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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by karaS on September 15, 2004, at 21:40:58
What is the science behind the antidepressant effect of staying up all night? Is it cortisol related? Does MAO and reuptake of neurotransmitters have anything to do with it?
thanks,
K
Posted by Larry Hoover on September 16, 2004, at 7:35:38
In reply to Staying up all night as AD-raybakes? Larry? any?, posted by karaS on September 15, 2004, at 21:40:58
> What is the science behind the antidepressant effect of staying up all night? Is it cortisol related? Does MAO and reuptake of neurotransmitters have anything to do with it?
>
> thanks,
> KHey Kara. My brain went on holiday for a few days. Or, it had some ponderations to conclude. Or, my quitting coffee had something to do with it. Or, I'm just weird. Anyway...
What a coincidence! I was just reading a just-published study on this, last night. If you read the first and second abstracts, here, you might conclude that they show different cortisol responses in the responders. One says increase, the other decrease. But, the third abstract might have the answer. Failure of the the cortisol autoreceptors (I'm invoking the same paradoxical response paradigm as with stimulants, even though I don't even know if there are cortisol autoreceptors), might be the distinguishing factor, as dexamethasone suppression measures cortisol-feedback sensitivity.
The takehome message is that it looks like sleep deprivation kickstarts the growth hormone system which has been suppressed by excess cortisol associated with depression. Simultaneous to that is extra release of TSH, but there are two categories of feedback sensitivity there, too. Our bodies are very complicated systems, but then they'd have to be, to evolve so far from the natural chaos of unregulated systems.
Lar
Am J Psychiatry. 2004 Aug;161(8):1404-10.
Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients.Voderholzer U, Hohagen F, Klein T, Jungnickel J, Kirschbaum C, Berger M, Riemann D.
Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Freiburg, Germany. Ulrich_Voderholzer@psyallg.ukl.uni-freiburg.de
OBJECTIVE: One night of sleep deprivation induces a transient improvement in about 60% of depressed patients. Since depression is associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, the authors measured cortisol secretion before, during, and after therapeutic sleep deprivation for 1 night. METHOD: Fifteen unmedicated depressed inpatients participated in a combined polysomnographic and endocrine study. Blood was sampled at 30-minute intervals during 3 consecutive nights before, during, and after sleep deprivation. Saliva samples were collected at 30-minute intervals during the daytime before and after the sleep deprivation night. RESULTS: During the night of sleep deprivation, cortisol levels were significantly higher than at baseline. During the daytime, cortisol levels during the first half of the day were higher than at baseline in the patients who responded to sleep deprivation but not in the nonresponders. During recovery sleep, cortisol secretion returned to baseline values. CONCLUSIONS: This study demonstrated a significant stimulatory effect of 1 night of sleep deprivation on the HPA axis in unmedicated depressed patients. The results suggest that the short-term effects of antidepressant treatments on the HPA axis may differ from their long-term effects. A higher cortisol level after sleep deprivation might transiently improve negative feedback to the hypothalamus or interact with other neurotransmitter systems, thus mediating or contributing to the clinical response. The fast return to baseline values coincides with the short clinical effect.
Clin Endocrinol (Oxf). 1999 Aug;51(2):205-15.
Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: potential clinical implications.Vgontzas AN, Mastorakos G, Bixler EO, Kales A, Gold PW, Chrousos GP.
Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University, Hershey, PA 17033, USA.
OBJECTIVES: Although several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis. DESIGN AND SUBJECTS: After four consecutive nights in the Sleep Laboratory, 10 healthy young men were totally deprived of sleep during the fifth night, and then allowed to sleep again on nights six and seven. Twenty-four hour blood sampling was performed serially every 30 minutes on the fourth day, immediately following the previous night of sleep and on the sixth day, immediately after sleep deprivation. MEASUREMENT: Eight-hour sleep laboratory recording, including electroencephologram, electro-oculogram and electromyogram. Plasma cortisol and GH levels using specific immunoassay techniques. RESULTS: Mean plasma and time-integrated (AUC) cortisol levels were lower during the postdeprivation nighttime period than on the fourth night (P < 0.05). Pulsatile analysis showed significant reduction of both the 24 h and daytime peak area (P < 0.05) and of the pulse amplitude (P < 0.01), but not of the pulse frequency. Also, the amount of time-integrated GH was significantly higher for the first 4 h of the postdeprivation night compared to the predeprivation night (P < 0.05). Cross-correlation analyses between the absolute values of the time-series of each hormone value and percentage of each sleep stage per half hour revealed that slow wave sleep was negatively correlated with cortisol and positively correlated with GH with slow wave sleep preceding the secretion of these hormones. In contrast, indices of sleep disturbance, i.e. wake and stage 1 sleep, were positively correlated with cortisol and negatively correlated with GH. CONCLUSION: We conclude that sleep deprivation results in a significant reduction of cortisol secretion the next day and this reduction appears to be, to a large extent, driven by the increase of slow wave sleep during the recovery night. We propose that reduction of CRH and cortisol secretion may be the mechanism through which sleep deprivation relieves depression temporarily. Furthermore, deep sleep has an inhibitory effect on the HPA axis while it enhances the activity of the GH axis. In contrast, sleep disturbance has a stimulatory effect on the HPA axis and a suppressive effect on the GH axis. These results are consistent with the observed hypocortisolism in idiopathic hypersomnia and HPA axis relative activation in chronic insomnia. Finally, our findings support previous hypotheses about the restitution and immunoenhancement role of slow wave (deep) sleep.
J Psychiatr Res. 2001 Jul-Aug;35(4):239-47.
Sleep deprivation and hypothalamic-pituitary-adrenal (HPA) axis activity in depressed patients.Schule C, Baghai T, Zwanzger P, Minov C, Padberg F, Rupprecht R.
Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336 Munich, Germany. cornelius.schuele@psy.med.uni-muenchen.de
In the present study we investigated HPA axis activity in depressed patients treated with partial sleep deprivation (PSD) in order to identify endocrinological characteristics related to PSD responsiveness. Thirty-three drug-free patients (14 men, 19 women) suffering from major depression according to DSM-IV criteria were treated with PSD. Response to PSD was defined as a reduction of at least 30% according to the 6-item version of the Hamilton Depression Scale (6-HAMD). Subsequently, the combined dexamethasone-suppression/CRH-stimulation test (DEX/CRH test) was performed. Patients were pretreated with 1.5 mg dexamethasone (DEX) at 23:00 h and challenged with 100 microg corticotropin-releasing hormone (CRH) the following day. Postdexamethasone cortisol concentrations (before CRH administration) served as parameters for the DST status (dexamethasone suppression test). The cortisol stimulation after CRH was used as measurement for the DEX/CRH test status. Of the depressive patients, 54.5% (18 out of 33) responded to PSD. DST suppressors (postdexamethasone cortisol levels < 15 ng/ml) showed a significantly greater reduction in 6-HAMD scores after PSD than DST nonsuppressors. Furthermore, a significant negative correlation between postdexamethasone cortisol levels and reduction in 6-HAMD scores after PSD could be established. However, there was no relationship between the cortisol stimulation following CRH challenge and response to PSD. Although the combined DEX/CRH challenge test is a more sensitive marker for HPA axis dysregulation in depression than the standard DST, the negative feedback of the HPA system reflected by the DST status is apparently more closely associated with response to partial sleep deprivation in major depressive disorder.
Posted by linkadge on September 16, 2004, at 15:40:10
In reply to Re: Staying up all night as AD-raybakes? Larry? any? » karaS, posted by Larry Hoover on September 16, 2004, at 7:35:38
I also heard that SD decreases reputake of serotonin, and also releases an amphetamine like compound in the brain.
Linkadge
Posted by karaS on September 16, 2004, at 17:54:47
In reply to Re: Staying up all night as AD-raybakes? Larry? any?, posted by linkadge on September 16, 2004, at 15:40:10
> I also heard that SD decreases reputake of serotonin, and also releases an amphetamine like compound in the brain.
>
>
> Linkadge
Only serotonin? I would think it would decrease the reuptake of the other neurotransmitters as well? (Does reuptake occur at all times or only when we sleep?)
P.S. I hope you're doing better now, Linkadge. It's only the depression that isn't letting you know how truly smart your are. Everyone on these boards knows it!!!-K
Posted by karaS on September 16, 2004, at 17:58:18
In reply to Re: Staying up all night as AD-raybakes? Larry? any? » karaS, posted by Larry Hoover on September 16, 2004, at 7:35:38
> > What is the science behind the antidepressant effect of staying up all night? Is it cortisol related? Does MAO and reuptake of neurotransmitters have anything to do with it?
> >
> > thanks,
> > K
>
> Hey Kara. My brain went on holiday for a few days. Or, it had some ponderations to conclude. Or, my quitting coffee had something to do with it. Or, I'm just weird. Anyway...
>
> What a coincidence! I was just reading a just-published study on this, last night. If you read the first and second abstracts, here, you might conclude that they show different cortisol responses in the responders. One says increase, the other decrease. But, the third abstract might have the answer. Failure of the the cortisol autoreceptors (I'm invoking the same paradoxical response paradigm as with stimulants, even though I don't even know if there are cortisol autoreceptors), might be the distinguishing factor, as dexamethasone suppression measures cortisol-feedback sensitivity.
>
> The takehome message is that it looks like sleep deprivation kickstarts the growth hormone system which has been suppressed by excess cortisol associated with depression. Simultaneous to that is extra release of TSH, but there are two categories of feedback sensitivity there, too. Our bodies are very complicated systems, but then they'd have to be, to evolve so far from the natural chaos of unregulated systems.
>
> Lar
>
>
> Am J Psychiatry. 2004 Aug;161(8):1404-10.
>
> Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients.
>
> Voderholzer U, Hohagen F, Klein T, Jungnickel J, Kirschbaum C, Berger M, Riemann D.
>
> Department of Psychiatry and Psychotherapy, University Hospital of Freiburg, Freiburg, Germany. Ulrich_Voderholzer@psyallg.ukl.uni-freiburg.de
>
> OBJECTIVE: One night of sleep deprivation induces a transient improvement in about 60% of depressed patients. Since depression is associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, the authors measured cortisol secretion before, during, and after therapeutic sleep deprivation for 1 night. METHOD: Fifteen unmedicated depressed inpatients participated in a combined polysomnographic and endocrine study. Blood was sampled at 30-minute intervals during 3 consecutive nights before, during, and after sleep deprivation. Saliva samples were collected at 30-minute intervals during the daytime before and after the sleep deprivation night. RESULTS: During the night of sleep deprivation, cortisol levels were significantly higher than at baseline. During the daytime, cortisol levels during the first half of the day were higher than at baseline in the patients who responded to sleep deprivation but not in the nonresponders. During recovery sleep, cortisol secretion returned to baseline values. CONCLUSIONS: This study demonstrated a significant stimulatory effect of 1 night of sleep deprivation on the HPA axis in unmedicated depressed patients. The results suggest that the short-term effects of antidepressant treatments on the HPA axis may differ from their long-term effects. A higher cortisol level after sleep deprivation might transiently improve negative feedback to the hypothalamus or interact with other neurotransmitter systems, thus mediating or contributing to the clinical response. The fast return to baseline values coincides with the short clinical effect.
>
> Clin Endocrinol (Oxf). 1999 Aug;51(2):205-15.
>
> Sleep deprivation effects on the activity of the hypothalamic-pituitary-adrenal and growth axes: potential clinical implications.
>
> Vgontzas AN, Mastorakos G, Bixler EO, Kales A, Gold PW, Chrousos GP.
>
> Sleep Research and Treatment Center, Department of Psychiatry, Pennsylvania State University, Hershey, PA 17033, USA.
>
> OBJECTIVES: Although several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis. DESIGN AND SUBJECTS: After four consecutive nights in the Sleep Laboratory, 10 healthy young men were totally deprived of sleep during the fifth night, and then allowed to sleep again on nights six and seven. Twenty-four hour blood sampling was performed serially every 30 minutes on the fourth day, immediately following the previous night of sleep and on the sixth day, immediately after sleep deprivation. MEASUREMENT: Eight-hour sleep laboratory recording, including electroencephologram, electro-oculogram and electromyogram. Plasma cortisol and GH levels using specific immunoassay techniques. RESULTS: Mean plasma and time-integrated (AUC) cortisol levels were lower during the postdeprivation nighttime period than on the fourth night (P < 0.05). Pulsatile analysis showed significant reduction of both the 24 h and daytime peak area (P < 0.05) and of the pulse amplitude (P < 0.01), but not of the pulse frequency. Also, the amount of time-integrated GH was significantly higher for the first 4 h of the postdeprivation night compared to the predeprivation night (P < 0.05). Cross-correlation analyses between the absolute values of the time-series of each hormone value and percentage of each sleep stage per half hour revealed that slow wave sleep was negatively correlated with cortisol and positively correlated with GH with slow wave sleep preceding the secretion of these hormones. In contrast, indices of sleep disturbance, i.e. wake and stage 1 sleep, were positively correlated with cortisol and negatively correlated with GH. CONCLUSION: We conclude that sleep deprivation results in a significant reduction of cortisol secretion the next day and this reduction appears to be, to a large extent, driven by the increase of slow wave sleep during the recovery night. We propose that reduction of CRH and cortisol secretion may be the mechanism through which sleep deprivation relieves depression temporarily. Furthermore, deep sleep has an inhibitory effect on the HPA axis while it enhances the activity of the GH axis. In contrast, sleep disturbance has a stimulatory effect on the HPA axis and a suppressive effect on the GH axis. These results are consistent with the observed hypocortisolism in idiopathic hypersomnia and HPA axis relative activation in chronic insomnia. Finally, our findings support previous hypotheses about the restitution and immunoenhancement role of slow wave (deep) sleep.
>
> J Psychiatr Res. 2001 Jul-Aug;35(4):239-47.
>
> Sleep deprivation and hypothalamic-pituitary-adrenal (HPA) axis activity in depressed patients.
>
> Schule C, Baghai T, Zwanzger P, Minov C, Padberg F, Rupprecht R.
>
> Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336 Munich, Germany. cornelius.schuele@psy.med.uni-muenchen.de
>
> In the present study we investigated HPA axis activity in depressed patients treated with partial sleep deprivation (PSD) in order to identify endocrinological characteristics related to PSD responsiveness. Thirty-three drug-free patients (14 men, 19 women) suffering from major depression according to DSM-IV criteria were treated with PSD. Response to PSD was defined as a reduction of at least 30% according to the 6-item version of the Hamilton Depression Scale (6-HAMD). Subsequently, the combined dexamethasone-suppression/CRH-stimulation test (DEX/CRH test) was performed. Patients were pretreated with 1.5 mg dexamethasone (DEX) at 23:00 h and challenged with 100 microg corticotropin-releasing hormone (CRH) the following day. Postdexamethasone cortisol concentrations (before CRH administration) served as parameters for the DST status (dexamethasone suppression test). The cortisol stimulation after CRH was used as measurement for the DEX/CRH test status. Of the depressive patients, 54.5% (18 out of 33) responded to PSD. DST suppressors (postdexamethasone cortisol levels < 15 ng/ml) showed a significantly greater reduction in 6-HAMD scores after PSD than DST nonsuppressors. Furthermore, a significant negative correlation between postdexamethasone cortisol levels and reduction in 6-HAMD scores after PSD could be established. However, there was no relationship between the cortisol stimulation following CRH challenge and response to PSD. Although the combined DEX/CRH challenge test is a more sensitive marker for HPA axis dysregulation in depression than the standard DST, the negative feedback of the HPA system reflected by the DST status is apparently more closely associated with response to partial sleep deprivation in major depressive disorder.
>
No worries. (I just thought that your alter ego, Harry Loover, had taken over!) Anyway, how ironic that you were just reading about this very thing.P.S. I got that book by Dr. Perlmutter. It's much more general and geared towards the masses as you might imagine. I doubt you'd enjoy it as much as the article he wrote.
Thanks!
K
Posted by raybakes on September 22, 2004, at 5:56:08
In reply to Staying up all night as AD-raybakes? Larry? any?, posted by karaS on September 15, 2004, at 21:40:58
In line with my belief that depression is largely an inflammatory disease, found this on cortisol's anti inflammatory effects..
In response to an infection, or an inflammatory disorder like rheumatoid arthritis, cells of the immune system produce three substances that cause inflammation: interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor (TNF). These substances, working either singly or in combination with each other, cause the release of CRH. IL-6 also promotes the release of ACTH and cortisol. Cortisol and other compounds then suppress the release of IL-1, IL-6, and TNF, in the process switching off the inflammatory response.So inflammatory cytokines trigger the release of cortisol, which then, rather neatly, switches them off.....but only if the cortisol can cross the blood brain barrier efficiently, and reach the hypothalamus. I wonder if this feedback is hindered in any way (poor cell membrane response, maybe helped by omega 3s?), whether a massive hit of cortisol from sleep deprivation, can hit the off switch for a little while, suppressing inflammation and relieving depression?
this scientific american article seems an interesting read...
Posted by karaS on September 22, 2004, at 10:27:53
In reply to Re: Staying up all night as AD-raybakes? Larry? any? » karaS, posted by raybakes on September 22, 2004, at 5:56:08
> In line with my belief that depression is largely an inflammatory disease, found this on cortisol's anti inflammatory effects..
>
>
> In response to an infection, or an inflammatory disorder like rheumatoid arthritis, cells of the immune system produce three substances that cause inflammation: interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor (TNF). These substances, working either singly or in combination with each other, cause the release of CRH. IL-6 also promotes the release of ACTH and cortisol. Cortisol and other compounds then suppress the release of IL-1, IL-6, and TNF, in the process switching off the inflammatory response.
>
> So inflammatory cytokines trigger the release of cortisol, which then, rather neatly, switches them off.....but only if the cortisol can cross the blood brain barrier efficiently, and reach the hypothalamus. I wonder if this feedback is hindered in any way (poor cell membrane response, maybe helped by omega 3s?), whether a massive hit of cortisol from sleep deprivation, can hit the off switch for a little while, suppressing inflammation and relieving depression?
>
> this scientific american article seems an interesting read...
>
> http://people.brandeis.edu/~teuber/mind_body.pdf
Interesting. I always thought that high cortisol was associated with depression but I really have to do a lot of studying of the HPA axis. I haven't read the article yet (have to head out soon) but it seems that it's conjecture at this point as to why staying up all night would ease depression - but that it's cortisol related.
My theory was that staying up all night was preventing reuptake of neurotransmitters. Guess I was way off.
Would this also explain the feeling of being so lethargic and super depressed when sleeping more than 8 hours? I am especially sensitive to this. A little extra sleep (even if it's for catch-up) makes me into one horribly depressed zombie.
Also, how does your theory of inflammation being at the root of depression correlate with the use of antidepressants? If your theory is correct, then shouldn't antidepressants be useless? (probably I just don't know enough to understand the connection)
Kara
Posted by raybakes on September 22, 2004, at 12:16:43
In reply to Re: Staying up all night as AD-raybakes? Larry? any? » raybakes, posted by karaS on September 22, 2004, at 10:27:53
>Also, how does your theory of inflammation being at the root of depression correlate with the use of antidepressants? If your theory is correct, then shouldn't antidepressants be useless? (probably I just don't know enough to understand the connection
Not sure about the ins and outs of high or low cortisol, but it does seem that depression can result from either high or low cortisol, so maybe saying dysregulation of the hpa axis is related to depression might be more accurate?
There are a few studies that show antidepressants have an antiinflammatory effect if given for a longer duration, so there's still hope for the theory!..here's one...
Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice.
Kubera M, Simbirtsev A, Mathison R, Maes M.
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
This study examines the effects of repeated administration of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram (10 mg/kg, i.p.), on immunoreactivity in C57BL/6 mice. Immune functions were evaluated by the ability of splenocytes to reduce a tetrazolium salt to formazan (MTT test), to proliferate, and to produce cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN gamma). Citalopram administered for 1, 2 and 4 weeks stimulates the proliferative activity of splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 weeks, stimulates the proliferative activity of splenocytes, whereas a 4-week administration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citalopram and fluoxetine induces a significant increase in the production of IL-6 and IL-10, a cytokine with immunosuppressive and anti-inflammatory activities. The results show that, in C57BL/6 mice, the immunomodulatory effects of SSRIs depend on the SSRI used and the duration of administration.
Posted by karaS on September 22, 2004, at 22:35:37
In reply to Re: Staying up all night as AD-raybakes? Larry? any? » karaS, posted by raybakes on September 22, 2004, at 12:16:43
> >Also, how does your theory of inflammation being at the root of depression correlate with the use of antidepressants? If your theory is correct, then shouldn't antidepressants be useless? (probably I just don't know enough to understand the connection
>
> Not sure about the ins and outs of high or low cortisol, but it does seem that depression can result from either high or low cortisol, so maybe saying dysregulation of the hpa axis is related to depression might be more accurate?
>
> There are a few studies that show antidepressants have an antiinflammatory effect if given for a longer duration, so there's still hope for the theory!..here's one...
>
> Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice.
>
> Kubera M, Simbirtsev A, Mathison R, Maes M.
>
> Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Krakow, Poland.
>
> This study examines the effects of repeated administration of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram (10 mg/kg, i.p.), on immunoreactivity in C57BL/6 mice. Immune functions were evaluated by the ability of splenocytes to reduce a tetrazolium salt to formazan (MTT test), to proliferate, and to produce cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN gamma). Citalopram administered for 1, 2 and 4 weeks stimulates the proliferative activity of splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 weeks, stimulates the proliferative activity of splenocytes, whereas a 4-week administration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citalopram and fluoxetine induces a significant increase in the production of IL-6 and IL-10, a cytokine with immunosuppressive and anti-inflammatory activities. The results show that, in C57BL/6 mice, the immunomodulatory effects of SSRIs depend on the SSRI used and the duration of administration.
>
And the time frame seems to fit when the anti-d's would kick in...
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