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Breakthroughs in depression!

depression

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#241 Flex

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Posted 22 October 2015 - 07:05 PM

Forgott to mention: If You cant obtain some research chems, then look whether herbs, OTC, and compounds offer the same mechanism.

Could be that some are e.g. traditionaly used and the side-effects are know i.e. they could be safe

 

 

Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade

http://www.ncbi.nlm....les/PMC3817734/



#242 stillwater

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Posted 23 October 2015 - 07:55 PM

An interesting article today:

 

http://www.neuroscie...s-and-treatment

 



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#243 thomasanderson2

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Posted 24 October 2015 - 12:13 AM

An interesting article today:

 

http://www.neuroscie...s-and-treatment

 

My takeaway? Basically, the brain's *microglial* cells are responsible for maintaining brain health - and unhealthy, or poorly-functioning microglia in the brain may be responsible for depression.  

 

When a serious problem affects me personally, I generally deplore reading articles that posit a plausible physiological explanation -  but then offer no practical solution or intervention based on the concept (or even worse, suggest something trite and hopelessly elusive - like "researchers think this might be a valuable area for future exploration...blah, blah, blah...")   In other words: "here's something for you to worry about...  and the answer is vaporware".

 

That said, I did stumble upon this article that indicates maintaining a healthy guy is important for brain microglia:

http://www.alzforum....eed-healthy-gut

 

That link doesn't mention depression, but very interestingly, a friend of mine sent me this article some months ago - referring to your gut as involved in mood:

http://mobile.nytime...-your-mood.html

 

Maybe there is something going on here after all



#244 Flex

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Posted 25 October 2015 - 10:45 PM

Ive read the following papers a few months ago and IIRC it explains how inflammation causes that damaged cell´s secrete protein that attract microglias which then attack the cells and thus generate a vicious cycle.

 

Tetrahydrostilbene (from Fo Ti aka Polygonum Multiflorum / Chinese PinYin name: He Shou Wu) inhibit this:

 

Tetrahydroxystilbene Glucoside Attenuates Neuroinflammation through the Inhibition of Microglia Activation

http://www.hindawi.c...cl/2013/680545/


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#245 jefferson

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Posted 25 October 2015 - 11:54 PM

Forgott to mention: If You cant obtain some research chems, then look whether herbs, OTC, and compounds offer the same mechanism.

Could be that some are e.g. traditionaly used and the side-effects are know i.e. they could be safe

 

 

Current Evidence of Chinese Herbal Constituents with Effects on NMDA Receptor Blockade

http://www.ncbi.nlm....les/PMC3817734/

 

Unfortunately the vast majority of herbs and supplements will not cross the blood-brain barrier in sufficient quantities to provide a clinically relevant anti-depressant effect.



#246 luv2increase

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Posted 26 October 2015 - 12:00 AM



Unfortunately the vast majority of herbs and supplements will not cross the blood-brain barrier in sufficient quantities to provide a clinically relevant anti-depressant effect.

¡

I have not posted on here for a while but this has got to be the most ignorant post on this Forum I have seen in a long long while..

You could not be further from the truth.
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#247 jefferson

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Posted 26 October 2015 - 01:13 AM

 

Unfortunately the vast majority of herbs and supplements will not cross the blood-brain barrier in sufficient quantities to provide a clinically relevant anti-depressant effect.

¡

I have not posted on here for a while but this has got to be the most ignorant post on this Forum I have seen in a long long while..

You could not be further from the truth.

 

 

I can't exactly prove it as the vast majority of supplements have simply not been tested for blood-brain barrier penetration in vivo, but this is routinely the case for many herbs once investigated. Posting a page of supps that do influence mood from the hundreds that don't or probably don't but have never been tested does not disprove what I said.

 

EDIT: Here is a source. It is an exception rather than a rule for anything, plant or man-made, to cross the BBB. http://www.researchg...d_Brain_Barrier

 

 

To reach the brain, systemically circulating compounds have to cross this barrier, which separates the blood from brain tissue. However, more than 98% of small molecule drugs and almost all larger drug molecules, including recombinant proteins, monoclonal antibodies and gene therapeutics, do not overcome the BBB [9,10] as they do not cross the barrier because of their physicochemical properties (too hydro-philic) and/or because they are recognized by export proteins being expressed by brain capillary endothelial cells.

 

 

 


Edited by jefferson, 26 October 2015 - 01:37 AM.


#248 Flex

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Posted 26 October 2015 - 08:59 PM

Well its a good point. However You have also to count the synthetic stuff in. Every natural or synthetic that isnt either smaller than IIRC 10.000 Dalton (10k Da) or lipophylic couldn´t be permeable i.e. the ones which arent tested for.

 

On the other hand: 

1) Metagene has pointed out that Borneol can increase the blood brain barrier permeability as well as other Herbals/OTC stuff (adenosin receptors)

"Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB). Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinson's disease, Alzheimer's, multiple sclerosis, and cancers of the central nervous system."

https://en.wikipedia...osine_receptors

Adenosine receptor signaling modulates permeability of the blood-brain barrier.

http://www.ncbi.nlm....pubmed/21917810

 

Temporally increasing blood-brain barrier permeability?

http://www.longecity...r-permeability/

However the more components the more possible interactions like blood thinning properties & etc.

Btw: some Hebs/OTC´s do repair the blood brain barrier

Scutellaria baicalensis attenuates blood-brain barrier disruption after intracerebral hemorrhage in rats.

http://www.ncbi.nlm....pubmed/22298450

 

2) You can spend time to find whether it is active in vivo:

The posted study of Polygonum Multflorum does penetrate the BBB

Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells, reverses memory impairment.

http://www.ncbi.nlm....pubmed/26177968

 

The herb/compound (Achyranthes bidentatae polypeptides) that inhibits in vitro the NMDA subtype NR2B, as stated above, is active in vivo.

Intravenous Administration of Achyranthes Bidentata Polypeptides Supports Recovery from Experimental Ischemic Stroke in Vivo

http://journals.plos...al.pone.0057055

I couldnt find a 100% confirmation whether this one indeed affects the certain NMDA receptor but it looks to be the case because MK-801 is a NMDA inhibitor and both had the same effects :

..Furthermore, ABPP could exert protective effects against the serum deprivation induced apoptosis via PI3K/AKT/Gsk3β pathway...

..post-ischemia administration of ABPP at 0.2 mg/kg, 1 mg/kg, or MK-801 at 1 mg/kg resulted in about a 35%, 30%, or 40% decrease in the brain infarct volume, respectively, compared with the saline control group...

 

3) From Your posted study, its problematic on behalf of the Scientists to say that most Herbal compounds dont cross the BBB because many popular herbal products like Bacopa, Ashwagandha as well as Chinese Herbs (which are used and studied for Stroke, Dementia & etc.) exert their effect on the CNS.

+ The some stated compounds are active in the CNS:

Tanshinone IIA (TSA) and Cryptotanshinone are major lipidsoluble constituents of Danshen, the dried roots of Salvia miltiorrhiza Bunge, a well known traditional Chinese medicine,

which is used for the treatment of cerebrovascular diseases including stroke and less commonly Alzheimers disease..

 

Edit:

Excuses for the text-wall


Edited by Flex, 26 October 2015 - 09:03 PM.


#249 ILIkeBeer

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Posted 02 November 2015 - 02:46 AM

I found a great article that has 20 new depression treatments currently in clinical trials.  Some have already been discussed here but it is a good read.

 

http://mentalhealthd...linical-trials/

 


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#250 ILIkeBeer

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Posted 05 November 2015 - 02:28 AM

gah... I have anxiety now I hate it... I think I might have missed a dose of my medicine. :(



#251 ILIkeBeer

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Posted 05 November 2015 - 02:41 AM

I know I have posted this drug before.  It is hard to find information about it but doesn't this seem promising??

 

PH10

 

 

An investigational intranasal spray antidepressant known for now as PH10 shows early promise in addressing two major unmet needs in the treatment of major depressive disorder: faster-acting drugs with novel mechanisms of action.

PH10 showed a large antidepressant effect in a small phase II study after just 1 week, when the first scheduled assessment took place. Future studies will look for an antidepressant effect even sooner, perhaps as early as day 1 of treatment, Dr. Michael R. Liebowitz said at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

PH10 is a proprietary pherine. The pherines are a class of intranasally administered psychoactive therapeutic agents that bind locally on nasal chemosensory receptors and trigger responses in the hypothalamus, amygdala, prefrontal cortex, and hippocampus. They have an excellent safety and tolerability profile, are effective in nanogram quantities, and do not circulate systemically in the blood. Instead, they initiate neural impulses that follow defined pathways in order to directly affect brain function, explained Dr. Liebowitz, professor of clinical psychiatry at Columbia University, New York.

He presented an 8-week, phase II, double-blind, single-site pilot randomized trial involving 30 patients with major depressive disorder. None had treatment-resistant depression. The participants were randomized to two self-administered inhalations in each nostril twice daily at a dose of 3.2 mcg/day of PH10 from a metered-dose spray device, or a high-dose group receiving 6.4 mcg/day, or placebo spray.

Baseline scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) were in the low to mid 20s. After 8 weeks of treatment, mean HAM-D scores dropped by 10.9 points in the placebo-treated controls, 16.3 points in the low-dose PH10 group, and 17.8 points in the high-dose arm, said Dr. Liebowitz, also managing director and founder of the Medical Research Network.

Particularly intriguing were the results after just 1 week: a 4.2-point drop with placebo, compared with decreases of 8.4 and 10.1 points, respectively, in the low- and high-dose PH10 arms.

"The effect sizes are pretty substantial," Dr. Liebowitz noted. He cited the Cohen’s d value of 1.01 for the comparison between high-dose PH10 and placebo, indicative of a large effect size; and a Cohen’s d of 0.71, indicative of a moderate to large effect size, for low-dose PH10 vs. placebo.

 

Baseline scores on the patient self-rated Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) averaged 40 but improved by a mean of 20.3 points in the high-dose PH10 group, 15.3 points in the low-dose group, and 10.1 points in controls.

Remission as defined by a final HAM-D score of 7 or less occurred in 80% of the low-dose PH10 group in this small study, in 60% of those on high-dose therapy, and 20% on placebo.

The most common side effects reported in patients on PH10 were daytime sleepiness, nasal irritation, and headache. Three patients on high-dose PH10 reported an increase in appetite, as did one patient in the low-dose arm and two patients on placebo. No significant changes in body weight were seen in the 8-week study.

As was frequently noted at the NCDEU meeting, depression is the mental illness with the largest prescription drug market in the United States. The need for antidepressants with new mechanisms of action is underscored by the observation that 50%-70% of patients do not experience remission on selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor therapy.

Pherin Pharmaceuticals, which is developing PH10 as a treatment for depression, also has a handful of other intranasal pherines in its pipeline. Furthest along is aloradine, now in phase III clinical trials for social anxiety disorder. Meanwhile, phase II studies have been completed for an intranasal spray used to treat premenstrual dysphoric disorder called PH80-PMD, and phase III studies for this product are gearing up. Salubrin-HF is currently in phase II studies for menopausal hot flashes. And PH15 is in preclinical testing as a cognitive enhancement agent.

 

Edited by ILIkeBeer, 05 November 2015 - 02:42 AM.

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#252 xxxxxxxx

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Posted 05 November 2015 - 03:23 AM

I'm going to try the Scopolamine protocol, DIY style. I know I have a response from regular benadryl (though it's a very dirty approximation). The idea is that abruptly nuking your muscarinic acetylcholine receptors has some kind of downstream effect on glutamate receptors. It's kind of like how Ketamine and ECT work. Plus, there's little harm to be had for wearing an anti-seasickness skin patch for a few hours, once every few days, for a week or two. But hell, if at least a single person in a single respectable study got permanently cured....I'm game. http://www.ncbi.nlm....les/PMC3250308/

 

The funny thing is that they use scopolamine as an active placebo in antidepressant trials. Turns out it might be MEDICALLY active!


Edited by MiaouMixe, 05 November 2015 - 03:28 AM.


#253 ILIkeBeer

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Posted 05 November 2015 - 04:01 AM

Awesome man.... Message me how you got your hands on that? Please let us/me know how it goes

#254 xxxxxxxx

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Posted 05 November 2015 - 04:13 AM

hahaha. I have not gotten my hands on it yet, but when I do, I will for sure let everybody know. However, I don't expect this to be a magical cure all that will work for everyone. I think I'm just a very good candidate,  due to my reaction to a simple benadryl I've taken for particularly bad insomnia nights. I've repeated said benadryl experiment many times. 

 

My anhedonia is bad enough to where I'm so numb, I spend hours looking at gore/dead bodies/ hideous infected diabetic foot ulcers images because it's the only thing that will give me some kind of mild emotional reaction. Then I take a stupid allergy pill and feel noticeably better the next day. 

 

On the other hand, why in the world is something not available OTC when it is basically the same thing as benadryl, minus the H1 antagonism?! You can date rape people with regular benadryl just as well, you can also overdose and die. Yet, we have it no problem. *sigh* #FDA logic


Edited by MiaouMixe, 05 November 2015 - 04:14 AM.


#255 jefferson

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Posted 05 November 2015 - 05:55 AM

Pherines. Interesting.

 

 

I'm going to try the Scopolamine protocol, DIY style. I know I have a response from regular benadryl (though it's a very dirty approximation). The idea is that abruptly nuking your muscarinic acetylcholine receptors has some kind of downstream effect on glutamate receptors. It's kind of like how Ketamine and ECT work. Plus, there's little harm to be had for wearing an anti-seasickness skin patch for a few hours, once every few days, for a week or two. But hell, if at least a single person in a single respectable study got permanently cured....I'm game. http://www.ncbi.nlm....les/PMC3250308/

 

The funny thing is that they use scopolamine as an active placebo in antidepressant trials. Turns out it might be MEDICALLY active!

 

How much Benadryl do you take? Are you sure you're not just getting high?



#256 xxxxxxxx

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Posted 05 November 2015 - 07:24 AM

@Jefferson. Nope. I took a normal dose for sleeping (50mg). The label instructs to dose that much multiple times a day for simple anti allergy effect. I don't feel good right away, but the benefits emerge a full day or more after. I actually do not enjoy the acute effects at all (very dizzying)

However, I'd also taken some prescription Tianeptine (glutamatergic drug). It did not help and I'm discontinuing due to side effects, but I also feel like it sensitized me to the sedating effects of Benadryl. Now Benadryl is also an H1 antagonist (and wakefulness promoting agent modafinil is pro-histamine) so it could be that part that is sedating (though I can't see Tianeptine interaction mechanism there). Still...confounding factor.

Once again, this whole idea probably isn't ideal, but it's just so easy and risk free to try! You actually need less scopolamine than is used for the indicated seasickness purpose.

#257 xxxxxxxx

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Posted 05 November 2015 - 07:33 AM

Oh, I've also had mild luck with REM sleep deprivation, aka wake yourself at 4am. Good effects last until you fall asleep again. You also happen to be sleepy of course, so this is just a vacation, not a cure. Funny thing is that depressives have too much REM sleep, and REM is controlled by cholinergic mechanisms.

#258 Shai Hulud

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Posted 05 November 2015 - 12:14 PM

Do you have a source for me about REM sleep and acetylcholine?

#259 ILIkeBeer

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Posted 06 November 2015 - 01:58 AM

I might have posted about this... maybe not but this is available now.. anyone tried it?  It is called Spadin.  Here is a great article on it... seems like it might be worth a try for a quick pick me up.

 

http://mentalhealthd...antidepressant/

 



#260 jefferson

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Posted 06 November 2015 - 03:40 AM

I might have posted about this... maybe not but this is available now.. anyone tried it?  It is called Spadin.  Here is a great article on it... seems like it might be worth a try for a quick pick me up.

 

http://mentalhealthd...antidepressant/

 

As in available available? From where?



#261 ILIkeBeer

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Posted 06 November 2015 - 03:45 AM

 

I might have posted about this... maybe not but this is available now.. anyone tried it?  It is called Spadin.  Here is a great article on it... seems like it might be worth a try for a quick pick me up.

 

http://mentalhealthd...antidepressant/

 

As in available available? From where?

 

 

 

Here

 

http://www.tocris.co...26#.VjwiI_mrQ-U

 

it is expensive but perhaps ti goes a long way.



#262 eon

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Posted 09 November 2015 - 08:10 AM

For these reasons, selective serotonin releasing agents (SSRAs) such as MDAI and MMAI have been proposed as novel antidepressants with a putatively faster onset of action and improved effectiveness compared to current treatments.[65]

 

https://en.wikipedia...5-HT1A_receptor

 

MDAI may be hard to find but MMAI is unscheduled:

 

5-Methoxy-6-methyl-2-aminoindane (MMAI), is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University.[1] It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) and produces entactogen effects in humans.[1][2][3] It has been sold as a designer drug and research chemical online since 2010.[4]

 

 

MMAI has been shown to relieve stress-induced depression in rats more robustly than sertraline,[5] and as a result it has been suggested that SSRAs like MMAI and 4-MTA could be developed as novel antidepressants with a faster onset of therapeutic action and superior efficacy to current antidepressants such as the selective serotonin reuptake inhibitors (SSRIs).[6]

 

https://en.wikipedia.org/wiki/MMAI



#263 Shai Hulud

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Posted 09 November 2015 - 08:49 AM

I'd guess that SSRAs are to easy to abuse for this purpose.

#264 Irishdude

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Posted 09 November 2015 - 12:59 PM

I have stress induced depression, and it has destroyed my life and cognition for the last 3 years. Has anyone used this short term to reverse the damage on mood and cognition? Venlafaxine(SSRI@150mg) for me numbs my libido and stress response.



#265 xxxxxxxx

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Posted 09 November 2015 - 07:05 PM

@irishdude,

Have you tried any glutamatergics? You could try Tianeptine (though it didn't work for me). It also is meant to work within 2-4 weeks, not 6-8. I think it would be better for a more acute stress situation, rather than my weird prolonged anhedonia-from-nowhere. 

 

It has very few side effects, none of which are a damaged libido. 


Edited by MiaouMixe, 09 November 2015 - 07:06 PM.


#266 sant2060

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Posted 16 November 2015 - 07:59 AM

I have stress induced depression, and it has destroyed my life and cognition for the last 3 years. Has anyone used this short term to reverse the damage on mood and cognition? Venlafaxine(SSRI@150mg) for me numbs my libido and stress response.

Lucky bastard, I have same response from 57.25mg of Venlafaxine :)

My sweet spot is 37.5, taken twice daily.
Venlafaxine combines very nice with Mirtazepine...combo called Californian rocket fuel.

Mirtazepine also should have libido enhancing properties (albait not for me :( ), so being already on Venlafaxine maybe it would be smart to try this combo...You could probably lower Venla dose, experiment a bit.

I dont have access to Mirtazepine, and it previously had some wird effects on me (lower libido, racing thoughts), so currently I'm doing less known combo, 37.5 Venla+150mg Wellbutrin Xr.

Feeling pretty much normal, Most depression symptoms gone, able to work and concentrate for bigger periods of time, stress in normal range...just damn anhedonia still lingers, and libido is so-so.

Edited by sant2060, 16 November 2015 - 08:01 AM.


#267 ILIkeBeer

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Posted 25 November 2015 - 03:00 AM

I know this might be a little off topic.  But has anyone checked this guys videos out?  They are pretty good I know he is following the mindfulness type thing but I like how he explains it.

 

 

https://www.youtube....hElkrief/videos

 

 


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#268 ILIkeBeer

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Posted 30 November 2015 - 01:09 AM

Something That I just found and to me looks promising as something for extremely severe depression!!

 

Focused Ultrasound for depression.

 

http://www.medscape....warticle/851906

 

This is very new so there is little information out on it.

 

There is also a clinical trial underway!!  https://www.clinical...how/NCT02348411

 


Edited by ILIkeBeer, 30 November 2015 - 01:09 AM.


#269 thomasanderson2

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Posted 30 November 2015 - 05:28 PM

I stumbled upon this:

http://www.clinical-depression.co.uk/

Basically indicating that thinking and behavioral patterns are the treatment answer. 



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#270 Shai Hulud

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Posted 30 November 2015 - 05:42 PM

I stumbled upon this:

http://www.clinical-depression.co.uk/

Basically indicating that thinking and behavioral patterns are the treatment answer. 

 

This will work for some and of course psychotherapy is almost never a bad idea. For many it won't work, especially the ones with a higher level of genetic disposition. Also, it's hardly a breakthrough.







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