Cause of PSP....reflections:: Recently... - PSP Association

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Cause of PSP....reflections:

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Recently, there have been many posts relating to the cause of PSP, so I would like to give you some food for thought. I will have to leave out extensive information, but hopefully some of it will make sense.

All the neurological diseases (some discussed on this forum) have a common theme of one or two normal functioning brain proteins "going wrong", and not being eliminated by the usual mechanisms. Eventually they form "toxic" proteins (most likely responsible for neuron death, and it travels along neural pathways and turns normal tau into "toxic" tau). This damaged tau then ends up as (neurofibrillary) tangles. Each neurological disease is generally classified by the type of protein (or proteins) found in (responsible for) these tangles at autopsy, along with their shape and location both in different cells and areas of the brain.

When we ask the question about the cause for PSP, we should probably think about the other diseases that have the same protein as the most dominant feature (tau) "going wrong" (called pure tauopathies). There are at least 9 of these diseases (to name 3 others - CBD, FTD linked to chromosome 17 and Dementia Pugilistica. This latter one I will mention later).

Idiopathic Parkinson's (where PSP shares some symptoms) is associated with another protein called alpha synuclein (it forms Pick's bodies in the brain cells). So, perhaps in asking about the cause of PSP, we might find some answers in the causes for Parkinson's or any other of these neurological diseases. For example, Alzheimer's has two proteins that "go wrong" (tau and beta amyloid).

Of course, at this present time, medical science has not found any single cause for this host of neurological diseases (even in diseases like Multiple Sclerosis that is thought to be an autoimmune disease, the initiating reasons are unknown).

Having said all this, there are risk factors to many of these diseases, but there is often different findings among scientists concerning such factors e.g. do pesticides (like paraquat) induce Parkinson's.

With PSP there are some "named" risk factors such as genetics, environment and diet (no virus or similar has been found).

We have talked about genetics in a previous post and noted that although it does occur, it accounts for less than 1% of PSP conditions.

Consistent head trauma can cause a "tauopathy" similar to PSP/Parkinson's' (found as Dementia Pugilistica or "punch drunk" in sports people from recurring concussions - now called Chronic Traumatic Encephalopathy). Those who have posted about head or neck trauma being a cause of the PSP in their loved one may have some grounds for their concerns. Yet, this type of tauopathy has some characteristic symptoms not found in PSP. (It has been shown that Parkinson's' can occasionally be linked later in life to head trauma, affecting the dopaminergic nigro-striatal pathways).

Certain (neuro) toxins have been found in the diet of some communities that cause a PSP-like condition (annoniacin found in soursop and sweetsop fruits - it affects the mitochondria).

Even low education has been attributed to a factor in PSP that influences one's diet, occupation and the number of brain synapses developed!!! (papers by Dr Golbe - see his most recent 2013 review of PSP on YouTube or lecture notes: "Google" …PSP: A Medical Update -Society for Progressive Supranuclear Palsy).

There have been innumerable papers written on the possible effects of farming and industry with respect to finding a cause(s) for these neurological diseases. Nothing conclusive has emerged. This brings me to my "food for thought"……

Are we thinking PSP and associated diseases are "modern" and thus looking for a recent generational answer? (Idiopathic) Parkinson's' was so named in 1817, and was probably the disease known as "shaking palsy" in AD175. We have talked already on this forum about Charles Dickens in 1857 describing a man who had similar symptoms to PSP. Neurofibrilliary tangles were first "seen" in the beginning of the 1900's (in Alzheimer's). Multiple Sclerosis was desribed over 150 years ago.It seems plausible that most of the neurological diseases we see today have been around since time immemorial (like other diseases). In times when there were no pesticides or immunisations to blame etc etc.

While medical science is coming closer to understanding the mechanisms involved in these damaged brain proteins (and designing specific therapeutics), its unlikely these diseases will be attributable to a "cause". It is more likely to be multifaceted, and a combination of some yet unknown complex genetic factors, along with exacerbating inflammatory processes. In other words, factors that have also been around since the beginning of the human race.

Any thoughts?

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33 Replies
shasha profile image
shasha

wow strelley

i have thoughts but what to say about it all is a bit beyond me i am afraid - thank you though for taking the time to write it and i wilk look at the link too

love sha xx

cawbird59 profile image
cawbird59

I am now realizing why your posts are so popular! Thank you for your thoughts and facts... very interesting indeed.

Dear Strelley,

You are such a brain box, I love you for your input!!!!!

I need to think a bit more, but as i have said before, I use your postings to check my own rather less academic efforts to try to make sense of it all. Physiologically l find it fascinating but my memory is rather poor and I have to keep re-reading stuff. Sometimes I make notes just to cross reference etc.

We are all born to die at some point, our bodies just wear out in one way or another, but we are, in general all living longer. Like you, I think that the potential for these neurological diseases to develop in us has always been there but we are 'seeing' and being made more aware of them simply because we live longer for these malfunctions to show. In mediaevil times we had witches and we burned them or drowned them or the village kids threw stones at them. I am sure my mother would have been such a victim with her type of dementia. Now we nurture the sick so well that their symptoms become more distinct and can be separated into individual diseases and have become a separate branch of medicine in themselves.

I wonder if other primates, such as apes and monkeys get dementia or neurological mal- function like us? Some symptoms have been produced in rats, I think.

The difference between them and us, which makes us human, is of course the development our our state of self awareness and feelings and consequential thought. Perhaps in a troop of monkeys, if one poor soul became a bit different in behaviour, it would be ostracized and so die from a predator or lack of food and so those genes which were susceptible to the 'triggers' would be wiped out eventually; also usually it is only the strong healthy alpha male who breeds. So apart from having a less sophisticated brain to accentuate the stresses and worries of life which are draining physically, physiologically and psychologically and could lead to brain cell mal-function, it could be that basic animalistic savage behaviour may be working to their advantage. I think stress of one sort or another and how we deal with it, individually, is a big factor.

I mean, do we see dogs with dementia or pigs with dementia or neurological types of disease? Sometimes the mother of a litter will deliberately reject a new born, instinctively, swiftly, knowing that something is not right with it. Another aspect is the time of dependency of the young. Our children are with us for many years and exposed to our type of food, habitat and social structure before becoming independent and evidence of neurone mal-function for our type of disease is not shown for many years and after we have reproduced and passed on our chromosomes etc.and of course there is always the possibility of gene mutations.

Must rest now, my brain has given up, must have a cup of tea!

Have just come back from a meeting at dad's home on an assessment of his swallowing and speech and language. He is aphasic and has been for two years plus, cannot masticate his food but can suck up fluids with a straw, our main problem is pain from dystonia and can I get any help for him...NO. Our NHS is hopeless.

.

in reply to

Hi Nader

Loved your comments. It's true that by living longer (through medical advancements) more neurological conditions are coming to the forefront. Sadly, we have no cures for them yet, and the statistics for Alzheimer's by 2050 are frightening.

In my last post I was going to mention that dogs get a form of Parkinson's. Researchers can induce all sorts of neurological conditions in animals, so some may suffer "naturally" from them.

Sorry to hear about your dad's problems, especially the pain from the dystonia. To make our loved ones comfortable, unstressed and free from pain is paramount, so I do hope you'll be able to overcome any NHS barriers!

Take care.

SharonAB profile image
SharonAB

Dear Strelley,

More food for thought--- Where does the spinal cord fit into the picture, given it also fits in to the nervous system - Is much testing done in that area in relation to neurological disease analysis before and after life?

Regards,

Alana Bean

in reply toSharonAB

Hello Alana

It's interesting you should mention the spinal cord because I've been meaning to contact CurePSP who are keen on brain donations. I want to know if donating the brain also involves the spinal cord (it usually does, but I want to confirm this fact).

We do know that lesions are found in some of the nuclei in the spinal cord as they become damaged in PSP. One of the problems encountered with PSP is incontinence. While it can be caused by damage to some motor areas of the brain, it can present itself due to spinal cord damage. I've been interested to see that some PSP sufferers have had damage to the nucleus of Onuf in the spinal cord in the sacral region that controls (amongst other things) the sphincters for micturation (urine) and defeacation.

Not much testing is done during life on the spinal cord in PSP sufferers. They have taken Cerebrospinal Fluid to test for biochemical markers to help diagnose PSP, but as yet this has only been experimental (research) without conclusive results - unlike in Alzheimer's where a couple of substances are used to aid diagnosis.

All the best

Tony

shasha profile image
shasha in reply to

HELLO STRELLY

MY NEURO SAID THAT INCONTINENCE IS NOT A SYMPTOM OF PSP WHICH I THOUGHT IS WRONG AS SO MANY OF THE SUFFERERS HAVE IT ?

in reply toshasha

Hi Shasha

How are you?

I cannot understand any neurologist saying incontinence is not a symptom of PSP. They only have to read any of the descriptions of symptoms found on reputable clinical sites. There are dozens of papers written on the subject, and seminars dealing with issues of incontinence in PSP! (It is often worse in MSA, and is found in CBD).

Perhaps you can give your neurologist some information about PSP !!!!

Take care.

shasha profile image
shasha in reply to

YES I WILL NEXT TIME I SEE HIM !!

manitoba profile image
manitoba

Strelley, after being on this site for a short perid of time, I find your blogs very informative, although I must admit some of the technical data is beyond my comprehention. In your research have you ever found any discussions with respect to alcohol consumtion by someone with PSP? Would it in any way speed up the process? My wife still enjoys a glass of wine in the evening and I have been of the feeling that if this is one of the joys of life she can still have then so be it. I hope this in no way exaserbates the problem.

SharonAB profile image
SharonAB in reply tomanitoba

Dear Manitoba,

Perhaps not the scientific angle you are after from Strelley - however - ..

My husband's neurologist comment about a glass of wine or beer with the evening meal some years ago was - why stop!. Since then I've also read there can be changes in tastes so perhaps thats another reason to continue for now- the pinot noir, cab sav or merlot may gather dust or the champagne may loose its sparkle if left for tomorrow!

Regards,

Alana - Western Australia

manitoba profile image
manitoba in reply toSharonAB

Thanx Sharon, she will continue to enjoy her merlot

in reply tomanitoba

Hello manitoba

I haven't seen anything about alcohol and PSP except it being banned at PSP seminars!!

However, with PSP (and similar conditions) there are some real problems with a few of the neurotransmitters (due to damaged or dead neurons). Some of these neurotransmitters "excite" nerves while others "inhibit" nerves and usually this is wonderfully fine tuned. In PSP (and Parkinson's) this "goes wrong" and the sufferer ends up with balance and movement problems (plus other things).

Taking alcohol will affect a few neurotransmitters (it releases more of one that makes us feel good). I'm guessing that taking too much alcholol with PSP may exacerbate the already problemmatic neurotransmitter condition.

Having said that I'm not really the one to give the following advice, but taking the odd glass of wine each night with a meal should present very little problem. Continue to make it one of the joys of life for your wife. Although we don't drink wine, I let my wife (who has PSP) drink tea without thickeners, knowing she will occasionally "choke". She hates thickeners and loves her tea. While she still has a good cough reflex, I'm happy to give her such things that are frowned upon by her speech therapist!

All the best to you and your wife.

PS Sorry if my posts become too technical....we have such a wide variety of lovely people posting on this forum but I'm never too sure of the extent of information they require when asking questions.

manitoba profile image
manitoba in reply to

Thanx Strelley, Technical or not they are informative keep them comming.

Dear All,

I have, just this week end completed arrangements for brain and spinal chord donation to Queen's Hospital of Neurology, London. They did specifically ask for the spinal chord and any other bits they may choose. This body donation is my father's wish. The body has to be in cold storage within four hours of death so arrangements must be well organized.

SharonAB profile image
SharonAB

Dear Strelley,

MMMmmmm Is there a cause or is PSP multi- faceted? I'm hoping a cause - be easier to cure then??????

I have become rather 'googly eyed' looking at google - How many sites/links are there for PSP now????

After 1/2 hour of searching the only site I can find costs $US 29.95 to download just his document

Which perhaps means I'm developing 'Computer Overload PSP' (is that a disease?)

I sometimes feel like I am searching for confetti on screen. For me I feel there is no logical user friendly indexing system for searching on the Internet.

So 'Mr Strelley' if you still have your fingers walking - Can you place a copy of the link online for:

"papers by Dr Golbe - see his most recent 2013 review of PSP on YouTube or lecture notes: "Google" …PSP: A Medical Update -Society for Progressive Supranuclear Palsy"

Thankyou,

Alana - Western Australia

in reply toSharonAB

Hi Alana

I usually write these posts on my Android that unfortunately doesn't cut/copy/paste, so I just ask people to Google the title.

Here are the links from Google that directs one to the YouTube video but the PDF link doesn't seem to work.

Copy and paste this into your address line:

youtube.com/watch?v=8LC1COd...

I've tried this and it seems to take you to video!

Hope it works for you!

Cheers

T.‎

jillannf6 profile image
jillannf6

Hi all

It's been great being. Back on the site and getting your thoughts about the technical aspects (sttrelley)and despite not being able to understand it all i get the gist of it

Lol Jill da:-)

jimandsharynp profile image
jimandsharynp

Thanks Strelly. Do you thing that if a method/drug to stop the Tau tangles from happening there is hope the brain MIGHT, over time, reconnect those transmitters? The body has a way of restoring some nerves etc over time.

Jimbo

in reply tojimandsharynp

Hi Jim

Hope you are keeping well as you look after your dear wife.

There's some exciting research being done with respect to these nasty tau tangles. Researchers are now convinced it is not the tangles that "close down" neurons, but the preceding formation of what is called toxic tau (oligomers).

They are working out what drugs to use to interfere with this chain of events (starting with mitochondria that regulates brain cell protein production, through to stopping tau becoming toxic, and finding out ways to make these bad protein become degraded and removed from the brain cells. There's lots more but I think you'll get the picture) . They are trying all sorts of things that seem to have a measure of success in animal models, but it may be a long way from success in humans.

A lot of work is being done on Alzheimer's that would translate into useful work for PSP. For years, researchers have concentrated on beta amyloid that accumulates in Alzheimer's brains, but tau tangles are also present (a bit different in shape to those in PSP). Now they are concentrating on the toxic tau (because it is this protein that spreads and seems to be responsible for progression of the disease). Since more money is being thrown into Alzheimer's research than PSP, I guess we'll have to wait for major breakthroughs with that disease.

I am completely out of my depth for the next bit.....but I'll ramble on.......

With respect to your query about the brain recovering. As we know, PSP (and similar diseases, even Alzheimer's) disease processes start some 10-25 years before symptoms. All the drugs being tried at present are really attacking the problems once the disease process is quite advanced. We know in PSP that by the time symptoms show up (and we obtain that final diagnosis!!!) some parts of the brain have atrophied.

When we learn new things or exercise/train in certain ways, the brain can make new connections (synapses) and in rare cases new neurons can form. This area of study comes under a broad umbrella name of neuroplasticity. I'm guessing when I say that, in PSP, it would be most unlikely for the brain to remodel another area to perform the function of damaged/destroyed part ( I don't think it's like retraining a person to walk after a stroke etc). However, if the damage in PSP was slight, then stopping the progression of the disease may allow the brain to "kick along" (with a small measure of repair) for some of the symptoms.

In other words, I don't think such things like vertical gaze palsy could be improved because the "mechanism" that controls the oculomotor nerve has been destroyed (as seen on autopsy).

I am no expert in any of this and it would be good if some expert could tell me if I'm talking a load of rubbish! I wonder if neurologists ever read these posts?

All the best to you and your wife. Take care my friend.

T.

jimandsharynp profile image
jimandsharynp in reply to

Strelly, thanks for txh e response. It makes sense.

Jimbo

Interesting summary. A few observations. One of the problems with neurological disorders is that they are heavily underdiagnosed. Three years ago in Cambridgeshire there were 10 known cases of PSP, most were diagnosed in their last stages. Today we have 100 known cases of PSP / CBD. So one of the issues is that the illness most of the time was considered to be just old age. Reason is the lack of education of the GP's who mostly have never ever heard of this condition, let alone have diagnosed it. As they are being made more aware thanks to organisations such as the PSPA, but also due to high profile cases and public attention, e.g. during the latest Olympic Games in London, we gradually get more of a grip on the situation.

Unfortunately the medical community has only started recently to pay attention to those neurological disorders so we have a very long way to go.

Some think that these neurological disorders are triggered by damaged mitochondria. If that is the case we should see some evidence of an inheritance down the female line. I have not heard or read anything about that.

Another line of thought is that we have somehow acquired a nasty protein as is the case in mad cow disease. So food and food sources might be involved as well. Finally I would personally not exclude medication. We are more and more using medication to excess fighting symptoms rather than the source of an illness. Medication in my opinion should only be used if possible for a short period of time. But today the GP's tend to prescribe medication and want you to continue until death rather than to find out what the cause is of an illness, treat it, and then wean you off the medication again. Many medications interfere with the normal biological processes which in themselves have many different side effects and this becomes in particular an issue when they interfere with your nerve system. We know already so much that medication is working widely different in different people, which by the way is another new research area. Some people get relief, others nothing, others get very nasty side effects. Our medication today is still very much a machine gun approach and we will in future need to go more towards individualist treatments. So it is not impossible that taking certain medication can trigger those neurological disorders in some people, especially if those medications are interfering with the maintenance of your nerve system.

My wife was checked also for a possible infection in the spinal fluid. But the tests did not find anything.

in reply to

Hi Gerko

Thanks for your comments. Fortunately, the medical profession is becoming more aware of these neurological diseases like PSP, but anecdotal evidence from this site shows they have a long way to go!

As far as I understand it....."Mitochondrial disease" (or dysfunction) can be initiated by aberrations in both nuclear DNA and mitochondrial DNA. The latter would exhibit usual Mendelian traits (so wouldn't just be seen in the "female line"). However, "dysfunctional" mitochondrial DNA will still pass to males and females from the mother, but the males will not pass on any disease defects. While there is no proof at present that mitochondria are the cause of PSP (only that deficits are found, and so have a role to play in the chain of events), even if they were, males would still be venerable and show disease signs. So, seeing a definite "female line" would not necessarily occur (it's a bit more complex than described but I think this may explain your query).

There is no evidence on autopsy of "foreign" proteins like prions in PSP brains examined so far.

I do agree with you that we are overmedicated, and certain medication can certainly exacerbate some neurological conditions like PSP.

Asyou have seen, my post was to think about the probabilty that diseases like PSP have been around since the beginning of time. In days when the things we suggest for the cause were not around, like pesticides, pharmaceuticals, heavy metals, man made associated radioactivity, immunisations, pollution and the like. So, perhaps we have to look for other causes. This does not negate the possibility that medications in the modern era may be an "added" cause!

It's a good discussion, and one we'll continue to have, especially as more and more are being diagnosed with these terrible diseases.

All the best!

Dear Gerko and All,

How right you are! So many of our doctors are so ignorant in the area of neurological diseases and what is so frightening is that they have so much power as they hold the key to referral for access to specialist consultant's advice in this country(GB).

Another point which your note brought to my mind with regards to early diagnosis is that both my mother and my father were in fact aware that 'things' were not quite right with them for a good few years before we had to turn to the medics for help. My mother,who had Altzheimer's, knew that she could not remember things and in fact would turn very aggressive, only verbally, thank goodness, if she was found out , but she did frighten me; and my father, now with this PSP diagnosis tried his best to hide his symptoms, eg, he grew a 'heavy' beard so we could not see his drooling, he masked the fact that he was falling backwards by bending and stooping forwards. They really were masters of the art of covering up their problems.

Regarding medications, I think my father's dystonia is actually Levadopa induced, as he has been taking it for five years and he never had Parkinson's in the first place! He was assessed in a hospital after about two years of symptoms after he had fallen down for the last time and could not get up and never walked again. The hospital neurologists said he was not levadopa responsive but once in the nursing home a G.P. put him back on Levadopa and so he has remained on it for all these years.

I have a horrible suspicion that there is no relief to be found for this kind of dystonia, but we will see.

Yes, we need to seriously consider all the medicines we take along the way!

easterncedar profile image
easterncedar

Thanks, Strelley and all. I'm new to this site, but have found the sharing of information and experience extremely helpful and comforting. I very much appreciate the scientific information and historic perspective of the original post. It put together many of the pieces I found while trying to inform myself, while adding much more, very clearly explained. Thanks again.

NannaB profile image
NannaB

Thanks for your interesting, informative blogs Strelley. My husband has suffered with ulceratve collitis since 1977 and has been on medication for it most of the time since then. He did, however stop taking it when he felt better on 4 occasions and ended up in hospital each time, when a colostomy was the next step. Each time the doctors changed their mind as they saw a slight improvement. His bowel was so inflamed however, that nutrients were not getting into his blood stream and he was deficient in many minerals, vitamins etc. I wonder if lack of nutrients to the brain had anything to do with PSP developing. He was 62 when diagnosed, has never had head trauma, always eaten healthy food avoiding 'junk', only drank occasional glasses of wine or shandy, never smoked. We both completed forms for brain donation soon after his diagnosis, much to the surprise of his neurologist who said he has to discuss a difficult subject with us when we saw him this year. Lets hope the more brains the experts examine, the more chance there is of finding the answers.

Nanna B

jimandsharynp profile image
jimandsharynp

Strelly, TV news reported that Tony Dorsett (Dallas Cowboy's football) is suffering with CTE. This brain disorder is supposedly caused by head trauma during his playing days. Interesting though is that the culprit Tau is doing the same, or similar, thing in his brain that it does in PSP patients. Of course they can't tell if it is truly CTE or PSP until his brain is biopsied at death. If you know the difference in CTE and PSP please post and let us know. Of course Tau is also a factor in Alzheimer's disease, to some extent. So I guess in response to what causes PSP or what causes Tau to do what it does in PSP there is no definative answer. My PSP wife never had head trauma and probably many PSP patients didn't either. Thanks for all your postings.

Jimbo

in reply tojimandsharynp

Hi Jimbo

As you say, CTE brains at autopsy show tau (neurofibrillary tangles). However, they also show other protein deposits found in a certain type of FrontoTemporal Dementia(FTD), plus occasionally a damaged protein found in Alzheimer's (AD) - apart from tau, called beta amyloid. The damage to areas of the brain are far more extensive than in PSP. So apart from seeing typical Parkinson's symptoms ( gait and balance problems as in PSP) there is far more dementia (that can be similar to FTD and AD). The symptoms appear over time (in those who have had many concussions or sub concussions). I don't think they experience vertical gaze palsy, so that would be a distinguishing clinical sign with respect to PSP.

I knew CTE broke down areas of the Blood Brain Barrier (that highly impenetrable barrier that keeps our brain safe from many things - sadly, not "recreational drugs"). However, in CTE, apparently a certain type of brain protein leaks into the general circulation and the body develops antibodies to this brain protein. After a long period of time, theses antibodies pass back into the brain via the damaged Blood Brain Barrier and start destroying certain brain tissue!

Cheers

T.

blux profile image
blux

Great info..thanks

jimandsharynp profile image
jimandsharynp

Strelly You may be correct but I think the number of cases on the increase speaks to "modern" activators of these diseases. I agree the have been around for many years, just undiagnosed or misdiagnosed. Misdiagnosis still happens even today. Great post. Thanks.

Jimbo

very interesting account, did you have a science background. I did actually do some work ofr UK gov departments on pesticides and parkinsons. The counter argument was that the association was rural background, farm work, rather than any specific pesticide. It is possible that a specific pesticide could be associated but it would be a very weeak association. The structural analogy of paraquat to MPTP did give rise to some theroretical suspicion but again never proved. Just before I retired, I was interested in role of mitochondria in environmental chemical induced disease. It was known over 30 years ago that benzo(a)pyrene from tobacco smoke etc (as just one example chemical) more specifically targets mitochondrial DNA rather than nuclear DNA, although all the evidence for lung cancer is related to nuclear DNA mutation. But the question is what is the result of the effects on mitochondrial DNA. We now know the mitochondrial DNA functions are very imporatnt to cell homeostasis. Its a possible target for neurodegenerative diseases. But I guess wont be researched or proved for many years to come. Of course none of this helps with the day to day problems of PSP.

best wishes

jmbb

in reply to

Hi jmbb

Thanks for your observations. To answer your question, I spent the first 6 years of my working life in pharmaceutical research in the UK. Then I settled in Australia ....and for the last 40 years I worked as a Medical Scientist before retiring 5 years ago.

Cheers

T.

in reply to

I spent 34 y in various UK government agencies, HSE, HPA DH etc before retiring to look after my wife. 46 y is a good career duration to have had. I was pleased I got the 34 y in, 20 publications, poor for research scientist but good for government scientist. Best wishes

jmbb

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