Loading…
Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model
Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD). Periodontal disease was induced thr...
Saved in:
Published in: | Journal of photochemistry and photobiology. B, Biology Biology, 2017-02, Vol.167, p.208-215 |
---|---|
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-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863 |
---|---|
cites | cdi_FETCH-LOGICAL-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863 |
container_end_page | 215 |
container_issue | |
container_start_page | 208 |
container_title | Journal of photochemistry and photobiology. B, Biology |
container_volume | 167 |
creator | de Moraes, Maiara Vasconcelos, Roseane Carvalho Longo, João Paulo Figueiró Muehlmann, Luis Alexandre de Azevedo, Ricardo Bentes de Araújo Júnior, Raimundo Fernandes Araujo, Aurigena Antunes de Lisboa Lopes Costa, Antonio |
description | Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD).
Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA).
Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone.
It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction.
•We evaluated the delivery of the nanoemulsion of chloro-aluminum phthalocyanine with light in inflamed gingival tissue of rats.•We suggest decreased inflammatory response in animals specimens subjected to photodynamic therapy (PDT).•PDT mediated by the nanoemulsion can produce a tissue response, in this case with reduced levels of TNF-α.•The therapy causes tissue destruction in gingival tissues of rats. |
doi_str_mv | 10.1016/j.jphotobiol.2016.12.031 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1861524199</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1011134415302268</els_id><sourcerecordid>1937412904</sourcerecordid><originalsourceid>FETCH-LOGICAL-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863</originalsourceid><addsrcrecordid>eNqFkU-P1iAQxhujcdfVr2BI9uKllaEtbzm6G_8lm-hBz4TC1NJQqNAa-xX81FLfVRMvcoGZ_OaZYZ6iIEAroMBfTtW0jGENvQ2uYjlTAatoDQ-KS-hOdcl4xx7mNwUooW6ai-JJShPNp-Wnx8UF62jHgcFl8ePjoWN2r2aryTpiVMtOtmT9F6JHF2Ioldtm67eZLOM6Khf0rrz1SAzqiCphItYPTs2zWkPcScS0BJ8wZ4nyBL8vGO2MflWORLWSIwwm_IqNTYcCmYNB97R4NCiX8Nn9fVV8fvP60-278u7D2_e3r-5K3VC2lj22SouODaIXgirVnmgHQKlpeGM0b0ULHAXvDfZdA6gVitNQD4OuB6Z5x-ur4sVZd4nh64ZplbNNGp1THsOWJOTVtKwBITJ6_Q86hS36PJ0EUZ8aYII2merOlI4hpYiDXPKPVdwlUHn4JSf51y95-CWByexXLn1-32DrZzR_Cn8blIGbM4B5I98sRpm0Ra_R2Ih6lSbY_3f5CawDsDM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1937412904</pqid></control><display><type>article</type><title>Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model</title><source>Elsevier</source><creator>de Moraes, Maiara ; Vasconcelos, Roseane Carvalho ; Longo, João Paulo Figueiró ; Muehlmann, Luis Alexandre ; de Azevedo, Ricardo Bentes ; de Araújo Júnior, Raimundo Fernandes ; Araujo, Aurigena Antunes ; de Lisboa Lopes Costa, Antonio</creator><creatorcontrib>de Moraes, Maiara ; Vasconcelos, Roseane Carvalho ; Longo, João Paulo Figueiró ; Muehlmann, Luis Alexandre ; de Azevedo, Ricardo Bentes ; de Araújo Júnior, Raimundo Fernandes ; Araujo, Aurigena Antunes ; de Lisboa Lopes Costa, Antonio</creatorcontrib><description>Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD).
Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA).
Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone.
It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction.
•We evaluated the delivery of the nanoemulsion of chloro-aluminum phthalocyanine with light in inflamed gingival tissue of rats.•We suggest decreased inflammatory response in animals specimens subjected to photodynamic therapy (PDT).•PDT mediated by the nanoemulsion can produce a tissue response, in this case with reduced levels of TNF-α.•The therapy causes tissue destruction in gingival tissues of rats.</description><identifier>ISSN: 1011-1344</identifier><identifier>EISSN: 1873-2682</identifier><identifier>DOI: 10.1016/j.jphotobiol.2016.12.031</identifier><identifier>PMID: 28086121</identifier><language>eng</language><publisher>Switzerland: Elsevier B.V</publisher><subject>Aluminum ; Animals ; Cotton ; Cytokines ; Disease Models, Animal ; Emulsions ; Enzyme-linked immunosorbent assay ; Experiments ; Female ; Gingiva ; Immunomodulation ; Indoles - therapeutic use ; Inflammation ; Inflammatory response ; Interleukin 10 ; Levels ; Mandible ; Mice ; Molars ; Nanoemulsions ; Organometallic Compounds - therapeutic use ; Periodontal disease ; Periodontics ; Periodontitis - drug therapy ; Periodontitis - pathology ; Periodontitis - prevention & control ; Photobiology ; Photochemotherapy ; Photodynamic therapy ; Photosensitizing agents ; Photosensitizing Agents - therapeutic use ; Rats ; Rats, Wistar ; Rodents ; Teeth ; Tissues ; Tumor necrosis factor</subject><ispartof>Journal of photochemistry and photobiology. B, Biology, 2017-02, Vol.167, p.208-215</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Feb 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863</citedby><cites>FETCH-LOGICAL-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28086121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Moraes, Maiara</creatorcontrib><creatorcontrib>Vasconcelos, Roseane Carvalho</creatorcontrib><creatorcontrib>Longo, João Paulo Figueiró</creatorcontrib><creatorcontrib>Muehlmann, Luis Alexandre</creatorcontrib><creatorcontrib>de Azevedo, Ricardo Bentes</creatorcontrib><creatorcontrib>de Araújo Júnior, Raimundo Fernandes</creatorcontrib><creatorcontrib>Araujo, Aurigena Antunes</creatorcontrib><creatorcontrib>de Lisboa Lopes Costa, Antonio</creatorcontrib><title>Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model</title><title>Journal of photochemistry and photobiology. B, Biology</title><addtitle>J Photochem Photobiol B</addtitle><description>Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD).
Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA).
Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone.
It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction.
•We evaluated the delivery of the nanoemulsion of chloro-aluminum phthalocyanine with light in inflamed gingival tissue of rats.•We suggest decreased inflammatory response in animals specimens subjected to photodynamic therapy (PDT).•PDT mediated by the nanoemulsion can produce a tissue response, in this case with reduced levels of TNF-α.•The therapy causes tissue destruction in gingival tissues of rats.</description><subject>Aluminum</subject><subject>Animals</subject><subject>Cotton</subject><subject>Cytokines</subject><subject>Disease Models, Animal</subject><subject>Emulsions</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Experiments</subject><subject>Female</subject><subject>Gingiva</subject><subject>Immunomodulation</subject><subject>Indoles - therapeutic use</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Interleukin 10</subject><subject>Levels</subject><subject>Mandible</subject><subject>Mice</subject><subject>Molars</subject><subject>Nanoemulsions</subject><subject>Organometallic Compounds - therapeutic use</subject><subject>Periodontal disease</subject><subject>Periodontics</subject><subject>Periodontitis - drug therapy</subject><subject>Periodontitis - pathology</subject><subject>Periodontitis - prevention & control</subject><subject>Photobiology</subject><subject>Photochemotherapy</subject><subject>Photodynamic therapy</subject><subject>Photosensitizing agents</subject><subject>Photosensitizing Agents - therapeutic use</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>Teeth</subject><subject>Tissues</subject><subject>Tumor necrosis factor</subject><issn>1011-1344</issn><issn>1873-2682</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFkU-P1iAQxhujcdfVr2BI9uKllaEtbzm6G_8lm-hBz4TC1NJQqNAa-xX81FLfVRMvcoGZ_OaZYZ6iIEAroMBfTtW0jGENvQ2uYjlTAatoDQ-KS-hOdcl4xx7mNwUooW6ai-JJShPNp-Wnx8UF62jHgcFl8ePjoWN2r2aryTpiVMtOtmT9F6JHF2Ioldtm67eZLOM6Khf0rrz1SAzqiCphItYPTs2zWkPcScS0BJ8wZ4nyBL8vGO2MflWORLWSIwwm_IqNTYcCmYNB97R4NCiX8Nn9fVV8fvP60-278u7D2_e3r-5K3VC2lj22SouODaIXgirVnmgHQKlpeGM0b0ULHAXvDfZdA6gVitNQD4OuB6Z5x-ur4sVZd4nh64ZplbNNGp1THsOWJOTVtKwBITJ6_Q86hS36PJ0EUZ8aYII2merOlI4hpYiDXPKPVdwlUHn4JSf51y95-CWByexXLn1-32DrZzR_Cn8blIGbM4B5I98sRpm0Ra_R2Ih6lSbY_3f5CawDsDM</recordid><startdate>201702</startdate><enddate>201702</enddate><creator>de Moraes, Maiara</creator><creator>Vasconcelos, Roseane Carvalho</creator><creator>Longo, João Paulo Figueiró</creator><creator>Muehlmann, Luis Alexandre</creator><creator>de Azevedo, Ricardo Bentes</creator><creator>de Araújo Júnior, Raimundo Fernandes</creator><creator>Araujo, Aurigena Antunes</creator><creator>de Lisboa Lopes Costa, Antonio</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QP</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>201702</creationdate><title>Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model</title><author>de Moraes, Maiara ; Vasconcelos, Roseane Carvalho ; Longo, João Paulo Figueiró ; Muehlmann, Luis Alexandre ; de Azevedo, Ricardo Bentes ; de Araújo Júnior, Raimundo Fernandes ; Araujo, Aurigena Antunes ; de Lisboa Lopes Costa, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aluminum</topic><topic>Animals</topic><topic>Cotton</topic><topic>Cytokines</topic><topic>Disease Models, Animal</topic><topic>Emulsions</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Experiments</topic><topic>Female</topic><topic>Gingiva</topic><topic>Immunomodulation</topic><topic>Indoles - therapeutic use</topic><topic>Inflammation</topic><topic>Inflammatory response</topic><topic>Interleukin 10</topic><topic>Levels</topic><topic>Mandible</topic><topic>Mice</topic><topic>Molars</topic><topic>Nanoemulsions</topic><topic>Organometallic Compounds - therapeutic use</topic><topic>Periodontal disease</topic><topic>Periodontics</topic><topic>Periodontitis - drug therapy</topic><topic>Periodontitis - pathology</topic><topic>Periodontitis - prevention & control</topic><topic>Photobiology</topic><topic>Photochemotherapy</topic><topic>Photodynamic therapy</topic><topic>Photosensitizing agents</topic><topic>Photosensitizing Agents - therapeutic use</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Teeth</topic><topic>Tissues</topic><topic>Tumor necrosis factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Moraes, Maiara</creatorcontrib><creatorcontrib>Vasconcelos, Roseane Carvalho</creatorcontrib><creatorcontrib>Longo, João Paulo Figueiró</creatorcontrib><creatorcontrib>Muehlmann, Luis Alexandre</creatorcontrib><creatorcontrib>de Azevedo, Ricardo Bentes</creatorcontrib><creatorcontrib>de Araújo Júnior, Raimundo Fernandes</creatorcontrib><creatorcontrib>Araujo, Aurigena Antunes</creatorcontrib><creatorcontrib>de Lisboa Lopes Costa, Antonio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of photochemistry and photobiology. B, Biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Moraes, Maiara</au><au>Vasconcelos, Roseane Carvalho</au><au>Longo, João Paulo Figueiró</au><au>Muehlmann, Luis Alexandre</au><au>de Azevedo, Ricardo Bentes</au><au>de Araújo Júnior, Raimundo Fernandes</au><au>Araujo, Aurigena Antunes</au><au>de Lisboa Lopes Costa, Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model</atitle><jtitle>Journal of photochemistry and photobiology. B, Biology</jtitle><addtitle>J Photochem Photobiol B</addtitle><date>2017-02</date><risdate>2017</risdate><volume>167</volume><spage>208</spage><epage>215</epage><pages>208-215</pages><issn>1011-1344</issn><eissn>1873-2682</eissn><abstract>Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD).
Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA).
Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone.
It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction.
•We evaluated the delivery of the nanoemulsion of chloro-aluminum phthalocyanine with light in inflamed gingival tissue of rats.•We suggest decreased inflammatory response in animals specimens subjected to photodynamic therapy (PDT).•PDT mediated by the nanoemulsion can produce a tissue response, in this case with reduced levels of TNF-α.•The therapy causes tissue destruction in gingival tissues of rats.</abstract><cop>Switzerland</cop><pub>Elsevier B.V</pub><pmid>28086121</pmid><doi>10.1016/j.jphotobiol.2016.12.031</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1011-1344 |
ispartof | Journal of photochemistry and photobiology. B, Biology, 2017-02, Vol.167, p.208-215 |
issn | 1011-1344 1873-2682 |
language | eng |
recordid | cdi_proquest_miscellaneous_1861524199 |
source | Elsevier |
subjects | Aluminum Animals Cotton Cytokines Disease Models, Animal Emulsions Enzyme-linked immunosorbent assay Experiments Female Gingiva Immunomodulation Indoles - therapeutic use Inflammation Inflammatory response Interleukin 10 Levels Mandible Mice Molars Nanoemulsions Organometallic Compounds - therapeutic use Periodontal disease Periodontics Periodontitis - drug therapy Periodontitis - pathology Periodontitis - prevention & control Photobiology Photochemotherapy Photodynamic therapy Photosensitizing agents Photosensitizing Agents - therapeutic use Rats Rats, Wistar Rodents Teeth Tissues Tumor necrosis factor |
title | Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T20%3A35%3A25IST&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=Photodynamic%20therapy%20using%20chloro-aluminum%20phthalocyanine%20decreases%20inflammatory%20response%20in%20an%20experimental%20rat%20periodontal%20disease%20model&rft.jtitle=Journal%20of%20photochemistry%20and%20photobiology.%20B,%20Biology&rft.au=de%20Moraes,%20Maiara&rft.date=2017-02&rft.volume=167&rft.spage=208&rft.epage=215&rft.pages=208-215&rft.issn=1011-1344&rft.eissn=1873-2682&rft_id=info:doi/10.1016/j.jphotobiol.2016.12.031&rft_dat=%3Cproquest_cross%3E1937412904%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c402t-be5ac982f9b990aa57081100d464dc659516e96bdeb841ecae97f3ffc3f2c6863%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1937412904&rft_id=info:pmid/28086121&rfr_iscdi=true |