An Investigation of Uterine Nitric Oxide Production in Mares Susceptible and Resistant to Persistent Breeding-Induced Endometritis and the Effects of Immunomodulation

Contents The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding‐induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PB...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Reproduction in domestic animals 2013-08, Vol.48 (4), p.554-561
Hauptverfasser: Woodward, EM, Christoffersen, M, Campos, J, Horohov, DW, Scoggin, KE, Squires, E, Troedsson, MHT
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 561
container_issue 4
container_start_page 554
container_title Reproduction in domestic animals
container_volume 48
creator Woodward, EM
Christoffersen, M
Campos, J
Horohov, DW
Scoggin, KE
Squires, E
Troedsson, MHT
description Contents The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding‐induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexamethasone or mycobacterial cell wall extract (MCWE) on uterine NO production and endometrial iNOS mRNA expression. Six susceptible mares were inseminated over three cycles with (i) killed spermatozoa without treatment (control), (ii) killed spermatozoa with 50 mg of dexamethasone IV or (iii) MCWE IV 24 h prior to insemination with killed spermatozoa. Six resistant mares were inseminated with killed spermatozoa as a control. Six hours after breeding, uterine biopsies and secretions were collected and evaluated for NO and iNOS mRNA. In Experiment 1, resistant mares had an increase in iNOS mRNA expression 2 h post‐breeding compared to baseline (p = 0.045), 12 h (p = 0.014) and 24 h (p = 0.001). Susceptible mares had higher expression 2 h compared to 6 h (p = 0.046). No differences were observed in mRNA or protein expression of iNOS between resistant and susceptible mares. Resistant mares had a relatively steady amount of total intrauterine NO over 24 h, while susceptible mares had an increase over time, with a significantly higher increase in total NO than resistant mares at 6 (p = 0.04) and 12 h (p = 0.032). In Experiment 2, no differences were observed for iNOS mRNA expression. Susceptible mares had increased NO when compared to resistant mares (p = 0.008) and MCWE decreased NO (p = 0.047).
doi_str_mv 10.1111/rda.12124
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1430850611</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1430850611</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4594-436e1ad26947f873ec10bcd75a960fe1659dde1d2954f67e82982ae3ebd6d8503</originalsourceid><addsrcrecordid>eNqNkc1u1DAUhS0EokNhwQsgS2xgkdY_sZMsp53pMGL6o0LF0vLEN8UlcQbbKe0L8Zw4M20XSEh4c3Wl7xzfew9Cbyk5oOkdeqMPKKMsf4YmNOdVRgSnz9GEVFxmspDlHnoVwg0hVJRF8RLtMc5YSQiZoN9Th5fuFkK01zra3uG-wVcRvHWAz2z0tsbnd9YAvvC9GeotYh0-1R4C_jKEGjbRrlvA2hl8CcGGqF3EsccX4McOUnfkAYx119nSJQ8weO5M30FyjzZslfE74HnTQB3DOMGy6wbXd-nHdjvVa_Si0W2ANw91H12dzL8ef8pW54vl8XSV1bmo8iznEqg2TFZ50ZQFh5qSdW0KoStJGqBSVMYANawSeSMLKFlVMg0c1kaaUhC-jz7sfDe-_zmkq6jOphXbVjvoh6DSdUniJKX_gRLCq4qJIqHv_0Jv-sG7tIiiCRGccD5SH3dU7fsQPDRq422n_b2iRI05q5Sz2uac2HcPjsO6A_NEPgabgMMd8Mu2cP9vJ3U5mz5aZjvFmNndk0L7H0oWvBDq29lCrWYLcko-r9SM_wHw8sJE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1399530337</pqid></control><display><type>article</type><title>An Investigation of Uterine Nitric Oxide Production in Mares Susceptible and Resistant to Persistent Breeding-Induced Endometritis and the Effects of Immunomodulation</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Woodward, EM ; Christoffersen, M ; Campos, J ; Horohov, DW ; Scoggin, KE ; Squires, E ; Troedsson, MHT</creator><creatorcontrib>Woodward, EM ; Christoffersen, M ; Campos, J ; Horohov, DW ; Scoggin, KE ; Squires, E ; Troedsson, MHT</creatorcontrib><description>Contents The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding‐induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexamethasone or mycobacterial cell wall extract (MCWE) on uterine NO production and endometrial iNOS mRNA expression. Six susceptible mares were inseminated over three cycles with (i) killed spermatozoa without treatment (control), (ii) killed spermatozoa with 50 mg of dexamethasone IV or (iii) MCWE IV 24 h prior to insemination with killed spermatozoa. Six resistant mares were inseminated with killed spermatozoa as a control. Six hours after breeding, uterine biopsies and secretions were collected and evaluated for NO and iNOS mRNA. In Experiment 1, resistant mares had an increase in iNOS mRNA expression 2 h post‐breeding compared to baseline (p = 0.045), 12 h (p = 0.014) and 24 h (p = 0.001). Susceptible mares had higher expression 2 h compared to 6 h (p = 0.046). No differences were observed in mRNA or protein expression of iNOS between resistant and susceptible mares. Resistant mares had a relatively steady amount of total intrauterine NO over 24 h, while susceptible mares had an increase over time, with a significantly higher increase in total NO than resistant mares at 6 (p = 0.04) and 12 h (p = 0.032). In Experiment 2, no differences were observed for iNOS mRNA expression. Susceptible mares had increased NO when compared to resistant mares (p = 0.008) and MCWE decreased NO (p = 0.047).</description><identifier>ISSN: 0936-6768</identifier><identifier>EISSN: 1439-0531</identifier><identifier>DOI: 10.1111/rda.12124</identifier><identifier>PMID: 23228000</identifier><language>eng</language><publisher>Germany: Blackwell Publishing Ltd</publisher><subject>Animal diseases ; Animal reproduction ; Animals ; Biopsy ; Breeding ; Cell Wall - immunology ; Dexamethasone - administration &amp; dosage ; Disease Resistance ; Disease Susceptibility - immunology ; Disease Susceptibility - veterinary ; Endometritis - etiology ; Endometritis - immunology ; Endometritis - veterinary ; Endometrium - enzymology ; Female ; Hormones ; Horse Diseases - etiology ; Horse Diseases - immunology ; Horses ; Horses - immunology ; Horses - metabolism ; Immunomodulation ; Insemination, Artificial - veterinary ; Mycobacterium ; Mycobacterium - immunology ; Nitric oxide ; Nitric Oxide - biosynthesis ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; Polymerase Chain Reaction - veterinary ; RNA, Messenger - analysis ; Uterus - metabolism</subject><ispartof>Reproduction in domestic animals, 2013-08, Vol.48 (4), p.554-561</ispartof><rights>2012 Blackwell Verlag GmbH</rights><rights>2012 Blackwell Verlag GmbH.</rights><rights>Copyright © 2013 Blackwell Verlag GmbH</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4594-436e1ad26947f873ec10bcd75a960fe1659dde1d2954f67e82982ae3ebd6d8503</citedby><cites>FETCH-LOGICAL-c4594-436e1ad26947f873ec10bcd75a960fe1659dde1d2954f67e82982ae3ebd6d8503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Frda.12124$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Frda.12124$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23228000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Woodward, EM</creatorcontrib><creatorcontrib>Christoffersen, M</creatorcontrib><creatorcontrib>Campos, J</creatorcontrib><creatorcontrib>Horohov, DW</creatorcontrib><creatorcontrib>Scoggin, KE</creatorcontrib><creatorcontrib>Squires, E</creatorcontrib><creatorcontrib>Troedsson, MHT</creatorcontrib><title>An Investigation of Uterine Nitric Oxide Production in Mares Susceptible and Resistant to Persistent Breeding-Induced Endometritis and the Effects of Immunomodulation</title><title>Reproduction in domestic animals</title><addtitle>Reprod Domest Anim</addtitle><description>Contents The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding‐induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexamethasone or mycobacterial cell wall extract (MCWE) on uterine NO production and endometrial iNOS mRNA expression. Six susceptible mares were inseminated over three cycles with (i) killed spermatozoa without treatment (control), (ii) killed spermatozoa with 50 mg of dexamethasone IV or (iii) MCWE IV 24 h prior to insemination with killed spermatozoa. Six resistant mares were inseminated with killed spermatozoa as a control. Six hours after breeding, uterine biopsies and secretions were collected and evaluated for NO and iNOS mRNA. In Experiment 1, resistant mares had an increase in iNOS mRNA expression 2 h post‐breeding compared to baseline (p = 0.045), 12 h (p = 0.014) and 24 h (p = 0.001). Susceptible mares had higher expression 2 h compared to 6 h (p = 0.046). No differences were observed in mRNA or protein expression of iNOS between resistant and susceptible mares. Resistant mares had a relatively steady amount of total intrauterine NO over 24 h, while susceptible mares had an increase over time, with a significantly higher increase in total NO than resistant mares at 6 (p = 0.04) and 12 h (p = 0.032). In Experiment 2, no differences were observed for iNOS mRNA expression. Susceptible mares had increased NO when compared to resistant mares (p = 0.008) and MCWE decreased NO (p = 0.047).</description><subject>Animal diseases</subject><subject>Animal reproduction</subject><subject>Animals</subject><subject>Biopsy</subject><subject>Breeding</subject><subject>Cell Wall - immunology</subject><subject>Dexamethasone - administration &amp; dosage</subject><subject>Disease Resistance</subject><subject>Disease Susceptibility - immunology</subject><subject>Disease Susceptibility - veterinary</subject><subject>Endometritis - etiology</subject><subject>Endometritis - immunology</subject><subject>Endometritis - veterinary</subject><subject>Endometrium - enzymology</subject><subject>Female</subject><subject>Hormones</subject><subject>Horse Diseases - etiology</subject><subject>Horse Diseases - immunology</subject><subject>Horses</subject><subject>Horses - immunology</subject><subject>Horses - metabolism</subject><subject>Immunomodulation</subject><subject>Insemination, Artificial - veterinary</subject><subject>Mycobacterium</subject><subject>Mycobacterium - immunology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - biosynthesis</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Polymerase Chain Reaction - veterinary</subject><subject>RNA, Messenger - analysis</subject><subject>Uterus - metabolism</subject><issn>0936-6768</issn><issn>1439-0531</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhS0EokNhwQsgS2xgkdY_sZMsp53pMGL6o0LF0vLEN8UlcQbbKe0L8Zw4M20XSEh4c3Wl7xzfew9Cbyk5oOkdeqMPKKMsf4YmNOdVRgSnz9GEVFxmspDlHnoVwg0hVJRF8RLtMc5YSQiZoN9Th5fuFkK01zra3uG-wVcRvHWAz2z0tsbnd9YAvvC9GeotYh0-1R4C_jKEGjbRrlvA2hl8CcGGqF3EsccX4McOUnfkAYx119nSJQ8weO5M30FyjzZslfE74HnTQB3DOMGy6wbXd-nHdjvVa_Si0W2ANw91H12dzL8ef8pW54vl8XSV1bmo8iznEqg2TFZ50ZQFh5qSdW0KoStJGqBSVMYANawSeSMLKFlVMg0c1kaaUhC-jz7sfDe-_zmkq6jOphXbVjvoh6DSdUniJKX_gRLCq4qJIqHv_0Jv-sG7tIiiCRGccD5SH3dU7fsQPDRq422n_b2iRI05q5Sz2uac2HcPjsO6A_NEPgabgMMd8Mu2cP9vJ3U5mz5aZjvFmNndk0L7H0oWvBDq29lCrWYLcko-r9SM_wHw8sJE</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Woodward, EM</creator><creator>Christoffersen, M</creator><creator>Campos, J</creator><creator>Horohov, DW</creator><creator>Scoggin, KE</creator><creator>Squires, E</creator><creator>Troedsson, MHT</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201308</creationdate><title>An Investigation of Uterine Nitric Oxide Production in Mares Susceptible and Resistant to Persistent Breeding-Induced Endometritis and the Effects of Immunomodulation</title><author>Woodward, EM ; Christoffersen, M ; Campos, J ; Horohov, DW ; Scoggin, KE ; Squires, E ; Troedsson, MHT</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4594-436e1ad26947f873ec10bcd75a960fe1659dde1d2954f67e82982ae3ebd6d8503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal diseases</topic><topic>Animal reproduction</topic><topic>Animals</topic><topic>Biopsy</topic><topic>Breeding</topic><topic>Cell Wall - immunology</topic><topic>Dexamethasone - administration &amp; dosage</topic><topic>Disease Resistance</topic><topic>Disease Susceptibility - immunology</topic><topic>Disease Susceptibility - veterinary</topic><topic>Endometritis - etiology</topic><topic>Endometritis - immunology</topic><topic>Endometritis - veterinary</topic><topic>Endometrium - enzymology</topic><topic>Female</topic><topic>Hormones</topic><topic>Horse Diseases - etiology</topic><topic>Horse Diseases - immunology</topic><topic>Horses</topic><topic>Horses - immunology</topic><topic>Horses - metabolism</topic><topic>Immunomodulation</topic><topic>Insemination, Artificial - veterinary</topic><topic>Mycobacterium</topic><topic>Mycobacterium - immunology</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - biosynthesis</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Polymerase Chain Reaction - veterinary</topic><topic>RNA, Messenger - analysis</topic><topic>Uterus - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Woodward, EM</creatorcontrib><creatorcontrib>Christoffersen, M</creatorcontrib><creatorcontrib>Campos, J</creatorcontrib><creatorcontrib>Horohov, DW</creatorcontrib><creatorcontrib>Scoggin, KE</creatorcontrib><creatorcontrib>Squires, E</creatorcontrib><creatorcontrib>Troedsson, MHT</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Reproduction in domestic animals</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Woodward, EM</au><au>Christoffersen, M</au><au>Campos, J</au><au>Horohov, DW</au><au>Scoggin, KE</au><au>Squires, E</au><au>Troedsson, MHT</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Investigation of Uterine Nitric Oxide Production in Mares Susceptible and Resistant to Persistent Breeding-Induced Endometritis and the Effects of Immunomodulation</atitle><jtitle>Reproduction in domestic animals</jtitle><addtitle>Reprod Domest Anim</addtitle><date>2013-08</date><risdate>2013</risdate><volume>48</volume><issue>4</issue><spage>554</spage><epage>561</epage><pages>554-561</pages><issn>0936-6768</issn><eissn>1439-0531</eissn><abstract>Contents The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding‐induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexamethasone or mycobacterial cell wall extract (MCWE) on uterine NO production and endometrial iNOS mRNA expression. Six susceptible mares were inseminated over three cycles with (i) killed spermatozoa without treatment (control), (ii) killed spermatozoa with 50 mg of dexamethasone IV or (iii) MCWE IV 24 h prior to insemination with killed spermatozoa. Six resistant mares were inseminated with killed spermatozoa as a control. Six hours after breeding, uterine biopsies and secretions were collected and evaluated for NO and iNOS mRNA. In Experiment 1, resistant mares had an increase in iNOS mRNA expression 2 h post‐breeding compared to baseline (p = 0.045), 12 h (p = 0.014) and 24 h (p = 0.001). Susceptible mares had higher expression 2 h compared to 6 h (p = 0.046). No differences were observed in mRNA or protein expression of iNOS between resistant and susceptible mares. Resistant mares had a relatively steady amount of total intrauterine NO over 24 h, while susceptible mares had an increase over time, with a significantly higher increase in total NO than resistant mares at 6 (p = 0.04) and 12 h (p = 0.032). In Experiment 2, no differences were observed for iNOS mRNA expression. Susceptible mares had increased NO when compared to resistant mares (p = 0.008) and MCWE decreased NO (p = 0.047).</abstract><cop>Germany</cop><pub>Blackwell Publishing Ltd</pub><pmid>23228000</pmid><doi>10.1111/rda.12124</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0936-6768
ispartof Reproduction in domestic animals, 2013-08, Vol.48 (4), p.554-561
issn 0936-6768
1439-0531
language eng
recordid cdi_proquest_miscellaneous_1430850611
source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Animal diseases
Animal reproduction
Animals
Biopsy
Breeding
Cell Wall - immunology
Dexamethasone - administration & dosage
Disease Resistance
Disease Susceptibility - immunology
Disease Susceptibility - veterinary
Endometritis - etiology
Endometritis - immunology
Endometritis - veterinary
Endometrium - enzymology
Female
Hormones
Horse Diseases - etiology
Horse Diseases - immunology
Horses
Horses - immunology
Horses - metabolism
Immunomodulation
Insemination, Artificial - veterinary
Mycobacterium
Mycobacterium - immunology
Nitric oxide
Nitric Oxide - biosynthesis
Nitric Oxide Synthase Type II - genetics
Nitric Oxide Synthase Type II - metabolism
Polymerase Chain Reaction - veterinary
RNA, Messenger - analysis
Uterus - metabolism
title An Investigation of Uterine Nitric Oxide Production in Mares Susceptible and Resistant to Persistent Breeding-Induced Endometritis and the Effects of Immunomodulation
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T23%3A45%3A48IST&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=An%20Investigation%20of%20Uterine%20Nitric%20Oxide%20Production%20in%20Mares%20Susceptible%20and%20Resistant%20to%20Persistent%20Breeding-Induced%20Endometritis%20and%20the%20Effects%20of%20Immunomodulation&rft.jtitle=Reproduction%20in%20domestic%20animals&rft.au=Woodward,%20EM&rft.date=2013-08&rft.volume=48&rft.issue=4&rft.spage=554&rft.epage=561&rft.pages=554-561&rft.issn=0936-6768&rft.eissn=1439-0531&rft_id=info:doi/10.1111/rda.12124&rft_dat=%3Cproquest_cross%3E1430850611%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1399530337&rft_id=info:pmid/23228000&rfr_iscdi=true