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Thoughts on the methylation treatment for CFS

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Jul 14, 2010.

  1. dannybex

    dannybex Senior Member

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    Lots to think about (if only my brain was working)...

    Just my two cents, but it seems to me that it is indeed probably multifactorial (is that a word?) and will be different for everyone. But I wouldn't be surprised that many of us are not getting enough of the trace minerals needed to support the conversion of glutamate to glutamine, nor the amino acids like glycine and taurine which have been reported to help lower/convert glutamate levels.

    And the accumulation of heavy metals/pesticides/chemicals over one's lifetime makes a lot of sense Rich. Hardly anyone mentions pesticides these days, despite the increasing evidence of their involvement in many different diseases/syndromes.

    Here's something perhaps to add to the mix -- salicylate intolerance:

    10 years ago I had an amino acid profile done by Great Smokies, and am only now finally waking up to it's significance. I was very low in glycine (required to detoxify benzoates (described as excitotoxins by Usman) and salicylates), was also low in taurine, and the highest amino tested was...glutamate. The results way back then suggested "nitrogen insufficiency", "impaired xenobiotic detoxification" and an "increased susceptibility to occlusive arterial disease". :eek:

    (Why my docs back then didn't take this more seriously is confounding, but since they didn't, I didn't. (Perhaps it's because the lab test results were printed in rainbow colors and the lab's name was "Great Smokies" instead of the more legit-sounding "Genova".)

    The CFS - Autism connection is fascinating. A sub-group of autistic kids have been found to react to salicylates (found in artificial colors, and also at high levels in certain common vegetables, fruits, and spices, etc.). If we're all a part of a 'spectrum', then it might make sense that over time certain amino acids (esp glycine) become depleted as a result of trying to detoxify these salicylates or phenolic compounds. Sals can cause hyperactivity (to say the least), anxiety, tinnitus, difficulty concentrating/finding the right words(!), digestion problems, etc. I've definitely had an anxiety issue even before developing CFS, so am hoping there is a salicylate connection, and that might explain why my glycine was so low.

    Do the digestive problems occur because they body is basically saying NO to any more of these compounds until amino acid levels increase?

    Does correcting the methylation block using b12/folates expose other detoxification pathway problems -- sulfation, amino acid conjugation, acetylation, etc. -- or is one getting increased excitoxicity because now that methylation is working well, the other pathways become more imbalanced?

    Just my two cents,

    Dan

    p.s. For those who can tolerate it, might SAM-e be a way to increase ATP levels?
  2. Graeme

    Graeme almost there...

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    Hi Rich, thanks for tackling this aspect of the illness. I experience extreme excitotoxicity. It's gotten to the point where I can't raise my energy in any way without suffering the consequences -so I'm virtually supplement free and can't even use acupuncture or reiki. Obviously the following is just my interpretation of things; if people are feeling better, I think that justifies the protocol, however...

    The list of supplements that produce excitotoxicity in me is 100% compatible with Dr. Cheney's ETM-determined toxic therapies. Therapies that counter my toxicity are: wormwood/artemisinin, magnesium, opiates -also supported by ETM. (I'll add that a perceptible benefit from wormwood is not attainable by swishing it around in your mouth. A dose at the level used to treat parasitic infection would have to be used for a few days.) This convinces me that Cheney's oxygen toxicity and supplement toxicity is in fact excitotoxicity. They're one and the same. Of course he claims this is present in all PWC's he's tested, not just a third. Following this, excitotoxicity may be the rule, not the exception.

    I once tolerated methylation supplements but received little benefit from them. Then years later I retried them and experienced a boost whose repercussions were not so severe at first. So I used them on and off for several months thinking the giddiness I felt the following day was detoxification. It didn't take long to realize this wasn't the case and that if I continued it would be the death of me. If I'm well rested and receive a shot of MB12 I feel wonderful, healthy, if a bit wired. The next day I feel spacey and wiped out, muscles twitching, etc. I've read similar accounts by PWC veterans. I agree reduced glutathione can be low because it's being used up on things healthy folks don't have to deal with. And Cheney believes it's superoxide dismutase that's being used up. What's causing this is the million dollar question? Throwing more energy into the cell while this is going on only makes it worse. Maybe the toxicity is kept in check by various buffering systems, like Cheney explains in his 2009 lecture: HPA axis, P 450, etc. And you may even feel a little lift while this is straining your system, but when the buffers begin to fatigue, and fail to keep it under control the toxicity runs unrestrained and is finally felt by the sufferer. I think most PWC's would say they have a certain sensitivity to light, sound, and experience muscle twitching or some other symptom like "feeling wired" even while not trying to increase methylation. I believe treating this toxicity is the key to treating the illness.

    I've done a whole lot of chelating with lipoic acid which didn't better the situation, though the recycling effects of LA were greatly appreciated, as were those of curcummin. Unfortunately these supplements now cause toxicity as well. A mold clean up cleared up my head a whole lot but didn't mitigate toxicity. In my experience GSH also causes excitotoxicity.

    Rich, I'd like to know if you know of anyone who's experienced excitotoxicity and rid themselves of it. Also, can you explain what effect wormwood could have on the methylation cycle that would reduce toxicity and increase energy?

    Thanks, Graeme
  3. dannybex

    dannybex Senior Member

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    one more question...

    Is it possible that higher amounts of b12/folate may deplete levels of the other b-vitamins?

    Dr. Myhill recommends niacinamide as being very helpful to recycle ADP into ATP...so I wonder if the b12/folate might reduce b-3 or other b's?
  4. dannybex

    dannybex Senior Member

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    Interesting Graeme. I definitely have had more muscle twitching lately too. It's been and off and on thing for years, but will go away for literally years. My vitamin d levels were tested recently, and found to be 36.7 -- lower than ideal. So will see if increasing d might help resolve the twitching. I can't recall that I ever had a prolonged twitching issue during the summer months...

    Re Alpha Lipoic acid: Did you take it on the 'every three hours' plan, as recommended by Andrew Cutler?

    Dan
  5. Graeme

    Graeme almost there...

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    My vitamin D is borderline too. I kind of like Trevor Marshall's explanation for this one, because I know I have some intracellular bugs. And, of course, I'm exctitotoxic from vit. D.

    Lipoic acid I did just as Cutler suggested with DMSA for the first four months. The detox symptoms faded but I continued on with fairly large amounts of LA daily. For about a year and a half this probably doubled my endurance, not to mention picked up my mood considerably. That's something I'd like to stress concerning my experience with excitotoxicity; a supplement may be great for a while and then turn toxic. However, according to Cheney there are universally toxic substances for PWC's.
  6. dannybex

    dannybex Senior Member

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    Yeah, I think we can become hypersensitive to anything if we take it or eat it every day. Two of the people I know who have recovered both went on strict rotation diets, and I think may still be on them...and one of them rotates her probiotics every day.

    We'll have to agree to disagree re Marshall, but that's another novel that would take this thread way off topic. Perhaps you might be able to tolerate a different form of d-3, like 'dry' instead of fat-based? Some have found that starting low and increasing it slowly can help. Also...calcium has been described as exicitotoxic by autism experts, so perhaps if you're taking that, or getting "too much" (?) in the diet, that may be the problem, along with insufficient magnesium. I think the latter is true in my case...but it takes a long time to raise mag levels...

    d.
  7. Rosemary

    Rosemary Senior Member

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    Hi Rich,

    I just wanted to share this interesting research that I read today ...

    Astrocytes Control Breathing Through pH-Dependent Release of ATP

    Alexander V. Gourine,1,* Vitaliy Kasymov,1 Nephtali Marina,1 Feige Tang,2 Melina F. Figueiredo,2 Samantha Lane,2 Anja G. Teschemacher,2 K. Michael Spyer,1 Karl Deisseroth,3 Sergey Kasparov2,*

    Astrocytes provide structural and metabolic support for neuronal networks, but direct evidence demonstrating their active role in complex behaviors is limited. Central respiratory chemosensitivity is an essential mechanism which, via regulation of breathing, maintains constant levels of blood and brain PCO2/pH. We found that astrocytes of the brainstem chemoreceptor areas are highly chemosensitive. They responded to physiological decreases in pH with vigorous elevations in intracellular Ca2+ and release of ATP. ATP propagated astrocytic Ca2+ excitation, activated chemoreceptor neurons, and induced adaptive increases in breathing. Mimicking pH-evoked Ca2+ responses by optogenetic stimulation of astrocytes expressing channelrhodopsin-2 activated chemoreceptor neurons via ATP-dependent mechanism and triggered robust respiratory responses in vivo. This demonstrates a potentially crucial role for brain glial cells in mediating a fundamental physiological reflex.

  8. richvank

    richvank Senior Member

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    Hi, Rosemary.

    Thank you for posting this. It's interesting to see that astrocytes do this. In the past, it has been known that astrocytes provide various types of support to the neurons, and the neurons have been thought to be the "actors" in the brain. This work indicates that the astrocytes take a more active role in controlling the breathing. It looks as though they still operate through the neurons in doing so, though, by activating the chemoreceptor neurons.

    In CFS, because of the mitochondrial dysfunction (which I believe starts with glutathione depletion in the mitochondria), there is less carbon dioxide produced, on a total body basis, than normal. The result is that the cells in the respiratory center in the brain, including the chemoreceptor neurons and the astrocytes, detect this and send nerve signals that cause the breathing to slow down and become more shallow, in a attempt to raise the carbon dioxide level. However, in CFS, this can result in an apnea condition, in which the oxygen level goes too low in the blood.

    Best regards,

    Rich
  9. carolwxyz99

    carolwxyz99 Senior Member

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    I've not done the short protocol for ME/CFS.I was going to do it 2 1/2 years ago and then went down with breast cancer so didn't want to start messing around with things like folate without an expert to help.

    I've just seen an environmental doc in the UK and had a few SNP tests done from a european lab as they are much cheaper now. I am homozygous for MTHFR (C677T). I am also heterozygous for NAT2 (*5A) and NAT2 (*6A). GST SNPs were OK.

    I have not spoken to the doc to get the results interpreted yet. I assume that 5-methyltetrahydrofolate would be a useful thing to take. Interestingly I had the supplements from short protocol tested energetically 2 years ago and that is the one that came up. I am currently on B12 sublingual, pus plenty of other things.
  10. richvank

    richvank Senior Member

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    Hi, Carol.

    I'm glad you survived the breast cancer. I'm a colorectal cancer survivor myself.

    Sounds as though you have some relevant polymorphisms.

    The combination of 5-methyl tetrahydrofolate with a sufficient dosage of B12 has been very effective in raising the partial block in the methylation cycle in many people with CFS. I would encourage you to discuss this with your physician.

    Best regards,

    Rich
  11. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    Satratoxin and Astrocytes

    Here's an abstract of a paper suggesting that satratoxin (poison made by Stachybotrys mold) can have an effect on the astrocytes.



    Karunasena E, Larraaga MD, Simoni JS, Douglas DR, Straus DC. Building-Associated Neurological Damage Modeled in Human Cells: A Mechanism of Neurotoxic Effects by Exposure to Mycotoxins in the Indoor Environment. Mycopathologia. 2010 Jun 13. PMID: 20549560.

    Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.
  12. richvank

    richvank Senior Member

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    Hi. slaya.

    Thanks for posting this. Satratoxin H is definitely very bad stuff!

    Rich
  13. niker

    niker

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    Hi Rich, Just wondering if this is new protocol from Dr. Amy and have you stopped endorsing your previous formula as described here
    http://www.ei-resource.org/articles/chronic-fatigue-syndrome-articles/the-methylation-cycle/

    The reason I am asking is that I am not in US and I have hard time getting patented formulas such as Acitfolate, Folapro and Hydroxycobalmin. However I can still get Methy B12, Phosphotidyl serine, P5P , Glutathiaon etc. Do you have apprehensions using this formula ? I would be using it for brain fog, extreme lack of mental energy, focus, low blood pressure, food(gluten) sensititvies to name a few among a host of health issues. Also how Glutathion relagated to back bench in new protocol while showing promise in the old protocol?
    Thanks
    Niker
  14. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    hi rich, in the start of this thread you mention excitotoxicity, im wondering your opinion on amino acid phenylalinine(spelling??) causing this as its present in a lot of diet soft drinks. Do u have an opinion on injectable hydroxycobalmin, also i have access to a formula that contains 500mcg of hydroxy and 15mg of folic acid per ml. Also with other nutrients that you mention , in particular different amino acids, if on a high protein diet, is there a need to supplement these as most of these aminos are in meat as well as alot of b vitamins. Just as a point of interest, vegetables are considered high in vitamins but most only contain a few where as meat seems to contain a high content of many nutrients, the only one i can see that maybe lacking is vitamin c which is easily supplemented with and cheap as chips. I understand that b12 is high in meat but is subject to absorption factors as in pernicious anemia. i have had some success with b12 injections(at one time was using hydroxy 5000mcg 3 times a week), i folllow a high protein diet aka atkins style and was using alot of diet soft drink but after cutting back (no caffeine) i havent found it affecting my sleep(insomnia) in any positive way. Supplement wise i use fishoil, vit e and c, d, nac, lipoic acid and whey protein. One more question, do u know if they do the vitamin type testing u mention in australia. What a loaded paragraph ive written, dont think i could add too many more questions, lol!!!

    cheers!!!
  15. richvank

    richvank Senior Member

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    Hi, Dan.

    I think the digestive problems are one of the most complex aspects of CFS, and often one of the most stubborn. I think there can be quite a few factors involved in causing them. I favor getting a comprehensive stool test to sort out the problems. One of the best offered in the U.S., in my opinion, is the Diagnos-techs Expanded G.I. panel. For those in Europe, I think that Dr. Kenny de Meirleir is the world leader in sorting out and treating the digestive system problems in CFS. and he probably does the most comprehensive testing, including lactose and fructose intolerance breath tests, a urine test for hydrogen sulfide, a blood test for D-lactate, stool testing that includes protection of the anaerobic bacteria, an Immunobilan test to look for overgrowth of certain bacteria as well as leaky gut. He may also do some food allergy and sensitivity testing, I'm not sure about that. I think he looks for parasites, also. All these things can be issues for the digestive system. In addition, I think that low folates can interfere with replacement of the enterocytes, and disturbances in acetylcholine and serotonin levels can interfere with normal intestinal motility. Glutathione depletion removes protection from toxins in the gut. There are a lot of issues in the gut in CFS, and I think that's why we have such a hard time fixing the gut.

    Correcting the methylation cycle block should bring the sulfur metabolism back to normal, and that impacts several aspects of the detox system: cysteine, glutathione, taurine and sulfate. Glutathione is involved in both Phase I and Phase II detox. The other Phase II pathways, such as glucuronidation and acetylation should not be affected.

    SAMe can help to increase the methylation capacity, which will bring up glutathione, and that in turn can remedy the mito dysfunction, raising the rate of APT production. As you suggest, though, SAMe is not well tolerated by everyone with CFS.

    Best regards,

    Rich
  16. richvank

    richvank Senior Member

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    Hi, Graeme.

    I'm sorry that excitotoxicity is such a major issue for you and for quite a few others as well. As I wrote, I suspect that glutathione depletion is at the basis of it in CFS, and I think the fact that glutathione depletion seems to be present in most people with CFS is consistent with the presence of at least some excitotoxicity in most PWCs, as you mentioned. If the glutathione level is restored, I think that will be the key to CFS in general and to correcting the excitotoxicity in particular, so I agree with you that treating excitotoxicity is also the key to treating CFS. Lifing the methylation cycle block appears to be the key to raising glutathione, but unfortunately, treating the methylation cycle block probably lowers glutathione more in the short term, because of the shunting of the homocysteine flow away from the transsulfuration pathway, toward making methionine. That's why I'm thinking that doing something to boost glutathione while this is going on might help to relieve the excitotoxicity.

    It's interesting that Dr. Cheney's ETM testing results give you reliable guidance for avoiding increased excitotoxicity. This makes sense to me, in that he is measuring the first, short-term response of the heart muscle mitochondria to the addition of various supplements. If a supplement increases oxidative stress in these mitochondria, it will exacerbate the existing mito dysfunction, lower the rate of ATP production further, worsen the diastolic dysfunction, and thus raise the IVRT, which he measures. And if a supplement increases oxidative stress in the heart muscle cells, it will likely also deplete glutathione further in the cells of the brain, thus increasing excitotoxicity.

    I have heard that excitotoxicity has decreased in some people over time. It seems to be a gradual process, probably because the rise in glutathione can be slow.

    Artimisinin is still a puzzle to me. It is thought to work by generating reactive oxygen species, because it contains a peroxide bridge than can be released in the body. However, this would increase oxidative stress, not decrease it. As you may know, it is used in treating malaria, and the mechanism seems to be that it raises the level of oxidative stress to the point that red blood cells in which the malaria parasite is active are killed, together with the parasite. I think it might be effective against Babesia, also, since it is a related parasite that occupies red blood cells.

    Best regards,

    Rich
  17. richvank

    richvank Senior Member

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    Hi, Dan.

    I don't know for sure if B12/folate will deplete other B vitamins, but perhaps it will, because some of the enzymes in the methylation cycle and related pathways do use other B vitamins as coenzymes, and even though a coenzyme is unchanged by the reaction it supports, there is always some attrition as these coenzymes are used. I do know that many PWCs test low for various B vitamins.

    Best regards,

    Rich
  18. Misfit Toy

    Misfit Toy Senior Member

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    This is my 2nd time trying the folapro and B12 Perque. The first time I got sick after 3 months or even before. I was taking a half to a quarter a day of the folapro. As time went on I was having horrific pain and super charged up feelings. I stopped taking it and felt great brain wise. Better than I had in a long time. That was in 2007.

    This time I am taking much less, although I went up to a 1/4 of a pill again and within one month was in horrific pain again. So much so that the other day I spent in bed. I had to stop the treatment for a few days. I am wondering now if I should take it every other day or maybe only twice a week. It's so hard to know. I do know that I feel better mentally on it. This is where it becomes tough because I feel better in some ways and every now and then it becomes too much for me. Decisions, decisions. Any advice?

    UGH.
  19. richvank

    richvank Senior Member

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    Hi, Niker.

    The website you cited. as you know, comes from Dr. Sarah Myhill's. It's true that Dr. Myhill began treating the methylation cycle based on my work, but she has not used exactly the same protocol I suggested. I think the reasons for this were the unavailability of certain supplements in the UK, and the fact that Dr. Myhill had some ideas of her own about how to deal with this issue. She is an experienced and knowledgeable physician, and I have a high regard for her, as you can see from the letter of support I sent to the GMC on her behalf, which has been posted on her support sites. So my original protocol from 2007 was not the same as the one she has on her website.

    I'm not able to say which is superior, because there has been no clinical study comparing the two treatments. I know that Dr. Myhill's protocol has been helpful to some patients, because I have received emails from them reporting this.

    The most important components in my original protocol, and in the revised one posted at www.cfsresearch.org , are the hydroxocobalamin and the active, reduced forms of folate (5-methyltetrahydrofolate and folinic acid). The other supplements are mainly supportive nutritional supplements and are included because many PWCs are depleted in some of the essential nutrients, though the multi that is included gives some specific support to the methylation cycle and related pathways.

    With regard to glutathione, it was actually not included in my 2007 protocol. Dr. Myhill did include it in her protocol, and she used an ordinary oral form. This form is mostly broken down in the gut, but it does supply the amino acids that form glutathione, and the liver probably receives some of them and uses them to reform glutathione.

    I have sort of come full circle on glutathione. From 1999 through 2004, I encouraged PWCs to try to build their glutathione levels by various routes, both direct and via amino acids supplementation. I found that this was only a temporary fix, since glutathione appeared to drop back down if the supplementation was stopped. When I became aware of the connection between the partial methylation cycle block and glutathione depletion, I then shifted my efforts toward treating the partial methylation cycle block, and no longer recommended boosting glutathione, because if the partial methylation block is lifted, glutathione comes up automatically. However, treatment to lift the partial methylation cycle block has been found to exacerbate the excitotoxicity. I now suspect that the reason this happens is that the methylation cycle treatment initially lowers glutathione even further, because of diversion of the homocysteine flow away from the transsulfuration pathway. Therefore, I'm now warming up to the idea of trying to support glutathione while the methylation cycle block is being lifted.

    I would be very interested in hearing from people who have tried boosting glutathione while doing the methylation cycle treatment, to find out if it helps to suppress the excitoxicity.

    Best regards,

    Rich
  20. serg1942

    serg1942 Senior Member

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    To Rich: Motility on CFS and ATP in glucuronidation


    Hi Rich,

    I really would like to know your opinion on my experience taking antidepressants, as this may shed some light as to how to treat GI issues in CFS.

    My main disabling symptoms, aside from my extreme fatigue, are my GI issues, specifically low HCL and low motility that cause horrible nausea, never-ending digestions, and food intolrances.

    Well, I have been thinking for a long time that my past experience with antidepressants should explain some of the reasons for suffering theses symptoms. For a few months I was taking Ludiomil, a norepinephrine reuptake inhibitor, and then I switched to Prozac, a selective serotonin reuptake inhibitor, which I took for a few months more.

    Ok, Back then, I suffered from similar symptoms, and ALL of them were CURED during the time I was on these antidepressants.

    So, even though I certainly had huge dysbiosis issues, hypochloridia, probably leaky gut, etc., it seems that by raising either serotonin or norepinephrine available levels, my gut problems completely disappeared. Im not sure, but I think that by raising these neurotransmitters, I was mainly improving motilityCertainly I wasnt improving my ATP levels, and so the HCL amount, and I dont think I was healing my dysbiotic state either.

    So it seems that motility could be the main think to look at, when it comes to GI issues in CFS.

    What do you think about this?

    Thank you so much,
    Sergio

    P.S. RE: glucuronidation, you wrote it is not dependant on the methylation cycle. However, as far as I know, the limiting factor for this detoxification route is ATP, and this would match with my tests results, showing low glucoronodation activity, as well as those of other patients Ive seen.

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