Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity
Background: Chronic and excessive alcohol consumption enhances the formation of reactive oxygen species (ROS) and ethanol‐derived free radicals. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is a marker to estimate ROS‐induced DNA damage. The study objective was to compare serum 8‐OHdG levels between patien...
Gespeichert in:
Veröffentlicht in: | Alcoholism, clinical and experimental research clinical and experimental research, 2011-02, Vol.35 (2), p.338-344 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 344 |
---|---|
container_issue | 2 |
container_start_page | 338 |
container_title | Alcoholism, clinical and experimental research |
container_volume | 35 |
creator | Chen, Chun-Hsin Pan, Chun-Hung Chen, Chiao-Chicy Huang, Ming-Chyi |
description | Background: Chronic and excessive alcohol consumption enhances the formation of reactive oxygen species (ROS) and ethanol‐derived free radicals. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is a marker to estimate ROS‐induced DNA damage. The study objective was to compare serum 8‐OHdG levels between patients with alcohol dependence and healthy controls and to investigate the correlation between this marker and the severity of alcohol withdrawal syndrome (AWS).
Methods: We recruited 79 patients with alcohol dependence and 63 healthy control subjects. The severity of AWS was evaluated using the Chinese version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar‐C) every 8 hours. Levels of 8‐OHdG, malondialdehyde (MDA), and other biologic indexes were assayed at baseline for patient and control groups, and after 1‐week detoxification for the patient group.
Results: The 8‐OHdG and MDA levels in the alcoholic group were significantly higher than those in the control group (0.34 vs. 0.27 ng/ml and 13.5 vs. 10.1 μM, respectively). Both 8‐OHdG and MDA were significantly correlated with the highest CIWA‐Ar‐C (correlation coefficient = 0.39, p |
doi_str_mv | 10.1111/j.1530-0277.2010.01349.x |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_907152693</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>907152693</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4989-eb6fe3536c36a15dd2225c3fdbc387abb549a6ddf688ed1fe4eb06b3ad27b7a93</originalsourceid><addsrcrecordid>eNqFkl9v0zAUxSMEYmXwFZAlhHhK8b_YyQtS1W6l0tgQDO3Rcuwb5pI6nZ2u7bfHoaUIXvCL7Xt-OpbvPVmGCB6TtN4vx6RgOMdUyjHFqYoJ49V49yQbnYSn2QgTXuQC4_IsexHjEmPMSyGeZ2eUYIlpQUbZduFNAB3Bopuds7p3j4Bm1xM00yv9HZDz6HMqgu8junP9PZq0prvvWjSDNXgL3gDS3qJF0qddCNAmuvN_s8PFBr3VLfoKjxBcv3-ZPWt0G-HVcT_Pvl1e3E4_5lc388V0cpUbXpVVDrVogBVMGCY0KayllBaGNbY2rJS6rgteaWFtI8oSLGmAQ41FzbSlspa6YufZu4PvOnQPG4i9WrlooG21h24TVYUlKaio2H_JkkvOGGUkkW_-IZfdJvj0DUUKzqVMHR-o10dqU6_AqnVwKx326nfvE_D2COhodNsE7Y2LfzhWpseqMnEfDtzWtbA_6QSrIQtqqYaRq2HkasiC-pUFtVOT6cWX4ZgM8oOBiz3sTgY6_FBCMlmou-u5muJPl7fVPJmyn2qqtco</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1544770081</pqid></control><display><type>article</type><title>Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity</title><source>MEDLINE</source><source>Wiley Journals</source><source>Journals@Ovid Complete</source><creator>Chen, Chun-Hsin ; Pan, Chun-Hung ; Chen, Chiao-Chicy ; Huang, Ming-Chyi</creator><creatorcontrib>Chen, Chun-Hsin ; Pan, Chun-Hung ; Chen, Chiao-Chicy ; Huang, Ming-Chyi</creatorcontrib><description>Background: Chronic and excessive alcohol consumption enhances the formation of reactive oxygen species (ROS) and ethanol‐derived free radicals. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is a marker to estimate ROS‐induced DNA damage. The study objective was to compare serum 8‐OHdG levels between patients with alcohol dependence and healthy controls and to investigate the correlation between this marker and the severity of alcohol withdrawal syndrome (AWS).
Methods: We recruited 79 patients with alcohol dependence and 63 healthy control subjects. The severity of AWS was evaluated using the Chinese version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar‐C) every 8 hours. Levels of 8‐OHdG, malondialdehyde (MDA), and other biologic indexes were assayed at baseline for patient and control groups, and after 1‐week detoxification for the patient group.
Results: The 8‐OHdG and MDA levels in the alcoholic group were significantly higher than those in the control group (0.34 vs. 0.27 ng/ml and 13.5 vs. 10.1 μM, respectively). Both 8‐OHdG and MDA were significantly correlated with the highest CIWA‐Ar‐C (correlation coefficient = 0.39, p < 0.001 and 0.26, p = 0.02, respectively). In linear regression analysis, only 8‐OHdG level was significantly correlated with the highest CIWA‐Ar, but not MDA level (regression coefficient beta = 0.33, p = 0.003 and 0.17, p = 0.12, respectively). MDA, but not 8‐OHdG levels, significantly decreased after 1 week of detoxification.
Conclusions: These results indicate that our alcohol‐dependent individuals are vulnerable to excessive production of free radicals. Notably, the oxidative DNA damage persisted after 1‐week detoxification. The AWS severity was correlated with the increase in oxidative stress, particularly the 8‐OHdG levels. The impact of sustained abstinence in alcoholic patients needs to be investigated in future studies.</description><identifier>ISSN: 0145-6008</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/j.1530-0277.2010.01349.x</identifier><identifier>PMID: 21070251</identifier><identifier>CODEN: ACRSDM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>8-Hydroxy-2′-Deoxyguanosine ; Addictive behaviors ; Adult ; Adult and adolescent clinical studies ; Alcohol Dependence ; Alcohol Withdrawal ; Alcoholics ; Alcoholism ; Alcoholism - metabolism ; Alcoholism and acute alcohol poisoning ; Biological and medical sciences ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - blood ; Detoxification ; DNA Damage ; Drug abuse ; Drug dependence ; Ethanol ; Female ; Free radicals ; Humans ; Liver Function Tests ; Male ; Malondialdehyde ; Malondialdehyde - blood ; Medical sciences ; Middle Aged ; Oxidation-Reduction ; Oxidative Stress ; Psychiatric Status Rating Scales ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Regression analysis ; Severity of Illness Index ; Substance Withdrawal Syndrome - complications ; Toxicology ; Young Adult</subject><ispartof>Alcoholism, clinical and experimental research, 2011-02, Vol.35 (2), p.338-344</ispartof><rights>Copyright © 2010 by the Research Society on Alcoholism</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 by the Research Society on Alcoholism.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4989-eb6fe3536c36a15dd2225c3fdbc387abb549a6ddf688ed1fe4eb06b3ad27b7a93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1530-0277.2010.01349.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1530-0277.2010.01349.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23823198$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21070251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Chun-Hsin</creatorcontrib><creatorcontrib>Pan, Chun-Hung</creatorcontrib><creatorcontrib>Chen, Chiao-Chicy</creatorcontrib><creatorcontrib>Huang, Ming-Chyi</creatorcontrib><title>Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description>Background: Chronic and excessive alcohol consumption enhances the formation of reactive oxygen species (ROS) and ethanol‐derived free radicals. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is a marker to estimate ROS‐induced DNA damage. The study objective was to compare serum 8‐OHdG levels between patients with alcohol dependence and healthy controls and to investigate the correlation between this marker and the severity of alcohol withdrawal syndrome (AWS).
Methods: We recruited 79 patients with alcohol dependence and 63 healthy control subjects. The severity of AWS was evaluated using the Chinese version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar‐C) every 8 hours. Levels of 8‐OHdG, malondialdehyde (MDA), and other biologic indexes were assayed at baseline for patient and control groups, and after 1‐week detoxification for the patient group.
Results: The 8‐OHdG and MDA levels in the alcoholic group were significantly higher than those in the control group (0.34 vs. 0.27 ng/ml and 13.5 vs. 10.1 μM, respectively). Both 8‐OHdG and MDA were significantly correlated with the highest CIWA‐Ar‐C (correlation coefficient = 0.39, p < 0.001 and 0.26, p = 0.02, respectively). In linear regression analysis, only 8‐OHdG level was significantly correlated with the highest CIWA‐Ar, but not MDA level (regression coefficient beta = 0.33, p = 0.003 and 0.17, p = 0.12, respectively). MDA, but not 8‐OHdG levels, significantly decreased after 1 week of detoxification.
Conclusions: These results indicate that our alcohol‐dependent individuals are vulnerable to excessive production of free radicals. Notably, the oxidative DNA damage persisted after 1‐week detoxification. The AWS severity was correlated with the increase in oxidative stress, particularly the 8‐OHdG levels. The impact of sustained abstinence in alcoholic patients needs to be investigated in future studies.</description><subject>8-Hydroxy-2′-Deoxyguanosine</subject><subject>Addictive behaviors</subject><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Alcohol Dependence</subject><subject>Alcohol Withdrawal</subject><subject>Alcoholics</subject><subject>Alcoholism</subject><subject>Alcoholism - metabolism</subject><subject>Alcoholism and acute alcohol poisoning</subject><subject>Biological and medical sciences</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - blood</subject><subject>Detoxification</subject><subject>DNA Damage</subject><subject>Drug abuse</subject><subject>Drug dependence</subject><subject>Ethanol</subject><subject>Female</subject><subject>Free radicals</subject><subject>Humans</subject><subject>Liver Function Tests</subject><subject>Male</subject><subject>Malondialdehyde</subject><subject>Malondialdehyde - blood</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Regression analysis</subject><subject>Severity of Illness Index</subject><subject>Substance Withdrawal Syndrome - complications</subject><subject>Toxicology</subject><subject>Young Adult</subject><issn>0145-6008</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkl9v0zAUxSMEYmXwFZAlhHhK8b_YyQtS1W6l0tgQDO3Rcuwb5pI6nZ2u7bfHoaUIXvCL7Xt-OpbvPVmGCB6TtN4vx6RgOMdUyjHFqYoJ49V49yQbnYSn2QgTXuQC4_IsexHjEmPMSyGeZ2eUYIlpQUbZduFNAB3Bopuds7p3j4Bm1xM00yv9HZDz6HMqgu8junP9PZq0prvvWjSDNXgL3gDS3qJF0qddCNAmuvN_s8PFBr3VLfoKjxBcv3-ZPWt0G-HVcT_Pvl1e3E4_5lc388V0cpUbXpVVDrVogBVMGCY0KayllBaGNbY2rJS6rgteaWFtI8oSLGmAQ41FzbSlspa6YufZu4PvOnQPG4i9WrlooG21h24TVYUlKaio2H_JkkvOGGUkkW_-IZfdJvj0DUUKzqVMHR-o10dqU6_AqnVwKx326nfvE_D2COhodNsE7Y2LfzhWpseqMnEfDtzWtbA_6QSrIQtqqYaRq2HkasiC-pUFtVOT6cWX4ZgM8oOBiz3sTgY6_FBCMlmou-u5muJPl7fVPJmyn2qqtco</recordid><startdate>201102</startdate><enddate>201102</enddate><creator>Chen, Chun-Hsin</creator><creator>Pan, Chun-Hung</creator><creator>Chen, Chiao-Chicy</creator><creator>Huang, Ming-Chyi</creator><general>Blackwell Publishing Ltd</general><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>K7.</scope><scope>K9.</scope><scope>7X8</scope><scope>7TM</scope></search><sort><creationdate>201102</creationdate><title>Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity</title><author>Chen, Chun-Hsin ; Pan, Chun-Hung ; Chen, Chiao-Chicy ; Huang, Ming-Chyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4989-eb6fe3536c36a15dd2225c3fdbc387abb549a6ddf688ed1fe4eb06b3ad27b7a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>8-Hydroxy-2′-Deoxyguanosine</topic><topic>Addictive behaviors</topic><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Alcohol Dependence</topic><topic>Alcohol Withdrawal</topic><topic>Alcoholics</topic><topic>Alcoholism</topic><topic>Alcoholism - metabolism</topic><topic>Alcoholism and acute alcohol poisoning</topic><topic>Biological and medical sciences</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - blood</topic><topic>Detoxification</topic><topic>DNA Damage</topic><topic>Drug abuse</topic><topic>Drug dependence</topic><topic>Ethanol</topic><topic>Female</topic><topic>Free radicals</topic><topic>Humans</topic><topic>Liver Function Tests</topic><topic>Male</topic><topic>Malondialdehyde</topic><topic>Malondialdehyde - blood</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Regression analysis</topic><topic>Severity of Illness Index</topic><topic>Substance Withdrawal Syndrome - complications</topic><topic>Toxicology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Chun-Hsin</creatorcontrib><creatorcontrib>Pan, Chun-Hung</creatorcontrib><creatorcontrib>Chen, Chiao-Chicy</creatorcontrib><creatorcontrib>Huang, Ming-Chyi</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Chun-Hsin</au><au>Pan, Chun-Hung</au><au>Chen, Chiao-Chicy</au><au>Huang, Ming-Chyi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2011-02</date><risdate>2011</risdate><volume>35</volume><issue>2</issue><spage>338</spage><epage>344</epage><pages>338-344</pages><issn>0145-6008</issn><eissn>1530-0277</eissn><coden>ACRSDM</coden><abstract>Background: Chronic and excessive alcohol consumption enhances the formation of reactive oxygen species (ROS) and ethanol‐derived free radicals. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) is a marker to estimate ROS‐induced DNA damage. The study objective was to compare serum 8‐OHdG levels between patients with alcohol dependence and healthy controls and to investigate the correlation between this marker and the severity of alcohol withdrawal syndrome (AWS).
Methods: We recruited 79 patients with alcohol dependence and 63 healthy control subjects. The severity of AWS was evaluated using the Chinese version of the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA‐Ar‐C) every 8 hours. Levels of 8‐OHdG, malondialdehyde (MDA), and other biologic indexes were assayed at baseline for patient and control groups, and after 1‐week detoxification for the patient group.
Results: The 8‐OHdG and MDA levels in the alcoholic group were significantly higher than those in the control group (0.34 vs. 0.27 ng/ml and 13.5 vs. 10.1 μM, respectively). Both 8‐OHdG and MDA were significantly correlated with the highest CIWA‐Ar‐C (correlation coefficient = 0.39, p < 0.001 and 0.26, p = 0.02, respectively). In linear regression analysis, only 8‐OHdG level was significantly correlated with the highest CIWA‐Ar, but not MDA level (regression coefficient beta = 0.33, p = 0.003 and 0.17, p = 0.12, respectively). MDA, but not 8‐OHdG levels, significantly decreased after 1 week of detoxification.
Conclusions: These results indicate that our alcohol‐dependent individuals are vulnerable to excessive production of free radicals. Notably, the oxidative DNA damage persisted after 1‐week detoxification. The AWS severity was correlated with the increase in oxidative stress, particularly the 8‐OHdG levels. The impact of sustained abstinence in alcoholic patients needs to be investigated in future studies.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21070251</pmid><doi>10.1111/j.1530-0277.2010.01349.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0145-6008 |
ispartof | Alcoholism, clinical and experimental research, 2011-02, Vol.35 (2), p.338-344 |
issn | 0145-6008 1530-0277 |
language | eng |
recordid | cdi_proquest_miscellaneous_907152693 |
source | MEDLINE; Wiley Journals; Journals@Ovid Complete |
subjects | 8-Hydroxy-2′-Deoxyguanosine Addictive behaviors Adult Adult and adolescent clinical studies Alcohol Dependence Alcohol Withdrawal Alcoholics Alcoholism Alcoholism - metabolism Alcoholism and acute alcohol poisoning Biological and medical sciences Deoxyguanosine - analogs & derivatives Deoxyguanosine - blood Detoxification DNA Damage Drug abuse Drug dependence Ethanol Female Free radicals Humans Liver Function Tests Male Malondialdehyde Malondialdehyde - blood Medical sciences Middle Aged Oxidation-Reduction Oxidative Stress Psychiatric Status Rating Scales Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Reactive oxygen species Reactive Oxygen Species - metabolism Regression analysis Severity of Illness Index Substance Withdrawal Syndrome - complications Toxicology Young Adult |
title | Increased Oxidative DNA Damage in Patients With Alcohol Dependence and Its Correlation With Alcohol Withdrawal Severity |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T04%3A37%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Increased%20Oxidative%20DNA%20Damage%20in%20Patients%20With%20Alcohol%20Dependence%20and%20Its%20Correlation%20With%20Alcohol%20Withdrawal%20Severity&rft.jtitle=Alcoholism,%20clinical%20and%20experimental%20research&rft.au=Chen,%20Chun-Hsin&rft.date=2011-02&rft.volume=35&rft.issue=2&rft.spage=338&rft.epage=344&rft.pages=338-344&rft.issn=0145-6008&rft.eissn=1530-0277&rft.coden=ACRSDM&rft_id=info:doi/10.1111/j.1530-0277.2010.01349.x&rft_dat=%3Cproquest_pubme%3E907152693%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1544770081&rft_id=info:pmid/21070251&rfr_iscdi=true |