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Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: Evidence for an altered maturational trajectory in ASD / Russell G. PORT in Autism Research, 10-4 (April 2017)
[article]
Titre : Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: Evidence for an altered maturational trajectory in ASD Type de document : Texte imprimé et/ou numérique Auteurs : Russell G. PORT, Auteur ; William GAETZ, Auteur ; Luke BLOY, Auteur ; Dah-Jyuu WANG, Auteur ; Lisa BLASKEY, Auteur ; Emily S. KUSCHNER, Auteur ; Susan E. LEVY, Auteur ; Edward S. BRODKIN, Auteur ; Timothy P. L. ROBERTS, Auteur Article en page(s) : p.593-607 Langues : Anglais (eng) Mots-clés : magnetoencephalography gamma-band GABA MEGA-PRESS magnetic resonance spectroscopy auditory autism spectrum disorder excitatory/inhibitory Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between excitatory and inhibitory neurotransmission (E/I imbalance). Studies have demonstrated E/I imbalance in individuals with ASD and also corresponding rodent models. One neural process thought to be reliant on E/I balance is gamma-band activity (Gamma), with support arising from observed correlations between motor, as well as visual, Gamma and underlying GABA concentrations in healthy adults. Additionally, decreased Gamma has been observed in ASD individuals and relevant animal models, though the direct relationship between Gamma and GABA concentrations in ASD remains unexplored. This study combined magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in 27 typically developing individuals (TD) and 30 individuals with ASD. Auditory cortex localized phase-locked Gamma was compared to resting Superior Temporal Gyrus relative cortical GABA concentrations for both children/adolescents and adults. Children/adolescents with ASD exhibited significantly decreased GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these children/adolescents lacked the typical maturation of GABA+/Cr concentrations and gamma-band coherence. Furthermore, children/adolescents with ASD additionally failed to exhibit the typical GABA+/Cr to gamma-band coherence association. This altered coupling during childhood/adolescence may result in Gamma decreases observed in the adults with ASD. Therefore, individuals with ASD exhibit improper local neuronal circuitry maturation during a childhood/adolescence critical period, when GABA is involved in configuring of such circuit functioning. Provocatively a novel line of treatment is suggested (with a critical time window); by increasing neural GABA levels in children/adolescents with ASD, proper local circuitry maturation may be restored resulting in typical Gamma in adulthood. En ligne : http://dx.doi.org/10.1002/aur.1686 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307
in Autism Research > 10-4 (April 2017) . - p.593-607[article] Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: Evidence for an altered maturational trajectory in ASD [Texte imprimé et/ou numérique] / Russell G. PORT, Auteur ; William GAETZ, Auteur ; Luke BLOY, Auteur ; Dah-Jyuu WANG, Auteur ; Lisa BLASKEY, Auteur ; Emily S. KUSCHNER, Auteur ; Susan E. LEVY, Auteur ; Edward S. BRODKIN, Auteur ; Timothy P. L. ROBERTS, Auteur . - p.593-607.
Langues : Anglais (eng)
in Autism Research > 10-4 (April 2017) . - p.593-607
Mots-clés : magnetoencephalography gamma-band GABA MEGA-PRESS magnetic resonance spectroscopy auditory autism spectrum disorder excitatory/inhibitory Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between excitatory and inhibitory neurotransmission (E/I imbalance). Studies have demonstrated E/I imbalance in individuals with ASD and also corresponding rodent models. One neural process thought to be reliant on E/I balance is gamma-band activity (Gamma), with support arising from observed correlations between motor, as well as visual, Gamma and underlying GABA concentrations in healthy adults. Additionally, decreased Gamma has been observed in ASD individuals and relevant animal models, though the direct relationship between Gamma and GABA concentrations in ASD remains unexplored. This study combined magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in 27 typically developing individuals (TD) and 30 individuals with ASD. Auditory cortex localized phase-locked Gamma was compared to resting Superior Temporal Gyrus relative cortical GABA concentrations for both children/adolescents and adults. Children/adolescents with ASD exhibited significantly decreased GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these children/adolescents lacked the typical maturation of GABA+/Cr concentrations and gamma-band coherence. Furthermore, children/adolescents with ASD additionally failed to exhibit the typical GABA+/Cr to gamma-band coherence association. This altered coupling during childhood/adolescence may result in Gamma decreases observed in the adults with ASD. Therefore, individuals with ASD exhibit improper local neuronal circuitry maturation during a childhood/adolescence critical period, when GABA is involved in configuring of such circuit functioning. Provocatively a novel line of treatment is suggested (with a critical time window); by increasing neural GABA levels in children/adolescents with ASD, proper local circuitry maturation may be restored resulting in typical Gamma in adulthood. En ligne : http://dx.doi.org/10.1002/aur.1686 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307 Increased prefrontal GABA concentrations in adults with autism spectrum disorders / Simon MAIER in Autism Research, 15-7 (July 2022)
[article]
Titre : Increased prefrontal GABA concentrations in adults with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Simon MAIER, Auteur ; Ansgard Lena DÜPPERS, Auteur ; Kimon RUNGE, Auteur ; Michael DACKO, Auteur ; Thomas LANGE, Auteur ; Thomas FANGMEIER, Auteur ; Andreas RIEDEL, Auteur ; Dieter EBERT, Auteur ; Dominique ENDRES, Auteur ; Katharina DOMSCHKE, Auteur ; Evgeniy PERLOV, Auteur ; Kathrin NICKEL, Auteur ; Ludger TEBARTZ VAN ELST, Auteur Article en page(s) : p.1222-1236 Langues : Anglais (eng) Mots-clés : Gaba anterior cingulate cortex autism spectrum disorder dorsolateral prefrontal cortex gamma-aminobutyric acid glutamate Index. décimale : PER Périodiques Résumé : The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY: Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders. En ligne : http://dx.doi.org/10.1002/aur.2740 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476
in Autism Research > 15-7 (July 2022) . - p.1222-1236[article] Increased prefrontal GABA concentrations in adults with autism spectrum disorders [Texte imprimé et/ou numérique] / Simon MAIER, Auteur ; Ansgard Lena DÜPPERS, Auteur ; Kimon RUNGE, Auteur ; Michael DACKO, Auteur ; Thomas LANGE, Auteur ; Thomas FANGMEIER, Auteur ; Andreas RIEDEL, Auteur ; Dieter EBERT, Auteur ; Dominique ENDRES, Auteur ; Katharina DOMSCHKE, Auteur ; Evgeniy PERLOV, Auteur ; Kathrin NICKEL, Auteur ; Ludger TEBARTZ VAN ELST, Auteur . - p.1222-1236.
Langues : Anglais (eng)
in Autism Research > 15-7 (July 2022) . - p.1222-1236
Mots-clés : Gaba anterior cingulate cortex autism spectrum disorder dorsolateral prefrontal cortex gamma-aminobutyric acid glutamate Index. décimale : PER Périodiques Résumé : The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY: Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders. En ligne : http://dx.doi.org/10.1002/aur.2740 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies / Natascia BRONDINO in Journal of Autism and Developmental Disorders, 46-3 (March 2016)
[article]
Titre : Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies Type de document : Texte imprimé et/ou numérique Auteurs : Natascia BRONDINO, Auteur ; Laura FUSAR-POLI, Auteur ; Cristina PANISI, Auteur ; Stefano DAMIANI, Auteur ; Francesco BARALE, Auteur ; Pierluigi POLITI, Auteur Article en page(s) : p.825-839 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder GABA Clinical trials Systematic review Index. décimale : PER Périodiques Résumé : Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic system and be a potential treatment for people with ASD. The present systematic review aimed at evaluating the state-of-the-art of clinical trials of GABA modulators in autism. To date there is insufficient evidence to suggest the use of these drugs in autistic subjects, even if data are promising. Of note, short-term use of all the reviewed medications appears to be safe. Future well designed trials are needed to elucidate these preliminary findings. En ligne : http://dx.doi.org/10.1007/s10803-015-2619-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=281
in Journal of Autism and Developmental Disorders > 46-3 (March 2016) . - p.825-839[article] Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies [Texte imprimé et/ou numérique] / Natascia BRONDINO, Auteur ; Laura FUSAR-POLI, Auteur ; Cristina PANISI, Auteur ; Stefano DAMIANI, Auteur ; Francesco BARALE, Auteur ; Pierluigi POLITI, Auteur . - p.825-839.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 46-3 (March 2016) . - p.825-839
Mots-clés : Autism spectrum disorder GABA Clinical trials Systematic review Index. décimale : PER Périodiques Résumé : Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic system and be a potential treatment for people with ASD. The present systematic review aimed at evaluating the state-of-the-art of clinical trials of GABA modulators in autism. To date there is insufficient evidence to suggest the use of these drugs in autistic subjects, even if data are promising. Of note, short-term use of all the reviewed medications appears to be safe. Future well designed trials are needed to elucidate these preliminary findings. En ligne : http://dx.doi.org/10.1007/s10803-015-2619-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=281 Reduced GABA and altered somatosensory function in children with autism spectrum disorder / Nicolaas A. J. PUTS in Autism Research, 10-4 (April 2017)
[article]
Titre : Reduced GABA and altered somatosensory function in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Nicolaas A. J. PUTS, Auteur ; Ericka L. WODKA, Auteur ; Ashley D. HARRIS, Auteur ; Deana CROCETTI, Auteur ; Mark TOMMERDAHL, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A. E. EDDEN, Auteur Article en page(s) : p.608-619 Langues : Anglais (eng) Mots-clés : autism somatosensory GABA magnetic resonance spectroscopy tactile MRS touch Index. décimale : PER Périodiques Résumé : Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. En ligne : http://dx.doi.org/10.1002/aur.1691 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307
in Autism Research > 10-4 (April 2017) . - p.608-619[article] Reduced GABA and altered somatosensory function in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Nicolaas A. J. PUTS, Auteur ; Ericka L. WODKA, Auteur ; Ashley D. HARRIS, Auteur ; Deana CROCETTI, Auteur ; Mark TOMMERDAHL, Auteur ; Stewart H. MOSTOFSKY, Auteur ; Richard A. E. EDDEN, Auteur . - p.608-619.
Langues : Anglais (eng)
in Autism Research > 10-4 (April 2017) . - p.608-619
Mots-clés : autism somatosensory GABA magnetic resonance spectroscopy tactile MRS touch Index. décimale : PER Périodiques Résumé : Background: Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods: GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results: Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions: GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. En ligne : http://dx.doi.org/10.1002/aur.1691 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307 Altered tactile processing in children with autism spectrum disorder / Teresa TAVASSOLI in Autism Research, 9-6 (June 2016)
[article]
Titre : Altered tactile processing in children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Teresa TAVASSOLI, Auteur ; Katherine BELLESHEIM, Auteur ; Mark TOMMERDAHL, Auteur ; Jameson M. HOLDEN, Auteur ; Alexander KOLEVZON, Auteur ; Joseph D. BUXBAUM, Auteur Article en page(s) : p.616-620 Langues : Anglais (eng) Mots-clés : tactile processing inhibition autism spectrum disorder GABA Index. décimale : PER Périodiques Résumé : Although tactile reactivity issues are commonly reported in children with autism spectrum disorder (ASD), the underlying mechanisms are poorly understood. Less feed-forward inhibition has been proposed as a potential mechanism for some symptoms of ASD. We tested static and dynamic tactile thresholds as a behavioral proxy of feed-forward inhibition in 42 children (21 children with ASD and 21 typically developing [TD] children). Subthreshold conditioning typically raises the dynamic detection threshold, thus comparison of the dynamic to the static threshold generates a metric that predicts gamma-aminobutyric acid (GABA) mediated feed-forward inhibition. Children with ASD had marginally higher static thresholds and a significantly lower ratio between thresholds as compared with TD children. The lower ratio, only seen in children with ASD, might be indicative of less inhibition. Static thresholds were correlated with autism spectrum quotient scores, indicating the higher the tactile threshold, the more ASD traits. The amount of feed-forward inhibition (ratio between dynamic/static) was negatively correlated with autism diagnostic observation schedule repetitive behavior scores, meaning the less inhibition the more ASD symptoms. In summary, children with ASD showed altered tactile processing compared with TD children; thus measuring static and dynamic thresholds could be a potential biomarker for ASD and might be useful for prediction of treatment response with therapeutics, including those that target the GABAergic system. Autism Res 2016, 9: 616–620. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1563 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290
in Autism Research > 9-6 (June 2016) . - p.616-620[article] Altered tactile processing in children with autism spectrum disorder [Texte imprimé et/ou numérique] / Teresa TAVASSOLI, Auteur ; Katherine BELLESHEIM, Auteur ; Mark TOMMERDAHL, Auteur ; Jameson M. HOLDEN, Auteur ; Alexander KOLEVZON, Auteur ; Joseph D. BUXBAUM, Auteur . - p.616-620.
Langues : Anglais (eng)
in Autism Research > 9-6 (June 2016) . - p.616-620
Mots-clés : tactile processing inhibition autism spectrum disorder GABA Index. décimale : PER Périodiques Résumé : Although tactile reactivity issues are commonly reported in children with autism spectrum disorder (ASD), the underlying mechanisms are poorly understood. Less feed-forward inhibition has been proposed as a potential mechanism for some symptoms of ASD. We tested static and dynamic tactile thresholds as a behavioral proxy of feed-forward inhibition in 42 children (21 children with ASD and 21 typically developing [TD] children). Subthreshold conditioning typically raises the dynamic detection threshold, thus comparison of the dynamic to the static threshold generates a metric that predicts gamma-aminobutyric acid (GABA) mediated feed-forward inhibition. Children with ASD had marginally higher static thresholds and a significantly lower ratio between thresholds as compared with TD children. The lower ratio, only seen in children with ASD, might be indicative of less inhibition. Static thresholds were correlated with autism spectrum quotient scores, indicating the higher the tactile threshold, the more ASD traits. The amount of feed-forward inhibition (ratio between dynamic/static) was negatively correlated with autism diagnostic observation schedule repetitive behavior scores, meaning the less inhibition the more ASD symptoms. In summary, children with ASD showed altered tactile processing compared with TD children; thus measuring static and dynamic thresholds could be a potential biomarker for ASD and might be useful for prediction of treatment response with therapeutics, including those that target the GABAergic system. Autism Res 2016, 9: 616–620. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1563 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290 Enhanced Social Dominance and Altered Neuronal Excitability in the Prefrontal Cortex of Male KCC2b Mutant Mice / A. M. J. ANACKER in Autism Research, 12-5 (May 2019)
PermalinkHypothesis-driven investigations of diverse pharmacological targets in two mouse models of autism / M. A. RHINE in Autism Research, 12-3 (March 2019)
PermalinkImproving emotional face perception in autism with diuretic bumetanide: A proof-of-concept behavioral and functional brain imaging pilot study / Nouchine HADJIKHANI in Autism, 19-2 (February 2015)
PermalinkNon-Invasive Evaluation of the GABAergic/Glutamatergic System in Autistic Patients Observed by MEGA-Editing Proton MR Spectroscopy Using a Clinical 3 Tesla Instrument / Masafumi HARADA in Journal of Autism and Developmental Disorders, 41-4 (April 2011)
PermalinkPrediction learning in adults with autism and its molecular correlates / L. A. SAPEY-TRIOMPHE in Molecular Autism, 12 (2021)
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