Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats
Abstract Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (ST...
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| Veröffentlicht in: | Journal of neuropathology and experimental neurology 2020-12, Vol.79 (12), p.1320-1343 |
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| creator | Shayea, Abdulaziz M F Mousa, Alyaa M A Renno, Waleed M Nadar, Mohammed Shaban Qabazard, Bedoor Yousif, Mariam H M |
| description | Abstract
Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p |
| doi_str_mv | 10.1093/jnen/nlaa127 |
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Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p < 0.05) and mechanical hyperalgesia (p < 0.01) and restored thermal hyperalgesia (p < 0.001) compared with diabetic rats. The treatment decreased the microglial response and increased astrocyte counts in spinal cord gray and white matter compared with untreated diabetic rats. Proinflammatory cytokines were reduced in the treated group compared with diabetic rats. These results suggest that H2S has a potentially ameliorative effect on the neuropathic pain through the control of astrocyte activation and microglia-mediated inflammation, which may be considered as a possible treatment of peripheral nerve hypersensitivity in diabetic patients.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nlaa127</identifier><identifier>PMID: 33271602</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Astrocytes - drug effects ; Astrocytes - metabolism ; Cytokines ; Cytokines - metabolism ; Diabetes ; Diabetes Mellitus, Experimental - metabolism ; Diabetic Neuropathies - drug therapy ; Diabetic Neuropathies - metabolism ; Diabetic neuropathy ; Hyperalgesia ; Hyperalgesia - drug therapy ; Hyperalgesia - metabolism ; Inflammation Mediators - metabolism ; Male ; Microglia - drug effects ; Microglia - metabolism ; Morpholines - pharmacology ; Morpholines - therapeutic use ; Neuroprotective Agents - pharmacology ; Neuroprotective Agents - therapeutic use ; Organothiophosphorus Compounds - pharmacology ; Organothiophosphorus Compounds - therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rodents ; Spinal cord ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Treatment Outcome</subject><ispartof>Journal of neuropathology and experimental neurology, 2020-12, Vol.79 (12), p.1320-1343</ispartof><rights>2020 American Association of Neuropathologists, Inc. All rights reserved. 2020</rights><rights>2020 by American Association of Neuropathologists, Inc.</rights><rights>2020 American Association of Neuropathologists, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4348-9397f9a7a699098e071add127d90cd85fdcda5b28793d9560e6bf6eb033c0043</citedby><cites>FETCH-LOGICAL-c4348-9397f9a7a699098e071add127d90cd85fdcda5b28793d9560e6bf6eb033c0043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33271602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shayea, Abdulaziz M F</creatorcontrib><creatorcontrib>Mousa, Alyaa M A</creatorcontrib><creatorcontrib>Renno, Waleed M</creatorcontrib><creatorcontrib>Nadar, Mohammed Shaban</creatorcontrib><creatorcontrib>Qabazard, Bedoor</creatorcontrib><creatorcontrib>Yousif, Mariam H M</creatorcontrib><title>Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>Abstract
Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p < 0.05) and mechanical hyperalgesia (p < 0.01) and restored thermal hyperalgesia (p < 0.001) compared with diabetic rats. The treatment decreased the microglial response and increased astrocyte counts in spinal cord gray and white matter compared with untreated diabetic rats. Proinflammatory cytokines were reduced in the treated group compared with diabetic rats. These results suggest that H2S has a potentially ameliorative effect on the neuropathic pain through the control of astrocyte activation and microglia-mediated inflammation, which may be considered as a possible treatment of peripheral nerve hypersensitivity in diabetic patients.</description><subject>Animals</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetic Neuropathies - drug therapy</subject><subject>Diabetic Neuropathies - metabolism</subject><subject>Diabetic neuropathy</subject><subject>Hyperalgesia</subject><subject>Hyperalgesia - drug therapy</subject><subject>Hyperalgesia - metabolism</subject><subject>Inflammation Mediators - metabolism</subject><subject>Male</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Morpholines - pharmacology</subject><subject>Morpholines - therapeutic use</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neuroprotective Agents - therapeutic use</subject><subject>Organothiophosphorus Compounds - pharmacology</subject><subject>Organothiophosphorus Compounds - therapeutic use</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Spinal cord</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - metabolism</subject><subject>Treatment Outcome</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1vEzEQhi0EoqFw44wsceDSpbP2fvkYpfRDKkIikVBPK68923XY2IvtpQo_ht-KowSOnOZDz4zemZeQtzl8zEHwy61Fe2lHKXNWPyOLvCyLrCrr5jlZADCWcajEGXkVwhYABIjiJTnjnNV5BWxBfq8G76xRdONRxh3aSL-ZONDbvfbuES1dz2NvNNIrZ52nNw8PRc5r-tlE8ygjhpSpBI5GjlRaTZcheqf2EelSRfNTRuMsNZbGAel6MjZhK-c1dT1dR49TdL9cdMrY7M7qWaGmV0Z2GJOirzKG1-RFL8eAb07xnGyuP21Wt9n9l5u71fI-UwUvmkxwUfdC1rIS6cIGoc6l1ukhWoDSTdlrpWXZsaYWXIuyAqy6vsIOOFcABT8n749rJ-9-zBhiu3WzT2JDy0pggnMoIFEXRypdHILHvp282Um_b3NoD160By_akxcJf3daOnc71P_gv89PQHEEntwY0Yfv4_yEvh1QjnFok1tQQs0yBgxylqrs0GrS2IfjmJun_yv4A0TjpIA</recordid><startdate>20201204</startdate><enddate>20201204</enddate><creator>Shayea, Abdulaziz M F</creator><creator>Mousa, Alyaa M A</creator><creator>Renno, Waleed M</creator><creator>Nadar, Mohammed Shaban</creator><creator>Qabazard, Bedoor</creator><creator>Yousif, Mariam H M</creator><general>Oxford University Press</general><general>by American Association of Neuropathologists, 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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope></search><sort><creationdate>20201204</creationdate><title>Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats</title><author>Shayea, Abdulaziz M F ; Mousa, Alyaa M A ; Renno, Waleed M ; Nadar, Mohammed Shaban ; Qabazard, Bedoor ; Yousif, Mariam H M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4348-9397f9a7a699098e071add127d90cd85fdcda5b28793d9560e6bf6eb033c0043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetic Neuropathies - drug therapy</topic><topic>Diabetic Neuropathies - metabolism</topic><topic>Diabetic neuropathy</topic><topic>Hyperalgesia</topic><topic>Hyperalgesia - drug therapy</topic><topic>Hyperalgesia - metabolism</topic><topic>Inflammation Mediators - metabolism</topic><topic>Male</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Morpholines - pharmacology</topic><topic>Morpholines - therapeutic use</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Neuroprotective Agents - therapeutic use</topic><topic>Organothiophosphorus Compounds - pharmacology</topic><topic>Organothiophosphorus Compounds - therapeutic use</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Spinal cord</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - metabolism</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shayea, Abdulaziz M F</creatorcontrib><creatorcontrib>Mousa, Alyaa M A</creatorcontrib><creatorcontrib>Renno, Waleed M</creatorcontrib><creatorcontrib>Nadar, Mohammed Shaban</creatorcontrib><creatorcontrib>Qabazard, Bedoor</creatorcontrib><creatorcontrib>Yousif, Mariam H M</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 Central (Corporate)</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Databases</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</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>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shayea, Abdulaziz M F</au><au>Mousa, Alyaa M A</au><au>Renno, Waleed M</au><au>Nadar, Mohammed Shaban</au><au>Qabazard, Bedoor</au><au>Yousif, Mariam H M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2020-12-04</date><risdate>2020</risdate><volume>79</volume><issue>12</issue><spage>1320</spage><epage>1343</epage><pages>1320-1343</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>Abstract
Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p < 0.05) and mechanical hyperalgesia (p < 0.01) and restored thermal hyperalgesia (p < 0.001) compared with diabetic rats. The treatment decreased the microglial response and increased astrocyte counts in spinal cord gray and white matter compared with untreated diabetic rats. Proinflammatory cytokines were reduced in the treated group compared with diabetic rats. These results suggest that H2S has a potentially ameliorative effect on the neuropathic pain through the control of astrocyte activation and microglia-mediated inflammation, which may be considered as a possible treatment of peripheral nerve hypersensitivity in diabetic patients.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33271602</pmid><doi>10.1093/jnen/nlaa127</doi><tpages>24</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Astrocytes - drug effects Astrocytes - metabolism Cytokines Cytokines - metabolism Diabetes Diabetes Mellitus, Experimental - metabolism Diabetic Neuropathies - drug therapy Diabetic Neuropathies - metabolism Diabetic neuropathy Hyperalgesia Hyperalgesia - drug therapy Hyperalgesia - metabolism Inflammation Mediators - metabolism Male Microglia - drug effects Microglia - metabolism Morpholines - pharmacology Morpholines - therapeutic use Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Organothiophosphorus Compounds - pharmacology Organothiophosphorus Compounds - therapeutic use Rats Rats, Sprague-Dawley Rodents Spinal cord Spinal Cord - drug effects Spinal Cord - metabolism Treatment Outcome |
| title | Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats |
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