Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre‐term‐born adults
Pre‐term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre‐term birth per se causes these effects remains unclear. Therefore, we aimed to assess...
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description | Pre‐term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre‐term birth per se causes these effects remains unclear. Therefore, we aimed to assess pulmonary ventilation and blood gases under various environmental conditions, comparing 17 healthy prematurely born individuals (mean ± SD; gestational age, 28 ± 2 weeks; age, 21 ± 4 years; peak oxygen uptake, 48.1 ± 11.2 ml kg−1 min−1) with 16 well‐matched adults born at term (gestational age, 40 ± 1 weeks; age, 22 ± 2 years; peak oxygen uptake, 51.2 ± 7.7 ml kg−1 min−1). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO2), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O2 and CO2 were similar in pre‐term and full‐term individuals under all conditions. Higher ventilation in hypoxia compared to normoxia was only observed at terrestrial altitude, despite an equivalent (normobaric) hypoxic stimulus administered at sea level (0.138 FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}$). Assessment of oscillations in key variables revealed that combined hypoxic hypercapnia induced greater underlying fluctuations in ventilation in pre‐term individuals only. In general, higher pulse oxygen saturation fluctuations were observed with hypoxia, and lower fluctuations in end‐tidal CO2 with hypercapnia, despite similar ventilatory oscillations observed between conditions. These findings suggest that healthy prematurely born adults display similar overall ventilation to their term‐born counterparts under various environmental stressors, but that combined ventilatory stimuli could induce an irregular underlying ventilatory pattern. Moreover, barometric pressure may be an important factor when assessing ventilatory responsiveness to moderate hypoxic stimuli.
Key points
Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre‐term birth. Whether pre‐term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term‐born individuals.
According to the present data, there is no difference between healthy pre‐term and well‐matched term‐born individuals in the magnitude of pulmonary ventilation or arterial blood gas |
doi_str_mv | 10.1113/JP285300 |
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Key points
Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre‐term birth. Whether pre‐term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term‐born individuals.
According to the present data, there is no difference between healthy pre‐term and well‐matched term‐born individuals in the magnitude of pulmonary ventilation or arterial blood gases during independent and combined hypobaria, hypoxia and hypercapnia.
Terrestrial altitude (hypobaria) was necessary to induce differences in ventilation between normoxia and a hypoxic stimulus equivalent to ∼3375 m of altitude. Furthermore, peak power in pulse oxygen saturation was similar between hypobaric normoxia and normobaric hypoxia.
The observed similarities between groups suggest that ventilatory regulation under various environmental stimuli is not impaired by pre‐term birth per se. Instead, an integrated combination of neonatal treatment strategies and cardiorespiratory fitness/disease status might underlie previously observed chemosensitivity impairments.
figure legend The long‐term physiological effect of pre‐term birth is a growing area of research. In particular, existing evidence shows unique ventilatory responses to various environmental stimuli in prematurely born adults, suggesting that pre‐term birth modulates chemosensitivity. In this study, a group of young, healthy and physically active prematurely born adults were recruited and intentionally well‐matched to a term‐born group of control participants. The two groups were exposed to seven different combinations of hypoxia, hypercapnia and hypobaria across testing visits conducted near sea level (295 m) and at altitude (3375 m). Frequency‐domain analysis of relevant cardiorespiratory data suggested that combined hypoxic hypercapnia elicited a ventilatory instability in the pre‐term group. However, the magnitude of the ventilatory responses to all conditions, and the corresponding arterialized capillary partial pressures of oxygen or carbon dioxide were similar between groups. This study indicates that a combination of advancements in neonatal treatment strategies and the health/fitness status of individuals within this population are critical factors underpinning the manifestation of long‐term physiological sequelae. Created with BioRender.com.</description><identifier>ISSN: 0022-3751</identifier><identifier>ISSN: 1469-7793</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/JP285300</identifier><identifier>PMID: 37796451</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Altitude ; Birth ; Carbon dioxide ; Carbon Dioxide - blood ; Carbon Dioxide - metabolism ; Cardiorespiratory fitness ; chemosensitivity ; Complications ; Environmental conditions ; Environmental effects ; Female ; Gestational age ; Humans ; Hypercapnia ; Hypercapnia - physiopathology ; hypobaria ; Hypoxia ; Hypoxia - physiopathology ; Male ; Maximum oxygen consumption ; Neonates ; Oscillations ; Oxygen saturation ; prematurity ; Pulmonary Ventilation ; Respiration ; Respiratory function ; Ventilation ; Ventilators ; Ventilatory behavior ; Young Adult</subject><ispartof>The Journal of physiology, 2024-11, Vol.602 (21), p.5943-5958</ispartof><rights>2023 The Authors. published by John Wiley & Sons Ltd on behalf of The Physiological Society.</rights><rights>2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3840-90f0d6c241405c7d6c2a654f3801d8368a079b7c5f41ecefbb0c95135e382bb73</citedby><cites>FETCH-LOGICAL-c3840-90f0d6c241405c7d6c2a654f3801d8368a079b7c5f41ecefbb0c95135e382bb73</cites><orcidid>0000-0002-7812-5626 ; 0000-0001-8081-4423 ; 0000-0001-7053-3978 ; 0000-0001-9529-4977 ; 0000-0001-6791-2002</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1113%2FJP285300$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1113%2FJP285300$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37796451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Narang, Benjamin J.</creatorcontrib><creatorcontrib>Manferdelli, Giorgio</creatorcontrib><creatorcontrib>Bourdillon, Nicolas</creatorcontrib><creatorcontrib>Millet, Grégoire P.</creatorcontrib><creatorcontrib>Debevec, Tadej</creatorcontrib><title>Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre‐term‐born adults</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>Pre‐term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre‐term birth per se causes these effects remains unclear. Therefore, we aimed to assess pulmonary ventilation and blood gases under various environmental conditions, comparing 17 healthy prematurely born individuals (mean ± SD; gestational age, 28 ± 2 weeks; age, 21 ± 4 years; peak oxygen uptake, 48.1 ± 11.2 ml kg−1 min−1) with 16 well‐matched adults born at term (gestational age, 40 ± 1 weeks; age, 22 ± 2 years; peak oxygen uptake, 51.2 ± 7.7 ml kg−1 min−1). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO2), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O2 and CO2 were similar in pre‐term and full‐term individuals under all conditions. Higher ventilation in hypoxia compared to normoxia was only observed at terrestrial altitude, despite an equivalent (normobaric) hypoxic stimulus administered at sea level (0.138 FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}$). Assessment of oscillations in key variables revealed that combined hypoxic hypercapnia induced greater underlying fluctuations in ventilation in pre‐term individuals only. In general, higher pulse oxygen saturation fluctuations were observed with hypoxia, and lower fluctuations in end‐tidal CO2 with hypercapnia, despite similar ventilatory oscillations observed between conditions. These findings suggest that healthy prematurely born adults display similar overall ventilation to their term‐born counterparts under various environmental stressors, but that combined ventilatory stimuli could induce an irregular underlying ventilatory pattern. Moreover, barometric pressure may be an important factor when assessing ventilatory responsiveness to moderate hypoxic stimuli.
Key points
Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre‐term birth. Whether pre‐term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term‐born individuals.
According to the present data, there is no difference between healthy pre‐term and well‐matched term‐born individuals in the magnitude of pulmonary ventilation or arterial blood gases during independent and combined hypobaria, hypoxia and hypercapnia.
Terrestrial altitude (hypobaria) was necessary to induce differences in ventilation between normoxia and a hypoxic stimulus equivalent to ∼3375 m of altitude. Furthermore, peak power in pulse oxygen saturation was similar between hypobaric normoxia and normobaric hypoxia.
The observed similarities between groups suggest that ventilatory regulation under various environmental stimuli is not impaired by pre‐term birth per se. Instead, an integrated combination of neonatal treatment strategies and cardiorespiratory fitness/disease status might underlie previously observed chemosensitivity impairments.
figure legend The long‐term physiological effect of pre‐term birth is a growing area of research. In particular, existing evidence shows unique ventilatory responses to various environmental stimuli in prematurely born adults, suggesting that pre‐term birth modulates chemosensitivity. In this study, a group of young, healthy and physically active prematurely born adults were recruited and intentionally well‐matched to a term‐born group of control participants. The two groups were exposed to seven different combinations of hypoxia, hypercapnia and hypobaria across testing visits conducted near sea level (295 m) and at altitude (3375 m). Frequency‐domain analysis of relevant cardiorespiratory data suggested that combined hypoxic hypercapnia elicited a ventilatory instability in the pre‐term group. However, the magnitude of the ventilatory responses to all conditions, and the corresponding arterialized capillary partial pressures of oxygen or carbon dioxide were similar between groups. This study indicates that a combination of advancements in neonatal treatment strategies and the health/fitness status of individuals within this population are critical factors underpinning the manifestation of long‐term physiological sequelae. Created with BioRender.com.</description><subject>Adult</subject><subject>Altitude</subject><subject>Birth</subject><subject>Carbon dioxide</subject><subject>Carbon Dioxide - blood</subject><subject>Carbon Dioxide - metabolism</subject><subject>Cardiorespiratory fitness</subject><subject>chemosensitivity</subject><subject>Complications</subject><subject>Environmental conditions</subject><subject>Environmental effects</subject><subject>Female</subject><subject>Gestational age</subject><subject>Humans</subject><subject>Hypercapnia</subject><subject>Hypercapnia - physiopathology</subject><subject>hypobaria</subject><subject>Hypoxia</subject><subject>Hypoxia - physiopathology</subject><subject>Male</subject><subject>Maximum oxygen consumption</subject><subject>Neonates</subject><subject>Oscillations</subject><subject>Oxygen saturation</subject><subject>prematurity</subject><subject>Pulmonary Ventilation</subject><subject>Respiration</subject><subject>Respiratory function</subject><subject>Ventilation</subject><subject>Ventilators</subject><subject>Ventilatory behavior</subject><subject>Young Adult</subject><issn>0022-3751</issn><issn>1469-7793</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp10dFq1jAUB_AgivvchD3BCHjjhZ0nSdO0l2M4dQzcxeZtSdJTvow26ZKWrXc-gs-4JzGf2xQEb3JOyI8_hxxCDhkcM8bEx_NLXksB8IJsWFk1hVKNeEk2AJwXQkm2R96kdAPABDTNa7InMqhKyTbk_jv62Q16DnGlEdMUfMJE50Cd73DCfPiZat9RG0bjPHZ0u07h3ukPuwaj1ZN3-rfYPRgd8815ukU9zNuVThEffvycMY65mBA91d0yzOmAvOr1kPDtU90n12efrk6_FBffPn89PbkorKhLKBrooassL1kJ0qpdqytZ9qIG1tWiqjWoxigr-5Khxd4YsI1kQqKouTFK7JP3j7lTDLcLprkdXbI4DNpjWFLLayW4ZEqKTN_9Q2_CEn2erhWMs4ZnWP8NtDGkFLFvp-hGHdeWQbvbRvu8jUyPngIXM2L3Bz5_fwbHj-DODbj-N6i9Or9kUlUgfgG4FJT-</recordid><startdate>20241101</startdate><enddate>20241101</enddate><creator>Narang, Benjamin J.</creator><creator>Manferdelli, Giorgio</creator><creator>Bourdillon, Nicolas</creator><creator>Millet, Grégoire P.</creator><creator>Debevec, Tadej</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><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>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7812-5626</orcidid><orcidid>https://orcid.org/0000-0001-8081-4423</orcidid><orcidid>https://orcid.org/0000-0001-7053-3978</orcidid><orcidid>https://orcid.org/0000-0001-9529-4977</orcidid><orcidid>https://orcid.org/0000-0001-6791-2002</orcidid></search><sort><creationdate>20241101</creationdate><title>Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre‐term‐born adults</title><author>Narang, Benjamin J. ; Manferdelli, Giorgio ; Bourdillon, Nicolas ; Millet, Grégoire P. ; Debevec, Tadej</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3840-90f0d6c241405c7d6c2a654f3801d8368a079b7c5f41ecefbb0c95135e382bb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Altitude</topic><topic>Birth</topic><topic>Carbon dioxide</topic><topic>Carbon Dioxide - blood</topic><topic>Carbon Dioxide - metabolism</topic><topic>Cardiorespiratory fitness</topic><topic>chemosensitivity</topic><topic>Complications</topic><topic>Environmental conditions</topic><topic>Environmental effects</topic><topic>Female</topic><topic>Gestational age</topic><topic>Humans</topic><topic>Hypercapnia</topic><topic>Hypercapnia - physiopathology</topic><topic>hypobaria</topic><topic>Hypoxia</topic><topic>Hypoxia - physiopathology</topic><topic>Male</topic><topic>Maximum oxygen consumption</topic><topic>Neonates</topic><topic>Oscillations</topic><topic>Oxygen saturation</topic><topic>prematurity</topic><topic>Pulmonary Ventilation</topic><topic>Respiration</topic><topic>Respiratory function</topic><topic>Ventilation</topic><topic>Ventilators</topic><topic>Ventilatory behavior</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Narang, Benjamin J.</creatorcontrib><creatorcontrib>Manferdelli, Giorgio</creatorcontrib><creatorcontrib>Bourdillon, Nicolas</creatorcontrib><creatorcontrib>Millet, Grégoire P.</creatorcontrib><creatorcontrib>Debevec, Tadej</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><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>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Narang, Benjamin J.</au><au>Manferdelli, Giorgio</au><au>Bourdillon, Nicolas</au><au>Millet, Grégoire P.</au><au>Debevec, Tadej</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre‐term‐born adults</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2024-11-01</date><risdate>2024</risdate><volume>602</volume><issue>21</issue><spage>5943</spage><epage>5958</epage><pages>5943-5958</pages><issn>0022-3751</issn><issn>1469-7793</issn><eissn>1469-7793</eissn><abstract>Pre‐term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre‐term birth per se causes these effects remains unclear. Therefore, we aimed to assess pulmonary ventilation and blood gases under various environmental conditions, comparing 17 healthy prematurely born individuals (mean ± SD; gestational age, 28 ± 2 weeks; age, 21 ± 4 years; peak oxygen uptake, 48.1 ± 11.2 ml kg−1 min−1) with 16 well‐matched adults born at term (gestational age, 40 ± 1 weeks; age, 22 ± 2 years; peak oxygen uptake, 51.2 ± 7.7 ml kg−1 min−1). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO2), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O2 and CO2 were similar in pre‐term and full‐term individuals under all conditions. Higher ventilation in hypoxia compared to normoxia was only observed at terrestrial altitude, despite an equivalent (normobaric) hypoxic stimulus administered at sea level (0.138 FiO2${F_{{\mathrm{i}}{{\mathrm{O}}_{\mathrm{2}}}$). Assessment of oscillations in key variables revealed that combined hypoxic hypercapnia induced greater underlying fluctuations in ventilation in pre‐term individuals only. In general, higher pulse oxygen saturation fluctuations were observed with hypoxia, and lower fluctuations in end‐tidal CO2 with hypercapnia, despite similar ventilatory oscillations observed between conditions. These findings suggest that healthy prematurely born adults display similar overall ventilation to their term‐born counterparts under various environmental stressors, but that combined ventilatory stimuli could induce an irregular underlying ventilatory pattern. Moreover, barometric pressure may be an important factor when assessing ventilatory responsiveness to moderate hypoxic stimuli.
Key points
Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre‐term birth. Whether pre‐term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term‐born individuals.
According to the present data, there is no difference between healthy pre‐term and well‐matched term‐born individuals in the magnitude of pulmonary ventilation or arterial blood gases during independent and combined hypobaria, hypoxia and hypercapnia.
Terrestrial altitude (hypobaria) was necessary to induce differences in ventilation between normoxia and a hypoxic stimulus equivalent to ∼3375 m of altitude. Furthermore, peak power in pulse oxygen saturation was similar between hypobaric normoxia and normobaric hypoxia.
The observed similarities between groups suggest that ventilatory regulation under various environmental stimuli is not impaired by pre‐term birth per se. Instead, an integrated combination of neonatal treatment strategies and cardiorespiratory fitness/disease status might underlie previously observed chemosensitivity impairments.
figure legend The long‐term physiological effect of pre‐term birth is a growing area of research. In particular, existing evidence shows unique ventilatory responses to various environmental stimuli in prematurely born adults, suggesting that pre‐term birth modulates chemosensitivity. In this study, a group of young, healthy and physically active prematurely born adults were recruited and intentionally well‐matched to a term‐born group of control participants. The two groups were exposed to seven different combinations of hypoxia, hypercapnia and hypobaria across testing visits conducted near sea level (295 m) and at altitude (3375 m). Frequency‐domain analysis of relevant cardiorespiratory data suggested that combined hypoxic hypercapnia elicited a ventilatory instability in the pre‐term group. However, the magnitude of the ventilatory responses to all conditions, and the corresponding arterialized capillary partial pressures of oxygen or carbon dioxide were similar between groups. This study indicates that a combination of advancements in neonatal treatment strategies and the health/fitness status of individuals within this population are critical factors underpinning the manifestation of long‐term physiological sequelae. Created with BioRender.com.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37796451</pmid><doi>10.1113/JP285300</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-7812-5626</orcidid><orcidid>https://orcid.org/0000-0001-8081-4423</orcidid><orcidid>https://orcid.org/0000-0001-7053-3978</orcidid><orcidid>https://orcid.org/0000-0001-9529-4977</orcidid><orcidid>https://orcid.org/0000-0001-6791-2002</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Altitude Birth Carbon dioxide Carbon Dioxide - blood Carbon Dioxide - metabolism Cardiorespiratory fitness chemosensitivity Complications Environmental conditions Environmental effects Female Gestational age Humans Hypercapnia Hypercapnia - physiopathology hypobaria Hypoxia Hypoxia - physiopathology Male Maximum oxygen consumption Neonates Oscillations Oxygen saturation prematurity Pulmonary Ventilation Respiration Respiratory function Ventilation Ventilators Ventilatory behavior Young Adult |
title | Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre‐term‐born adults |
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