Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver Tissue and Morphological Development of Rats at Different Periods of Ontogenesis

This study aimed to evaluate the reaction of organism of laboratory animals on deuterium-depleted drinking diet. To assess the cell energy metabolism, the effect of a liquid medium with different deuterium contents on isolated liver mitochondria of random bred rats and Wistar rats was studied. This...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Iranian biomedical journal 2019-03, Vol.23 (2), p.129-141
Hauptverfasser: Alexandr Alexandrovich, Basov, Аnna Anatolyevna, Elkina, Andrei Alexandrovich, Samkov, Nikita Nikolaevich, Volchenko, Arcadii Victorovich, Moiseev, Liliya Viacheslavovna, Fedulova, Mikhail Gennadievich, Baryshev, Stepan Sergeevich, Dzhimak
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 141
container_issue 2
container_start_page 129
container_title Iranian biomedical journal
container_volume 23
creator Alexandr Alexandrovich, Basov
Аnna Anatolyevna, Elkina
Andrei Alexandrovich, Samkov
Nikita Nikolaevich, Volchenko
Arcadii Victorovich, Moiseev
Liliya Viacheslavovna, Fedulova
Mikhail Gennadievich, Baryshev
Stepan Sergeevich, Dzhimak
description This study aimed to evaluate the reaction of organism of laboratory animals on deuterium-depleted drinking diet. To assess the cell energy metabolism, the effect of a liquid medium with different deuterium contents on isolated liver mitochondria of random bred rats and Wistar rats was studied. This experimental study on the effect of deuterium-depleted drinking water (DDW) on 16-week-old male Wistar rats lasted for four weeks. Energy metabolism of mitochondria was examined through the production of hydrogen peroxide using an Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Modification of isotope (deuterium-protium [D/H]) composition of rats’ blood and organ tissues with DDW (-705‰), introduced into rats’ diet within four weeks, leads to the formation of isotope D/H gradient between blood plasma and organ tissues and affects isotope D/H exchange reactions on the adaptive processes. The isolated liver mitochondria from the random bred rats consumed DDW presented a maximum increase in H2O2 production during the incubation in DDW medium. This increased level of H2O2 production was higher than that of the isolated liver mitochondria of the rats consuming natural deuterium content drinking water (-24‰). The obtained results indicate the possibility of nutritional correction of isotope D/H metabolism in the blood by means of products with modified isotope composition, as well as the prospects of using isotope exchange reactions in case of imbalance in function of the body's defense systems in different generations of animals.
doi_str_mv 10.29252/ibj.23.2.129
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2108269113</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2351553425</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2059-f2d4ef7405bb3302ad4d262b939a57722eb324da429d302cb2886b23e1e417513</originalsourceid><addsrcrecordid>eNpdkUFv3CAQhVGUKtmmPfZaIeWSizcwmLV9jHbTZqWtUlWpmhvCZpywssEBHKl_pr-1bJP20BNo3jcPZh4hHzhbQgMSLm27X4JYwpJDc0QWwFhd1CDuj8mCM8h3Cfen5G2Me8aE5FV1Qk4FA2C84Qvya-v6YUbXIfU93eCcMNh5LDY4DZjQ0B86V6h3ND0i3Uaf_IR0c3lD136cfLTJZi237uxz5u5sjDNS7Qz94sP06Af_YDs9ZOdnHPw0oksH-ptOkepEN7bvMRyKX_O73sSDeOuSf0CH0cZ35E2vh4jvX88z8v3T9d36ptjdft6ur3ZFB0w2RQ-mxL4qmWxbkYfTpjSwgrYRjZZVBYCtgNLoEhqT5a6Ful61IJBjySvJxRm5ePGdgn-aMSY12tjhMGiHfo4KOKth1XAuMnr-H7r3c3D5dwryfqUUJchMFS9UF3yMAXs1BTvq8FNxpv4Ep3JwuUOBysFl_uOr69yOaP7Rf5MSvwFsFZRf</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2351553425</pqid></control><display><type>article</type><title>Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver Tissue and Morphological Development of Rats at Different Periods of Ontogenesis</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Alexandr Alexandrovich, Basov ; Аnna Anatolyevna, Elkina ; Andrei Alexandrovich, Samkov ; Nikita Nikolaevich, Volchenko ; Arcadii Victorovich, Moiseev ; Liliya Viacheslavovna, Fedulova ; Mikhail Gennadievich, Baryshev ; Stepan Sergeevich, Dzhimak</creator><creatorcontrib>Alexandr Alexandrovich, Basov ; Аnna Anatolyevna, Elkina ; Andrei Alexandrovich, Samkov ; Nikita Nikolaevich, Volchenko ; Arcadii Victorovich, Moiseev ; Liliya Viacheslavovna, Fedulova ; Mikhail Gennadievich, Baryshev ; Stepan Sergeevich, Dzhimak ; Kuban State Agrarian University, Krasnodar, Russian Federation, Russia; 4The V.M. Gorbatov Federal Research Center for Food Systems of Russian Academy of Sciences, Moscow, Russian Federation, Russia ; Kuban State University, Krasnodar, Russian Federation, Russia</creatorcontrib><description>This study aimed to evaluate the reaction of organism of laboratory animals on deuterium-depleted drinking diet. To assess the cell energy metabolism, the effect of a liquid medium with different deuterium contents on isolated liver mitochondria of random bred rats and Wistar rats was studied. This experimental study on the effect of deuterium-depleted drinking water (DDW) on 16-week-old male Wistar rats lasted for four weeks. Energy metabolism of mitochondria was examined through the production of hydrogen peroxide using an Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Modification of isotope (deuterium-protium [D/H]) composition of rats’ blood and organ tissues with DDW (-705‰), introduced into rats’ diet within four weeks, leads to the formation of isotope D/H gradient between blood plasma and organ tissues and affects isotope D/H exchange reactions on the adaptive processes. The isolated liver mitochondria from the random bred rats consumed DDW presented a maximum increase in H2O2 production during the incubation in DDW medium. This increased level of H2O2 production was higher than that of the isolated liver mitochondria of the rats consuming natural deuterium content drinking water (-24‰). The obtained results indicate the possibility of nutritional correction of isotope D/H metabolism in the blood by means of products with modified isotope composition, as well as the prospects of using isotope exchange reactions in case of imbalance in function of the body's defense systems in different generations of animals.</description><identifier>ISSN: 1028-852X</identifier><identifier>EISSN: 2008-823X</identifier><identifier>DOI: 10.29252/ibj.23.2.129</identifier><identifier>PMID: 30220191</identifier><language>eng</language><publisher>Iran: Pasteur Institute of Iran</publisher><subject>Animals ; Blood ; Blood plasma ; Depletion ; Deuterium ; Diet ; Drinking water ; Energy metabolism ; Exchanging ; Hydrogen peroxide ; Hydrogen production ; Isotope composition ; Laboratory animals ; Liver ; Metabolism ; Mitochondria ; Peroxidase ; Rodents ; Tissues</subject><ispartof>Iranian biomedical journal, 2019-03, Vol.23 (2), p.129-141</ispartof><rights>2019. This work is published under https://creativecommons.org/licenses/by-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2059-f2d4ef7405bb3302ad4d262b939a57722eb324da429d302cb2886b23e1e417513</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30220191$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alexandr Alexandrovich, Basov</creatorcontrib><creatorcontrib>Аnna Anatolyevna, Elkina</creatorcontrib><creatorcontrib>Andrei Alexandrovich, Samkov</creatorcontrib><creatorcontrib>Nikita Nikolaevich, Volchenko</creatorcontrib><creatorcontrib>Arcadii Victorovich, Moiseev</creatorcontrib><creatorcontrib>Liliya Viacheslavovna, Fedulova</creatorcontrib><creatorcontrib>Mikhail Gennadievich, Baryshev</creatorcontrib><creatorcontrib>Stepan Sergeevich, Dzhimak</creatorcontrib><creatorcontrib>Kuban State Agrarian University, Krasnodar, Russian Federation, Russia; 4The V.M. Gorbatov Federal Research Center for Food Systems of Russian Academy of Sciences, Moscow, Russian Federation, Russia</creatorcontrib><creatorcontrib>Kuban State University, Krasnodar, Russian Federation, Russia</creatorcontrib><title>Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver Tissue and Morphological Development of Rats at Different Periods of Ontogenesis</title><title>Iranian biomedical journal</title><addtitle>Iran Biomed J</addtitle><description>This study aimed to evaluate the reaction of organism of laboratory animals on deuterium-depleted drinking diet. To assess the cell energy metabolism, the effect of a liquid medium with different deuterium contents on isolated liver mitochondria of random bred rats and Wistar rats was studied. This experimental study on the effect of deuterium-depleted drinking water (DDW) on 16-week-old male Wistar rats lasted for four weeks. Energy metabolism of mitochondria was examined through the production of hydrogen peroxide using an Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Modification of isotope (deuterium-protium [D/H]) composition of rats’ blood and organ tissues with DDW (-705‰), introduced into rats’ diet within four weeks, leads to the formation of isotope D/H gradient between blood plasma and organ tissues and affects isotope D/H exchange reactions on the adaptive processes. The isolated liver mitochondria from the random bred rats consumed DDW presented a maximum increase in H2O2 production during the incubation in DDW medium. This increased level of H2O2 production was higher than that of the isolated liver mitochondria of the rats consuming natural deuterium content drinking water (-24‰). The obtained results indicate the possibility of nutritional correction of isotope D/H metabolism in the blood by means of products with modified isotope composition, as well as the prospects of using isotope exchange reactions in case of imbalance in function of the body's defense systems in different generations of animals.</description><subject>Animals</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>Depletion</subject><subject>Deuterium</subject><subject>Diet</subject><subject>Drinking water</subject><subject>Energy metabolism</subject><subject>Exchanging</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen production</subject><subject>Isotope composition</subject><subject>Laboratory animals</subject><subject>Liver</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Peroxidase</subject><subject>Rodents</subject><subject>Tissues</subject><issn>1028-852X</issn><issn>2008-823X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpdkUFv3CAQhVGUKtmmPfZaIeWSizcwmLV9jHbTZqWtUlWpmhvCZpywssEBHKl_pr-1bJP20BNo3jcPZh4hHzhbQgMSLm27X4JYwpJDc0QWwFhd1CDuj8mCM8h3Cfen5G2Me8aE5FV1Qk4FA2C84Qvya-v6YUbXIfU93eCcMNh5LDY4DZjQ0B86V6h3ND0i3Uaf_IR0c3lD136cfLTJZi237uxz5u5sjDNS7Qz94sP06Af_YDs9ZOdnHPw0oksH-ptOkepEN7bvMRyKX_O73sSDeOuSf0CH0cZ35E2vh4jvX88z8v3T9d36ptjdft6ur3ZFB0w2RQ-mxL4qmWxbkYfTpjSwgrYRjZZVBYCtgNLoEhqT5a6Ful61IJBjySvJxRm5ePGdgn-aMSY12tjhMGiHfo4KOKth1XAuMnr-H7r3c3D5dwryfqUUJchMFS9UF3yMAXs1BTvq8FNxpv4Ep3JwuUOBysFl_uOr69yOaP7Rf5MSvwFsFZRf</recordid><startdate>201903</startdate><enddate>201903</enddate><creator>Alexandr Alexandrovich, Basov</creator><creator>Аnna Anatolyevna, Elkina</creator><creator>Andrei Alexandrovich, Samkov</creator><creator>Nikita Nikolaevich, Volchenko</creator><creator>Arcadii Victorovich, Moiseev</creator><creator>Liliya Viacheslavovna, Fedulova</creator><creator>Mikhail Gennadievich, Baryshev</creator><creator>Stepan Sergeevich, Dzhimak</creator><general>Pasteur Institute of Iran</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201903</creationdate><title>Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver Tissue and Morphological Development of Rats at Different Periods of Ontogenesis</title><author>Alexandr Alexandrovich, Basov ; Аnna Anatolyevna, Elkina ; Andrei Alexandrovich, Samkov ; Nikita Nikolaevich, Volchenko ; Arcadii Victorovich, Moiseev ; Liliya Viacheslavovna, Fedulova ; Mikhail Gennadievich, Baryshev ; Stepan Sergeevich, Dzhimak</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2059-f2d4ef7405bb3302ad4d262b939a57722eb324da429d302cb2886b23e1e417513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Blood</topic><topic>Blood plasma</topic><topic>Depletion</topic><topic>Deuterium</topic><topic>Diet</topic><topic>Drinking water</topic><topic>Energy metabolism</topic><topic>Exchanging</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen production</topic><topic>Isotope composition</topic><topic>Laboratory animals</topic><topic>Liver</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>Peroxidase</topic><topic>Rodents</topic><topic>Tissues</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alexandr Alexandrovich, Basov</creatorcontrib><creatorcontrib>Аnna Anatolyevna, Elkina</creatorcontrib><creatorcontrib>Andrei Alexandrovich, Samkov</creatorcontrib><creatorcontrib>Nikita Nikolaevich, Volchenko</creatorcontrib><creatorcontrib>Arcadii Victorovich, Moiseev</creatorcontrib><creatorcontrib>Liliya Viacheslavovna, Fedulova</creatorcontrib><creatorcontrib>Mikhail Gennadievich, Baryshev</creatorcontrib><creatorcontrib>Stepan Sergeevich, Dzhimak</creatorcontrib><creatorcontrib>Kuban State Agrarian University, Krasnodar, Russian Federation, Russia; 4The V.M. Gorbatov Federal Research Center for Food Systems of Russian Academy of Sciences, Moscow, Russian Federation, Russia</creatorcontrib><creatorcontrib>Kuban State University, Krasnodar, Russian Federation, Russia</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</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>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Middle East &amp; Africa Database</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</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>Iranian biomedical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alexandr Alexandrovich, Basov</au><au>Аnna Anatolyevna, Elkina</au><au>Andrei Alexandrovich, Samkov</au><au>Nikita Nikolaevich, Volchenko</au><au>Arcadii Victorovich, Moiseev</au><au>Liliya Viacheslavovna, Fedulova</au><au>Mikhail Gennadievich, Baryshev</au><au>Stepan Sergeevich, Dzhimak</au><aucorp>Kuban State Agrarian University, Krasnodar, Russian Federation, Russia; 4The V.M. Gorbatov Federal Research Center for Food Systems of Russian Academy of Sciences, Moscow, Russian Federation, Russia</aucorp><aucorp>Kuban State University, Krasnodar, Russian Federation, Russia</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver Tissue and Morphological Development of Rats at Different Periods of Ontogenesis</atitle><jtitle>Iranian biomedical journal</jtitle><addtitle>Iran Biomed J</addtitle><date>2019-03</date><risdate>2019</risdate><volume>23</volume><issue>2</issue><spage>129</spage><epage>141</epage><pages>129-141</pages><issn>1028-852X</issn><eissn>2008-823X</eissn><abstract>This study aimed to evaluate the reaction of organism of laboratory animals on deuterium-depleted drinking diet. To assess the cell energy metabolism, the effect of a liquid medium with different deuterium contents on isolated liver mitochondria of random bred rats and Wistar rats was studied. This experimental study on the effect of deuterium-depleted drinking water (DDW) on 16-week-old male Wistar rats lasted for four weeks. Energy metabolism of mitochondria was examined through the production of hydrogen peroxide using an Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Modification of isotope (deuterium-protium [D/H]) composition of rats’ blood and organ tissues with DDW (-705‰), introduced into rats’ diet within four weeks, leads to the formation of isotope D/H gradient between blood plasma and organ tissues and affects isotope D/H exchange reactions on the adaptive processes. The isolated liver mitochondria from the random bred rats consumed DDW presented a maximum increase in H2O2 production during the incubation in DDW medium. This increased level of H2O2 production was higher than that of the isolated liver mitochondria of the rats consuming natural deuterium content drinking water (-24‰). The obtained results indicate the possibility of nutritional correction of isotope D/H metabolism in the blood by means of products with modified isotope composition, as well as the prospects of using isotope exchange reactions in case of imbalance in function of the body's defense systems in different generations of animals.</abstract><cop>Iran</cop><pub>Pasteur Institute of Iran</pub><pmid>30220191</pmid><doi>10.29252/ibj.23.2.129</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1028-852X
ispartof Iranian biomedical journal, 2019-03, Vol.23 (2), p.129-141
issn 1028-852X
2008-823X
language eng
recordid cdi_proquest_miscellaneous_2108269113
source DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Animals
Blood
Blood plasma
Depletion
Deuterium
Diet
Drinking water
Energy metabolism
Exchanging
Hydrogen peroxide
Hydrogen production
Isotope composition
Laboratory animals
Liver
Metabolism
Mitochondria
Peroxidase
Rodents
Tissues
title Influence of Deuterium-Depleted Water on the Isotope D/H Composition of Liver Tissue and Morphological Development of Rats at Different Periods of Ontogenesis
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T11%3A21%3A00IST&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=Influence%20of%20Deuterium-Depleted%20Water%20on%20the%20Isotope%20D/H%20Composition%20of%20Liver%20Tissue%20and%20Morphological%20Development%20of%20Rats%20at%20Different%20Periods%20of%20Ontogenesis&rft.jtitle=Iranian%20biomedical%20journal&rft.au=Alexandr%20Alexandrovich,%20Basov&rft.aucorp=Kuban%20State%20Agrarian%20University,%20Krasnodar,%20Russian%20Federation,%20Russia;%204The%20V.M.%20Gorbatov%20Federal%20Research%20Center%20for%20Food%20Systems%20of%20Russian%20Academy%20of%20Sciences,%20Moscow,%20Russian%20Federation,%20Russia&rft.date=2019-03&rft.volume=23&rft.issue=2&rft.spage=129&rft.epage=141&rft.pages=129-141&rft.issn=1028-852X&rft.eissn=2008-823X&rft_id=info:doi/10.29252/ibj.23.2.129&rft_dat=%3Cproquest_cross%3E2351553425%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=2351553425&rft_id=info:pmid/30220191&rfr_iscdi=true