TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin
Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications—the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mech...
Gespeichert in:
Veröffentlicht in: | Journal of dental research 2017-07, Vol.96 (7), p.832-839 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 839 |
---|---|
container_issue | 7 |
container_start_page | 832 |
container_title | Journal of dental research |
container_volume | 96 |
creator | López-González, M.J. Luis, E. Fajardo, O. Meseguer, V. Gers-Barlag, K. Niñerola, S. Viana, F. |
description | Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications—the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue. Cultured HGFs responded with intracellular calcium elevations to phenytoin and to the canonical TRPA1 agonist allyl isothiocyanate. Application of phenytoin activated a nonselective cationic current in HGFs with a typical signature for TRPA1 channels. Moreover, this activation was blocked by HC030031, a specific TRPA1 blocker. Similarly, the use of shRNAs against hTRPA1 in HGFs reduced TRPA1 expression and activation by phenytoin. In addition, we show that phenytoin increased intracellular calcium levels in cells transfected with mouse or human TRPA1 channels. Responses to phenytoin were not observed in untransfected cells or cells expressing TRPM8 or TRPV1. The activation of HGFs by phenytoin was markedly reduced in the presence of antioxidant vitamins: ascorbic acid, folic acid, and α-tocopherol. By performing cell proliferation assays, we found that phenytoin did not augment the proliferation rate of HGFs. In contrast, alcian blue and picrosirius red staining of long-term HGFs cultures indicated that phenytoin induces extracellular matrix accumulation of collagen. Collectively, these findings support an important role of TRPA1 channels in phenytoin-induced GE, provide insight into the pathophysiologic mechanism, and offer novel therapeutic opportunities for its treatment. |
doi_str_mv | 10.1177/0022034517695518 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1905739748</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0022034517695518</sage_id><sourcerecordid>2300626379</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-e730e1884d01a0ff1c47667518574db04621b6017a78ad220f707c4a37c47e863</originalsourceid><addsrcrecordid>eNp1kM1Lw0AQxRdRbK3ePUnAi5fozH4mx1JsKyiWUs9hk2zalHRTs4nQ_94trQoFLzOH-c2bN4-QW4RHRKWeACgFxgUqGQuB0Rnpo-A8BBHjOenvx-F-3iNXzq0BMKYRuyQ9GgmFgso-GS_msyEGo5W21lQueDN5qVsTTLuNtsGktMvyS1fBuEybOq20a4O5cdvaOhO0dTBbGbtr69Jek4tCV87cHPuAfIyfF6Np-Po-eRkNX8OMSdGGRjEwGEU8B9RQFJhxJaXyzoXieQpcUkwloNIq0rn_rVCgMq6ZL8pEkg3Iw0F329SfnXFtsildZqpKW1N3LsEYhGKx4pFH70_Qdd011rtLKAOQVDIVewoOVNbUzjWmSLZNudHNLkFI9hknpxn7lbujcJduTP678BOqB8ID4PTS_F39V_Abs-B_3Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2300626379</pqid></control><display><type>article</type><title>TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin</title><source>MEDLINE</source><source>SAGE Complete A-Z List</source><source>Alma/SFX Local Collection</source><creator>López-González, M.J. ; Luis, E. ; Fajardo, O. ; Meseguer, V. ; Gers-Barlag, K. ; Niñerola, S. ; Viana, F.</creator><creatorcontrib>López-González, M.J. ; Luis, E. ; Fajardo, O. ; Meseguer, V. ; Gers-Barlag, K. ; Niñerola, S. ; Viana, F.</creatorcontrib><description>Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications—the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue. Cultured HGFs responded with intracellular calcium elevations to phenytoin and to the canonical TRPA1 agonist allyl isothiocyanate. Application of phenytoin activated a nonselective cationic current in HGFs with a typical signature for TRPA1 channels. Moreover, this activation was blocked by HC030031, a specific TRPA1 blocker. Similarly, the use of shRNAs against hTRPA1 in HGFs reduced TRPA1 expression and activation by phenytoin. In addition, we show that phenytoin increased intracellular calcium levels in cells transfected with mouse or human TRPA1 channels. Responses to phenytoin were not observed in untransfected cells or cells expressing TRPM8 or TRPV1. The activation of HGFs by phenytoin was markedly reduced in the presence of antioxidant vitamins: ascorbic acid, folic acid, and α-tocopherol. By performing cell proliferation assays, we found that phenytoin did not augment the proliferation rate of HGFs. In contrast, alcian blue and picrosirius red staining of long-term HGFs cultures indicated that phenytoin induces extracellular matrix accumulation of collagen. Collectively, these findings support an important role of TRPA1 channels in phenytoin-induced GE, provide insight into the pathophysiologic mechanism, and offer novel therapeutic opportunities for its treatment.</description><identifier>ISSN: 0022-0345</identifier><identifier>EISSN: 1544-0591</identifier><identifier>DOI: 10.1177/0022034517695518</identifier><identifier>PMID: 28571526</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Acetanilides - pharmacology ; Allyl isothiocyanate ; Animals ; Anticonvulsants ; Anticonvulsants - adverse effects ; Antihypertensives ; Antioxidants ; Antioxidants - pharmacology ; Ascorbic acid ; Blotting, Western ; Calcium (intracellular) ; Calcium channels ; Calcium Channels - metabolism ; Calcium permeability ; Capsaicin ; Capsaicin receptors ; Cell Line ; Cell proliferation ; Collagen ; Dentistry ; Experiments ; Extracellular matrix ; Fibroblasts ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Folic acid ; Gingiva ; Gingiva - cytology ; Gingival Overgrowth - chemically induced ; Humans ; Hypotheses ; Intracellular ; Isothiocyanate ; Laboratories ; Molecular modelling ; Nerve Tissue Proteins - metabolism ; Oral hygiene ; Oxidative stress ; Patch-Clamp Techniques ; Penicillin ; Phenytoin ; Phenytoin - adverse effects ; Polymerase chain reaction ; Purines - pharmacology ; Real-Time Polymerase Chain Reaction ; Reverse transcription ; Staining and Labeling ; Transient Receptor Potential Channels - metabolism ; Transient receptor potential proteins ; TRPA1 Cation Channel ; TRPV Cation Channels - metabolism ; Vitamin E ; Vitamins</subject><ispartof>Journal of dental research, 2017-07, Vol.96 (7), p.832-839</ispartof><rights>International & American Associations for Dental Research 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-e730e1884d01a0ff1c47667518574db04621b6017a78ad220f707c4a37c47e863</citedby><cites>FETCH-LOGICAL-c365t-e730e1884d01a0ff1c47667518574db04621b6017a78ad220f707c4a37c47e863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0022034517695518$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0022034517695518$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28571526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>López-González, M.J.</creatorcontrib><creatorcontrib>Luis, E.</creatorcontrib><creatorcontrib>Fajardo, O.</creatorcontrib><creatorcontrib>Meseguer, V.</creatorcontrib><creatorcontrib>Gers-Barlag, K.</creatorcontrib><creatorcontrib>Niñerola, S.</creatorcontrib><creatorcontrib>Viana, F.</creatorcontrib><title>TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin</title><title>Journal of dental research</title><addtitle>J Dent Res</addtitle><description>Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications—the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue. Cultured HGFs responded with intracellular calcium elevations to phenytoin and to the canonical TRPA1 agonist allyl isothiocyanate. Application of phenytoin activated a nonselective cationic current in HGFs with a typical signature for TRPA1 channels. Moreover, this activation was blocked by HC030031, a specific TRPA1 blocker. Similarly, the use of shRNAs against hTRPA1 in HGFs reduced TRPA1 expression and activation by phenytoin. In addition, we show that phenytoin increased intracellular calcium levels in cells transfected with mouse or human TRPA1 channels. Responses to phenytoin were not observed in untransfected cells or cells expressing TRPM8 or TRPV1. The activation of HGFs by phenytoin was markedly reduced in the presence of antioxidant vitamins: ascorbic acid, folic acid, and α-tocopherol. By performing cell proliferation assays, we found that phenytoin did not augment the proliferation rate of HGFs. In contrast, alcian blue and picrosirius red staining of long-term HGFs cultures indicated that phenytoin induces extracellular matrix accumulation of collagen. Collectively, these findings support an important role of TRPA1 channels in phenytoin-induced GE, provide insight into the pathophysiologic mechanism, and offer novel therapeutic opportunities for its treatment.</description><subject>Acetanilides - pharmacology</subject><subject>Allyl isothiocyanate</subject><subject>Animals</subject><subject>Anticonvulsants</subject><subject>Anticonvulsants - adverse effects</subject><subject>Antihypertensives</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Ascorbic acid</subject><subject>Blotting, Western</subject><subject>Calcium (intracellular)</subject><subject>Calcium channels</subject><subject>Calcium Channels - metabolism</subject><subject>Calcium permeability</subject><subject>Capsaicin</subject><subject>Capsaicin receptors</subject><subject>Cell Line</subject><subject>Cell proliferation</subject><subject>Collagen</subject><subject>Dentistry</subject><subject>Experiments</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Folic acid</subject><subject>Gingiva</subject><subject>Gingiva - cytology</subject><subject>Gingival Overgrowth - chemically induced</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Intracellular</subject><subject>Isothiocyanate</subject><subject>Laboratories</subject><subject>Molecular modelling</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Oral hygiene</subject><subject>Oxidative stress</subject><subject>Patch-Clamp Techniques</subject><subject>Penicillin</subject><subject>Phenytoin</subject><subject>Phenytoin - adverse effects</subject><subject>Polymerase chain reaction</subject><subject>Purines - pharmacology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse transcription</subject><subject>Staining and Labeling</subject><subject>Transient Receptor Potential Channels - metabolism</subject><subject>Transient receptor potential proteins</subject><subject>TRPA1 Cation Channel</subject><subject>TRPV Cation Channels - metabolism</subject><subject>Vitamin E</subject><subject>Vitamins</subject><issn>0022-0345</issn><issn>1544-0591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1Lw0AQxRdRbK3ePUnAi5fozH4mx1JsKyiWUs9hk2zalHRTs4nQ_94trQoFLzOH-c2bN4-QW4RHRKWeACgFxgUqGQuB0Rnpo-A8BBHjOenvx-F-3iNXzq0BMKYRuyQ9GgmFgso-GS_msyEGo5W21lQueDN5qVsTTLuNtsGktMvyS1fBuEybOq20a4O5cdvaOhO0dTBbGbtr69Jek4tCV87cHPuAfIyfF6Np-Po-eRkNX8OMSdGGRjEwGEU8B9RQFJhxJaXyzoXieQpcUkwloNIq0rn_rVCgMq6ZL8pEkg3Iw0F329SfnXFtsildZqpKW1N3LsEYhGKx4pFH70_Qdd011rtLKAOQVDIVewoOVNbUzjWmSLZNudHNLkFI9hknpxn7lbujcJduTP678BOqB8ID4PTS_F39V_Abs-B_3Q</recordid><startdate>201707</startdate><enddate>201707</enddate><creator>López-González, M.J.</creator><creator>Luis, E.</creator><creator>Fajardo, O.</creator><creator>Meseguer, V.</creator><creator>Gers-Barlag, K.</creator><creator>Niñerola, S.</creator><creator>Viana, F.</creator><general>SAGE Publications</general><general>SAGE PUBLICATIONS, INC</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>201707</creationdate><title>TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin</title><author>López-González, M.J. ; Luis, E. ; Fajardo, O. ; Meseguer, V. ; Gers-Barlag, K. ; Niñerola, S. ; Viana, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-e730e1884d01a0ff1c47667518574db04621b6017a78ad220f707c4a37c47e863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetanilides - pharmacology</topic><topic>Allyl isothiocyanate</topic><topic>Animals</topic><topic>Anticonvulsants</topic><topic>Anticonvulsants - adverse effects</topic><topic>Antihypertensives</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>Ascorbic acid</topic><topic>Blotting, Western</topic><topic>Calcium (intracellular)</topic><topic>Calcium channels</topic><topic>Calcium Channels - metabolism</topic><topic>Calcium permeability</topic><topic>Capsaicin</topic><topic>Capsaicin receptors</topic><topic>Cell Line</topic><topic>Cell proliferation</topic><topic>Collagen</topic><topic>Dentistry</topic><topic>Experiments</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Folic acid</topic><topic>Gingiva</topic><topic>Gingiva - cytology</topic><topic>Gingival Overgrowth - chemically induced</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Intracellular</topic><topic>Isothiocyanate</topic><topic>Laboratories</topic><topic>Molecular modelling</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Oral hygiene</topic><topic>Oxidative stress</topic><topic>Patch-Clamp Techniques</topic><topic>Penicillin</topic><topic>Phenytoin</topic><topic>Phenytoin - adverse effects</topic><topic>Polymerase chain reaction</topic><topic>Purines - pharmacology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse transcription</topic><topic>Staining and Labeling</topic><topic>Transient Receptor Potential Channels - metabolism</topic><topic>Transient receptor potential proteins</topic><topic>TRPA1 Cation Channel</topic><topic>TRPV Cation Channels - metabolism</topic><topic>Vitamin E</topic><topic>Vitamins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>López-González, M.J.</creatorcontrib><creatorcontrib>Luis, E.</creatorcontrib><creatorcontrib>Fajardo, O.</creatorcontrib><creatorcontrib>Meseguer, V.</creatorcontrib><creatorcontrib>Gers-Barlag, K.</creatorcontrib><creatorcontrib>Niñerola, S.</creatorcontrib><creatorcontrib>Viana, F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of dental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>López-González, M.J.</au><au>Luis, E.</au><au>Fajardo, O.</au><au>Meseguer, V.</au><au>Gers-Barlag, K.</au><au>Niñerola, S.</au><au>Viana, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin</atitle><jtitle>Journal of dental research</jtitle><addtitle>J Dent Res</addtitle><date>2017-07</date><risdate>2017</risdate><volume>96</volume><issue>7</issue><spage>832</spage><epage>839</epage><pages>832-839</pages><issn>0022-0345</issn><eissn>1544-0591</eissn><abstract>Drug-induced gingival enlargement (GE) is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications—the antiepileptic phenytoin being the main drug associated with GE due to its high incidence (around 50%). The molecular mechanisms behind drug-induced gingival overgrowth are still unknown. By reverse transcription polymerase chain reaction, we demonstrate that the calcium-permeable ion channels TRPA1, TRPV1, and its capsaicin-insensitive isoform TRPV1b are expressed in human gingival fibroblasts (HGFs), the most abundant cellular type in periodontal tissue. Cultured HGFs responded with intracellular calcium elevations to phenytoin and to the canonical TRPA1 agonist allyl isothiocyanate. Application of phenytoin activated a nonselective cationic current in HGFs with a typical signature for TRPA1 channels. Moreover, this activation was blocked by HC030031, a specific TRPA1 blocker. Similarly, the use of shRNAs against hTRPA1 in HGFs reduced TRPA1 expression and activation by phenytoin. In addition, we show that phenytoin increased intracellular calcium levels in cells transfected with mouse or human TRPA1 channels. Responses to phenytoin were not observed in untransfected cells or cells expressing TRPM8 or TRPV1. The activation of HGFs by phenytoin was markedly reduced in the presence of antioxidant vitamins: ascorbic acid, folic acid, and α-tocopherol. By performing cell proliferation assays, we found that phenytoin did not augment the proliferation rate of HGFs. In contrast, alcian blue and picrosirius red staining of long-term HGFs cultures indicated that phenytoin induces extracellular matrix accumulation of collagen. Collectively, these findings support an important role of TRPA1 channels in phenytoin-induced GE, provide insight into the pathophysiologic mechanism, and offer novel therapeutic opportunities for its treatment.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>28571526</pmid><doi>10.1177/0022034517695518</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-0345 |
ispartof | Journal of dental research, 2017-07, Vol.96 (7), p.832-839 |
issn | 0022-0345 1544-0591 |
language | eng |
recordid | cdi_proquest_miscellaneous_1905739748 |
source | MEDLINE; SAGE Complete A-Z List; Alma/SFX Local Collection |
subjects | Acetanilides - pharmacology Allyl isothiocyanate Animals Anticonvulsants Anticonvulsants - adverse effects Antihypertensives Antioxidants Antioxidants - pharmacology Ascorbic acid Blotting, Western Calcium (intracellular) Calcium channels Calcium Channels - metabolism Calcium permeability Capsaicin Capsaicin receptors Cell Line Cell proliferation Collagen Dentistry Experiments Extracellular matrix Fibroblasts Fibroblasts - drug effects Fibroblasts - metabolism Folic acid Gingiva Gingiva - cytology Gingival Overgrowth - chemically induced Humans Hypotheses Intracellular Isothiocyanate Laboratories Molecular modelling Nerve Tissue Proteins - metabolism Oral hygiene Oxidative stress Patch-Clamp Techniques Penicillin Phenytoin Phenytoin - adverse effects Polymerase chain reaction Purines - pharmacology Real-Time Polymerase Chain Reaction Reverse transcription Staining and Labeling Transient Receptor Potential Channels - metabolism Transient receptor potential proteins TRPA1 Cation Channel TRPV Cation Channels - metabolism Vitamin E Vitamins |
title | TRPA1 Channels Mediate Human Gingival Fibroblast Response to Phenytoin |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T23%3A41%3A57IST&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=TRPA1%20Channels%20Mediate%20Human%20Gingival%20Fibroblast%20Response%20to%20Phenytoin&rft.jtitle=Journal%20of%20dental%20research&rft.au=L%C3%B3pez-Gonz%C3%A1lez,%20M.J.&rft.date=2017-07&rft.volume=96&rft.issue=7&rft.spage=832&rft.epage=839&rft.pages=832-839&rft.issn=0022-0345&rft.eissn=1544-0591&rft_id=info:doi/10.1177/0022034517695518&rft_dat=%3Cproquest_cross%3E2300626379%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=2300626379&rft_id=info:pmid/28571526&rft_sage_id=10.1177_0022034517695518&rfr_iscdi=true |