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Measures of tonic and phasic activity of the locus coeruleus-norepinephrine system in children with autism spectrum disorder: An event-related potential and pupillometry study / Yesol KIM in Autism Research, 15-12 (December 2022)
[article]
Titre : Measures of tonic and phasic activity of the locus coeruleus-norepinephrine system in children with autism spectrum disorder: An event-related potential and pupillometry study Type de document : Texte imprimé et/ou numérique Auteurs : Yesol KIM, Auteur ; Girija KADLASKAR, Auteur ; Rebecca McNally KEEHN, Auteur ; Brandon KEEHN, Auteur Article en page(s) : p.2250-2264 Langues : Anglais (eng) Mots-clés : Child Humans Locus Coeruleus Autism Spectrum Disorder Norepinephrine Attention/physiology Evoked Potentials autism spectrum disorder electrophysiology eye-tracking locus coeruleus Index. décimale : PER Périodiques Résumé : A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event-related potential [ERP]) indices may provide meaningful insights about the nature of LC-NE function in ASD. Twenty-four children with ASD and 27 age- and nonverbal-IQ matched typically developing (TD) children completed two experiments: (1) a resting eye-tracking task to measure tonic pupil diameter, and (2) a three-stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC-NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC-NE indices were primarily related to measures of attention-deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC-NE activation may be associated with atypical arousal and decreased responsivity to behaviorally-relevant information in ASD. En ligne : http://dx.doi.org/10.1002/aur.2820 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488
in Autism Research > 15-12 (December 2022) . - p.2250-2264[article] Measures of tonic and phasic activity of the locus coeruleus-norepinephrine system in children with autism spectrum disorder: An event-related potential and pupillometry study [Texte imprimé et/ou numérique] / Yesol KIM, Auteur ; Girija KADLASKAR, Auteur ; Rebecca McNally KEEHN, Auteur ; Brandon KEEHN, Auteur . - p.2250-2264.
Langues : Anglais (eng)
in Autism Research > 15-12 (December 2022) . - p.2250-2264
Mots-clés : Child Humans Locus Coeruleus Autism Spectrum Disorder Norepinephrine Attention/physiology Evoked Potentials autism spectrum disorder electrophysiology eye-tracking locus coeruleus Index. décimale : PER Périodiques Résumé : A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event-related potential [ERP]) indices may provide meaningful insights about the nature of LC-NE function in ASD. Twenty-four children with ASD and 27 age- and nonverbal-IQ matched typically developing (TD) children completed two experiments: (1) a resting eye-tracking task to measure tonic pupil diameter, and (2) a three-stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC-NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC-NE indices were primarily related to measures of attention-deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC-NE activation may be associated with atypical arousal and decreased responsivity to behaviorally-relevant information in ASD. En ligne : http://dx.doi.org/10.1002/aur.2820 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488 Pupillometric measures of altered stimulus-evoked locus coeruleus-norepinephrine activity explain attenuated social attention in preschoolers with autism spectrum disorder / Leonie POLZER in Autism Research, 15-11 (November 2022)
[article]
Titre : Pupillometric measures of altered stimulus-evoked locus coeruleus-norepinephrine activity explain attenuated social attention in preschoolers with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Leonie POLZER, Auteur ; Christine M. FREITAG, Auteur ; Nico BAST, Auteur Article en page(s) : p.2167-2180 Langues : Anglais (eng) Mots-clés : Child Humans Child, Preschool Autism Spectrum Disorder/diagnosis Locus Coeruleus Norepinephrine Attention/physiology Pupil/physiology attention eye-tracking technology preschool pupil Index. décimale : PER Périodiques Résumé : Attenuated social attention has been described as a reduced preference for social compared to geometric motion in preschoolers with autism spectrum disorder (ASD). The locus coeruleus-norpinephrine (LC-NE) system modulates sensory reactivity and is a promising underlying mechanism. LC-NE activity is indexed by a stimulus-evoked pupillary response (SEPR) and partially by a luminance-adaptation pupillary response (LAPR), which were both shown to be aberrant in ASD. We examined whether SEPR and LAPR explain an attenuated social motion preference. We applied pupillometry via video-based eye tracking in young children (18-65 months) with ASD (n = 57) and typically developing (TD) children (n = 39) during a preferential looking paradigm of competing social and geometric motion and a changing light condition paradigm. We found an attenuated social motion preference in the ASD compared to the TD group. This was accompanied by atypical pupillometry showing a smaller SEPR to social motion, a larger SEPR to geometric motion and a reduced LAPR to a dark screen. SEPR but not LAPR explained the group difference in social motion preference. An ASD diagnosis was statistically predicted by the social motion preference, while this effect was mediated by the inclusion of SEPR to geometric and social motion. Our findings suggest a decreased sensory reactivity to social and increased reactivity to non-social motion in ASD, which may concurrently contribute to an attenuated social attention. The LC-NE system is supported as a promising underlying mechanism of altered social attention in young children with ASD, while the specificity of findings remains to be addressed. En ligne : http://dx.doi.org/10.1002/aur.2818 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488
in Autism Research > 15-11 (November 2022) . - p.2167-2180[article] Pupillometric measures of altered stimulus-evoked locus coeruleus-norepinephrine activity explain attenuated social attention in preschoolers with autism spectrum disorder [Texte imprimé et/ou numérique] / Leonie POLZER, Auteur ; Christine M. FREITAG, Auteur ; Nico BAST, Auteur . - p.2167-2180.
Langues : Anglais (eng)
in Autism Research > 15-11 (November 2022) . - p.2167-2180
Mots-clés : Child Humans Child, Preschool Autism Spectrum Disorder/diagnosis Locus Coeruleus Norepinephrine Attention/physiology Pupil/physiology attention eye-tracking technology preschool pupil Index. décimale : PER Périodiques Résumé : Attenuated social attention has been described as a reduced preference for social compared to geometric motion in preschoolers with autism spectrum disorder (ASD). The locus coeruleus-norpinephrine (LC-NE) system modulates sensory reactivity and is a promising underlying mechanism. LC-NE activity is indexed by a stimulus-evoked pupillary response (SEPR) and partially by a luminance-adaptation pupillary response (LAPR), which were both shown to be aberrant in ASD. We examined whether SEPR and LAPR explain an attenuated social motion preference. We applied pupillometry via video-based eye tracking in young children (18-65 months) with ASD (n = 57) and typically developing (TD) children (n = 39) during a preferential looking paradigm of competing social and geometric motion and a changing light condition paradigm. We found an attenuated social motion preference in the ASD compared to the TD group. This was accompanied by atypical pupillometry showing a smaller SEPR to social motion, a larger SEPR to geometric motion and a reduced LAPR to a dark screen. SEPR but not LAPR explained the group difference in social motion preference. An ASD diagnosis was statistically predicted by the social motion preference, while this effect was mediated by the inclusion of SEPR to geometric and social motion. Our findings suggest a decreased sensory reactivity to social and increased reactivity to non-social motion in ASD, which may concurrently contribute to an attenuated social attention. The LC-NE system is supported as a promising underlying mechanism of altered social attention in young children with ASD, while the specificity of findings remains to be addressed. En ligne : http://dx.doi.org/10.1002/aur.2818 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488 Arousal-modulated memory encoding and retrieval in adults with autism spectrum disorder / Nico BAST in Autism Research, 15-9 (September 2022)
[article]
Titre : Arousal-modulated memory encoding and retrieval in adults with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Nico BAST, Auteur ; Sebastian B. GAIGG, Auteur ; Dermot M. BOWLER, Auteur ; Veit ROESSNER, Auteur ; Christine M. FREITAG, Auteur ; Melanie RING, Auteur Article en page(s) : p.1609-1620 Langues : Anglais (eng) Mots-clés : Adult Arousal/physiology Autism Spectrum Disorder/complications Humans Locus Coeruleus Pupil/physiology Recognition, Psychology Asd locus coeruleus-norepinephrine system memory pupillometry Index. décimale : PER Périodiques Résumé : Recently, we have shown that pupil dilation during a recognition memory task can serve as an index of memory retrieval difficulties in autism. At the time of publication, we were unaware of specific data-analysis methods that can be used to shed further light on the origins of such memory related pupil dilation. Specifically, by distinguishing "tonic" from "phasic" changes in pupil dilation and considering their temporal progression, it is possible to draw inferences about the functional integrity of a locus coeruleus-norepinephrine system (LC-NE) that is known to play a key role in regulating memory encoding and retrieval processes. We therefore apply these analyses to our previously published eye-tracking data of adults with ASD (NÂ =Â 24) and neurotypical development (TD, NÂ =Â 30) during the recognition memory task. In this re-analysis, we related pupil dilation during encoding and retrieval to recognition accuracy in a per-trial analysis of linear mixed models. In ASD, we replicated attenuated recognition accuracy, which was accompanied by attenuated pupil dilation during encoding and retrieval. Group differences in pupil dilation during retrieval occurred late during the trial (after 1.75s) and indicated an altered top-down processing like attenuated attribution of semantic salience in response to previously encoded stimuli. In addition, only in the ASD group were higher pupil dilation during encoding and lower pupil dilation during retrieval associated with decreased recognition accuracy. This supports altered modulation of memory encoding and retrieval in ASD, with LC-NE phasic activity as promising underlying mechanism. LAY SUMMARY: We investigated the changes of pupil size during memory testing in autism spectrum disorder. Adults with ASD remembered fewer items correctly than neurotypical individuals (TD). This reduced memory was related to increased pupillary responses at study and decreased pupil dilation at test only for adults with ASD indicating a different modulation of memory by the locus coeruleus. En ligne : http://dx.doi.org/10.1002/aur.2784 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=483
in Autism Research > 15-9 (September 2022) . - p.1609-1620[article] Arousal-modulated memory encoding and retrieval in adults with autism spectrum disorder [Texte imprimé et/ou numérique] / Nico BAST, Auteur ; Sebastian B. GAIGG, Auteur ; Dermot M. BOWLER, Auteur ; Veit ROESSNER, Auteur ; Christine M. FREITAG, Auteur ; Melanie RING, Auteur . - p.1609-1620.
Langues : Anglais (eng)
in Autism Research > 15-9 (September 2022) . - p.1609-1620
Mots-clés : Adult Arousal/physiology Autism Spectrum Disorder/complications Humans Locus Coeruleus Pupil/physiology Recognition, Psychology Asd locus coeruleus-norepinephrine system memory pupillometry Index. décimale : PER Périodiques Résumé : Recently, we have shown that pupil dilation during a recognition memory task can serve as an index of memory retrieval difficulties in autism. At the time of publication, we were unaware of specific data-analysis methods that can be used to shed further light on the origins of such memory related pupil dilation. Specifically, by distinguishing "tonic" from "phasic" changes in pupil dilation and considering their temporal progression, it is possible to draw inferences about the functional integrity of a locus coeruleus-norepinephrine system (LC-NE) that is known to play a key role in regulating memory encoding and retrieval processes. We therefore apply these analyses to our previously published eye-tracking data of adults with ASD (NÂ =Â 24) and neurotypical development (TD, NÂ =Â 30) during the recognition memory task. In this re-analysis, we related pupil dilation during encoding and retrieval to recognition accuracy in a per-trial analysis of linear mixed models. In ASD, we replicated attenuated recognition accuracy, which was accompanied by attenuated pupil dilation during encoding and retrieval. Group differences in pupil dilation during retrieval occurred late during the trial (after 1.75s) and indicated an altered top-down processing like attenuated attribution of semantic salience in response to previously encoded stimuli. In addition, only in the ASD group were higher pupil dilation during encoding and lower pupil dilation during retrieval associated with decreased recognition accuracy. This supports altered modulation of memory encoding and retrieval in ASD, with LC-NE phasic activity as promising underlying mechanism. LAY SUMMARY: We investigated the changes of pupil size during memory testing in autism spectrum disorder. Adults with ASD remembered fewer items correctly than neurotypical individuals (TD). This reduced memory was related to increased pupillary responses at study and decreased pupil dilation at test only for adults with ASD indicating a different modulation of memory by the locus coeruleus. En ligne : http://dx.doi.org/10.1002/aur.2784 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=483 Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats / Y. WU in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
[article]
Titre : Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats Type de document : Texte imprimé et/ou numérique Auteurs : Y. WU, Auteur ; W. ZHONG, Auteur ; N. CUI, Auteur ; C. M. JOHNSON, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur Article en page(s) : p.23 Langues : Anglais (eng) Mots-clés : Behaviors Breathing Locus coeruleus Mecp2-null rat Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters. En ligne : http://dx.doi.org/10.1186/s11689-016-9156-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.23[article] Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats [Texte imprimé et/ou numérique] / Y. WU, Auteur ; W. ZHONG, Auteur ; N. CUI, Auteur ; C. M. JOHNSON, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur . - p.23.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.23
Mots-clés : Behaviors Breathing Locus coeruleus Mecp2-null rat Rett syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in RTT research, results obtained need to be validated in other species. Therefore, we performed these studies to characterize phenotypes of a novel Mecp2 (-/Y) rat model and compared them with the Mecp2 (tm1.1Bird) mouse model of RTT. METHODS: RTT-like phenotypes were systematically studied and compared between Mecp2 (-/Y) rats and Mecp2 (-/Y) mice. In-cage conditions of the rats were monitored. Grip strength and spontaneous locomotion were used to evaluate the motor function. Three-chamber test was performed to show autism-type behaviors. Breathing activity was recorded with the plethysmograph. Individual neurons in the locus coeruleus (LC) were studied in the whole-cell current clamp. The lifespan of the rats was determined with their survival time. RESULTS: Mecp2 (-/Y) rats displayed growth retardation, malocclusion, and lack of movements, while hindlimb clasping was not seen. They had weaker forelimb grip strength and a lower rate of locomotion than the WT littermates. Defects in social interaction with other rats were obvious. Breathing frequency variation and apnea in the null rats were significantly higher than in the WT. LC neurons in the null rats showed excessive firing activity. A half of the null rats died in 2 months. Most of the RTT-like symptoms were comparable to those seen in Mecp2 (-/Y) mice, while some appeared more or less severe. The findings that most RTT-like symptoms exist in the rat model with moderate variations and differences from the mouse models support the usefulness of both Mecp2 (-/Y) rodent models. CONCLUSIONS: The novel Mecp2 (-/Y) rat model recapitulated numerous RTT-like symptoms as Mecp2 (-/Y) mouse models did, which makes it a valuable alternative model in the RTT studies when the body size matters. En ligne : http://dx.doi.org/10.1186/s11689-016-9156-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome / W. ZHONG in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
[article]
Titre : Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome Type de document : Texte imprimé et/ou numérique Auteurs : W. ZHONG, Auteur ; C. M. JOHNSON, Auteur ; Y. WU, Auteur ; N. CUI, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur Article en page(s) : p.37 Langues : Anglais (eng) Mots-clés : Behavior Gaboxadol Locus coeruleus Mecp2 Rett syndrome Thip Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABAARs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABAARs, there is a group of GABAARs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. METHODS: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. RESULTS: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. CONCLUSIONS: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well. En ligne : http://dx.doi.org/10.1186/s11689-016-9169-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37[article] Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome [Texte imprimé et/ou numérique] / W. ZHONG, Auteur ; C. M. JOHNSON, Auteur ; Y. WU, Auteur ; N. CUI, Auteur ; H. XING, Auteur ; S. ZHANG, Auteur ; C. JIANG, Auteur . - p.37.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.37
Mots-clés : Behavior Gaboxadol Locus coeruleus Mecp2 Rett syndrome Thip Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies indicate that augmenting synaptic GABA receptors (GABAARs) can alleviate RTT-like symptoms in mice. In addition to the synaptic GABAARs, there is a group of GABAARs found outside the synaptic cleft with the capability to produce sustained inhibition, which may be potential therapeutic targets for the control of neuronal excitability in RTT. METHODS: Wild-type and MECP2-null mice were randomly divided into four groups, receiving the extrasynaptic GABAAR agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride (THIP) and vehicle control, respectively. Low-dose THIP was administered to neonatal mice through lactation. RTT-like symptoms including lifespan, breathing, motor function, and social behaviors were studied when mice became mature. Changes in neuronal excitability and norepinephrine biosynthesis enzyme expression were studied in electrophysiology and molecular biology. RESULTS: With no evident sedation and other adverse side effects, early-life exposure to THIP extended the lifespan, alleviated breathing abnormalities, enhanced motor function, and improved social behaviors of MECP2-null mice. Such beneficial effects were associated with stabilization of locus coeruleus neuronal excitability and improvement of norepinephrine biosynthesis enzyme expression. CONCLUSIONS: THIP treatment in early lives might be a therapeutic approach to RTT-like symptoms in MECP2-null mice and perhaps in people with RTT as well. En ligne : http://dx.doi.org/10.1186/s11689-016-9169-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 PermalinkSaccade dysmetria indicates attenuated visual exploration in autism spectrum disorder / Nico BAST in Journal of Child Psychology and Psychiatry, 62-2 (February 2021)
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