Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)

Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol‐induced developmental defect using zebrafish as a model was determined. Ethanol‐induced oxidative stress is one of the major m...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of food science 2017-09, Vol.82 (9), p.2221-2225
Hauptverfasser: Muralidharan, Pooja, Connors, Craig T., Mohammed, Arooj S., Sarmah, Swapnalee, Marrs, Kathleen, Marrs, James A., Chism, Grady W.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2225
container_issue 9
container_start_page 2221
container_title Journal of food science
container_volume 82
creator Muralidharan, Pooja
Connors, Craig T.
Mohammed, Arooj S.
Sarmah, Swapnalee
Marrs, Kathleen
Marrs, James A.
Chism, Grady W.
description Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol‐induced developmental defect using zebrafish as a model was determined. Ethanol‐induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol‐induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol‐treated embryos. The mechanism underlying the rescue remains to be determined. Practical Application Fetal alcohol spectrum disorder is an umbrella term describing a range of defects caused by prenatal alcohol exposure. FASD prevalence ranges from 0.3% to 5% of the live born infants, and can be as high as 8.9% in low socioeconomic populations. These defects include mental retardation, learning and behavioral disabilities, and growth defects. Identifying the mechanism of the rescue effect of turmeric could lead to potential preventative treatments.
doi_str_mv 10.1111/1750-3841.13830
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5938731</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1927836308</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4680-2f1db7b4b3887e32e7c7965ee065a1672fe8ce1e472e0d3587074fd3c559be223</originalsourceid><addsrcrecordid>eNqFkTFP3DAYhq2qqFxp527IUhcYAnacxL4F6cTdtVSgSj26dLEc5wsxcuLDTqBs7T_ob-wvwenRU2GpF8v240d-_SL0jpIjGscx5TlJmMjoEWWCkRdost15iSaEpGlCacZ30esQrsm4ZsUrtJsKPi0YJRP083LwLXij8eJ775Xu8RcIeoCAF32jOmd___h11lWDhgrP4RasW7fQ9crGVQ0RNx3uG8DfoPSqNqHBF64Ci2vn8RJGbma1a5zFq3XE_dDiuQnOV-DxwXK2mh--QTu1sgHePs576OtycXn6MTn__OHsdHae6KwQJElrWpW8zEomBAeWAtcxQw5AilzRgqc1CA0UMp4CqVguOOFZXTGd59MSYu49dLLxroeyhUrHFF5ZufamVf5eOmXk05PONPLK3cp8ygRnNAoOHgXe3cQf6mVrggZrVQduCJJOUy5YwYiI6Ptn6LUbfBfjRYoV-agcqeMNpb0LwUO9fQwlcqxXjmXKsUz5p954Y__fDFv-b58RKDbAnbFw_z-f_LScrzbmBzLRsOA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1936559388</pqid></control><display><type>article</type><title>Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Muralidharan, Pooja ; Connors, Craig T. ; Mohammed, Arooj S. ; Sarmah, Swapnalee ; Marrs, Kathleen ; Marrs, James A. ; Chism, Grady W.</creator><creatorcontrib>Muralidharan, Pooja ; Connors, Craig T. ; Mohammed, Arooj S. ; Sarmah, Swapnalee ; Marrs, Kathleen ; Marrs, James A. ; Chism, Grady W.</creatorcontrib><description>Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol‐induced developmental defect using zebrafish as a model was determined. Ethanol‐induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol‐induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol‐treated embryos. The mechanism underlying the rescue remains to be determined. Practical Application Fetal alcohol spectrum disorder is an umbrella term describing a range of defects caused by prenatal alcohol exposure. FASD prevalence ranges from 0.3% to 5% of the live born infants, and can be as high as 8.9% in low socioeconomic populations. These defects include mental retardation, learning and behavioral disabilities, and growth defects. Identifying the mechanism of the rescue effect of turmeric could lead to potential preventative treatments.</description><identifier>ISSN: 0022-1147</identifier><identifier>EISSN: 1750-3841</identifier><identifier>DOI: 10.1111/1750-3841.13830</identifier><identifier>PMID: 28796310</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Alcohols ; Animals ; Antioxidants ; Body length ; Curcuma - anatomy &amp; histology ; Curcuma - chemistry ; Curcumin ; Defects ; Dietary Supplements - analysis ; Disabilities ; Disease Models, Animal ; Embryo, Nonmammalian ; Embryos ; Ethanol ; Ethanol - toxicity ; ethanol‐induced defects ; Exposure ; Female ; fetal alcohol spectrum disorder ; Fetal Alcohol Spectrum Disorders - physiopathology ; Fetal Alcohol Spectrum Disorders - prevention &amp; control ; Fetal alcohol syndrome ; Gastrulation ; Humans ; Infants ; Male ; nutritional supplement ; Organogenesis ; Oxidative stress ; Plant Extracts - administration &amp; dosage ; Plant Extracts - analysis ; Powder ; Prenatal experience ; Supplements ; turmeric ; Zebrafish ; Zebrafish - growth &amp; development</subject><ispartof>Journal of food science, 2017-09, Vol.82 (9), p.2221-2225</ispartof><rights>2017 Institute of Food Technologists</rights><rights>2017 Institute of Food Technologists®.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4680-2f1db7b4b3887e32e7c7965ee065a1672fe8ce1e472e0d3587074fd3c559be223</citedby><cites>FETCH-LOGICAL-c4680-2f1db7b4b3887e32e7c7965ee065a1672fe8ce1e472e0d3587074fd3c559be223</cites><orcidid>0000-0002-7781-9247</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2F1750-3841.13830$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2F1750-3841.13830$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28796310$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muralidharan, Pooja</creatorcontrib><creatorcontrib>Connors, Craig T.</creatorcontrib><creatorcontrib>Mohammed, Arooj S.</creatorcontrib><creatorcontrib>Sarmah, Swapnalee</creatorcontrib><creatorcontrib>Marrs, Kathleen</creatorcontrib><creatorcontrib>Marrs, James A.</creatorcontrib><creatorcontrib>Chism, Grady W.</creatorcontrib><title>Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)</title><title>Journal of food science</title><addtitle>J Food Sci</addtitle><description>Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol‐induced developmental defect using zebrafish as a model was determined. Ethanol‐induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol‐induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol‐treated embryos. The mechanism underlying the rescue remains to be determined. Practical Application Fetal alcohol spectrum disorder is an umbrella term describing a range of defects caused by prenatal alcohol exposure. FASD prevalence ranges from 0.3% to 5% of the live born infants, and can be as high as 8.9% in low socioeconomic populations. These defects include mental retardation, learning and behavioral disabilities, and growth defects. Identifying the mechanism of the rescue effect of turmeric could lead to potential preventative treatments.</description><subject>Alcohols</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Body length</subject><subject>Curcuma - anatomy &amp; histology</subject><subject>Curcuma - chemistry</subject><subject>Curcumin</subject><subject>Defects</subject><subject>Dietary Supplements - analysis</subject><subject>Disabilities</subject><subject>Disease Models, Animal</subject><subject>Embryo, Nonmammalian</subject><subject>Embryos</subject><subject>Ethanol</subject><subject>Ethanol - toxicity</subject><subject>ethanol‐induced defects</subject><subject>Exposure</subject><subject>Female</subject><subject>fetal alcohol spectrum disorder</subject><subject>Fetal Alcohol Spectrum Disorders - physiopathology</subject><subject>Fetal Alcohol Spectrum Disorders - prevention &amp; control</subject><subject>Fetal alcohol syndrome</subject><subject>Gastrulation</subject><subject>Humans</subject><subject>Infants</subject><subject>Male</subject><subject>nutritional supplement</subject><subject>Organogenesis</subject><subject>Oxidative stress</subject><subject>Plant Extracts - administration &amp; dosage</subject><subject>Plant Extracts - analysis</subject><subject>Powder</subject><subject>Prenatal experience</subject><subject>Supplements</subject><subject>turmeric</subject><subject>Zebrafish</subject><subject>Zebrafish - growth &amp; development</subject><issn>0022-1147</issn><issn>1750-3841</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTFP3DAYhq2qqFxp527IUhcYAnacxL4F6cTdtVSgSj26dLEc5wsxcuLDTqBs7T_ob-wvwenRU2GpF8v240d-_SL0jpIjGscx5TlJmMjoEWWCkRdost15iSaEpGlCacZ30esQrsm4ZsUrtJsKPi0YJRP083LwLXij8eJ775Xu8RcIeoCAF32jOmd___h11lWDhgrP4RasW7fQ9crGVQ0RNx3uG8DfoPSqNqHBF64Ci2vn8RJGbma1a5zFq3XE_dDiuQnOV-DxwXK2mh--QTu1sgHePs576OtycXn6MTn__OHsdHae6KwQJElrWpW8zEomBAeWAtcxQw5AilzRgqc1CA0UMp4CqVguOOFZXTGd59MSYu49dLLxroeyhUrHFF5ZufamVf5eOmXk05PONPLK3cp8ygRnNAoOHgXe3cQf6mVrggZrVQduCJJOUy5YwYiI6Ptn6LUbfBfjRYoV-agcqeMNpb0LwUO9fQwlcqxXjmXKsUz5p954Y__fDFv-b58RKDbAnbFw_z-f_LScrzbmBzLRsOA</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Muralidharan, Pooja</creator><creator>Connors, Craig T.</creator><creator>Mohammed, Arooj S.</creator><creator>Sarmah, Swapnalee</creator><creator>Marrs, Kathleen</creator><creator>Marrs, James A.</creator><creator>Chism, Grady W.</creator><general>Wiley Subscription Services, 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>7QO</scope><scope>7QR</scope><scope>7ST</scope><scope>7T7</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7781-9247</orcidid></search><sort><creationdate>201709</creationdate><title>Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)</title><author>Muralidharan, Pooja ; Connors, Craig T. ; Mohammed, Arooj S. ; Sarmah, Swapnalee ; Marrs, Kathleen ; Marrs, James A. ; Chism, Grady W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4680-2f1db7b4b3887e32e7c7965ee065a1672fe8ce1e472e0d3587074fd3c559be223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Alcohols</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Body length</topic><topic>Curcuma - anatomy &amp; histology</topic><topic>Curcuma - chemistry</topic><topic>Curcumin</topic><topic>Defects</topic><topic>Dietary Supplements - analysis</topic><topic>Disabilities</topic><topic>Disease Models, Animal</topic><topic>Embryo, Nonmammalian</topic><topic>Embryos</topic><topic>Ethanol</topic><topic>Ethanol - toxicity</topic><topic>ethanol‐induced defects</topic><topic>Exposure</topic><topic>Female</topic><topic>fetal alcohol spectrum disorder</topic><topic>Fetal Alcohol Spectrum Disorders - physiopathology</topic><topic>Fetal Alcohol Spectrum Disorders - prevention &amp; control</topic><topic>Fetal alcohol syndrome</topic><topic>Gastrulation</topic><topic>Humans</topic><topic>Infants</topic><topic>Male</topic><topic>nutritional supplement</topic><topic>Organogenesis</topic><topic>Oxidative stress</topic><topic>Plant Extracts - administration &amp; dosage</topic><topic>Plant Extracts - analysis</topic><topic>Powder</topic><topic>Prenatal experience</topic><topic>Supplements</topic><topic>turmeric</topic><topic>Zebrafish</topic><topic>Zebrafish - growth &amp; development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muralidharan, Pooja</creatorcontrib><creatorcontrib>Connors, Craig T.</creatorcontrib><creatorcontrib>Mohammed, Arooj S.</creatorcontrib><creatorcontrib>Sarmah, Swapnalee</creatorcontrib><creatorcontrib>Marrs, Kathleen</creatorcontrib><creatorcontrib>Marrs, James A.</creatorcontrib><creatorcontrib>Chism, Grady W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology &amp; Engineering</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of food science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muralidharan, Pooja</au><au>Connors, Craig T.</au><au>Mohammed, Arooj S.</au><au>Sarmah, Swapnalee</au><au>Marrs, Kathleen</au><au>Marrs, James A.</au><au>Chism, Grady W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)</atitle><jtitle>Journal of food science</jtitle><addtitle>J Food Sci</addtitle><date>2017-09</date><risdate>2017</risdate><volume>82</volume><issue>9</issue><spage>2221</spage><epage>2225</epage><pages>2221-2225</pages><issn>0022-1147</issn><eissn>1750-3841</eissn><abstract>Prenatal ethanol exposure causes the most frequent preventable birth disorder, fetal alcohol spectrum disorder (FASD). The effect of turmeric extracts in rescuing an ethanol‐induced developmental defect using zebrafish as a model was determined. Ethanol‐induced oxidative stress is one of the major mechanisms underlying FASD. We hypothesize that antioxidant inducing properties of turmeric may alleviate ethanol‐induced defects. Curcuminoid content of the turmeric powder extract (5 mg/mL turmeric in ethanol) was determined by UPLC and found to contain Curcumin (124.1 ± 0.2 μg/mL), Desmethoxycurcumin (43.4 ± 0.1 μg/mL), and Bisdemethoxycurcumin (36.6 ± 0.1 μg/mL). Zebrafish embryos were treated with 100 mM (0.6% v/v) ethanol during gastrulation through organogenesis (2 to 48 h postfertilization (hpf)) and supplemented with turmeric extract to obtain total curcuminoid concentrations of 0, 1.16, 1.72, or 2.32 μM. Turmeric supplementation showed significant rescue of the body length at 72 hpf compared to ethanol‐treated embryos. The mechanism underlying the rescue remains to be determined. Practical Application Fetal alcohol spectrum disorder is an umbrella term describing a range of defects caused by prenatal alcohol exposure. FASD prevalence ranges from 0.3% to 5% of the live born infants, and can be as high as 8.9% in low socioeconomic populations. These defects include mental retardation, learning and behavioral disabilities, and growth defects. Identifying the mechanism of the rescue effect of turmeric could lead to potential preventative treatments.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28796310</pmid><doi>10.1111/1750-3841.13830</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-7781-9247</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0022-1147
ispartof Journal of food science, 2017-09, Vol.82 (9), p.2221-2225
issn 0022-1147
1750-3841
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5938731
source Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Alcohols
Animals
Antioxidants
Body length
Curcuma - anatomy & histology
Curcuma - chemistry
Curcumin
Defects
Dietary Supplements - analysis
Disabilities
Disease Models, Animal
Embryo, Nonmammalian
Embryos
Ethanol
Ethanol - toxicity
ethanol‐induced defects
Exposure
Female
fetal alcohol spectrum disorder
Fetal Alcohol Spectrum Disorders - physiopathology
Fetal Alcohol Spectrum Disorders - prevention & control
Fetal alcohol syndrome
Gastrulation
Humans
Infants
Male
nutritional supplement
Organogenesis
Oxidative stress
Plant Extracts - administration & dosage
Plant Extracts - analysis
Powder
Prenatal experience
Supplements
turmeric
Zebrafish
Zebrafish - growth & development
title Turmeric Extract Rescues Ethanol‐Induced Developmental Defect in the Zebrafish Model for Fetal Alcohol Spectrum Disorder (FASD)
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T13%3A47%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Turmeric%20Extract%20Rescues%20Ethanol%E2%80%90Induced%20Developmental%20Defect%20in%20the%20Zebrafish%20Model%20for%20Fetal%20Alcohol%20Spectrum%20Disorder%20(FASD)&rft.jtitle=Journal%20of%20food%20science&rft.au=Muralidharan,%20Pooja&rft.date=2017-09&rft.volume=82&rft.issue=9&rft.spage=2221&rft.epage=2225&rft.pages=2221-2225&rft.issn=0022-1147&rft.eissn=1750-3841&rft_id=info:doi/10.1111/1750-3841.13830&rft_dat=%3Cproquest_pubme%3E1927836308%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1936559388&rft_id=info:pmid/28796310&rfr_iscdi=true