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12-09-2015, 08:46 AM   #61
ganesha
 
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I've seen the articles on crohnsforum but I've searched and did not find this compilation:

http://crohnsmapvaccine.com/pdfs/lit...ses-crohns.pdf
Quite an interesting summary.
12-09-2015, 05:39 PM   #62
JMC
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I've seen the articles on crohnsforum but I've searched and did not find this compilation:

http://crohnsmapvaccine.com/pdfs/lit...ses-crohns.pdf
Quite an interesting summary.
That is the brief summary, there is a much bigger list of about 500 papers compiled by Prof John Hermon-Taylor which will be put on the CMV website at some point. Unfortunately, the vast majority of research is still published in journals which require a paid subscription to read the papers, so it is not possible to legally share the full articles. I find this situation in the internet age, frankly, rather ridiculous and I believe is a factor holding back scientific progress. The sooner everyone has access to all scientific knowledge ever published the better!
12-10-2015, 05:14 AM   #63
ganesha
 
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That is the brief summary, there is a much bigger list of about 500 papers compiled by Prof John Hermon-Taylor which will be put on the CMV website at some point. Unfortunately, the vast majority of research is still published in journals which require a paid subscription to read the papers, so it is not possible to legally share the full articles. I find this situation in the internet age, frankly, rather ridiculous and I believe is a factor holding back scientific progress. The sooner everyone has access to all scientific knowledge ever published the better!
Indeed, this is just a brief summary. I've read much more and downloaded lots of interesting articles (thanks to access granted by a university subscription). I cannot agree more on scientific information sharing. Paying $30-50 for every single article (or subscribing to tens of journals) in the internet era is definitely ridiculous.
12-10-2015, 11:56 PM   #64
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That is the brief summary, there is a much bigger list of about 500 papers compiled by Prof John Hermon-Taylor which will be put on the CMV website at some point. Unfortunately, the vast majority of research is still published in journals which require a paid subscription to read the papers, so it is not possible to legally share the full articles. I find this situation in the internet age, frankly, rather ridiculous and I believe is a factor holding back scientific progress. The sooner everyone has access to all scientific knowledge ever published the better!
you can rent limited access to papers cheaply on sites like readcube and deepdyve, its like 4-5 bucks for 48 hours access with no printing abilities, that's good enough for someone who doesn't do it for a living.
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12-11-2015, 04:59 AM   #65
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you can rent limited access to papers cheaply on sites like readcube and deepdyve, its like 4-5 bucks for 48 hours access with no printing abilities, that's good enough for someone who doesn't do it for a living.
Thanks. I know, but I'll stick to my opinion - sharing builds knowledge.
12-11-2015, 03:21 PM   #66
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you can rent limited access to papers cheaply on sites like readcube and deepdyve, its like 4-5 bucks for 48 hours access with no printing abilities, that's good enough for someone who doesn't do it for a living.
Given a lot of University research is funded by tax payers money, does it not seem a little strange that the knowledge it generates is then sold back to us by multi-billion dollar publishing companies? In the era of journals printed on paper, you might have been able to justify some of the cost, but now? It just feels like robbery...
12-23-2015, 10:44 PM   #67
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Not sure if this one is on the thread, and I can only see the abstract. Very frustrating. Looks interesting.

http://www.ncbi.nlm.nih.gov/pubmed/25994082

Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease.

Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.
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Past (failed) Treatments: Remicade, Humira, Prednisone, Pentasa, Azulfadine, Lialda, No gluten/dairy/sugar/coffee or processed food in general. Flagyl worked but not long term.
12-24-2015, 09:03 AM   #68
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http://www.ncbi.nlm.nih.gov/pubmed/25994082

Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease.
Great paper with some very interesting results. Looking back through my email I read a pre-print of this back in May 2015. One of the authors is Tim Bull who has done a lot of work with Prof John Hermon-Taylor on MAP.

A few other papers from JHT on EColi you might find interesting:
http://www.ncbi.nlm.nih.gov/pubmed/25809337

http://www.ncbi.nlm.nih.gov/pubmed/26137941
12-24-2015, 09:18 AM   #69
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Given a lot of University research is funded by tax payers money, does it not seem a little strange that the knowledge it generates is then sold back to us by multi-billion dollar publishing companies? In the era of journals printed on paper, you might have been able to justify some of the cost, but now? It just feels like robbery...
We have to pay to publish our research, too, in most journals. There are some free ones for scientists to publish in that are top quality, not many though. That can be something of a problem, sometimes. I remember two particular papers that were an absolute joke - but because they were published and in my field, dufus here had to spend 3 months trying to replicate their work (which I couldn't).

It's a careful balance...the editors and workers for these places need the cash, most already have full time jobs in research...it's either increase the fees that scientists have to pay to publish their work so they can hire someone full time to take some of the load, versus charging a prescription fee for the same purpose. Most journals strike a balance, but some are blatantly unfair, usually the "higher end" journals, like nature medicine or some such, though I've read the odd piece of woo woo in there too.

A way around this for access though, and it may not work these days as you usually have to log on to a computer at universities, is to simply walk into one and access them via the computer. Any university with a standard science/medical faculty will have access to pubmed central etc. Alternatively, be very nice to anyone in research. Most would be on your side and download 'em for you to a usb.
12-24-2015, 10:09 AM   #70
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Thanks SauceyScience for the additional info. There are always two (or more!) sides to every story. The researchers I know sometimes send me these, and would if I ask, but I hate bugging them since they're so busy researching! I figure if it's something they need me to know, it will appear in my inbox. Plus, the abstracts are usually an excellent summary and good enough for my purposes. I didn't know that journals charged the scientists. Seems that charging the scientists would lead to bias, as you describe. I figured they'd get their income from subscriptions or ads.

Appreciate the info and wish you the best!
12-24-2015, 03:11 PM   #71
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Not sure if this one is on the thread, and I can only see the abstract. Very frustrating. Looks interesting.

...whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. ...
Quite interesting that the AIEC was undetectable in the healthy control group while MAP was present in 38% of that same control group. Like MAP on its own is not the culprit, and suggests AIEC may play a much more important role in CD than MAP.

I'm so glad the Qu trials are happening right now too and that they'll be releasing some data in the next three months or so. It may help shed some needed light on this disease and raise hope that we can one day soon be able to control this disease much more effectively.
12-24-2015, 07:40 PM   #72
JMC
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Quite interesting that the AIEC was undetectable in the healthy control group while MAP was present in 38% of that same control group. Like MAP on its own is not the culprit, and suggests AIEC may play a much more important role in CD than MAP.
MAP causes dysregulation of the immune system which then leads to nasty infections such as AIEC - see this infographic for a simple explanation:

http://crohnsmapvaccine.com/map/

If it can be proven that Crohn's patients have AIEC infection without MAP, then that would be significant.
12-25-2015, 05:40 AM   #73
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It's a careful balance...the editors and workers for these places need the cash, most already have full time jobs in research...it's either increase the fees that scientists have to pay to publish their work so they can hire someone full time to take some of the load, versus charging a prescription fee for the same purpose.
The internet has changed fundamentally, how information is distributed, why is that not happening with scientific? Web based publishing allows you scale massively without needing to employ large numbers of paid staff or incur proportionate costs. I would seriously question why there continues to be a need to employee many of these people and would be interested to know exactly what they are doing!?

A way around this for access though, and it may not work these days as you usually have to log on to a computer at universities, is to simply walk into one and access them via the computer. Any university with a standard science/medical faculty will have access to pubmed central etc. Alternatively, be very nice to anyone in research. Most would be on your side and download 'em for you to a usb.
This must surely be illegal, otherwise all papers would be downloaded and redistributed. Was this not exactly what Aaron Swatz may have been intending to do? He certainly felt the full force of the US authorities when this hugely lucrative business was threatened...
12-25-2015, 07:16 AM   #74
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The internet has changed fundamentally, how information is distributed, why is that not happening with scientific? Web based publishing allows you scale massively without needing to employ large numbers of paid staff or incur proportionate costs. I would seriously question why there continues to be a need to employee many of these people and would be interested to know exactly what they are doing!?



This must surely be illegal, otherwise all papers would be downloaded and redistributed. Was this not exactly what Aaron Swatz may have been intending to do? He certainly felt the full force of the US authorities when this hugely lucrative business was threatened...

https://www.plos.org/publications/publication-fees/

That's what they're doing.

Also, plos is a good example. 100,000 articles, almost. And growing. That's pdfs. Plus other formats. I believe the last paper my group submitted was almost 18 Mb. And that was a small paper with few images. Maintaining, backing up, keeping access open on the internet. Costs pile up.

Whose going to format and put these papers in publishable format? The editor? The editors of most journals are not paid. Maybe expenses if they have to fly somewhere for a meeting, etc, otherwise zilch. They spend most days, including weekends reading papers, assessing their worth for further review, coordinating with peer reviewers, authors. And that's on top of a job that anyone who knows anything about research knows it is not a 9-5 job, and one that's usually on the line every 3-5 years dependent upon funding. So they hire desktop publishers, graphic designers. Peer reviewers are rarely, if ever, paid either. Although I have heard of some reimbursement, such as with the Lancet, overall it's rare.
01-04-2016, 05:48 PM   #75
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Hey JMC,

I've seen you mention that MAP is in milk and such, but have you looked into other things its in.

http://www.telegraph.co.uk/news/scie...s-disease.html

In this article it suggests MAP is in our water supply.
01-09-2016, 10:09 AM   #76
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Hey JMC,

I've seen you mention that MAP is in milk and such, but have you looked into other things its in.

http://www.telegraph.co.uk/news/scie...s-disease.html

In this article it suggests MAP is in our water supply.
That article refers to a paper published in 2014, Prof John Hermon-Taylor was one of the authors (see here and here). One of the significant open questions is how people are getting infected with MAP and whether it is through consuming dairy produce or another route.
01-09-2016, 10:21 AM   #77
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I think the significance of this paper will become clear in the coming months, as the results from the MAP Test are published.

On deaf ears, Mycobacterium avium paratuberculosis in pathogenesis Crohn's and other diseases.


http://www.ncbi.nlm.nih.gov/pubmed/26730151

The historic suggestion that Mycobacterium avium subsp. paratuberculosis (Map) might be a zoonotic pathogen was based on the apparent similarity of lesions in the intestine of patients with Crohn's disease (CD) with those present in cattle infected with Map, the etiological agent of Johne's disease. Reluctance to fully explore this possibility has been attributed to the difficulty in demonstrating the presence of Map in tissues from patients with CD. Advances in technology have resolved this problem and revealed the presence of Map in a significant proportion of patients with CD and other diseases. The seminal finding from recent investigations, however, is the detection of Map in healthy individuals with no clinical signs of disease. The latter observation indicates all humans are susceptible to infection with Map and lends support to the thesis that Map is zoonotic, with a latent stage of infection similar to tuberculosis, where infection leads to the development of an immune response that controls but does not eliminate the pathogen. This clarifies one of the reasons why it has been so difficult to document that Map is zoonotic and associated with the pathogenesis of CD and other diseases. As discussed in the present review, a better understanding of the immune response to Map is needed to determine how infection is usually kept under immune control during the latent stage of infection and elucidate the triggering events that lead to disease progression in the natural host and pathogenesis of CD and immune related diseases in humans.
01-09-2016, 10:49 AM   #78
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JMC - Fully agree. I saw this a couple days ago and was incredibly frustrated that I couldn't read the full article! The naysayers seem to think that the presence of MAP in controls works against it being classified as zoonotic/pathogenic, but I think it's just the opposite - that the human MAP variant is finding a way to live in the majority of the population which corresponds to the rise in CD and other immune mediated conditions. MAP in controls is a very scary prospect to me. Because of the latent nature of onset of these conditions post initial infection, it will probably be too late to prevent the spread of MAP by the time long term studies are completed. It may be too late now.
01-09-2016, 12:43 PM   #79
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JMC - Fully agree. I saw this a couple days ago and was incredibly frustrated that I couldn't read the full article! The naysayers seem to think that the presence of MAP in controls works against it being classified as zoonotic/pathogenic, but I think it's just the opposite - that the human MAP variant is finding a way to live in the majority of the population which corresponds to the rise in CD and other immune mediated conditions. MAP in controls is a very scary prospect to me. Because of the latent nature of onset of these conditions post initial infection, it will probably be too late to prevent the spread of MAP by the time long term studies are completed. It may be too late now.
When I first started looking at MAP test results, and everyone was testing positive, I was initially alarmed, but it makes sense.

Ask yourself this, though, If MAP is the cause of many immune mediated diseases, what are the other factors that determine whether you get Crohn's, psoriasis, diabetes, RA, etc? Why don't we get all of them at once?

Is it another bacteria, a virus, a specific genetic defect in your immune system? I don't think anyone can answer that question at the moment (and I have asked the right people).

If I was a betting man, there certainly seems to be some evidence that MAP + AIEC = Crohn's...
01-09-2016, 01:30 PM   #80
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Actually it is the same with any disease. Not everyone exposed to TB, Influenza, yellow fever.... develop the disease. An old term in medicine, although some might consider it obsolete, is idiosyncrasy and is still in use. There are various theories regarding the abnormal susceptibility of developing a disease (NOD2/CARD15 for example). What leads to the polymorphisms is the actual debate.

...

Ask yourself this, though, If MAP is the cause of many immune mediated diseases, what are the other factors that determine whether you get Crohn's, psoriasis, diabetes, RA, etc? Why don't we get all of them at once?

Is it another bacteria, a virus, a specific genetic defect in your immune system? I don't think anyone can answer that question at the moment (and I have asked the right people).

If I was a betting man, there certainly seems to be some evidence that MAP + AIEC = Crohn's...
01-09-2016, 01:35 PM   #81
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I think the formula might look something like this:

MAP+AIEC may=Crohns.

MAP+AIEC+H-Pylori may=Crohns.

MAP+AIEC+H-Pyori+Mycoplasma may=Crohns

Mycoplasma may=Crohns.

H-Pylori may=Crohns.

Possibly other variations unknown.

It depends on if, where, and how much of each is present to get to the stage where it is diagnosed.

I think it is likely that MAP & AIEC is present in most cases of Crohns, but it can be further aggregated by the others.

Just my take on it.

Dan
01-09-2016, 06:06 PM   #82
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This week's announcement by Enterome that it's entered into agreements with two major players in the CD treatment space (J&J and Takeda for Remidcade and Entivyo, respectively) suggests there's some rising interest in AIEC.

Enterome is developing both diagnostic and treatments for AIEC.

Here's a a video on their hypothesis on how AIEC may contribute to CD. It really starts getting into it at around the 1 minute mark.

https://www.youtube.com/watch?v=aTeZZ7ydmfM
01-12-2016, 05:48 AM   #83
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great video - that bird knows her stuff.
01-12-2016, 10:43 AM   #84
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Colicins, but finding the right probiotic seems somewhat difficult.
Nissle 1917 might have been one, but that is taken off the market by the FDA.
Old Mike
http://www.ncbi.nlm.nih.gov/pubmed/26177305

here is something a little off the wall ecoli is rescued from colicin by B12,
the receptor sites are the same.
http://www.sciencedirect.com/science...7810979490104X

http://www.ncbi.nlm.nih.gov/pubmed/4579869

anyone get worse on B12 taken orally

western diet, GPR43 agonists are short chain fatty acids
http://www.ncbi.nlm.nih.gov/pubmed/26742586
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Last edited by mf15; 01-12-2016 at 06:27 PM.
01-12-2016, 05:56 PM   #85
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Posting the link to the full article for irishgal
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690169/
01-12-2016, 08:55 PM   #86
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Thanks xmdmom!! You're awesome!! Looking forward to reading this tonight. I want to see their proof and theories on healthy controls to see if it's what I expect or if there's something more. Really appreciate this!
01-17-2016, 04:15 PM   #87
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Thanks xmdmom!! You're awesome!! Looking forward to reading this tonight. I want to see their proof and theories on healthy controls to see if it's what I expect or if there's something more. Really appreciate this!
Sorry, I thought I had posted the direct link to the full paper already as it is a Free PMC paper. I also exchanged a few emails with William Davis and he emailed me a few more papers, just pm me if you want to read them and I will forward to you.
01-18-2016, 02:00 PM   #88
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Let me run this by everyone.

One reason MAP and AIEC can survive inside macrophages is that
either by immune subversion or some genetic defect, the phagasomes are not acidified enough. and low NO production possibly nos2 (macrophage inducible NO) and possibly arginine transport,or some form of alternate activation
which lowers NO.



https://books.google.com/books?id=68...ginine&f=false

http://www.jleukbio.org/content/49/4/380.short

NO resistant strains
http://iai.asm.org/content/61/5/1980.short

extra NO might make things worse as usual conflicting info
http://www.jimmunol.org/content/162/11/6734.short

NO and human TB
http://immunenetwork.org/DOIx.php?id...in.2009.9.2.46

I have UC and when I take arginine I get worse, too much iNOS, a way to
lower inos in the colon is lots of dietary nitrate,which goes into the entero salivary nitrite NO pathway, and curcumin.

Now a question might be would arginine supplementation help with crohns by increasing intracellular macrophage killing of AIEC and MAP.

Start researching phagasome acidification, nos2,intracellular killing.

Has anyone tried arginine for crohn's,.

So in a nutshell high nos2 activity for crohns, low inos activity for UC.
High dietary arginine for crohns, high dietary nitrate for UC.

Old Mike

Last edited by mf15; 01-18-2016 at 02:53 PM.
01-22-2016, 09:03 AM   #89
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Not sure, mf15. I know that arginine consumption can bring HSV-1 out of latency, so for anyone that has HSV-1 it might be best to avoid it.

That said, arginine can be purchased in bulk cheaply, so if you don't have HSV-1, or are willing to risk an outbreak, it's probably worth a shot.
01-22-2016, 06:02 PM   #90
JMC
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Crohn’s Disease: A Case for MAP Targeted Therapy

https://www.ecronicon.com/ecmi/pdf/ECMI-01-000S1.pdf

Crohn’s disease (CD) is a severe intestinal inflammatory disease, for which currently no full cure is possible, and of which the pathogenesis is still not fully elucidated. Intestinal bacteria are thought to play a role in the onset, combined with environmental factors, immune factors, and genetic susceptibility of the host. However, we do not fully understand the nature of the disease yet, and as a consequence, this lack in our knowledge may prevent us from developing effective and curative therapies. If we are able to revisit our views on involvement of Mycobacterium avium ssp. paratuberculosis (MAP) a as an important player in this disease, this might open up new options for therapeutic targets
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