Loading…
Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles
Purpose To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle. Methods Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles....
Saved in:
Published in: | Archives of gynecology and obstetrics 2010-08, Vol.282 (2), p.207-213 |
---|---|
Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33 |
---|---|
cites | cdi_FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33 |
container_end_page | 213 |
container_issue | 2 |
container_start_page | 207 |
container_title | Archives of gynecology and obstetrics |
container_volume | 282 |
creator | Capobianco, Giampiero de Muro, Pierina Cherchi, Gian Mario Formato, Marilena Lepedda, Antonio Junior Cigliano, Antonio Zinellu, Elisabetta Dessole, Francesco Gordini, Laila Dessole, Salvatore |
description | Purpose
To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle.
Methods
Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2–3), periovulatory phase (days 12–13), and luteal phase (days 23–24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE).
Results
In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles.
Conclusions
There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon
. |
doi_str_mv | 10.1007/s00404-010-1432-2 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733630155</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2261882487</sourcerecordid><originalsourceid>FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33</originalsourceid><addsrcrecordid>eNp1kc1u1TAQhS0EopfCA7BBlliwITC2EydlV13xJ1WCBawt155UqRw7eJKL7rPwsjg3hUpIrOaM_M2xx4ex5wLeCID2LQHUUFcgoBK1kpV8wHYnAa0QD9kOLlYNuj1jT4huAYTsOv2YnUlQoEE3O_bra7A0Wh7wgIF46vm-ymjdPByQTznNOMTX5XSah8ht9PwmHF0iOw4xrdJG4n7JQ7zhNKU424hpIT5ipDkvNnB3dAHfcT_0PWaMDolf4_wTMfJ0WIKdUz6ejG28709D9JQ96m0gfHZXz9n3D--_7T9VV18-ft5fXlWuVu1c1coLqZ13FmXfWKd9Y2t0ru-63uumaYWXvm5raFQpyupWS4U9glXuwnmlztmrzbfs-2NBms04kMMQtmVMq5RWIJqmkC__IW_TkmN5nJFSi66TddcWSmyUy4koY2-mPIw2H40AswZntuAMrH3Jy8gy8-LOebke0f-d-JNUAeQG0LT-Nub7q__v-hsrX6du</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2261882487</pqid></control><display><type>article</type><title>Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles</title><source>Springer Link</source><creator>Capobianco, Giampiero ; de Muro, Pierina ; Cherchi, Gian Mario ; Formato, Marilena ; Lepedda, Antonio Junior ; Cigliano, Antonio ; Zinellu, Elisabetta ; Dessole, Francesco ; Gordini, Laila ; Dessole, Salvatore</creator><creatorcontrib>Capobianco, Giampiero ; de Muro, Pierina ; Cherchi, Gian Mario ; Formato, Marilena ; Lepedda, Antonio Junior ; Cigliano, Antonio ; Zinellu, Elisabetta ; Dessole, Francesco ; Gordini, Laila ; Dessole, Salvatore</creatorcontrib><description>Purpose
To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle.
Methods
Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2–3), periovulatory phase (days 12–13), and luteal phase (days 23–24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE).
Results
In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles.
Conclusions
There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon
.</description><identifier>ISSN: 0932-0067</identifier><identifier>EISSN: 1432-0711</identifier><identifier>DOI: 10.1007/s00404-010-1432-2</identifier><identifier>PMID: 20306065</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Adult ; Anovulation - blood ; C-Reactive Protein - analysis ; Endocrinology ; Estradiol - blood ; Female ; Follicle Stimulating Hormone - blood ; Glycosaminoglycans - blood ; Gynecology ; Human Genetics ; Humans ; Leptin - blood ; Luteinizing Hormone - blood ; Medicine ; Medicine & Public Health ; Menstrual Cycle - blood ; Menstruation ; Obstetrics/Perinatology/Midwifery ; Ovulation - blood ; Progesterone - blood ; Reproductive Medicine ; Young Adult</subject><ispartof>Archives of gynecology and obstetrics, 2010-08, Vol.282 (2), p.207-213</ispartof><rights>Springer-Verlag 2010</rights><rights>Archives of Gynecology and Obstetrics is a copyright of Springer, (2010). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33</citedby><cites>FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20306065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Capobianco, Giampiero</creatorcontrib><creatorcontrib>de Muro, Pierina</creatorcontrib><creatorcontrib>Cherchi, Gian Mario</creatorcontrib><creatorcontrib>Formato, Marilena</creatorcontrib><creatorcontrib>Lepedda, Antonio Junior</creatorcontrib><creatorcontrib>Cigliano, Antonio</creatorcontrib><creatorcontrib>Zinellu, Elisabetta</creatorcontrib><creatorcontrib>Dessole, Francesco</creatorcontrib><creatorcontrib>Gordini, Laila</creatorcontrib><creatorcontrib>Dessole, Salvatore</creatorcontrib><title>Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles</title><title>Archives of gynecology and obstetrics</title><addtitle>Arch Gynecol Obstet</addtitle><addtitle>Arch Gynecol Obstet</addtitle><description>Purpose
To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle.
Methods
Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2–3), periovulatory phase (days 12–13), and luteal phase (days 23–24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE).
Results
In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles.
Conclusions
There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon
.</description><subject>Adult</subject><subject>Anovulation - blood</subject><subject>C-Reactive Protein - analysis</subject><subject>Endocrinology</subject><subject>Estradiol - blood</subject><subject>Female</subject><subject>Follicle Stimulating Hormone - blood</subject><subject>Glycosaminoglycans - blood</subject><subject>Gynecology</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Leptin - blood</subject><subject>Luteinizing Hormone - blood</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Menstrual Cycle - blood</subject><subject>Menstruation</subject><subject>Obstetrics/Perinatology/Midwifery</subject><subject>Ovulation - blood</subject><subject>Progesterone - blood</subject><subject>Reproductive Medicine</subject><subject>Young Adult</subject><issn>0932-0067</issn><issn>1432-0711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp1kc1u1TAQhS0EopfCA7BBlliwITC2EydlV13xJ1WCBawt155UqRw7eJKL7rPwsjg3hUpIrOaM_M2xx4ex5wLeCID2LQHUUFcgoBK1kpV8wHYnAa0QD9kOLlYNuj1jT4huAYTsOv2YnUlQoEE3O_bra7A0Wh7wgIF46vm-ymjdPByQTznNOMTX5XSah8ht9PwmHF0iOw4xrdJG4n7JQ7zhNKU424hpIT5ipDkvNnB3dAHfcT_0PWaMDolf4_wTMfJ0WIKdUz6ejG28709D9JQ96m0gfHZXz9n3D--_7T9VV18-ft5fXlWuVu1c1coLqZ13FmXfWKd9Y2t0ru-63uumaYWXvm5raFQpyupWS4U9glXuwnmlztmrzbfs-2NBms04kMMQtmVMq5RWIJqmkC__IW_TkmN5nJFSi66TddcWSmyUy4koY2-mPIw2H40AswZntuAMrH3Jy8gy8-LOebke0f-d-JNUAeQG0LT-Nub7q__v-hsrX6du</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Capobianco, Giampiero</creator><creator>de Muro, Pierina</creator><creator>Cherchi, Gian Mario</creator><creator>Formato, Marilena</creator><creator>Lepedda, Antonio Junior</creator><creator>Cigliano, Antonio</creator><creator>Zinellu, Elisabetta</creator><creator>Dessole, Francesco</creator><creator>Gordini, Laila</creator><creator>Dessole, Salvatore</creator><general>Springer-Verlag</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20100801</creationdate><title>Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles</title><author>Capobianco, Giampiero ; de Muro, Pierina ; Cherchi, Gian Mario ; Formato, Marilena ; Lepedda, Antonio Junior ; Cigliano, Antonio ; Zinellu, Elisabetta ; Dessole, Francesco ; Gordini, Laila ; Dessole, Salvatore</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Anovulation - blood</topic><topic>C-Reactive Protein - analysis</topic><topic>Endocrinology</topic><topic>Estradiol - blood</topic><topic>Female</topic><topic>Follicle Stimulating Hormone - blood</topic><topic>Glycosaminoglycans - blood</topic><topic>Gynecology</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Leptin - blood</topic><topic>Luteinizing Hormone - blood</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Menstrual Cycle - blood</topic><topic>Menstruation</topic><topic>Obstetrics/Perinatology/Midwifery</topic><topic>Ovulation - blood</topic><topic>Progesterone - blood</topic><topic>Reproductive Medicine</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Capobianco, Giampiero</creatorcontrib><creatorcontrib>de Muro, Pierina</creatorcontrib><creatorcontrib>Cherchi, Gian Mario</creatorcontrib><creatorcontrib>Formato, Marilena</creatorcontrib><creatorcontrib>Lepedda, Antonio Junior</creatorcontrib><creatorcontrib>Cigliano, Antonio</creatorcontrib><creatorcontrib>Zinellu, Elisabetta</creatorcontrib><creatorcontrib>Dessole, Francesco</creatorcontrib><creatorcontrib>Gordini, Laila</creatorcontrib><creatorcontrib>Dessole, Salvatore</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Archives of gynecology and obstetrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Capobianco, Giampiero</au><au>de Muro, Pierina</au><au>Cherchi, Gian Mario</au><au>Formato, Marilena</au><au>Lepedda, Antonio Junior</au><au>Cigliano, Antonio</au><au>Zinellu, Elisabetta</au><au>Dessole, Francesco</au><au>Gordini, Laila</au><au>Dessole, Salvatore</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles</atitle><jtitle>Archives of gynecology and obstetrics</jtitle><stitle>Arch Gynecol Obstet</stitle><addtitle>Arch Gynecol Obstet</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>282</volume><issue>2</issue><spage>207</spage><epage>213</epage><pages>207-213</pages><issn>0932-0067</issn><eissn>1432-0711</eissn><abstract>Purpose
To assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle.
Methods
Eighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2–3), periovulatory phase (days 12–13), and luteal phase (days 23–24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE).
Results
In the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles.
Conclusions
There are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon
.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>20306065</pmid><doi>10.1007/s00404-010-1432-2</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0932-0067 |
ispartof | Archives of gynecology and obstetrics, 2010-08, Vol.282 (2), p.207-213 |
issn | 0932-0067 1432-0711 |
language | eng |
recordid | cdi_proquest_miscellaneous_733630155 |
source | Springer Link |
subjects | Adult Anovulation - blood C-Reactive Protein - analysis Endocrinology Estradiol - blood Female Follicle Stimulating Hormone - blood Glycosaminoglycans - blood Gynecology Human Genetics Humans Leptin - blood Luteinizing Hormone - blood Medicine Medicine & Public Health Menstrual Cycle - blood Menstruation Obstetrics/Perinatology/Midwifery Ovulation - blood Progesterone - blood Reproductive Medicine Young Adult |
title | Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T16%3A03%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Plasma%20levels%20of%20C-reactive%20protein,%20leptin%20and%20glycosaminoglycans%20during%20spontaneous%20menstrual%20cycle:%20differences%20between%20ovulatory%20and%20anovulatory%20cycles&rft.jtitle=Archives%20of%20gynecology%20and%20obstetrics&rft.au=Capobianco,%20Giampiero&rft.date=2010-08-01&rft.volume=282&rft.issue=2&rft.spage=207&rft.epage=213&rft.pages=207-213&rft.issn=0932-0067&rft.eissn=1432-0711&rft_id=info:doi/10.1007/s00404-010-1432-2&rft_dat=%3Cproquest_cross%3E2261882487%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c437t-43d126cdcae2f5ac6d5a4eccf88fd65571d2d474053d473a67623efe0a3c9cd33%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2261882487&rft_id=info:pmid/20306065&rfr_iscdi=true |