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In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections
The aim of this study was to analyze the antibacterial activity of four essential oils (EOs), , , and in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing and , metallo-beta-lactamase (MBL)-producing and carbapenemase (KPC)-producing . A total of 60 strains were...
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Published in: | Antibiotics (Basel) 2020-05, Vol.9 (5), p.272 |
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description | The aim of this study was to analyze the antibacterial activity of four essential oils (EOs),
,
,
and
in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing
and
, metallo-beta-lactamase (MBL)-producing
and carbapenemase (KPC)-producing
. A total of 60 strains were obtained from the stock collection from the Microbiology Laboratory of Hesperia Hospital, Modena, Italy. Twenty ESBL-producing
, 5
, 13 KPC-producing
and 20 MBL-producing
were cultured and reconfirmed as ESBL and carbapenamase producers. Polymerase chain reaction was used for the detection of genes responsible for antibiotic resistance (ESBL and KPC/MBL). Antibacterial activity of the EOs was determined using the agar disk diffusion assay, and minimal inhibitory concentrations (MICs) were also evaluated. Lastly, adhesion capability and biofilm formation on polystyrene and glass surfaces were studied in 24 randomly selected strains.
and
EOs showed the best antibacterial activity against all tested strains and, as revealed by agar disk diffusion assay,
was the most effective, even at low concentrations. This effect was also confirmed by MICs, with values ranging from 0.5 to 16 µg/mL and from 1 to 16 µg/mL, for
and
EOs, respectively. The EOs' antibacterial activity compared to antibiotics confirmed
EO as the best antibacterial agent.
EO also showed a good antibacterial activity with MICs lower than both reference antibiotics. Lastly, a significant anti-biofilm activity was observed for the two EOs (
< 0.05 and
< 0.01 for
and
EOs, respectively). A good antibacterial and anti-biofilm activity of
and
.
s EOs against all selected strains was observed, thus demonstrating a future possible use of these EOs to treat infections caused by ESBL/carbapenemase-producing strains, even in association with antibiotics. |
doi_str_mv | 10.3390/antibiotics9050272 |
format | article |
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,
,
and
in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing
and
, metallo-beta-lactamase (MBL)-producing
and carbapenemase (KPC)-producing
. A total of 60 strains were obtained from the stock collection from the Microbiology Laboratory of Hesperia Hospital, Modena, Italy. Twenty ESBL-producing
, 5
, 13 KPC-producing
and 20 MBL-producing
were cultured and reconfirmed as ESBL and carbapenamase producers. Polymerase chain reaction was used for the detection of genes responsible for antibiotic resistance (ESBL and KPC/MBL). Antibacterial activity of the EOs was determined using the agar disk diffusion assay, and minimal inhibitory concentrations (MICs) were also evaluated. Lastly, adhesion capability and biofilm formation on polystyrene and glass surfaces were studied in 24 randomly selected strains.
and
EOs showed the best antibacterial activity against all tested strains and, as revealed by agar disk diffusion assay,
was the most effective, even at low concentrations. This effect was also confirmed by MICs, with values ranging from 0.5 to 16 µg/mL and from 1 to 16 µg/mL, for
and
EOs, respectively. The EOs' antibacterial activity compared to antibiotics confirmed
EO as the best antibacterial agent.
EO also showed a good antibacterial activity with MICs lower than both reference antibiotics. Lastly, a significant anti-biofilm activity was observed for the two EOs (
< 0.05 and
< 0.01 for
and
EOs, respectively). A good antibacterial and anti-biofilm activity of
and
.
s EOs against all selected strains was observed, thus demonstrating a future possible use of these EOs to treat infections caused by ESBL/carbapenemase-producing strains, even in association with antibiotics.</description><identifier>ISSN: 2079-6382</identifier><identifier>EISSN: 2079-6382</identifier><identifier>DOI: 10.3390/antibiotics9050272</identifier><identifier>PMID: 32466117</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adhesion tests ; Agar ; Antibacterial activity ; Antibiotic resistance ; Antibiotics ; Antimicrobial agents ; Bacteria ; Bacterial infections ; biofilm ; Biofilms ; Carbapenemase ; Diffusion ; E coli ; ESBL ; Essential oils ; Eucalyptus ; Gram-negative bacteria ; Klebsiella ; Klebsiella pneumoniae ; KPC ; Low concentrations ; MBL ; Metabolites ; Metallo-β-lactamase ; Metallography ; Microbiology ; Microorganisms ; Nosocomial infection ; Nosocomial infections ; Oils & fats ; Pathogens ; Polymerase chain reaction ; Polystyrene ; Polystyrene resins ; Pseudomonas aeruginosa ; Strains (organisms) ; β Lactamase</subject><ispartof>Antibiotics (Basel), 2020-05, Vol.9 (5), p.272</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-b4c22ea54e8614561e7966652cba221d369c15344157450c0a77752b0b0bf9b23</citedby><cites>FETCH-LOGICAL-c496t-b4c22ea54e8614561e7966652cba221d369c15344157450c0a77752b0b0bf9b23</cites><orcidid>0000-0002-3042-4168 ; 0000-0003-3153-426X ; 0000-0001-8949-1915 ; 0000-0002-3491-0163 ; 0000-0003-3071-3258 ; 0000-0002-2452-5763 ; 0000-0001-8122-9170 ; 0000-0003-3221-5172</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2407687887/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2407687887?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32466117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iseppi, Ramona</creatorcontrib><creatorcontrib>Di Cerbo, Alessandro</creatorcontrib><creatorcontrib>Aloisi, Piero</creatorcontrib><creatorcontrib>Manelli, Mattia</creatorcontrib><creatorcontrib>Pellesi, Veronica</creatorcontrib><creatorcontrib>Provenzano, Cinzia</creatorcontrib><creatorcontrib>Camellini, Stefania</creatorcontrib><creatorcontrib>Messi, Patrizia</creatorcontrib><creatorcontrib>Sabia, Carla</creatorcontrib><title>In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections</title><title>Antibiotics (Basel)</title><addtitle>Antibiotics (Basel)</addtitle><description>The aim of this study was to analyze the antibacterial activity of four essential oils (EOs),
,
,
and
in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing
and
, metallo-beta-lactamase (MBL)-producing
and carbapenemase (KPC)-producing
. A total of 60 strains were obtained from the stock collection from the Microbiology Laboratory of Hesperia Hospital, Modena, Italy. Twenty ESBL-producing
, 5
, 13 KPC-producing
and 20 MBL-producing
were cultured and reconfirmed as ESBL and carbapenamase producers. Polymerase chain reaction was used for the detection of genes responsible for antibiotic resistance (ESBL and KPC/MBL). Antibacterial activity of the EOs was determined using the agar disk diffusion assay, and minimal inhibitory concentrations (MICs) were also evaluated. Lastly, adhesion capability and biofilm formation on polystyrene and glass surfaces were studied in 24 randomly selected strains.
and
EOs showed the best antibacterial activity against all tested strains and, as revealed by agar disk diffusion assay,
was the most effective, even at low concentrations. This effect was also confirmed by MICs, with values ranging from 0.5 to 16 µg/mL and from 1 to 16 µg/mL, for
and
EOs, respectively. The EOs' antibacterial activity compared to antibiotics confirmed
EO as the best antibacterial agent.
EO also showed a good antibacterial activity with MICs lower than both reference antibiotics. Lastly, a significant anti-biofilm activity was observed for the two EOs (
< 0.05 and
< 0.01 for
and
EOs, respectively). A good antibacterial and anti-biofilm activity of
and
.
s EOs against all selected strains was observed, thus demonstrating a future possible use of these EOs to treat infections caused by ESBL/carbapenemase-producing strains, even in association with antibiotics.</description><subject>Adhesion tests</subject><subject>Agar</subject><subject>Antibacterial activity</subject><subject>Antibiotic resistance</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Bacteria</subject><subject>Bacterial infections</subject><subject>biofilm</subject><subject>Biofilms</subject><subject>Carbapenemase</subject><subject>Diffusion</subject><subject>E coli</subject><subject>ESBL</subject><subject>Essential oils</subject><subject>Eucalyptus</subject><subject>Gram-negative bacteria</subject><subject>Klebsiella</subject><subject>Klebsiella pneumoniae</subject><subject>KPC</subject><subject>Low concentrations</subject><subject>MBL</subject><subject>Metabolites</subject><subject>Metallo-β-lactamase</subject><subject>Metallography</subject><subject>Microbiology</subject><subject>Microorganisms</subject><subject>Nosocomial infection</subject><subject>Nosocomial infections</subject><subject>Oils & fats</subject><subject>Pathogens</subject><subject>Polymerase chain reaction</subject><subject>Polystyrene</subject><subject>Polystyrene resins</subject><subject>Pseudomonas aeruginosa</subject><subject>Strains (organisms)</subject><subject>β Lactamase</subject><issn>2079-6382</issn><issn>2079-6382</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNplks9u1DAQxiMEolXpC3BAlriUQ6jtJP5zQdpdLe1Kq7ZSgWs0cZzFS2IvtrOir9Wn6IlnwtstVQv2wdb4-34ejyfL3hL8sSgkPgUbTWNcNCpIXGHK6YvskGIuc1YI-vLJ_iA7DmGN05CkEFi8zg4KWjJGCD_M7hYWfTPROzRR0WxNvEGuQ_MQdOJDjy5NH9BkBcaGiK56sD-is0YhsC2aGteZfkAz3SfRzvYratvqNr_eaBX9OKDft_kSVIQBgkYn8-vp8sPpDHwDG23vg_mVd-2ojF2hMw9DfqFXkPLQaJps2htAC7t1_Va3yFh0Pg5g0YULTrlhl97Cdukm42x4k73qoA_6-GE9yr5-nn-ZnefLy7PFbLLMVSlZzJtSUaqhKrVgpKwY0VwyxiqqGqCUtAWTilRFWZKKlxVWGDjnFW1wmp1saHGULfbc1sG63ngzgL-pHZj6PuD8qgaffqXXddU2WBDa4Y7LEqiQreAgJZCOYM2ZTqxPe9ZmbAbdqlRzD_0z6PMTa77XK7etOeWc8TIBTh4A3v0cdYj1YIJK3wFWuzHUtMSCYszFTvr-H-najd6mUu1UnAkuBE8qulcp70LwuntMhuB613f1_32XTO-ePuPR8rfLij-sodlR</recordid><startdate>20200525</startdate><enddate>20200525</enddate><creator>Iseppi, Ramona</creator><creator>Di Cerbo, Alessandro</creator><creator>Aloisi, Piero</creator><creator>Manelli, Mattia</creator><creator>Pellesi, Veronica</creator><creator>Provenzano, Cinzia</creator><creator>Camellini, Stefania</creator><creator>Messi, Patrizia</creator><creator>Sabia, Carla</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3042-4168</orcidid><orcidid>https://orcid.org/0000-0003-3153-426X</orcidid><orcidid>https://orcid.org/0000-0001-8949-1915</orcidid><orcidid>https://orcid.org/0000-0002-3491-0163</orcidid><orcidid>https://orcid.org/0000-0003-3071-3258</orcidid><orcidid>https://orcid.org/0000-0002-2452-5763</orcidid><orcidid>https://orcid.org/0000-0001-8122-9170</orcidid><orcidid>https://orcid.org/0000-0003-3221-5172</orcidid></search><sort><creationdate>20200525</creationdate><title>In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections</title><author>Iseppi, Ramona ; Di Cerbo, Alessandro ; Aloisi, Piero ; Manelli, Mattia ; Pellesi, Veronica ; Provenzano, Cinzia ; Camellini, Stefania ; Messi, Patrizia ; Sabia, Carla</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-b4c22ea54e8614561e7966652cba221d369c15344157450c0a77752b0b0bf9b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adhesion tests</topic><topic>Agar</topic><topic>Antibacterial activity</topic><topic>Antibiotic resistance</topic><topic>Antibiotics</topic><topic>Antimicrobial agents</topic><topic>Bacteria</topic><topic>Bacterial infections</topic><topic>biofilm</topic><topic>Biofilms</topic><topic>Carbapenemase</topic><topic>Diffusion</topic><topic>E coli</topic><topic>ESBL</topic><topic>Essential oils</topic><topic>Eucalyptus</topic><topic>Gram-negative bacteria</topic><topic>Klebsiella</topic><topic>Klebsiella pneumoniae</topic><topic>KPC</topic><topic>Low concentrations</topic><topic>MBL</topic><topic>Metabolites</topic><topic>Metallo-β-lactamase</topic><topic>Metallography</topic><topic>Microbiology</topic><topic>Microorganisms</topic><topic>Nosocomial infection</topic><topic>Nosocomial infections</topic><topic>Oils & fats</topic><topic>Pathogens</topic><topic>Polymerase chain reaction</topic><topic>Polystyrene</topic><topic>Polystyrene resins</topic><topic>Pseudomonas aeruginosa</topic><topic>Strains (organisms)</topic><topic>β Lactamase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iseppi, Ramona</creatorcontrib><creatorcontrib>Di Cerbo, Alessandro</creatorcontrib><creatorcontrib>Aloisi, Piero</creatorcontrib><creatorcontrib>Manelli, Mattia</creatorcontrib><creatorcontrib>Pellesi, Veronica</creatorcontrib><creatorcontrib>Provenzano, Cinzia</creatorcontrib><creatorcontrib>Camellini, Stefania</creatorcontrib><creatorcontrib>Messi, Patrizia</creatorcontrib><creatorcontrib>Sabia, Carla</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Biological Sciences</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content 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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Antibiotics (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iseppi, Ramona</au><au>Di Cerbo, Alessandro</au><au>Aloisi, Piero</au><au>Manelli, Mattia</au><au>Pellesi, Veronica</au><au>Provenzano, Cinzia</au><au>Camellini, Stefania</au><au>Messi, Patrizia</au><au>Sabia, Carla</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections</atitle><jtitle>Antibiotics (Basel)</jtitle><addtitle>Antibiotics (Basel)</addtitle><date>2020-05-25</date><risdate>2020</risdate><volume>9</volume><issue>5</issue><spage>272</spage><pages>272-</pages><issn>2079-6382</issn><eissn>2079-6382</eissn><abstract>The aim of this study was to analyze the antibacterial activity of four essential oils (EOs),
,
,
and
in preventing the development and spread of extended-spectrum β-lactamase (ESBL)-producing
and
, metallo-beta-lactamase (MBL)-producing
and carbapenemase (KPC)-producing
. A total of 60 strains were obtained from the stock collection from the Microbiology Laboratory of Hesperia Hospital, Modena, Italy. Twenty ESBL-producing
, 5
, 13 KPC-producing
and 20 MBL-producing
were cultured and reconfirmed as ESBL and carbapenamase producers. Polymerase chain reaction was used for the detection of genes responsible for antibiotic resistance (ESBL and KPC/MBL). Antibacterial activity of the EOs was determined using the agar disk diffusion assay, and minimal inhibitory concentrations (MICs) were also evaluated. Lastly, adhesion capability and biofilm formation on polystyrene and glass surfaces were studied in 24 randomly selected strains.
and
EOs showed the best antibacterial activity against all tested strains and, as revealed by agar disk diffusion assay,
was the most effective, even at low concentrations. This effect was also confirmed by MICs, with values ranging from 0.5 to 16 µg/mL and from 1 to 16 µg/mL, for
and
EOs, respectively. The EOs' antibacterial activity compared to antibiotics confirmed
EO as the best antibacterial agent.
EO also showed a good antibacterial activity with MICs lower than both reference antibiotics. Lastly, a significant anti-biofilm activity was observed for the two EOs (
< 0.05 and
< 0.01 for
and
EOs, respectively). A good antibacterial and anti-biofilm activity of
and
.
s EOs against all selected strains was observed, thus demonstrating a future possible use of these EOs to treat infections caused by ESBL/carbapenemase-producing strains, even in association with antibiotics.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32466117</pmid><doi>10.3390/antibiotics9050272</doi><orcidid>https://orcid.org/0000-0002-3042-4168</orcidid><orcidid>https://orcid.org/0000-0003-3153-426X</orcidid><orcidid>https://orcid.org/0000-0001-8949-1915</orcidid><orcidid>https://orcid.org/0000-0002-3491-0163</orcidid><orcidid>https://orcid.org/0000-0003-3071-3258</orcidid><orcidid>https://orcid.org/0000-0002-2452-5763</orcidid><orcidid>https://orcid.org/0000-0001-8122-9170</orcidid><orcidid>https://orcid.org/0000-0003-3221-5172</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2079-6382 |
ispartof | Antibiotics (Basel), 2020-05, Vol.9 (5), p.272 |
issn | 2079-6382 2079-6382 |
language | eng |
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source | Publicly Available Content Database; PubMed |
subjects | Adhesion tests Agar Antibacterial activity Antibiotic resistance Antibiotics Antimicrobial agents Bacteria Bacterial infections biofilm Biofilms Carbapenemase Diffusion E coli ESBL Essential oils Eucalyptus Gram-negative bacteria Klebsiella Klebsiella pneumoniae KPC Low concentrations MBL Metabolites Metallo-β-lactamase Metallography Microbiology Microorganisms Nosocomial infection Nosocomial infections Oils & fats Pathogens Polymerase chain reaction Polystyrene Polystyrene resins Pseudomonas aeruginosa Strains (organisms) β Lactamase |
title | In Vitro Activity of Essential Oils Against Planktonic and Biofilm Cells of Extended-Spectrum β-Lactamase (ESBL)/Carbapenamase-Producing Gram-Negative Bacteria Involved in Human Nosocomial Infections |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T11%3A17%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20Vitro%20Activity%20of%20Essential%20Oils%20Against%20Planktonic%20and%20Biofilm%20Cells%20of%20Extended-Spectrum%20%CE%B2-Lactamase%20(ESBL)/Carbapenamase-Producing%20Gram-Negative%20Bacteria%20Involved%20in%20Human%20Nosocomial%20Infections&rft.jtitle=Antibiotics%20(Basel)&rft.au=Iseppi,%20Ramona&rft.date=2020-05-25&rft.volume=9&rft.issue=5&rft.spage=272&rft.pages=272-&rft.issn=2079-6382&rft.eissn=2079-6382&rft_id=info:doi/10.3390/antibiotics9050272&rft_dat=%3Cproquest_doaj_%3E2408200784%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c496t-b4c22ea54e8614561e7966652cba221d369c15344157450c0a77752b0b0bf9b23%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2407687887&rft_id=info:pmid/32466117&rfr_iscdi=true |