Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Mon Sep 23, 2013 1:33 am

From Multiple Sclerosis Research Australia
Great article in today's Australian Financial Review - Major MS Trial to throw light on Vitamin D link.
http://www.afr.com/p/business/companies ... ETWNqo3JPP
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Tue Sep 24, 2013 12:52 pm

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/24054766
PMID: 24054766
DOI: http://dx.doi.org/10.1016/j.lpm.2013.07.012
Journal Title: Presse medicale (Paris, France : 1983)
Journal Date: 18 Sep 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2405 ... t=abstract
Article Title: [Vitamin D and neurology.]
Article Authors: Eric Thouvenot,William Camu

Presse Med. 2013 Sep 18. pii: S0755-4982(13)00679-9. doi: 10.1016/j.lpm.2013.07.012. [Epub ahead of print]
[Vitamin D and neurology.]

[Article in French]
Thouvenot E, Camu W.

Hôpital Carémeau, service de neurologie, place du Pr-Debré, 30029 Nîmes cedex 9, France.

Abstract

Vitamin D deficiency is associated with a higher risk of multiple sclerosis and also with a higher relapse rate as well as a higher number of MRI lesions. Elders with vitamin D deficiency have worse cognitive performance. Vitamin D deficiency is a risk factor for developing Alzheimer's disease. Ischemic stroke are more frequent and more severe in patients with low vitamin D levels. Carotid atherosclerosis is more frequent and more severe in patients with vitamin D deficiency. Vitamin D deficiency is associated with a higher risk and worse prognosis of Parkinson's disease. In the different neurological disorders discussed herein, gene polymorphisms that could alter vitamin D metabolism are also associated with a higher incidence or a worse disease prognosis. Despite the links between vitamin D deficiency and the risks of developing neurological disorders, there is, to date, no proof that supplementation could alter the course of these diseases.

Copyright © 2013. Published by Elsevier Masson SAS.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Tue Sep 24, 2013 3:59 pm

Nigel, a link to another version of the story you cited above which required registration or a subscription. This one is from the The Australian Financial Review

Major MS trial to throw light on Vitamin D link

In the time it took to cross a Melbourne suburban street, Simon McKeon went from seeing the world in full colour to one of fuzzy darkness. It was 1999 and the investment banker, philanthropist and former Australian of the Year had experienced an episode of multiple sclerosis, a disease that attacks the brain and spinal cord.

“I left the pavement on one side and by the time I got to the other side I could only literally see a vague shape of a tree,” he says.

“I hugged this tree because it happened without warning.”

McKeon was not far from his home, so shuffled along the path and doesn’t remember much from there. He was helped into hospital and did not recover his sight for about 10 days. He didn’t make the link between an episode a few months before when he suddenly experienced paralysis from the hip down. But his neurologist quickly tied the two events together to diagnosis MS.

McKeon, who is executive chairman of Macquarie Bank, Melbourne, began working with MS Australia and in 2004 became the founding chairman of MS Research Australia.

MS occurs when white blood cells produced as part of a normal immune response erroneously attack myelin, which is like insulation that wraps around the nerves. The insulation allows electrical impulses to travel quickly to and from the brain, but when it is damaged, the messages are not relayed, which causes symptoms such as blindness and paralysis.

The disease afflicts about 23,000 Australians and this number is increasing at a rate of 5 per cent each year. Three out of four cases afflict women. There is no cure.

Equator offers clue

But a new trial being undertaken by MS Research Australia, the largest of its kind in the world, hopes to identify a link between the progression of MS and levels of Vitamin D in the body.

Researchers have long suspected such a link exists because of the varying incidence of MS depending on how far away from the equator a location is, said MSRA chief executive Matthew Miles.

Vitamin D is activated in the body by sunlight. How many degrees of latitude away from the equator a person lives generally gives a good indication of their levels of sun exposure and Vitamin D in the blood.

“The incidence of MS in Tasmania, Victoria or the ACT is much, much greater than the incidence in tropical far north Queensland or the Northern Territory,” Miles says. “That leads us to two things – either MS may be related to Vitamin D levels, or it might be related to UV radiation levels.”

The organisation hopes to recruit about 260 patients across 21 hospitals in Australia and New Zealand who have had their first clinically recognised episode of MS. Patients will be given one of three different doses of Vitamin D or a placebo.

The trial is double blind, which means neither the patient nor the doctor knows who gets which course of treatment. Participants’ exposure to sunlight will also be measured.

“What we’re hoping to find is that there is an ability of Vitamin D to prevent the onset or the incidence of people developing diagnosed MS,” Miles says.

Corporate world behind cause

McKeon is excited about the prospects of the trial. “There really hasn’t been a large-scale [trial] done on this anywhere around the world, particularly on such a spread of population and with a placebo and different doses,” he says.

MSRA has tapped into corporate networks and received commitments to fund $3 million worth of research annually for the next 10 years. Within five years of its establishment, the annual amount spent on new medical research into MS increased five-fold to just over $2 million.

McKeon has since been replaced as chair by former Goldman Sachs banker and company director Paul Murnane, although he is patron.

MS is one of a number of causes that McKeon backs but, unlike his work on indigenous disadvantage and the environment, he says it was his only philanthropic interest with a direct personal link. He calls it his “selfish” work.

“I can remember saying at the time, ‘my gosh – have I sailed my last yachting race and kicked my last footy with my kids?’  [I thought] if I somehow am not sentenced to a life in a wheelchair or whatever else, I will never take a day for granted. I’ve had my own version of a near-death experience. I didn’t die, but I’ve had that taste of what vulnerability is all about.”

“Sometimes in the philanthropic space it’s okay to be a bit self-motivated, so long as it’s not the only motivation,” he said. “It does add to the passion. For me it’s not just a another disease.”

McKeon doesn’t talk much about his own condition. His reluctance stems from a relatively clean bill of health after the initial episodes that lasted for about 18 months more than a decade ago. He is one of the lucky ones.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby MarkW » Thu Sep 26, 2013 11:36 am

Squeakycat wrote:
NZer1 wrote:Some more insights from a 'sceptic' of Vit D supplementing due to knowledge!
Given that Vit-D is a Hormone, it’s worth noting that ALL Hormones have a Target Cell and a Target Mission.

Nigel,
This utter nonsense. Vit D is in every cell in the body. It controls the adaptive immune response, among other things. The active form can be completely produced (given the raw materials) in a cell that needs vit D without liver or kidney metabolism.
I don't know where your source here is getting his or her information, but it shows a fundamental lack of knowledge of vit D and if this is what's informing your views on the subject, you need a much more informed source of information.
I would suggest as a starting point, some of Dr. Michael Holick's work including his books aimed at the public.


Ed,
You have the patience of a saint, many thanks for continuing to post.
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby MarkW » Thu Sep 26, 2013 11:59 am

Squeakycat wrote:
PointsNorth wrote:Hello I thought I'd chirp in. After taking an Organic Acids Test for D levels + much more I found out I was low in vitamin D. I was supplementing 6000iu/day (2 years). I have now increased to 10,000iu/day. I question how much we can take from serum levels. I think that a number of us have malabsorption/transport issues that leave us short of much.
PN,
I think there is considerable evidence that people with disorders such as MS probably do have problems with the absorption and transport of vit D.
There is also the question of whether low levels are the result of the disease process, ie, a higher demand for vit D by the body. This was suggested in one small study which showed that vit D levels decrease as people go from Clinically Isolated Syndrome to clinically diagnosed MS.
The easy way to find out if you have any of the genetic issues that effect how vit D is absorbed, converted or transported is to take adequate levels of vit D and see if this increases your level of 25(OH)D. If it doesn't, then further investigation at a genetic level would be warranted. No point though in doing expensive genetic testing before finding out if there is a problem.
A good guide to what levels of supplementation are needed to achieve different levels of 25(OH)D is provided by the group Grassroots Health. There is a table on their home page.

Hello PointsNorth and Squeakycat,
I try to offer inexpensive and easy to follow advice if possible.
If you are taking 10,000 IU D3 and it has not raised Vit D3 blood levels in a month, then add a multi-mineral and see what happens. Jimmylegs has posted about essential minerals earlier in this thread. The 21st century western diet may not provide every mineral that our bodies require. Obviously it would be better to eat organic wholefoods to get these, but that takes a lot of effort/time and money. You could get tested for low mineral levels but taking a multi-mineral is cheaper and our very clever bodies store or excrete what is not required.
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby MarkW » Thu Sep 26, 2013 12:11 pm

NZer1 wrote:From Multiple Sclerosis Research Australia
Great article in today's Australian Financial Review - Major MS Trial to throw light on Vitamin D link.
http://www.afr.com/p/business/companies ... ETWNqo3JPP


Unfortunately trials for MS and vit D3 must be conducted at a population level to show significance. I predict the conclusion will be 'more tests required' as significance not proven.
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Calcitriol + Vit D More Effective than Methylprednisone

Postby Squeakycat » Fri Sep 27, 2013 4:49 pm

I reported on this study earlier, but just got around to purchasing the article today as well as stumbled on a press release related to it which has a great summary:

  • First, Hayes' team compared the effectiveness of a single dose of calcitriol to that of a comparable dose of a glucocorticoid, a drug now administered to MS patients who experience a bad neurological episode. Calcitriol came out ahead, inducing a nine-day remission in 92 percent of mice on average, versus a six-day remission in 58 percent for mice that received glucocorticoid.
  • Next, Hayes' team tried a weekly dose of calcitriol. They found that a weekly dose reversed the disease and sustained remission indefinitely.
  • But calcitriol can carry some strong side effects -- it's a "biological sledgehammer" that can raise blood calcium levels in people, Hayes says -- so she tried a third regimen: a single dose of calcitriol, followed by ongoing vitamin D supplements in the diet. This one-two punch "was a runaway success," she says. "One hundred percent of mice responded."

Source URL: http://www.sciencecodex.com/mouse_studi ... _ms-120144
Here is a citation of this study:

Source URL: http://www.ncbi.nlm.nih.gov/pubmed/23968560
PMID: 23968560
DOI: http://dx.doi.org/10.1016/j.jneuroim.2013.07.016
Journal Title: Journal of neuroimmunology
Journal Date: 6 Aug 2013
Abstract URL: http://www.ncbi.nlm.nih.gov/pubmed/2396 ... t=abstract
Article Title: One calcitriol dose transiently increases Helios(+)FoxP3(+) T cells and ameliorates autoimmune demyelinating disease.
Article Authors: Faye E Nashold,Corwin D Nelson,Lauren M Brown,Colleen E Hayes

This is IMPORTANT. Yes, it is a test in EAE and there are other reasons it may not work in humans. But it is the third in a series of studies of calcitriol in EAE and they are all finding the same thing: it reverse the active inflammatory state and puts EAE into remission.

This would be very easy to test in humans and I have been discussing doing a test with five medical professionals who have MS.

Calcitriol is inexpensive and has been in use in human medicine for close to 30 years. Its risks are well known and manageable. It is a prescription drug so it does require a prescription to use.

While it may not have the same effect in humans as it does in mice, I think a good case can be made that because there is an active inflammatory state in EAE, it may well work when there is a relapse in humans.

What I am discussing with the medical professionals is a limited test of calcitriol + vitamin D when there is a flare-up, an active inflammatory state. The protocol is a single, high dose of calcitriol followed by relatively high doses of vitamin D.

At the start of the test, we will look at the 25(OH)D level (plus kidney function and levels of calcium and phosphorus) and provide a single dose of vitamin D3 to increase it to at least 125 nmol/L (50 ng/ml) and then the single dose of calcitriol followed by weekly doses of Vitamin D3, tentatively set at one 50,000 IU dose which is 7,143 IU a day as long as the 25(OH)D level remains above 125 nmol/L. If the 25(OH)D level rises significantly, the dose will be lowered by, for example, only taking one 50,000 IU pill every other week.

Another aspect of a test of this in humans is that in this recent study and the two previous ones in mice, calcium was supplemented in addition to vitamin D3. In one of the studies, it was explicitly stated and tested and found that this ONLY works with calcium. Calcitriol alone was not effective long term without calcium supplementation. The level is somewhere between the 800 mg and 1,200 mg levels that are well under the safe upper limit and low enough to allow for some level of dietary intake of calcium and have frequently been used in test of high levels of vitamin D3.

I have an issue with the statement above that calcitriol "can carry some strong side effects -- it's a "biological sledgehammer" that can raise blood calcium levels in people . . ."

Yes, it can, but this can usually be controlled by administering a single weekly pulse dose, rather than taking it daily. This problem has been managed for at least 20 years by pulse dosing when relatively high doses are involved.

I'm particularly upset that the current Hayes study and several other recent studies on this all cite Wingerchuk as the basis for concluding that there is a grave danger of hypercalcemia with high doses of calcitriol. I have addressed this issue here before, but because this keeps being thrown up, I want to point out once again that this is NOT what Wingerchuk says:

What the Wingerchuk study they cite actually found was that there was a problem when patients did not follow the study dietary guidelines, PERSISTENTLY failed to follow them!

Results: Two patients [out of 11] withdrew because of symptomatic hypercalcaemia (serum calcium >3.35 mmol/l in each case) resulting from persistent dietary indiscretion. Two diet compliant patients required temporary dose adjustments for mild asymptomatic hypercalcaemia.

Wingerchuk's conclusion is the opposite of what it is being cited as saying:
Oral calcitriol is safe and well tolerated for up to one year by diet compliant relapsing-remitting MS patients.

Source URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739797/
PMID: 16107372
DOI: 10.1136/jnnp.2004.056499
Journal Title: Journal of Neurology, Neurosurgery, and Psychiatry
Journal Date: September 2005
Journal Issue: 9
Journal Volume: 76
Journal First Page: 1294
Abstract URL: http://www.ncbi.nlm.nih.gov/pmc/article ... t=abstract
Article Title: A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing–remitting multiple sclerosis
Article Authors: D Wingerchuk, J Lesaux, G Rice, M Kremenchutzky, G Ebers

In fairness to Hayes, the dose of calcitriol if translated into a human dose on the basis of weight is vastly greater than the dose used in Wingerchuk. Sadly, neither Hayes nor Wingerchuk explain how they came up with the doses of calcitriol they used in their studies.

I am hoping that Dr. Hayes will clarify this issue. Meanwhile, it seems appropriate in human testing to use a lower dose than she used in her mice, but one that is higher than the dose used by Wingerchuk and offset this with a higher daily dose of vitamin D3, administered in a weekly pulse dose. The higher vitamin D3 dose is still lower than the upper limit for vitamin D3 and pulsed, should not cause any problems in terms of hypercalcemia.

So, the hope is that we can do a limited test of this at the time of a relapse. We won't need to measure anything other than whether it stops the relapse, something that should be obvious and should happen in days as it does with methylprednisone which was found to be less effective in mice.

Hayes is quoted in the press release saying:
"It's my hope that one day doctors will be able to say, 'We're going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we're going to follow you closely over the next few months. You're just going to have this one neurological episode and that will be the end of it,'" says Hayes. "That's my dream."

We don't really have to wait years for a clinical trial in humans to be organized and funded. Since calcitriol and Vitamin D3 are already available, we can test this today and see whether it works as well in humans as EAE mice.

I am writing up a test protocol with safety procedures, pre-test blood work and proposed doses of calcitriol and vitamin D3. I think we should first test this with medical professionals who are better able to assess the risks involved and then, if we get positive results, provide the test protocol to anyone who thinks they can persuade their primary care physician or neurologist to write a prescription for the testing and calcitriol and monitor ongoing blood tests to ensure that there are no problems with hypercalcemia.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Fri Sep 27, 2013 5:23 pm

Sounds positive Ed :)

Lucid thought came to me, this could be a link from EAE to RRMS?

Meaning that RRMS maybe a form of MS started from a pathogen or similar source of foreign infection?

And the possibility that the PPMS progressive forms have a different origin and that each form is related yet different until a maturity stage or immune system developmental stage?

As I said lucid, pulsing does that!

:)
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 27, 2013 5:26 pm

NZer1 wrote:Sounds positive Ed :)

Lucid thought came to me, this could be a link from EAE to RRMS?

Meaning that RRMS maybe a form of MS started from a pathogen or similar source of foreign infection?

And the possibility that the PPMS progressive forms have a different origin and that each form is related yet different until a maturity stage or immune system developmental stage?

As I said lucid, pulsing does that!

:)
Nigel
It doesn't really tell us about the origin of RRMS or Progressive. It simply says that there is an active inflammatory state in both cases, but nothing about what is causing it.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Fri Sep 27, 2013 5:43 pm

Squeakycat wrote:
NZer1 wrote:Sounds positive Ed :)

Lucid thought came to me, this could be a link from EAE to RRMS?

Meaning that RRMS maybe a form of MS started from a pathogen or similar source of foreign infection?

And the possibility that the PPMS progressive forms have a different origin and that each form is related yet different until a maturity stage or immune system developmental stage?

As I said lucid, pulsing does that!

:)
Nigel
It doesn't really tell us about the origin of RRMS or Progressive. It simply says that there is an active inflammatory state in both cases, but nothing about what is causing it.


Yes and no!
It tells us that the DMD's so far only work on RRMS form and the IV steroids only work on RRMS form and that dosing Cal and Vit D have an effect on EAE mice which is the form and clients that DMD's were designed for modifying the symptom expression but not the disease itself.
If EAE mice do better on Cal + Vit D there must be some extrapolation?

Probably the extrapolation is I should go for a nap! :)

;)
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby Squeakycat » Fri Sep 27, 2013 6:53 pm

NZer1 wrote:Probably the extrapolation is I should go for a nap! :)
;)
Nigel

You and Emirates Team New Zealand should go for a nap. Oh, wait. ETNZ already took their nap this week during the last 8 races in San Francisco. :>)

You may be right in your extrapolation, but I suspect that you are not for several reasons.

The first is that there is a good reason for only testing a drug with RRMS. Since the disease waxes and wanes in RRMS, the drug companies can play statistical games with their results and "prove" efficacy when in fact, it is just random chance made easier by the natural course of the disease.

Further, they are aimed at RRMS rather than PPMS because that's what they are tested for. They don't test the drugs in PPMS. They would have to actually work, not just meet some random statistical goals that are irrelevant to the course of the disease and aided by the natural course of the disease.

But I do think that there is a correlation between relapses, a state of active inflammation, and EAE which is also characterized by an active inflammatory state.

But who knows. I'm certainly not an expert in any of this.
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Americas Cup and D3 study

Postby MarkW » Sat Sep 28, 2013 8:23 am

Squeakycat wrote:..... Emirates Team New Zealand should go for a nap. Oh, wait. ETNZ already took their nap this week during the last 8 races in San Francisco. :>)

Hello Ed,
Before you take glory for Oracle Team USA, please remember that Ben Ainsley (Brit) and several Aussies held key positions on the boat. The racing was fantastic.

The D3 study sounds great news. Keep in mind that some pwMS appear to absorb D3 poorly (especially in tablet form) and need other minerals to utilise it.
Kind regards,
MarkW
Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Re: Americas Cup and D3 study

Postby Squeakycat » Sat Sep 28, 2013 9:16 am

MarkW wrote:
Squeakycat wrote:..... Emirates Team New Zealand should go for a nap. Oh, wait. ETNZ already took their nap this week during the last 8 races in San Francisco. :>)

Hello Ed,
Before you take glory for Oracle Team USA, please remember that Ben Ainsley (Brit) and several Aussies held key positions on the boat. The racing was fantastic.
I was rooting for ETNZ, not OTUSA which had a single American and if I'm not mistaken was built in NZ.

And much credit to Sir Ben since the races were mainly tactical battles between fairly evenly matched boats.
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Re: Americas Cup and D3 study

Postby Squeakycat » Sat Sep 28, 2013 9:19 am

MarkW wrote:The D3 study sounds great news. Keep in mind that some pwMS appear to absorb D3 poorly (especially in tablet form) and need other minerals to utilise it.
Kind regards,
MarkW

Very true, but I think yet to be fully studied. It will certainly be an issue in testing this in humans. With D3, this can be sorted out fairly easily. You take a loading dose and see if you get the expect rise in 25(OH)D. It is only a problem if that doesn't happen and can be dealt with at that point.
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Re: Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS

Postby NZer1 » Sat Sep 28, 2013 2:13 pm

Hi Ed, not sure if this is any help or not. The trial on Vit D ( http://www.msra.org.au/prevanz) 'might' be some help with what are proposing.
One challenge though is that there are quite a few MS Neuro's involved, could be good or bad and Debbie Mason (NZ) ( http://www.msra.org.au/early-detection- ... ms-improve ) has looked at the GM lesions and perfusion but does not support CCSVI and MS linkage theory at this time.

Thought that the study may or may not be able to interlink or for you to use some of their outcomes to help your project design.

The other person down under would be George Jelinek who has interest in Vit D and MS and has written and researched the research about Vit D.

;)
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