of time and stress induced a significant increase in both NPY (p = 0.002) and BDNF (p = 0.006) as well as ACTH (p < 0.001) and cortisol (p < 0.007). Alcohol-dependent and control groups did not significantly differ on any basal or stress-induced measure. Basal and delta responses of NPY and BDNF were not significantly correlated, and delta peak responses of NPY and BDNF did not correlate with one another or with their respective ACTH and cortisol responses.

Conclusions

These findings reveal that both serum NPY and BDNF are responsive to behavioral stressors, although their regulatory mechanisms appear to differ from one another and those of the hypothalamic–pituitary–adrenal axis. Differences in basal and stress-induced responses of NPY and BDNF were not supported between control and abstinent alcohol-dependent subjects.

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References

  • Acuna MJ, Martin JC, Graciani M, Cruces A, Gotor F (2010) A comparative study of the sexual function of institutionalized patients with schizophrenia. J Sex Med 7(10):3414–3423

    Article  PubMed  Google Scholar 

  • Adinoff B, Krebaum SR, Chandler PA, Ye W, Brown MB, Williams MJ (2005) Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 2: response to ovine corticotropin-releasing factor and naloxone. Alcohol Clin Exp Res 29:528–537

    Article  PubMed  CAS  Google Scholar 

  • Adlard PA, Perreau VM, Engesser-Cesar C, Cotman CW (2004) The timecourse of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise. Neurosci Lett 363:43–48

    Article  PubMed  CAS  Google Scholar 

  • Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1979) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    Google Scholar 

  • Begliuomini S, Lenzi E, Ninni F, Casarosa E, Merlini S, Pluchino N, Valentino V, Luisi S, Luisi M, Genazzani AR (2008) Plasma brain-derived neurotrophic factor daily variations in men: correlation with cortisol circadian rhythm. J Endocrinol 197:429–435

    Article  PubMed  CAS  Google Scholar 

  • Bernardy NC, King AC, Lovallo WR (2003) Cardiovascular responses to physical and psychological stress in female alcoholics with transitory hypertension after early abstinence. Alcohol Clin Exp Res 27:1489–1498

    Article  PubMed  Google Scholar 

  • Bhang SY, Choi SW, Ahn JH (2010) Changes in plasma brain-derived neurotrophic factor levels in smokers after smoking cessation. Neurosci Lett 468:7–11

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Hansen MJ, Jones JE, Vlahos R, Bozinovski S, Anderson GP, Morris MJ (2007) Regulation of hypothalamic NPY by diet and smoking. Peptides 28:384–389

    Article  PubMed  CAS  Google Scholar 

  • Cippitelli A, Damadzic R, Hansson AC, Singley E, Sommer WH, Eskay R, Thorsell A, Heilig M (2010) Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking. Psychopharmacology (Berl) 208:417–426

    Article  CAS  Google Scholar 

  • Coiro V, Vescovi PP (1999) Effect of cigarette smoking on ACTH/cortisol secretion in alcoholic after short- and medium-term abstinence. Alcohol Clin Exp Res 23:1515–1518

    Article  PubMed  CAS  Google Scholar 

  • Coiro V, Casti A, Jotti GS, Rubino P, Manfredi G, Maffei ML, Melani A, Volta E, Chiodera P (2007) Adrenocorticotropic hormone/cortisol response to physical exercise in abstinent alcoholic patients. Alcohol Clin Exp Res 31:901–906

    Article  PubMed  CAS  Google Scholar 

  • Derogatis LR, Melisaratos N (1983) The brief symptom inventory: an introductory report. Psychol Med 13:595–605

    Article  PubMed  CAS  Google Scholar 

  • Duncan LE, Hutchison KE, Carey G, Craighead WE (2009) Variation in brain-derived neurotrophic factor (BDNF) gene is associated with symptoms of depression. J Affect Disord 115:215–219

    Article  PubMed  CAS  Google Scholar 

  • Errico AL, Parsons OA, King AC, Lovallo WR (1993) Attenuated cortisol response to biobehavioral stressors in sober alcoholics. J Stud Alcohol 54:393–398

    PubMed  CAS  Google Scholar 

  • First MH, Spitzer RL, Gibbon M, Williams JBW (1996) Structured clinical interview for DSM-IV axis I disorders—patient edition (SCID-I/P, version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York

    Google Scholar 

  • Frankish HM, Dryden S, Wang Q, Bing C, MacFarlane IA, Williams G (1995) Nicotine administration reduces neuropeptide Y and neuropeptide Y mRNA concentrations in the rat hypothalamus: NPY may mediate nicotine's effects on energy balance. Brain Res 694:139–146

    Article  PubMed  CAS  Google Scholar 

  • Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, Sun B, Tandon NN (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734

    PubMed  CAS  Google Scholar 

  • Gilpin NW, Stewart RB, Murphy JM, Li TK, Badia-Elder NE (2003) Neuropeptide Y reduces oral ethanol intake in alcohol-preferring (P) rats following a period of imposed ethanol abstinence. Alcohol Clin Exp Res 27:787–794

    Article  PubMed  CAS  Google Scholar 

  • Gilpin NW, Henderson AN, Badia-Elder NE, Stewart RB (2011) Effects of neuropeptide Y and ethanol on arousal and anxiety-like behavior in alcohol-preferring rats. Alcohol 45:137–145

    Article  PubMed  CAS  Google Scholar 

  • Gold SM, Schulz KH, Hartmann S, Mladek M, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C (2003) Basal serum levels and reactivity of nerve growth factor and brain-derived neurotrophic factor to standardized acute exercise in multiple sclerosis and controls. J Neuroimmunol 138:99–105

    Article  PubMed  CAS  Google Scholar 

  • Goldstone AP, de Hernandez CG, Beaver JD, Muhammed K, Croese C, Bell G, Durighel G, Hughes E, Waldman AD, Frost G, Bell JD (2009) Fasting biases brain reward systems towards high-calorie foods. Eur J Neurosci 30:1625–1635

    Article  PubMed  Google Scholar 

  • Hashimoto K (2007) BDNF variant linked to anxiety-related behaviors. Bioessays 29:116–119

    Article  PubMed  CAS  Google Scholar 

  • Heberlein A, Muschler M, Wilhelm J, Frieling H, Lenz B, Groschl M, Kornhuber J, Bleich S, Hillemacher T (2010) BDNF and GDNF serum levels in alcohol-dependent patients during withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 34:1060–1064

    Article  PubMed  CAS  Google Scholar 

  • Heilig M, McLeod S, Brot M, Heinrichs SC, Menzaghi F, Koob GF, Britton KT (1993) Anxiolytic-like action of neuropeptide Y: mediation by Y1 receptors in amygdala, and dissociation from food intake effects. Neuropsychopharmacology 8:357–363

    PubMed  CAS  Google Scholar 

  • Huang MC, Chen CH, Liu SC, Ho CJ, Shen WW, Leu SJ (2008) Alterations of serum brain-derived neurotrophic factor levels in early alcohol withdrawal. Alcohol Alcohol 43:241–245

    PubMed  CAS  Google Scholar 

  • Jeanblanc J, He DY, Carnicella S, Kharazia V, Janak PH, Ron D (2009) Endogenous BDNF in the dorsolateral striatum gates alcohol drinking. J Neurosci 29:13494–13502

    Article  PubMed  CAS  Google Scholar 

  • Joe KH, Kim YK, Kim TS, Roh SW, Choi SW, Kim YB, Lee HJ, Kim DJ (2007) Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence. Alcohol Clin Exp Res 31:1833–1838

    Article  PubMed  CAS  Google Scholar 

  • Johnson RA, Rhodes JS, Jeffrey SL, Garland T Jr, Mitchell GS (2003) Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience 121:1–7

    Article  PubMed  Google Scholar 

  • Junghanns K, Backhaus J, Tietz U, Lange W, Bernzen J, Wetterling T, Rink L, Driessen M (2003) Impaired serum cortisol stress response is a predictor of early relapse. Alcohol Alcohol 38:189–193

    PubMed  CAS  Google Scholar 

  • Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G (2005) Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 57:1068–1072

    Article  PubMed  CAS  Google Scholar 

  • Kim TS, Kim DJ, Lee H, Kim YK (2007) Increased plasma brain-derived neurotrophic factor levels in chronic smokers following unaided smoking cessation. Neurosci Lett 423:53–57

    Article  PubMed  CAS  Google Scholar 

  • King A, Munisamy G, de Wit H, Lin S (2006) Attenuated cortisol response to alcohol in heavy social drinkers. Int J Psychophysiol 59:203–209

    Article  PubMed  Google Scholar 

  • Kinoshita H, Jessop DS, Finn DP, Coventry TL, Roberts DJ, Ameno K, Ijiri I, Harbuz MS (2000) Acute ethanol decreases NPY mRNA but not POMC mRNA in the arcuate nucleus. Neuroreport 11:3517–3519

    Article  PubMed  CAS  Google Scholar 

  • Kirschbaum C, Pirke KM, Hellhammer DH (1993) The 'Trier Social Stress Test'—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81

    Article  PubMed  CAS  Google Scholar 

  • Lee BH, Kim YK (2010) BDNF mRNA expression of peripheral blood mononuclear cells was decreased in depressive patients who had or had not recently attempted suicide. J Affect Disord 125:369–373

    Article  PubMed  CAS  Google Scholar 

  • Lee BC, Choi IG, Kim YK, Ham BJ, Yang BH, Roh S, Choi J, Lee JS, Oh DY, Chai YG (2009) Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence. Alcohol 43:265–269

    Article  PubMed  Google Scholar 

  • Li MD, Kane JK, Parker SL, McAllen K, Matta SG, Sharp BM (2000) Nicotine administration enhances NPY expression in the rat hypothalamus. Brain Res 867:157–164

    Article  PubMed  CAS  Google Scholar 

  • Lindell SG, Schwandt ML, Sun H, Sparenborg JD, Bjork K, Kasckow JW, Sommer WH, Goldman D, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. Arch Gen Psychiatry 67:423–431

    Article  PubMed  CAS  Google Scholar 

  • Lovallo WR, Dickensheets SL, Myers DA, Thomas TL, Nixon SJ (2000) Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men. Alcohol Clin Exp Res 24:651–658

    Article  PubMed  CAS  Google Scholar 

  • Matsushita S, Kimura M, Miyakawa T, Yoshino A, Murayama M, Masaki T, Higuchi S (2004) Association study of brain-derived neurotrophic factor gene polymorphism and alcoholism. Alcohol Clin Exp Res 28:1609–1612

    Article  PubMed  CAS  Google Scholar 

  • McGough NN, He DY, Logrip ML, Jeanblanc J, Phamluong K, Luong K, Kharazia V, Janak PH, Ron D (2004) RACK1 and brain-derived neurotrophic factor: a homeostatic pathway that regulates alcohol addiction. J Neurosci 24:10542–10552

    Article  PubMed  CAS  Google Scholar 

  • Miller WR, Tonigan JS, Longabaugh R (1995) The drinker inventory of consequences (DrlnC) An instrument for assessing adverse consequences of alcohol abuse. National Institutes of Health, Rockville

    Google Scholar 

  • Morgan CA 3rd, Rasmusson AM, Wang S, Hoyt G, Hauger RL, Hazlett G (2002) Neuropeptide-Y, cortisol, and subjective distress in humans exposed to acute stress: replication and extension of previous report. Biol Psychiatry 52:136–142

    Article  PubMed  CAS  Google Scholar 

  • Muschler MA, Heberlein A, Frieling H, Vogel N, Becker CM, Kornhuber J, Bleich S, Hillemacher T (2011) Brain-derived neurotrophic factor, Val66Met single nucleotide polymorphism is not associated with alcohol dependence. Psychiatr Genet 21:53–54

    Article  PubMed  Google Scholar 

  • Myers AK, Torres Duarte AP, Zukowska-Grojec Z (1993) Immunoreactive neuropeptide Y (NPY) in plasma and platelets of rat and mouse strains and human volunteers. Regul Pept 47:239–245

    Article  PubMed  CAS  Google Scholar 

  • Perkins KA, Lerman C, Mercincavage M, Fonte CA, Briski JL (2009) Nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene and short-term ability to quit smoking in response to nicotine patch. Cancer Epidemiol Biomarkers Prev 18:2608–2612

    Article  PubMed  CAS  Google Scholar 

  • Requena J, Aranaz JM, Gea MT, Limon R, Miralles JJ, Vitaller J (2010) [Evolution of the adverse effects prevalence related to healthcare in hospitals of the comunidad valenciana]. Rev Calid Asist 25(5):244–249

    Article  PubMed  CAS  Google Scholar 

  • Rojas Vega S, Struder HK, Vera Wahrmann B, Schmidt A, Bloch W, Hollmann W (2006) Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res 1121:59–65

    Article  PubMed  CAS  Google Scholar 

  • Roy A, Pandey SC (2002) The decreased cellular expression of neuropeptide Y protein in rat brain structures during ethanol withdrawal after chronic ethanol exposure. Alcoholism, Clinical and Experimental Research 26:796–803

    Article  PubMed  CAS  Google Scholar 

  • Sah R, Ekhator NN, Strawn JR, Sallee FR, Baker DG, Horn PS, Geracioti TD Jr (2009) Low cerebrospinal fluid neuropeptide Y concentrations in posttraumatic stress disorder. Biol Psychiatry 66:705–707

    Article  PubMed  CAS  Google Scholar 

  • Scarisbrick IA, Jones EG, Isackson PJ (1993) Coexpression of mRNAs for NGF, BDNF, and NT-3 in the cardiovascular system of the pre- and postnatal rat. J Neurosci 13:875–893

    PubMed  CAS  Google Scholar 

  • Shi SS, Shao SH, Yuan BP, Pan F, Li ZL (2010) Acute stress and chronic stress change brain-derived neurotrophic factor (BDNF) and tyrosine kinase-coupled receptor (TrkB) expression in both young and aged rat hippocampus. Yonsei Med J 51:661–71

    Article  PubMed  CAS  Google Scholar 

  • Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75

    Article  PubMed  CAS  Google Scholar 

  • Sobell MB, Sobell LC (1978) Behavioral treatment of alcohol problems. Plenum Press, NewYork

    Google Scholar 

  • Speilberger CD (1971) Trait-state anxiety and motor behavior. J Mot Behavior 3:265–279

    Google Scholar 

  • Tapia-Arancibia L, Rage F, Givalois L, Dingeon P, Arancibia S, Beauge F (2001) Effects of alcohol on brain-derived neurotrophic factor mRNA expression in discrete regions of the rat hippocampus and hypothalamus. J Neurosci Res 63:200–208

    Article  PubMed  CAS  Google Scholar 

  • Thorsell A, Svensson P, Wiklund L, Sommer W, Ekman R, Heilig M (1998) Suppressed neuropeptide Y (NPY) mRNA in rat amygdala following restraint stress. Regul Pept 75–76:247–254

    Article  PubMed  Google Scholar 

  • Thorsell A, Carlsson K, Ekman R, Heilig M (1999) Behavioral and endocrine adaptation, and up-regulation of NPY expression in rat amygdala following repeated restraint stress. Neuroreport 10:3003–3007

    Article  PubMed  CAS  Google Scholar 

  • Tsai SJ, Liao DL, Yu YW, Chen TJ, Wu HC, Lin CH, Cheng CY, Hong CJ (2005) A study of the association of (Val66Met) polymorphism in the brain-derived neurotrophic factor gene with alcohol dependence and extreme violence in Chinese males. Neurosci Lett 381:340–343

    Article  PubMed  CAS  Google Scholar 

  • Umene-Nakano W, Yoshimura R, Ikenouchi-Sugita A, Hori H, Hayashi K, Ueda N, Nakamura J (2009) Serum levels of brain-derived neurotrophic factor in comorbidity of depression and alcohol dependence. Hum Psychopharmacol 24:409–413

    Article  PubMed  CAS  Google Scholar 

  • Wand GS, Dobs AS (1991) Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics. J Clin Endocrinol Metab 72:1290–1295

    Article  PubMed  CAS  Google Scholar 

  • Wojnar M, Brower KJ, Strobbe S, Ilgen M, Matsumoto H, Nowosad I, Sliwerska E, Burmeister M (2009) Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. Alcohol Clin Exp Res 33:693–702

    Article  PubMed  CAS  Google Scholar 

  • Yang Z, Gaydos LM (2010) Reasons for and challenges of recent increases in teen birth rates: a study of family planning service policies and demographic changes at the state level. J Adolesc Health 46:517–524

    Article  PubMed  Google Scholar 

  • Yang K, Guan H, Arany E, Hill DJ, Cao X (2008) Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor. FASEB J 22:2452–2464

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Sakharkar AJ, Shi G, Ugale R, Prakash A, Pandey SC (2010) Neuropeptide Y signaling in the central nucleus of amygdala regulates alcohol-drinking and anxiety-like behaviors of alcohol-preferring rats. Alcohol Clin Exp Res 34:451–461

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Homeward Bound, Inc. and the Dallas VA Substance Abuse Team for their assistance in the recruitment and clinical care of patients and the UT Southwestern CTRC staff for their excellent patient care and meticulous attention to research protocol.

Role of funding source

Funding for this study was provided by NIH INIAStress U01AA13515, Department of Veterans Affairs, and NIH CTSA grant UL1 RR024982. None of the funding sources had a role in study design; in the collection, analysis, and interpretation of data; or in the writing of the report.

Conflict of interest

CN discloses employment by VA North Texas Health Care System, Dallas, TX, USA. Points of view in this document are those of the author(s) and do not necessarily represent the official position of NIMH, the Department of Veterans Affairs, or the US Government. Dr. North also discloses research support from NIAAA, NIMH, NIDDK, the American Orthopedic Association, the American Psychiatric Association, the Department of Veterans Affairs, and UT Southwestern Medical Center; consulting fees from the University of Oklahoma Health Sciences Center, Cubic, Inc., and the National Center for PTSD (Research Education in Disaster Mental Health); and honoraria from Washington University in St. Louis, the University of Alabama at Tuscaloosa, the Assisi Foundation of Memphis, and Magellan Health Services. BA received grant support from NIAAA, NIDA, and the Department of Veterans Affairs; consulted for Teva Pharmaceutical Industries Ltd., Shook, Hardy and Bacon LLP (medical malpractice for tobacco companies), and Paul J. Passante, P.C. (medical malpractice), and received honoraria from the Medical University of South Carolina, American Institute of Biological Sciences, American Academy of Addiction Psychiatry, Methodist Medical Center (Dallas, TX), Vanderbilt University, John Peter Smith Hospital, University of North Texas Health Science Center; American Academy of Addiction Psychiatry, University of New Mexico. YM, TW, UR, HX, and MJ declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8564, USA

    Donna Meng, TingChin Wu, Carol S. North & Bryon Adinoff

  2. Center for Molecular and Behavioral Neuroscience and Department of Psychiatry and Behavioral Sciences Meharry Medical College, 1005 Dr. D.B. Todd Jr. Boulevard, Nashville, TN, 37208, USA

    Uma Rao

  3. VA North Texas Health Care System, 4500 S. Lancaster Rd, Dallas, TX, 75216, USA

    Carol S. North & Bryon Adinoff

  4. Department of Family and Community Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8564, USA

    Hong Xiao

  5. Department of Psychiatry, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Martin A. Javors

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  1. Donna Meng
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  2. TingChin Wu
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  3. Uma Rao
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  4. Carol S. North
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  7. Bryon Adinoff
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Correspondence to Bryon Adinoff.

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Meng, D., Wu, T., Rao, U. et al. Serum NPY and BNDF response to a behavioral stressor in alcohol-dependent and healthy control participants. Psychopharmacology 218, 59–67 (2011). https://doi.org/10.1007/s00213-011-2414-1

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  • DOI: https://doi.org/10.1007/s00213-011-2414-1

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