Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women
Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede t...
Gespeichert in:
| Veröffentlicht in: | Journal of neurology 2017-05, Vol.264 (5), p.938-945 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 945 |
|---|---|
| container_issue | 5 |
| container_start_page | 938 |
| container_title | Journal of neurology |
| container_volume | 264 |
| creator | Barnes, Jill N. Harvey, Ronée E. Zuk, Samantha M. Lundt, Emily S. Lesnick, Timothy G. Gunter, Jeffrey L. Senjem, Matthew L. Shuster, Lynne T. Miller, Virginia M. Jack, Clifford R. Joyner, Michael J. Kantarci, Kejal |
| description | Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede the appearance of clinically defined hypertension but the relationship of aortic hemodynamics to development of WMH in women is not known. Therefore, this study aimed to characterize aortic hemodynamics in relationship to WMH in postmenopausal women. Aortic systolic and diastolic blood pressure (BP), aortic augmentation index (Alx) and aortic round trip travel time (Aortic
T
R
) by tonometry were examined in 53 postmenopausal women (age 60 ± 2 years). WMH was calculated from fluid-attenuated inversion recovery MRI using a semi-automated segmentation algorithm. WMH as a fraction of total white matter volume positively associated with aortic systolic BP (regression coefficient = 0.018;
p
= 0.04) after adjusting for age. In addition, WMH fraction was positively associated with AIx (0.025;
p
= 0.04), and inversely associated with Aortic
T
R
(−0.015;
p
= 0.04) after adjusting for age. Our results suggest that assessing aortic hemodynamics may identify individuals at risk for accelerated development of WMH and guide early treatment to reduce WMH burden and cognitive impairment in the future. |
| doi_str_mv | 10.1007/s00415-017-8476-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5413519</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899613287</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-c771d9b167206de3ddcf896dd25a282f2b2bdfa79369e646996a83d4e48328ea3</originalsourceid><addsrcrecordid>eNp1kU1rFTEYhYNY7LX6A9xIwI2b0XxOko1Qil9QcNNuugm5k3d6U2aSMcm03H9v6q2lCq5Ccp735LwchN5Q8oESoj4WQgSVHaGq00L1HX2GNlRw1lEhzXO0IVyQTnIpjtHLUm4IIboJL9Ax01wbJdgGXZ2mXMOAdzAnv49uDkPBLnp8twsV8OxqhYx3-wVyiBViCTVAwSHimPKcfr_cAl5SqTPEtLi1uAnfpXZ5hY5GNxV4_XCeoMsvny_OvnXnP75-Pzs97wbJ-9oNSlFvtrRXjPQeuPfDqE3vPZOOaTayLdv60SnDewO96I3pneZegNCcaXD8BH06-C7rdgY_QKzZTXbJYXZ5b5ML9m8lhp29TrdWCsolNc3g_YNBTj9XKNXOoQwwTS5CWoulWksjKSO8oe_-QW_SmmNbr1EtGW2RVKPogRpyKiXD-BiGEnvfnD00Z1tz9r45S9vM26dbPE78qaoB7ACUJsVryE--_q_rLyT5pos</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899613287</pqid></control><display><type>article</type><title>Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Barnes, Jill N. ; Harvey, Ronée E. ; Zuk, Samantha M. ; Lundt, Emily S. ; Lesnick, Timothy G. ; Gunter, Jeffrey L. ; Senjem, Matthew L. ; Shuster, Lynne T. ; Miller, Virginia M. ; Jack, Clifford R. ; Joyner, Michael J. ; Kantarci, Kejal</creator><creatorcontrib>Barnes, Jill N. ; Harvey, Ronée E. ; Zuk, Samantha M. ; Lundt, Emily S. ; Lesnick, Timothy G. ; Gunter, Jeffrey L. ; Senjem, Matthew L. ; Shuster, Lynne T. ; Miller, Virginia M. ; Jack, Clifford R. ; Joyner, Michael J. ; Kantarci, Kejal</creatorcontrib><description>Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede the appearance of clinically defined hypertension but the relationship of aortic hemodynamics to development of WMH in women is not known. Therefore, this study aimed to characterize aortic hemodynamics in relationship to WMH in postmenopausal women. Aortic systolic and diastolic blood pressure (BP), aortic augmentation index (Alx) and aortic round trip travel time (Aortic
T
R
) by tonometry were examined in 53 postmenopausal women (age 60 ± 2 years). WMH was calculated from fluid-attenuated inversion recovery MRI using a semi-automated segmentation algorithm. WMH as a fraction of total white matter volume positively associated with aortic systolic BP (regression coefficient = 0.018;
p
= 0.04) after adjusting for age. In addition, WMH fraction was positively associated with AIx (0.025;
p
= 0.04), and inversely associated with Aortic
T
R
(−0.015;
p
= 0.04) after adjusting for age. Our results suggest that assessing aortic hemodynamics may identify individuals at risk for accelerated development of WMH and guide early treatment to reduce WMH burden and cognitive impairment in the future.</description><identifier>ISSN: 0340-5354</identifier><identifier>EISSN: 1432-1459</identifier><identifier>DOI: 10.1007/s00415-017-8476-1</identifier><identifier>PMID: 28389742</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Age ; Aorta ; Blood pressure ; Blood Pressure - physiology ; Body Mass Index ; C-Reactive Protein - metabolism ; Circulatory system ; Cognitive ability ; Female ; Health risk assessment ; Hemodynamics ; Hemodynamics - physiology ; Hormone replacement therapy ; Humans ; Hypertension ; Image processing ; Image Processing, Computer-Assisted ; Leukoencephalopathies - diagnostic imaging ; Leukoencephalopathies - physiopathology ; Magnetic Resonance Imaging ; Medicine ; Medicine & Public Health ; Menopause ; Middle Aged ; Neurology ; Neuroradiology ; Neurosciences ; Original Communication ; Post-menopause ; Postmenopause ; Risk factors ; Segmentation ; Substantia alba ; White Matter - diagnostic imaging</subject><ispartof>Journal of neurology, 2017-05, Vol.264 (5), p.938-945</ispartof><rights>The Author(s) 2017</rights><rights>Journal of Neurology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-c771d9b167206de3ddcf896dd25a282f2b2bdfa79369e646996a83d4e48328ea3</citedby><cites>FETCH-LOGICAL-c536t-c771d9b167206de3ddcf896dd25a282f2b2bdfa79369e646996a83d4e48328ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00415-017-8476-1$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00415-017-8476-1$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28389742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barnes, Jill N.</creatorcontrib><creatorcontrib>Harvey, Ronée E.</creatorcontrib><creatorcontrib>Zuk, Samantha M.</creatorcontrib><creatorcontrib>Lundt, Emily S.</creatorcontrib><creatorcontrib>Lesnick, Timothy G.</creatorcontrib><creatorcontrib>Gunter, Jeffrey L.</creatorcontrib><creatorcontrib>Senjem, Matthew L.</creatorcontrib><creatorcontrib>Shuster, Lynne T.</creatorcontrib><creatorcontrib>Miller, Virginia M.</creatorcontrib><creatorcontrib>Jack, Clifford R.</creatorcontrib><creatorcontrib>Joyner, Michael J.</creatorcontrib><creatorcontrib>Kantarci, Kejal</creatorcontrib><title>Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women</title><title>Journal of neurology</title><addtitle>J Neurol</addtitle><addtitle>J Neurol</addtitle><description>Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede the appearance of clinically defined hypertension but the relationship of aortic hemodynamics to development of WMH in women is not known. Therefore, this study aimed to characterize aortic hemodynamics in relationship to WMH in postmenopausal women. Aortic systolic and diastolic blood pressure (BP), aortic augmentation index (Alx) and aortic round trip travel time (Aortic
T
R
) by tonometry were examined in 53 postmenopausal women (age 60 ± 2 years). WMH was calculated from fluid-attenuated inversion recovery MRI using a semi-automated segmentation algorithm. WMH as a fraction of total white matter volume positively associated with aortic systolic BP (regression coefficient = 0.018;
p
= 0.04) after adjusting for age. In addition, WMH fraction was positively associated with AIx (0.025;
p
= 0.04), and inversely associated with Aortic
T
R
(−0.015;
p
= 0.04) after adjusting for age. Our results suggest that assessing aortic hemodynamics may identify individuals at risk for accelerated development of WMH and guide early treatment to reduce WMH burden and cognitive impairment in the future.</description><subject>Age</subject><subject>Aorta</subject><subject>Blood pressure</subject><subject>Blood Pressure - physiology</subject><subject>Body Mass Index</subject><subject>C-Reactive Protein - metabolism</subject><subject>Circulatory system</subject><subject>Cognitive ability</subject><subject>Female</subject><subject>Health risk assessment</subject><subject>Hemodynamics</subject><subject>Hemodynamics - physiology</subject><subject>Hormone replacement therapy</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Image processing</subject><subject>Image Processing, Computer-Assisted</subject><subject>Leukoencephalopathies - diagnostic imaging</subject><subject>Leukoencephalopathies - physiopathology</subject><subject>Magnetic Resonance Imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Menopause</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Original Communication</subject><subject>Post-menopause</subject><subject>Postmenopause</subject><subject>Risk factors</subject><subject>Segmentation</subject><subject>Substantia alba</subject><subject>White Matter - diagnostic imaging</subject><issn>0340-5354</issn><issn>1432-1459</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1rFTEYhYNY7LX6A9xIwI2b0XxOko1Qil9QcNNuugm5k3d6U2aSMcm03H9v6q2lCq5Ccp735LwchN5Q8oESoj4WQgSVHaGq00L1HX2GNlRw1lEhzXO0IVyQTnIpjtHLUm4IIboJL9Ax01wbJdgGXZ2mXMOAdzAnv49uDkPBLnp8twsV8OxqhYx3-wVyiBViCTVAwSHimPKcfr_cAl5SqTPEtLi1uAnfpXZ5hY5GNxV4_XCeoMsvny_OvnXnP75-Pzs97wbJ-9oNSlFvtrRXjPQeuPfDqE3vPZOOaTayLdv60SnDewO96I3pneZegNCcaXD8BH06-C7rdgY_QKzZTXbJYXZ5b5ML9m8lhp29TrdWCsolNc3g_YNBTj9XKNXOoQwwTS5CWoulWksjKSO8oe_-QW_SmmNbr1EtGW2RVKPogRpyKiXD-BiGEnvfnD00Z1tz9r45S9vM26dbPE78qaoB7ACUJsVryE--_q_rLyT5pos</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Barnes, Jill N.</creator><creator>Harvey, Ronée E.</creator><creator>Zuk, Samantha M.</creator><creator>Lundt, Emily S.</creator><creator>Lesnick, Timothy G.</creator><creator>Gunter, Jeffrey L.</creator><creator>Senjem, Matthew L.</creator><creator>Shuster, Lynne T.</creator><creator>Miller, Virginia M.</creator><creator>Jack, Clifford R.</creator><creator>Joyner, Michael J.</creator><creator>Kantarci, Kejal</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</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>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170501</creationdate><title>Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women</title><author>Barnes, Jill N. ; Harvey, Ronée E. ; Zuk, Samantha M. ; Lundt, Emily S. ; Lesnick, Timothy G. ; Gunter, Jeffrey L. ; Senjem, Matthew L. ; Shuster, Lynne T. ; Miller, Virginia M. ; Jack, Clifford R. ; Joyner, Michael J. ; Kantarci, Kejal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-c771d9b167206de3ddcf896dd25a282f2b2bdfa79369e646996a83d4e48328ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Age</topic><topic>Aorta</topic><topic>Blood pressure</topic><topic>Blood Pressure - physiology</topic><topic>Body Mass Index</topic><topic>C-Reactive Protein - metabolism</topic><topic>Circulatory system</topic><topic>Cognitive ability</topic><topic>Female</topic><topic>Health risk assessment</topic><topic>Hemodynamics</topic><topic>Hemodynamics - physiology</topic><topic>Hormone replacement therapy</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Image processing</topic><topic>Image Processing, Computer-Assisted</topic><topic>Leukoencephalopathies - diagnostic imaging</topic><topic>Leukoencephalopathies - physiopathology</topic><topic>Magnetic Resonance Imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Menopause</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Original Communication</topic><topic>Post-menopause</topic><topic>Postmenopause</topic><topic>Risk factors</topic><topic>Segmentation</topic><topic>Substantia alba</topic><topic>White Matter - diagnostic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barnes, Jill N.</creatorcontrib><creatorcontrib>Harvey, Ronée E.</creatorcontrib><creatorcontrib>Zuk, Samantha M.</creatorcontrib><creatorcontrib>Lundt, Emily S.</creatorcontrib><creatorcontrib>Lesnick, Timothy G.</creatorcontrib><creatorcontrib>Gunter, Jeffrey L.</creatorcontrib><creatorcontrib>Senjem, Matthew L.</creatorcontrib><creatorcontrib>Shuster, Lynne T.</creatorcontrib><creatorcontrib>Miller, Virginia M.</creatorcontrib><creatorcontrib>Jack, Clifford R.</creatorcontrib><creatorcontrib>Joyner, Michael J.</creatorcontrib><creatorcontrib>Kantarci, Kejal</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>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>Medical Database</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barnes, Jill N.</au><au>Harvey, Ronée E.</au><au>Zuk, Samantha M.</au><au>Lundt, Emily S.</au><au>Lesnick, Timothy G.</au><au>Gunter, Jeffrey L.</au><au>Senjem, Matthew L.</au><au>Shuster, Lynne T.</au><au>Miller, Virginia M.</au><au>Jack, Clifford R.</au><au>Joyner, Michael J.</au><au>Kantarci, Kejal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women</atitle><jtitle>Journal of neurology</jtitle><stitle>J Neurol</stitle><addtitle>J Neurol</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>264</volume><issue>5</issue><spage>938</spage><epage>945</epage><pages>938-945</pages><issn>0340-5354</issn><eissn>1432-1459</eissn><abstract>Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede the appearance of clinically defined hypertension but the relationship of aortic hemodynamics to development of WMH in women is not known. Therefore, this study aimed to characterize aortic hemodynamics in relationship to WMH in postmenopausal women. Aortic systolic and diastolic blood pressure (BP), aortic augmentation index (Alx) and aortic round trip travel time (Aortic
T
R
) by tonometry were examined in 53 postmenopausal women (age 60 ± 2 years). WMH was calculated from fluid-attenuated inversion recovery MRI using a semi-automated segmentation algorithm. WMH as a fraction of total white matter volume positively associated with aortic systolic BP (regression coefficient = 0.018;
p
= 0.04) after adjusting for age. In addition, WMH fraction was positively associated with AIx (0.025;
p
= 0.04), and inversely associated with Aortic
T
R
(−0.015;
p
= 0.04) after adjusting for age. Our results suggest that assessing aortic hemodynamics may identify individuals at risk for accelerated development of WMH and guide early treatment to reduce WMH burden and cognitive impairment in the future.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>28389742</pmid><doi>10.1007/s00415-017-8476-1</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-5354 |
| ispartof | Journal of neurology, 2017-05, Vol.264 (5), p.938-945 |
| issn | 0340-5354 1432-1459 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5413519 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Age Aorta Blood pressure Blood Pressure - physiology Body Mass Index C-Reactive Protein - metabolism Circulatory system Cognitive ability Female Health risk assessment Hemodynamics Hemodynamics - physiology Hormone replacement therapy Humans Hypertension Image processing Image Processing, Computer-Assisted Leukoencephalopathies - diagnostic imaging Leukoencephalopathies - physiopathology Magnetic Resonance Imaging Medicine Medicine & Public Health Menopause Middle Aged Neurology Neuroradiology Neurosciences Original Communication Post-menopause Postmenopause Risk factors Segmentation Substantia alba White Matter - diagnostic imaging |
| title | Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T21%3A29%3A58IST&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=Aortic%20hemodynamics%20and%20white%20matter%20hyperintensities%20in%20normotensive%20postmenopausal%20women&rft.jtitle=Journal%20of%20neurology&rft.au=Barnes,%20Jill%20N.&rft.date=2017-05-01&rft.volume=264&rft.issue=5&rft.spage=938&rft.epage=945&rft.pages=938-945&rft.issn=0340-5354&rft.eissn=1432-1459&rft_id=info:doi/10.1007/s00415-017-8476-1&rft_dat=%3Cproquest_pubme%3E1899613287%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=1899613287&rft_id=info:pmid/28389742&rfr_iscdi=true |