GPC (choline), Uridine, DHA
#31
Posted 21 October 2011 - 06:02 AM
#32
Posted 21 October 2011 - 06:58 AM
I even dropped MB completely, as I found it an annoyance by comparison.
#33
Posted 21 October 2011 - 07:32 AM
The parkinson's trial showed an average of 11 days to repair and 2 weeks to be undone after stopping.. except for people who started the trial completely clean, with tremors, etc. - their neural repairs lasted 2-3 *months*.
#34
Posted 21 October 2011 - 08:17 AM
You have clearly established that you are more than capable of assembling a decent collection of absracts on Uridines nootropic potential(which seems high). However you are behaving remarkably immaturely and I believe you discredit these forums in that you have not shown that Uridine is significantly Genotoxic and Carcingenic(when it has been brought to your attention). Geez your indirectly supporting the prohabitation of nootropics in that your exposing the general population to partial misleading info, which could have deadly consequences.
Its possiable the Genotoxicity/Carcingenisty can be moderated to an acceptable level through various means, so maybe that should be your or someone elses Convo. Why bring up seldom used substance in a multipost thread aswell.
#35
Posted 21 October 2011 - 10:04 AM
Quote
More recently, uracil(uridine) incorporation into DNA of folate-deficient HL-60 cells and lymphocytes was reported (Wickramasinghe and Fida 1993). Increased dUTP/dTTP{uridine triphosphate/thymine tri posphate} ratios delayed progression of the DNA replication fork (Wickramasinghe and Hoffbrand 1980) and passage of cells through the cell cycle (James et al. 1994) and promoted genomic instability (Pogribny et al. 1995). In vitro studies demonstrated that increased dUTP/dTTP ratios promoted folate fragile site expression (Reidy 1987), DNA strand breaks (Li and Kaminskas 1984), error-prone DNA repair (Holliday 1985) and mutagenesis (Mattano et al. 1990). The role of folate deficiency in DNA damage was reviewed recently (Blout and Ames 1995).
Further evidence that an imbalance in nucleotide pools, specifically an increase in dUTP, is tumorigenic comes from studies indicating that an excess of dietary orotic acid, a precursor for uracil, promotes carcinogenesis in liver (Rao et al. 1983), mammary gland (Elliot and Visek 1989) and duodenum
Edited by QuantumTubule, 21 October 2011 - 10:07 AM.
#36
Posted 21 October 2011 - 10:09 AM
I think I get enough methylfolate from B9 and my diet to handle the additional uridine supplementation, but you're right - natural sources of uridine at least keep their own balance. 500ml of tomato juice may equal 15mg of uridine, so anyone who is concerned about genotoxicity would be advised to stick to natural sources.
It's funny that none of the human trials mentioned balancing with methylfolate, even up to 5g/day. I wonder how much of an issue it is at these levels - any papers/links? I haven't seen anything useful, at this point.
I can't see that these self-studies are any riskier than MB, at this stage. Thoughts?
Edited by MrHappy, 07 November 2012 - 11:50 PM.
#37
Posted 21 October 2011 - 10:11 AM
#38
Posted 21 October 2011 - 10:18 AM
OK, thanks - you must have been compiling those links while I was writing my last comment.
what ratio are you taking these three supplements in per day?
#39
Posted 21 October 2011 - 10:40 AM
All once per day.. Was contemplating an increase to 500mg of uridine after reading the parkinson's trial, although this is working well, so it's just curiosity.
Still chewing on the previous links for the moment.
#40
Posted 21 October 2011 - 11:51 AM
(thank you QuantumTubule)
Human chromosome hot points. IV. Uridine-induced hot-point breaks at 3p14 and 16q23-24 and increased expression of fragile site Xq27 in folate-free medium.
Li N, Zhou XT.
Abstract
Peripheral lymphocytes from 16 healthy adults, 9 pregnant women, and 3 fragile X syndrome patients were cultured in Eagle's minimum essential medium without folic acid (MEM-FA). The addition of 2 mM, 4 mM, or 8 mM uridine 24 h or 72 h prior to harvest resulted in increases of chromosome gaps or breaks, especially at hot points 3p14, 16q23-24, and at fragile site Xq27. Pregnant women showed higher frequencies of 3p14 breaks and total chromosome breaks than men and non-pregnant women. The other chromosome regions, such as 6q26, 7q23, 7q35, 6p25, Xp22, 14q23 and 11p13, also frequently showed gaps or breaks. The results indicated that the unbalance of nucleotide pools was one of the causes of chromosome breakages. The higher frequencies of chromosome gaps and breaks under the condition of thymidylate stress may be due to the misincorporation of uracil instead of thymine into DNA
&
Deranged DNA Synthesis by Bone Marrow from Vitamin B12-Deficient Humans†
Article first published online: 12 MAR 2008
DOI: 10.1111/j.1365-2141.1968.tb00364.
Summary. The synthesis of thymine DNA from deoxyuridine and uridine was studied by culturing human bone marrow for 1–3 hours in the presence of radioactive-labelled nucleosides. In the current study, this in vitro system appeared useful to test the potential efficacy of agents (such as methionine) which might be used to improve or retard improvement of patients with megaloblastic anaemia.
In the bone marrow from patients with B12-deficient or folate-deficient megaloblastic anaemia, there was defective incorporation of deoxyuridine into thymine DNA. This defect was partially corrected by added B12 in the B12-deficient but not the folate-deficient marrows, and completely corrected by folic acid (pteroylglutainic acid) in both types of deficient marrow. The folate antagonist rnethotrexate blocked the corrective effect of B12. Incorporation of labelled uridine into DNA of B12-deficient megaloblastic marrow was enhanced less by B12 than by PGA. Vitamin B12 antagonists failed to depress the incorporation of labelled uridine into DNA in bone marrows from both normal and B12-deficient patients.
These results support the concept that inadequate DNA synthesis in B12 deficiency is due in large measure to blockade in folate metabolism brought about by lack of B12. 5-Methyl-tetrahydrofolate, which may accumulate in B12 deficiency, failed to correct the defect in DNA synthesis, adding further evidence to the concept of metabolic trapping of this form of folate in B12 deficiency. Thus, riboside reduction in man may be independent of B12, as it is in E. coli, rather than dependent on B12, as it is in L. leichmannii.
#41
Posted 21 October 2011 - 12:33 PM
I've posted comments with the same warning on other threads where the topic has come up. Hopefully that should help prevent anything untoward occuring to anyone else new to uridine.
Again, it's interesting that none of the human studies mentioned supplementing folate or B12 as part of the trial.
Personally, I believe I am well covered by my existing Vitamin B complex supplement, but I'll definitely increase my B-complex supplementation proportionally, if I go up to 500-1000mg of uridine per day - or perhaps switch to a natural source, if I can find a suitable one.. ie. not yeast... or at least not ALIVE yeast.
Edited by MrHappy, 21 October 2011 - 12:54 PM.
#42
Posted 21 October 2011 - 03:13 PM
#43
Posted 21 October 2011 - 04:37 PM
#44
Posted 21 October 2011 - 05:55 PM
#45
Posted 21 October 2011 - 09:09 PM
1kg of tomatoes (dry weight) = 1g uridine.
(according to -sigh- wikipedia)
#46
Posted 21 October 2011 - 09:33 PM
I've noticed that good old berroca contains 400mcg of folic acid per tab and B12, of course. So.. Perhaps 1 tab per 500mg of consumed uridine is a good ratio.
Adding some natural folate, as well, would probably be a good idea. Here's a list of folate containing foods:
http://ods.od.nih.go...heets/folate#h2
#47
Posted 23 October 2011 - 02:26 AM
http://www.pnas.org/.../10123.full.pdf
It seems to have some other anti-tumour effects:
http://www.spirulina...anticancer.html
I also found a great article about nucelotide cycles:
http://themedicalbio...metabolism.html
There also seems to be some preference for reducing choline when using uridine for depression, relating to dopamine agonistic behaviour:
http://www.longecity...ridine-choline/
#48
Posted 23 October 2011 - 04:30 AM
New Studies Illuminate Brain's Complex Neurotransmission Machinery, Point to Potential Source of Problems Leading to Neurodegenerative and Psychiatric Conditions
NEW YORK (June 22, 2011) — Two studies featuring research from Weill Cornell Medical College have uncovered surprising details about the complex process that leads to the flow of neurotransmitters between brain neurons — a dance of chemical messages so delicate that missteps often lead to neurological dysfunction.
A recent Nature Neuroscience study led by Dr. Timothy Ryan, professor of biochemistry at Weill Cornell Medical College, demonstrates that individual neurons somehow control the speed by which they recycle synaptic vesicles that store neurotransmitters before they are released. No one had expected that neurons would have such a powerful "gas pedal," says Dr. Ryan.
Dr. Ryan is also contributing author of a second, Yale University–led study published today in the online edition of Neuron. It shows that the common understanding about how proteins help form these key storage vesicles is flawed.
The two findings help refine science's understanding of the biomechanics that control neurotransmission at the synaptic gap between brain neurons, Dr. Ryan says.
"We are looking under the hood of these machines for the first time," he says. "Many neurological diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia and other neurodegenerative and psychiatric disorders are considered to be synaptopathies — pathologies of synaptic function. So repairing them will require that we understand how they work."
Both studies focus on synaptic vesicles, which are bubble-like structures that store neurotransmitters within a bi-layer of fatty membranes at the synaptic junction.
Scientists know that in order to deliver neurotransmitter messages between cells, the synaptic vesicle merges with the surface of the brain cell at the synapse and releases the message. Then these synaptic vesicles, which are in limited supply, must be retrieved, rebuilt and refilled with neurotransmitters, Dr. Ryan says. "Failure to do so would result in the synapse running out of vesicles rather quickly, and proper neurotransmitter function depends on their continuous availability."
Measuring Neuronal Speed
The Nature Neuroscience study was designed to look at what controlled the speed of the vesicle recovery process. This speed, which dictates the availability of vesicles, has long been considered to be one of the limits as to how fast neurons can continuously communicate, especially in high-demand situations, Dr. Ryan says.
To study the speed of this recovery process, senior author Dr. Ryan and first author Moritz Armbruster, a Rockefeller University graduate student who worked in Dr. Ryan's laboratory, used a tool that took optical recordings of the speed of vesicle recycling across 84 different neurons.
They discovered something quite unexpected — an individual neuron retrieves all of its synaptic vesicles at pretty much the same speed. "It is as if the neuron is following orders from a cell-wide central gas pedal," Dr. Ryan says. They also found that while each cell had its own speed at recovering the vesicles, that rate varied four-fold across the different neurons — even if the neurons were performing identical functions, such as secreting the same neurotransmitter.
"When we compared different neurons, we found that each cell is telling its synapses to go at its own speed," he says. "The mystery that remains is the nature of this gas pedal, and if it might be important in therapeutic approaches to tackling synaptopathies."
Debunking the Dynamin Theory of Synaptic Recovery
The Neuron study looked at proteins involved in one phase of the recovery process, the separating and pinching off of the membrane of the synaptic vesicle from the membrane of the neuronal cell. It was led by Dr. Pietro De Camilli, a professor of cell biology and neurobiology at Yale University and a Howard Hughes Medical Institute investigator, and his colleague Dr. Shawn Ferguson, currently an assistant professor of cell biology also at Yale.
Based on studies in the 1980s, researchers had believed that a protein called dynamin, which comes in three forms (1, 2 and 3), was critical to this "membrane fission" step in the formation of vesicles.
In 2007, the Yale researchers tested whether dynamin 1, which represents 90 percent of all dynamin in the brain, was, as believed, the key protein involved in synaptic vesicle membrane fission. They generated a mouse that lacked the protein but found it produced only subtle differences in the fission process. This surprising discovery was published in Science.
In the new study, the research team, which included Drs. Ryan, Mr. Armbruster and others, looked at what happened when both dynamin 1 and dynamin 3, which makes up 99 percent of dynamin protein, are missing. They used the same optical methods employed in the Nature Neuroscience study to examine the speed of the synaptic vesicle retrieval process.
"Our studies showed that retrieval is now severely impaired when you have neither dynamin 1 nor dynamin 3, which shows us that dynamin 3 has a major presynaptic function," Dr. Ryan says. "Remarkably, however, the retrieval process still happens, and it is unknown whether that could be due to dynamin 2, because that protein accounts for only a tiny percentage of dynamin protein in the brain. It makes sense that there is another protein or biomechanical process that is contributing."
Dynamin is a protein known to play a critical role in synaptic vesicle retrieval. The observation that synaptic transmission can still occur, albeit in a much-impaired way, in the absence of the overwhelming majority of dynamin reveals a remarkable and unexpected plasticity of nerve terminals, says Dr. De Camilli.
The Nature Neuroscience study was funded by grants from the National Institutes of Health and the David Rockefeller Graduate Study of the Rockefeller University.
The Neuron study was supported in part by the G. Harold and Leila Y. Mathers Charitable Foundation, National Institutes of Health grants, and the W.M. Keck Foundation. Co-authors are, from Yale University School of Medicine: Andrea Raimondi, Shawn M. Ferguson, Xuelin Lou, Summer Paradise, Silvia Giovedi, Mirko Messa, Nao Kono, Junko Takasaki and Valentina Cappello; and Eileen O'Toole from the University of Colorado at Boulder
#49
Posted 23 October 2011 - 04:49 AM
Also:
http://www.freshpate...20100261669.php
(excerpt, but the whole page is worth a read..)
Nucleotides
The present composition preferably comprises uridine and/or an equivalent thereof, preferably at least one uridine or an equivalent thereof selected from the group consisting of uridine (i.e. ribosyl uracil), deoxyuridine (deoxyribosyl uracil), uridine phosphates (UMP, dUMP, UDP, UTP), nucleobase uracil and acylated uridine derivatives. Preferably the present composition comprises an uridine phosphate selected from the group consisting of uridine monophosphate (UMP), uridine diphosphate (UDP) and uridine triphosphate (UTP). Most preferably the present composition comprises UMP, as UMP is most efficiently being taken up by the body. Preferably at least 50 wt. % of the uridine in the present composition is provided by UMP, more preferably at least 75 wt. %, most preferably at least 95 wt. %.
The present method preferably comprises the administration of uridine (the cumulative amount of uridine, deoxyuridine, uridine phosphates, nucleobase uracil and acylated uridine derivatives) in an amount of 0.01-6 g per day, preferably 0.1-2 g per day, more preferably 0.2-1 g per day.
Preferably the present composition comprises uridine phosphate, preferably uridine monophosphate (UMP). The UMP is very efficiently taken up by the body. Hence, inclusion of UMP in the present composition enables a high effectivity at the lowest dosage and/or the administration of a low volume to the subject.
The present method preferably comprises the administration of a composition comprising uridine in an amount of 10-1000 mg per unit dose, preferably 20-600 mg per unit dose, more preferably 50-400 mg per unit dose, in particular at least 100 mg per unit dose, based on the dry weight of the unit dose. The relative amount of uridine and its equivalents is preferably 1-50 wt %, more preferably 2-40 wt %, most preferably 5-25 wt %, based on the total dry weight of the unit dose.
The required unit and daily dosages of the equivalents on a weight base can be calculated from the dose for uridine by taking equimolar amounts using the molecular weight of the equivalent and of uridine.
The present method preferably comprises the administration of uridine monophosphate (UMP) in an amount of 0.01-3 g per day, preferably 0.1-2 g per day, more preferably 0.2-1 g per day. Preferably 1-37.5 mg UMP per kilogram body weight is administered per day. The required unit and daily dosages of the equivalents on a weight base can be calculated from the dose for UMP by taking equimolar amounts using the molecular weight of the equivalent and of UMP, the latter being 324 Dalton.
In a further preferred embodiment the present composition preferably does not contain high amounts of other nucleotides. Hence, preferably the weight ratio adenosine/uridine in the present composition is below 0.1, more preferably below 0.01, most preferably 0. Preferably the weight ratio guanosine/uridine in the present composition is below 0.1, more preferably below 0.01, most preferably 0. Preferably the weight ratio inosine/uridine in the present composition is below 0.1, more preferably below 0.01, most preferably 0.
In the composition, it is preferred that the weight ratio of DHA and/or EPA to uridine and its equivalents, recalculated in equimolar amounts of UMP, is at least 1, more preferably at least 1.5. More preferably, DHA is predominant in the composition over uridine and its equivalents in terms of weight.
The composition may further include cytidine. Preferably the weight ratio of uridine to cytidine is larger that 1.0, more preferably 2.0, most preferably more than 5.0. The term uridine as used herein relates to uridine and/or equivalents thereof. The term cytidine as used herein relates to cytidine and/or equivalent thereof. Although cytidine is a precursor of uridine, which passes the blood brain barrier, it is more efficient and effective to include uridine in the present composition.
Tocopherol
The present composition further contains a tocopherol and/or an equivalent thereof, including methylated phenols derived there from. Tocopherols contain a chromanol ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals and a hydrophobic side chain. The definition also includes tocotrienols, which have structures corresponding to tocopherol, except with an unsaturated bond in each of the three isoprene units that form the hydrocarbon tail. Tocopherols have a saturated phytyl tail.
The term “a tocopherol and/or an equivalent thereof”, as used in this description, comprises tocopherols, tocotrienols, pharmaceutical and/or nutritional acceptable derivatives thereof and any combination thereof. Tocopherols and tocotrienols occur in alpha, beta, gamma and delta forms, determined by the number of methyl groups on the chromanol ring. Each form has slightly different biological activity. An example of a pharmaceutical and/or nutritional acceptable derivative is a salt such as, for instance an acetate or succinate.
More preferably, the composition comprises tocopherol family members, more preferably alpha-tocopherol and its nutritional and/or pharmaceutically acceptable equivalents.
The amount of tocopherol is preferably 0.1-50 mg per unit dose, more preferably 1-40 mg per unit dose, most preferably less than 30 mg per unit dose. These numbers correspond to the amount of alpha-tocopherol. The required unit and daily dosages of the equivalents of alpha-tocopherol on a weight base can be calculated using, for instance, the table provided below. Therein, the amount of 1.0 mg of the tocopherol equivalent is recalculated in terms of “x” mg α-TE. R stands for the side groups attached to the phenyl, which can be methyl or hydrogen, depending on the tocopherol at dispute.
Tocopherol form x mg α-TE IU vitamin E RRR-α-tocopherol 1.0 1.49 (d-α-tocopherol) all rac-α-tocopherol 0.74 1.10 (d,1-α-tocopherol) RRR-α-tocopheryl acetate 0.91 1.36 all rac-α-tocopheryl acetate 0.67 1.00 RRR-α-tocopheryl succinate 0.81 1.21 all rac-α-tocopheryl succinate 0.60 0.89 RRR-β-tocopherol 0.50 0.75 RRR-γ-tocopherol 0.10 0.15 RRR-δ-tocopherol 0.03 0.05 RRR-α-tocotrienol 0.50 0.75 RRR-β-tocotrienol 0.05 0.08
#50
Posted 02 November 2011 - 12:05 PM
#51
Posted 05 November 2011 - 01:31 PM
How long have you been using Uridine + Alpha GPC for now, and when did you first notice the effects of the Uridine?Bump. Anyone else with feedback?
What else are you taking in addition to Uridine, A-GPC and Flax?
MIT’s research has shown that administration of uridine increases the production of neurites and dendrites. These outgrowths from the nerve cell body are a natural part of neuron development.
This sounds really promising. I want to read the other large bodies of information in this thread but I just don't have the willpower/concentration to plow through it. I'll be starting Aniracetam tomorrow, maybe that will give me the boost I need to read more than a few paragraphs...
Either way, I'm definitely going to give Uridine a try some time in the near future.
#52
Posted 05 November 2011 - 05:05 PM
I'm also very interested in uridine, but am concerned about the possible cancer effect. I've read a study that 500mg CDP-Choline increases plasma uridine level by 70-90% (search CDP-Choline and uridine and you will find it). How is this comparing with direct intake of uridine and do you think taking CDP-Choline comparable to (or nearly so) uridine directly?
#53
Posted 05 November 2011 - 05:27 PM
I'm also very interested in uridine, but am concerned about the possible cancer effect. I've read a study that 500mg CDP-Choline increases plasma uridine level by 70-90% (search CDP-Choline and uridine and you will find it). How is this comparing with direct intake of uridine and do you think taking CDP-Choline comparable to (or nearly so) uridine directly?
Hmm, do you have a link or a reason to suspect a cancer effect?
CDP-choline(cytidine 5'-diphosphocholine) supplies cytidine(also a nucleoside) which is converted to uridine. So it's about the same thing.
#54
Posted 05 November 2011 - 07:21 PM
Hmm, do you have a link or a reason to suspect a cancer effect?
CDP-choline(cytidine 5'-diphosphocholine) supplies cytidine(also a nucleoside) which is converted to uridine. So it's about the same thing.
I don't have a link, but people have talked a lot in this thread and were suggesting taking folate with it.
I remember reading that cdp-choline converts to cytidine in rats but to uridine in human, and the study that showed a 70%-90% increase in plasma level was on human.
#55
Posted 05 November 2011 - 08:29 PM
I don't have a link, but people have talked a lot in this thread and were suggesting taking folate with it.
Yeah, I think it does cause a folate deficiency, i get tongue sores if I stop my b-complex for any length of time.
#56
Posted 05 November 2011 - 09:59 PM
Regarding cancer/genotoxicity:
The invitro studies were done in folate-free cells. Something that is unlikely to occur in nature. Supplementing folic acid - which, like uridine, you also obtain from your daily dietary intake, should be all that is required to prevent that scenario from ever occuring. The issue appears to be that if you uprate the production of new cells without sufficient building-blocks to support that function, you'll end up with transcription errors and strand-breakage in the new cells.
If you are concerned that you are unable to supplement sufficient folate (I just take a berocca with it), try a natural source of uridine, like spirulina (5%), yeast (3%), tomatoes (.1%).
Edited by MrHappy, 10 November 2012 - 09:38 AM.
#57
Posted 05 November 2011 - 10:10 PM
Effects:
It's quite different, in that there is no 'buzz' or stimulant effect whatsoever. The most obvious effect is increased mental clarity, calmness, cognitive ability and recall. A single dose would have little appreciable effect.
It will also raise your levels of acetylcholine *without* robbing the lipid membranes.
What it does is gradually repair and enhance your brain on a daily basis, by significantly promoting neurogenesis - you create or repair neurons, dendrites and lipid membranes. This includes receptors as well.
The overall 'effect' is that you feel like yourself, but unimpeded - existing cognitive or emotional issues disappear over a week or so and you start feeling and being awesome. Your capacity to learn and retain information is noticably better. Particularly when you relax and stop trying to mentally compare your responses to pre-supplementing days, I found.
My wife was recovering from Zoloft withdrawal, which left her with occasional anxiety attacks and obsessive behaviour. That just got better and then stopped altogether. Essentially she appears to have have made peace with her problems, as they arose, and moved on. Her critical thinking has improved and she is making better decisions overall. Her scores playing online Scrabble have increased to the point where she is just destroying the other players. She was smart to begin with, but now she appears to be 'unshackled', if you like.
In short, it just makes you a better and more capable person.
Side effects noticed: none noticed
Withdrawal effects: none
Interaction with drugs: none that I've been able to find on pubmed or google, other than mediating side-effects from neuroleptics and antidepressants.
My daily morning regime is:
500mg of alpha-gpc choline
250mg of uridine-5'-monophosphate
1 berocca
Washing down:
4 capsules of flaxseed oil (I'm vegetarian)
1 vitamin E capsule
1 grape-seed extract capsule equiv 12000mg
My nightly regime is:
1 lecithin capsule 1200mg
1 grape-seed extract capsule
Occasionally a bacopa capsule, 2 hours before sleep. It makes me too sleepy to feel like sex, so not an 'every day' supplement.
I found 2 American suppliers that sell bulk powder through their websites and also through ebay. Superiornutraceuticals - uridine and nutrabiolabs - alpha-gpc. Quality has been good. Shipping has been very quick.
The bulk alpha-gpc is annoying to dispense. The uridine jar comes with a 250mg scoop, but since the uridine sticks like crazy, I leave the scoop out of the jar, to prevent wasting it. 1 scoop of uridine in the cup, 2 scoops of alpha-gpc, then add the water and berocca. Stir. Voila.
Be sure to start adding some extra study matter to your routine - there's no point having extra cognitive ability and not using it to improve your knowledge-base!
#58
Posted 05 November 2011 - 11:10 PM
Cougar: I can't seem to upload this image easily, but I've used google image search to locate it!
http://images.google...iw=1118&bih=882
#59
Posted 05 November 2011 - 11:43 PM
#60
Posted 06 November 2011 - 12:02 AM
Also tagged with one or more of these keywords: choline, uridine, dha, omega-3, epa, ump, tau, b vitamins
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