Loading…
Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients
Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as ‘Th3 cells’...
Saved in:
Published in: | Microbial pathogenesis 2014-02, Vol.67-68, p.1-7 |
---|---|
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-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3 |
---|---|
cites | cdi_FETCH-LOGICAL-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3 |
container_end_page | 7 |
container_issue | |
container_start_page | 1 |
container_title | Microbial pathogenesis |
container_volume | 67-68 |
creator | Rahimian, Ghorbanali Sanei, Mohammad Hosein Shirzad, Hedayatollah Azadegan-Dehkordi, Fatemeh Taghikhani, Afshin Salimzadeh, Loghman Hashemzadeh-Chaleshtori, Morteza Rafieian-Kopaei, Mahmoud Bagheri, Nader |
description | Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as ‘Th3 cells’. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors.
Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR.
TGF-β1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1.
TGF-β1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA.
•TGF-β1 mRNA expression is increased in biopsies of H. pylori-infected patients.•An association exists between H. pylori virulence factors and TGF-β1 mRNA expression.•TGF-β1 mRNA expression in mucosa is higher in patients with vacA s1 and s1m1.•TGF-β1 may play a role in the inflammatory response in gastritis. |
doi_str_mv | 10.1016/j.micpath.2013.12.006 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1510400178</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0882401014000035</els_id><sourcerecordid>1510400178</sourcerecordid><originalsourceid>FETCH-LOGICAL-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3</originalsourceid><addsrcrecordid>eNqFkEuO1DAQhi0EYnoeRwB5ySahynHSzgq1RvOSRiChga3lOBVwk8TBTkb0gktxEM6EW93MdlYlub6_yvUx9gYhR8Dq_TYfnJ3M_D0XgEWOIgeoXrAVQl1lKEC9ZCtQSmQSEE7YaYxbAKhlUb9mJ0LKSqTGiv3-6sLS02iJd8bOPkTuO35LvbO-SQ8U-LTrfXD80dgNd6MNZCLxwYQf1PY7_s3EOTjLh8X6aHr-cHOd_f2DfPj8ccPp1xQoRufHlDyis4s8_dvROMdz9qozfaSLYz1jX66vHi5vs_tPN3eXm_vMFrKas64AJbG10qJSCtsSrTRK2mZdIhWqajqqi6ZuKtOYskgNCaUQ0rRGrcsCm-KMvTvMnYL_uVCc9eCipb43I_klaiwRJACuVULLA2qDjzFQp6fg0rU7jaD35vVWH83rvXmNQifzKff2uGJpBmqfUv9VJ-DDAaB06KOjoKN1e_GtC2Rn3Xr3zIp_3MeZWQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1510400178</pqid></control><display><type>article</type><title>Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Rahimian, Ghorbanali ; Sanei, Mohammad Hosein ; Shirzad, Hedayatollah ; Azadegan-Dehkordi, Fatemeh ; Taghikhani, Afshin ; Salimzadeh, Loghman ; Hashemzadeh-Chaleshtori, Morteza ; Rafieian-Kopaei, Mahmoud ; Bagheri, Nader</creator><creatorcontrib>Rahimian, Ghorbanali ; Sanei, Mohammad Hosein ; Shirzad, Hedayatollah ; Azadegan-Dehkordi, Fatemeh ; Taghikhani, Afshin ; Salimzadeh, Loghman ; Hashemzadeh-Chaleshtori, Morteza ; Rafieian-Kopaei, Mahmoud ; Bagheri, Nader</creatorcontrib><description>Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as ‘Th3 cells’. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors.
Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR.
TGF-β1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1.
TGF-β1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA.
•TGF-β1 mRNA expression is increased in biopsies of H. pylori-infected patients.•An association exists between H. pylori virulence factors and TGF-β1 mRNA expression.•TGF-β1 mRNA expression in mucosa is higher in patients with vacA s1 and s1m1.•TGF-β1 may play a role in the inflammatory response in gastritis.</description><identifier>ISSN: 0882-4010</identifier><identifier>EISSN: 1096-1208</identifier><identifier>DOI: 10.1016/j.micpath.2013.12.006</identifier><identifier>PMID: 24462401</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adult ; Bacterial Proteins - metabolism ; Female ; Gastric Mucosa - metabolism ; Gastric Mucosa - microbiology ; Gastritis ; Gastritis - genetics ; Gastritis - metabolism ; Gastritis - microbiology ; Helicobacter Infections - genetics ; Helicobacter Infections - metabolism ; Helicobacter Infections - microbiology ; Helicobacter pylori ; Helicobacter pylori - genetics ; Helicobacter pylori - metabolism ; Helicobacter pylori - pathogenicity ; Humans ; Male ; Middle Aged ; Retrospective Studies ; TGF-β1 ; Transforming Growth Factor beta1 - genetics ; Transforming Growth Factor beta1 - metabolism ; Virulence factors ; Virulence Factors - genetics ; Virulence Factors - metabolism ; Young Adult</subject><ispartof>Microbial pathogenesis, 2014-02, Vol.67-68, p.1-7</ispartof><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3</citedby><cites>FETCH-LOGICAL-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24462401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rahimian, Ghorbanali</creatorcontrib><creatorcontrib>Sanei, Mohammad Hosein</creatorcontrib><creatorcontrib>Shirzad, Hedayatollah</creatorcontrib><creatorcontrib>Azadegan-Dehkordi, Fatemeh</creatorcontrib><creatorcontrib>Taghikhani, Afshin</creatorcontrib><creatorcontrib>Salimzadeh, Loghman</creatorcontrib><creatorcontrib>Hashemzadeh-Chaleshtori, Morteza</creatorcontrib><creatorcontrib>Rafieian-Kopaei, Mahmoud</creatorcontrib><creatorcontrib>Bagheri, Nader</creatorcontrib><title>Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients</title><title>Microbial pathogenesis</title><addtitle>Microb Pathog</addtitle><description>Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as ‘Th3 cells’. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors.
Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR.
TGF-β1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1.
TGF-β1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA.
•TGF-β1 mRNA expression is increased in biopsies of H. pylori-infected patients.•An association exists between H. pylori virulence factors and TGF-β1 mRNA expression.•TGF-β1 mRNA expression in mucosa is higher in patients with vacA s1 and s1m1.•TGF-β1 may play a role in the inflammatory response in gastritis.</description><subject>Adult</subject><subject>Bacterial Proteins - metabolism</subject><subject>Female</subject><subject>Gastric Mucosa - metabolism</subject><subject>Gastric Mucosa - microbiology</subject><subject>Gastritis</subject><subject>Gastritis - genetics</subject><subject>Gastritis - metabolism</subject><subject>Gastritis - microbiology</subject><subject>Helicobacter Infections - genetics</subject><subject>Helicobacter Infections - metabolism</subject><subject>Helicobacter Infections - microbiology</subject><subject>Helicobacter pylori</subject><subject>Helicobacter pylori - genetics</subject><subject>Helicobacter pylori - metabolism</subject><subject>Helicobacter pylori - pathogenicity</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>TGF-β1</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Virulence factors</subject><subject>Virulence Factors - genetics</subject><subject>Virulence Factors - metabolism</subject><subject>Young Adult</subject><issn>0882-4010</issn><issn>1096-1208</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqFkEuO1DAQhi0EYnoeRwB5ySahynHSzgq1RvOSRiChga3lOBVwk8TBTkb0gktxEM6EW93MdlYlub6_yvUx9gYhR8Dq_TYfnJ3M_D0XgEWOIgeoXrAVQl1lKEC9ZCtQSmQSEE7YaYxbAKhlUb9mJ0LKSqTGiv3-6sLS02iJd8bOPkTuO35LvbO-SQ8U-LTrfXD80dgNd6MNZCLxwYQf1PY7_s3EOTjLh8X6aHr-cHOd_f2DfPj8ccPp1xQoRufHlDyis4s8_dvROMdz9qozfaSLYz1jX66vHi5vs_tPN3eXm_vMFrKas64AJbG10qJSCtsSrTRK2mZdIhWqajqqi6ZuKtOYskgNCaUQ0rRGrcsCm-KMvTvMnYL_uVCc9eCipb43I_klaiwRJACuVULLA2qDjzFQp6fg0rU7jaD35vVWH83rvXmNQifzKff2uGJpBmqfUv9VJ-DDAaB06KOjoKN1e_GtC2Rn3Xr3zIp_3MeZWQ</recordid><startdate>201402</startdate><enddate>201402</enddate><creator>Rahimian, Ghorbanali</creator><creator>Sanei, Mohammad Hosein</creator><creator>Shirzad, Hedayatollah</creator><creator>Azadegan-Dehkordi, Fatemeh</creator><creator>Taghikhani, Afshin</creator><creator>Salimzadeh, Loghman</creator><creator>Hashemzadeh-Chaleshtori, Morteza</creator><creator>Rafieian-Kopaei, Mahmoud</creator><creator>Bagheri, Nader</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>201402</creationdate><title>Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients</title><author>Rahimian, Ghorbanali ; Sanei, Mohammad Hosein ; Shirzad, Hedayatollah ; Azadegan-Dehkordi, Fatemeh ; Taghikhani, Afshin ; Salimzadeh, Loghman ; Hashemzadeh-Chaleshtori, Morteza ; Rafieian-Kopaei, Mahmoud ; Bagheri, Nader</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Bacterial Proteins - metabolism</topic><topic>Female</topic><topic>Gastric Mucosa - metabolism</topic><topic>Gastric Mucosa - microbiology</topic><topic>Gastritis</topic><topic>Gastritis - genetics</topic><topic>Gastritis - metabolism</topic><topic>Gastritis - microbiology</topic><topic>Helicobacter Infections - genetics</topic><topic>Helicobacter Infections - metabolism</topic><topic>Helicobacter Infections - microbiology</topic><topic>Helicobacter pylori</topic><topic>Helicobacter pylori - genetics</topic><topic>Helicobacter pylori - metabolism</topic><topic>Helicobacter pylori - pathogenicity</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Retrospective Studies</topic><topic>TGF-β1</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Virulence factors</topic><topic>Virulence Factors - genetics</topic><topic>Virulence Factors - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rahimian, Ghorbanali</creatorcontrib><creatorcontrib>Sanei, Mohammad Hosein</creatorcontrib><creatorcontrib>Shirzad, Hedayatollah</creatorcontrib><creatorcontrib>Azadegan-Dehkordi, Fatemeh</creatorcontrib><creatorcontrib>Taghikhani, Afshin</creatorcontrib><creatorcontrib>Salimzadeh, Loghman</creatorcontrib><creatorcontrib>Hashemzadeh-Chaleshtori, Morteza</creatorcontrib><creatorcontrib>Rafieian-Kopaei, Mahmoud</creatorcontrib><creatorcontrib>Bagheri, Nader</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Microbial pathogenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rahimian, Ghorbanali</au><au>Sanei, Mohammad Hosein</au><au>Shirzad, Hedayatollah</au><au>Azadegan-Dehkordi, Fatemeh</au><au>Taghikhani, Afshin</au><au>Salimzadeh, Loghman</au><au>Hashemzadeh-Chaleshtori, Morteza</au><au>Rafieian-Kopaei, Mahmoud</au><au>Bagheri, Nader</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients</atitle><jtitle>Microbial pathogenesis</jtitle><addtitle>Microb Pathog</addtitle><date>2014-02</date><risdate>2014</risdate><volume>67-68</volume><spage>1</spage><epage>7</epage><pages>1-7</pages><issn>0882-4010</issn><eissn>1096-1208</eissn><abstract>Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as ‘Th3 cells’. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors.
Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR.
TGF-β1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1.
TGF-β1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA.
•TGF-β1 mRNA expression is increased in biopsies of H. pylori-infected patients.•An association exists between H. pylori virulence factors and TGF-β1 mRNA expression.•TGF-β1 mRNA expression in mucosa is higher in patients with vacA s1 and s1m1.•TGF-β1 may play a role in the inflammatory response in gastritis.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>24462401</pmid><doi>10.1016/j.micpath.2013.12.006</doi><tpages>7</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0882-4010 |
ispartof | Microbial pathogenesis, 2014-02, Vol.67-68, p.1-7 |
issn | 0882-4010 1096-1208 |
language | eng |
recordid | cdi_proquest_miscellaneous_1510400178 |
source | ScienceDirect Freedom Collection 2022-2024 |
subjects | Adult Bacterial Proteins - metabolism Female Gastric Mucosa - metabolism Gastric Mucosa - microbiology Gastritis Gastritis - genetics Gastritis - metabolism Gastritis - microbiology Helicobacter Infections - genetics Helicobacter Infections - metabolism Helicobacter Infections - microbiology Helicobacter pylori Helicobacter pylori - genetics Helicobacter pylori - metabolism Helicobacter pylori - pathogenicity Humans Male Middle Aged Retrospective Studies TGF-β1 Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - metabolism Virulence factors Virulence Factors - genetics Virulence Factors - metabolism Young Adult |
title | Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T00%3A33%3A44IST&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=Virulence%20factors%20of%20Helicobacter%20pylori%20vacA%20increase%20markedly%20gastric%20mucosal%20TGF-%CE%B21%20mRNA%20expression%20in%20gastritis%20patients&rft.jtitle=Microbial%20pathogenesis&rft.au=Rahimian,%20Ghorbanali&rft.date=2014-02&rft.volume=67-68&rft.spage=1&rft.epage=7&rft.pages=1-7&rft.issn=0882-4010&rft.eissn=1096-1208&rft_id=info:doi/10.1016/j.micpath.2013.12.006&rft_dat=%3Cproquest_cross%3E1510400178%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c346t-f30841dc4c18881d51c4a84cb751e386bfe93b9b6aba5384c405224ada87531b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1510400178&rft_id=info:pmid/24462401&rfr_iscdi=true |