Cytomegalovirus (CMV / HHV-5) involved in high blood pressure?

Originally carrying out an investigation into the gene regulatory microRNA (miRNA) expression differences between Chinese patients with and without high blood pressure, the researchers soon discovered an obvious sign of HCMV infection in the form of a virally encoded miRNA.

Quantitatively determining the miRNA levels in blood samples, many miRNAs were up or down regulated but the group focused in on one in particular: hcmv-miR-UL112 - derived from HCMV that was shown to be highly expressed in those suffering from primary hypertension. These expression differences were thought to be down to endothelial cells within the blood sample, termed circulating endothelial cells. HCMV seropositivity as well as higher amounts of viral DNA, in general, was seen to be correlated with the high blood pressure group, especially when other factors were considered. This correlation was not seen with other common human viruses (Epstein-Barr and adenoviruses) suggesting a certain specificity.

Remember: That is only a possible correlation, not a definitive causative link.

Scientific process: Useless treatments found to be useless

As Tsouderos notes, complementary and alternative therapies are a $34 billion industry and 40% of U.S. adults report using some kind of alternative remedy in the last year. Wouldn't it make sense to study these remedies, given that they're being used so widely? For all we know, some of them are dangerous. Besides, even debunking useless claims would be a service to consumers. The problem is that NCCAM exists to validate alternative medicine, not to assess it critically.

NCCAM is a political oasis for research that could not compete in mainstream science. Sen. Tom Harkin (D-IA), one of the fathers of NCCAM, gave the game away when he lamented during a 2009 senate hearing that the center was disproving too many alternative therapies. "One of the purposes of this center was to investigate and validate alternative approaches. Quite frankly, I must say publicly that it has fallen short," Harkin said. If Harkin were interested in applying science to CAM, as opposed to confirming his bias towards complementary remedies, he would be happy that useless treatments were found to be useless.

Which reminds me of the study of the "Mikovits-XMRV-test".

The Problems with the Lombardi et al 2009 Science paper

Some of the problems of the Lombardi et al. 2009 Science paper, many of which should have been addressed prior to publication.

- Failure to state if samples were tested in a blinded fashion
- Failure to state the reason that not all tests were done on all samples
- Failure to sufficiently describe each employed test method
- Mislabeling of at least one slide
- Omission of the usage of 5AZA
- Failure to publish full viral gene-sequences
- Failure to show genetic variation expected of a retroviral pathogen vs. contamination
- Failure to show integration into the human genome

Plus Mikovits communicated tidbits about the study on her talks, instead of publishing them.

[Update]
Furthermore I would add these points:
- Failure to explain the rational to use nested PCR
- Failure to account for higher risk of contamination with nested PCR the way PCR was used

[Update]
- Usage of water only negative control samples
- Failure to report the use of positive control samples
- Failure to discuss the PCR sensitivity

[Update]

- again: Failure to report the use of positive control samples

- Failure to show control results of PCR without reverse transcriptase (RT) for detection of DNA (plasmid) contamination

[Update]
- Failure to supply a all test results for each sample (patients and controls)

[Update]
- The main result (67% PCR positive) is shown in one (!) sentence, without any supporting material

XMRV is not a human pathogen

Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.

XMRV as a human pathogen is dead as doornail. I repeat: XMRV does not cause ME/CFS.

Nature.com: "Fresh dispute about MMR 'fraud'"

Bjarnason says he doesn't believe they are sufficient to support claims in the Lancet paper of a new disease process. He also questions whether "non-specific" on the grading sheets refers to colitis, saying it could refer to any kind of gut changes. But he says that the forms don't clearly support charges that Wakefield deliberately misinterpreted the records. "The data are subjective. It's different to say it's deliberate falsification," he says.

I think Andrew Wakefield is a quack, but even he deserved a fair trial – with less foaming accusations and more scientific inquiry. Or did Bruno Bettelheim ever get the Wakefield treatment?

On CBT and GET

The CBT that is a defacto mandatory therapy for UK ME/CFS patients that want continuing medical care and at least limited disability benefits is nothing like coaching in my understanding. The behavioral therapy you describe could certainly be of use to ME/CFS patients that almost universally need to come to grips with new energy limitations and acquire time management skills to marshal their energies and survive. That is not what is being offered.

Instead, patients are subjected to therapy methods that are at best dishonest, and in the worse case coercive and stressful. It can be even physically harmful if combined with GET therapy. The CBT for UK patients has its roots in "reparative therapy", as I mentioned upstream in this thread.
http://en.wikipedia.org/wiki/Conversion_therapy

In reparative therapy, the operant reality construct is that gay patients are mentally ill and need to be repaired by "conditioning" methods. In CBT for CFS patients, the operant reality is that CFS patients are mentally ill and have "deconditioned" themselves. They need to be repaired by "conditioning" methods. If you add coercion in the form of Christian "guilting" of a homosexual patient, or the withholding of care and benefits in the case of CFS, then it is not helpful to the patients in the long view of things.

Sadly, the powers that be and vested interests in the UK have chosen to devote almost all available funding to CBT and GET therapies in the context of ME/CFS treatment and research efforts. It is the only game in town.

I have been banned from the mecfsforums :-)

Sorry Guest, you are banned from using this forum!
Trolling
This ban is not set to expire.

I'm being silenced! I'm a martyr! :-)

Phew. Thank Darwin I am banned from using that XMRV/HGRV Dooms-Day cult forum.

And Jamie is censoring my comments too – must be the season.

2009 Science paper about XMRV retracted

Alberts says the Blood Working Group finding was the final straw that led Science to request the full retraction. "The blood group study to me was dramatic evidence of poor science," says Alberts. "It gave us absolutely no confidence in the ability of the major labs involved to do the assays. I find that enormously disturbing." NCI's Francis Ruscetti, a prominent retrovirologist and one of the co-authors, attempted to coordinate a retraction with his colleagues but a dispute arose over wording that suggested some of the findings in the original paper were still valid. "We tried to get all of the authors to agree, but it got endless," says Alberts. "The responsibility that Science magazine has to the scientific community is to make a strong statement that we don't think anything in that paper can be relied on."

How endogenous retroviruses fuck up the immune-system

The endogenous guys are also berry sneaky. While they are no longer completely functional they still can transcribe-->translate a superantigen. Its a viral protein, but because it is expressed before the immune system matures, the immune system recognizes the viral protein as 'self.' That means that all the T-cells that would kill an MMTV infected cell are killed, like all T-cells that recognize 'self' proteins. Mice basically lose an arm of their immune system.

Remember the classes of T-Cell Receptors I was talking about with the possums? Endogenous MMTVs (and the infection of pups before their immune system matures) can cause the loss of all T-cells that have certain Variable Beta chains. This deletion increase the mouses susceptibility to new MMTV infections, and also increases susceptibility to other pathogens, like cholera. Yup-- A virus screwing around with how well you can fight off bacteria.

Lactose intolerance: More common than you think

The problems seemed ‘sporadic’ but frequent. His doctors never suggested lactose intolerance. We could have done a food elimination test, but that was time consuming and very inconvenient. In hindsight we should have done the slog of eliminating foods from the diet…but you know what they say about hindsight? (Or at least the Phantom Tollbooth).

This is interesting, because I know several people who went through something similar. The vast majority of Northern Europeans are lactose tolerant, at least judging by phenotype and that particular SNP. But, at least ~5% are not. That’s not a small number in absolute terms, and even proportionally it is common enough that if you know 13 random Northern Europeans, there’s a 50% probability that at least one of them is lactose intolerant.

Note: There are other SNPs which likely confer lactose tolerance. And, it seems likely that environmental factors, such as adaptation of your gut flora, also matter in the final phenotype. 

Why exercise (partially) counteracts a crappy diet

Cadmium (Cd), tungsten (W), tellurium (Te), beryllium (Be), and lead (Pb), are non-essential metals pervasive in the human environment. Studies on athletes during training periods compared to non-training control subjects, indicate increased loss of minerals through sweat and urine. The aim of this study was to compare the level of these trace elements, determined by inductively coupled plasma mass spectrometry (ICP-MS) in urine samples, between athletes and age-matched sedentary subjects … With the exception of Pb, urine toxic metal concentrations from athletes were higher than from sedentary subjects. This fact suggests that physical activity counteracts, at least in part, the cumulative effect of toxic environment by increasing the urine excretion of toxic metals in trained people. (via)

And the increased metabolism through exercise should help burn up any harmful proteins. Of course, foremost not eating toxic stuff would be the order of the day.

The XMRV mess will be sorted out

Drs. Judy Mikovits and Frank Ruscetti continue to be part of the Lipkin study.

“I have gone to great lengths to make sure they remain involved,” Lipkin said in a telephone interview.

Labs at the Whittemore Peterson Insititute will no longer be used in the Columbia University-based study since Mikovits’s split with the institute, Lipkin said. He instead has worked with Mikovits and Ruscetti to find a lab where they would be `comfortable’ working, he said. That lab has been found and there work has resumed, he said.

(via)

“[WPI] are no longer involved because the whole point was to have Mikovits try to reproduce her work, and having someone else at the institute do so wouldn’t address the questions,” Lipkin says. “It’s critical that she do the work. She doesn’t have a lab at present, so it’s going to be done at NCI.”

I really hope this will be the decisive "Yes or No" answer to the "XMRV/HGRV or Contamination" question. I trust Ian Lipkin to both be open and inquisitive while at the same time making sure the results stand up to scrutiny.

The Hammer Trap

I saw this quote in a Psychology today article recently (The right tool for the job). It’s not new of course, it’s one we’ve heard often. But as I reflect over my varied careers and life experiences, I realise how often I’ve fallen into the “hammer trap”, where a particular experience colours my world view profoundly.

It goes like this: Something I’ve tried – whether it be a diet (Zone, Paleo, low carb, raw vegan …, name yours) or some self improvement course, religion, inspirational book, peak experience, adventure, therapy, medication, sport, exercise.. you get the picture. This thing you experience – it changes your life in some way, in fact it makes it profound difference. Every issue / health problem you see others having – your recent discovery appears to you be the answer.

As a group of paleo nutrition, and often low carb advocates – we tend to view the world’s health / weight problems as though paleo / low carb is the answer to everything. E.g. low carb will fix everyone who is overweight, it’s even good for athletes once they get used to burning fat instead of carbs…

Bill Lands on Omega-3 fatty acids

A shorter excerpt on YouTube and the original at the NIH (action starts around minute 12).

Bill Lands hits all the right talking points, but by Darwin, he does an awful presentation…

British Psychology Journal, home to paranormal psychics

Stuart Ritchie, a psychology doctoral student in Edinburgh, worked with two colleagues to try to replicate the results of a famous recent experiment, claiming people could predict in advance whether they were about to be shown erotic images. When the three failed to find any such evidence for ESP they sent their results out for publication, and the British Psychology Journal, one of the journals to which it was sent, in turn sent the trio's article out for review. When Ritchie et al got the responses back '...there were two reviews, one very positive, urging publication, and one quite negative. This latter review didn’t find any problems in our methodology or writeup itself, but suggested that, since the three of us (Richard Wiseman, Chris French and I) are all skeptical of ESP, we might have unconsciously influenced the results using our own psychic powers.'

(via)

What could possibly go wrong?

Gumming Up Appetite to Treat Obesity: Researchers plan to create chewing gum that sneaks an appetite-suppressing hormone through the gut and into the blood.

By the looks of it, "diseases of civilization"–  including obesity – are caused by evolutionary novel food which contain compounds encountered by humans only in recent evolutionary times. So let us battle the problem by introducing even more novel compounds. Science – fuck yeah!

"Just tell them you’ve had your leg in the Thames."

“If you see any red streaks, if you get any shooting pains in your leg, or anything feels wrong, come back immediately,” she advised, eyeing my bandage warily. “No one’s going to mind. Just tell them you’ve had your leg in the Thames.”

I started doing some Google-based investigation. Just what was so bad about inviting some Thames water into my gaping, bleeding flesh? My findings led me to conclude that my leg was either about to shrivel up and fall off, or spontaneously sprout 8 smaller legs. Or eyes.

(via)

Why raw food and cooked food have different calories

But the Atwater Convention has two big flaws. First, it pays no attention to the extent to which food has been processed. For example, it treats grain as the same calorie value whether it is eaten whole or as highly milled flour. But smaller particles are less work to digest, and therefore provide more net energy. Second, it treats foods as equally digestible (meaning, having the same proportion digested) regardless of processing. But cooked foods, as we’ve seen, are more digestible than raw foods.

These flaws matter. According to the Atwater Convention raw foods have equal calorie content to cooked foods. So people can be deluded into thinking that feeding their children on 100% raw foods is a healthy practice, whereas I believe it would be dangerous for them.

A challenge to all ME/CFS patients who think VP62 matters

To all people who keep on posting about VP62!

I challenge the person (all those anonymous VP62 posts seem the same to me) to provide me the following:

1. The gene-sequence of XMRV/(P)MLV/"HGRV", as supplied from the Mikovits/WPI
2. The primer/probe sequences, as supplied by the Mikovits/WPI
3. The gene-sequence of VP62
4. The primer/probe sequences which are supposed to be "calibrated" only to VP62
5. A explanation (using the material above) why the primer/probes from (4) work only with regards to VP62 (3) – and why they can not work with XMRV (1).

As a bonus, explain why the primer/probe used by the WPI are better (or the only "true" ones to be used). And please explain how the "calibration" of the primer/probes to VP62 works.

Dr. Mikovits has supposedly worked with "HGRVs" for over two years, cultured them in the lab, categorically ruled out any form of contamination – so she should have lots and lots of data, which should have been published for other researchers to use.

Yet, somehow, I guess none of those anoymouses (in case there is more than one) who go on, and on, and on, and on, and on why VP62 matters, none will be able to provide this material. Prove me wrong.

[By the way, to all possible commenters: Post comments about VP62 here and only here. Any comments about VP62 on other posts will be deleted. You have been warned.]

One cause, different effects

If you have two faulty copies of this gene, your brain won't be normal, but what goes wrong varies widely amongst different people. Although the 9 cases had some features in common, such as microcephaly (small head and brain), in other respects they differed greatly.

As the authors put it, mutations in WDR62 cause
a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients... had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities.

These are distinct entities, in the sense that you can have any one of them, without having the others. And they are different brain changes. What the authors mean is that everyone assumed that, because they're different, they must have different genetic causes. They've just shown that this is wrong.

So what is WDR62 "for"? Experiments in mice showed it to be involved in the migration of new neurons from their origin to their final location in the brain. So it's "for" correct neuronal placement, although how it works remains unclear.

WDR62 ought to remind us that there's a long and winding road from gene to phenotype, and that the same gene can, when mutated, cause very different symptoms. This is especially interesting in the light of recent evidence showing that the same mutations can cause a range of behavioural disorders from autism to ADHD to schizophrenia.

(via)

Paleo for Multiple Sclerosis

Paleo-Zone Nutrition: Dr Terry Wahls reverses her own Multiple Sclerosis with hunter gatherer nutrition.

That Paleo Guy: Treating MS with a paleoesque diet.

Free The Animal: Don’t Listen to Me. Listen to Dr. Terry Wahls, Cured from Debilitating Multiple Sclerosis (MS) On a Paleo Diet

Study suggest Confirmation Bias is present in scientists

Like others with chronic fatigue syndrome, Dr. Schweitzer is used to having her illness ignored, mocked or treated as a manifestation of trauma, depression or hypochondria—not only by doctors, colleagues and strangers but by friends, family members and federal researchers, too. So when the U.S. Centers for Disease Control and Prevention reported last year that people with chronic fatigue syndrome are more likely to suffer from “maladaptive personality features”—in particular from “higher scores on neuroticism” and higher rates of “paranoid, schizoid, avoidant, obsessive-compulsive and depressive personality disorders”—Dr. Schweitzer dismissed the research as “incredibly stupid” but “not surprising.” In another recent study, the CDC had reported—also incredibly stupidly, from Dr. Schweitzer’s perspective–that childhood trauma, such as sexual or emotional abuse, was a “an important risk factor” for the illness.

It's the environment, stupid!

Critics, on the other hand, have argued all along that both twin studies and family studies are unable to disentangle the potential roles of genes and environment. They have pointed out for decades that the validity of equal environment assumption (EEA) of the twin method is not supported by the evidence, and that the much more similar environments experienced by reared-together monozygotic (MZ) versus reared-together dizygotic (DZ) twin pairs confound the results of the twin method. Therefore, both family studies and twin studies prove nothing about genetics and their results can be completely explained by non-genetic factors. Most behavioral geneticists agree with this assessment as it relates to family studies, but continue to maintain that twin studies provide conclusive evidence that genes play an important role. Critics have also pointed to the massive methodological problems and untenable assumptions found in psychological and psychiatric adoption studies, as well as the major problems and environmental confounds in studies of purportedly reared-apart twins

And:

In study after study, applying GWAs to every common (non-infectious) physical disease and mental disorder, the results have been remarkably consistent: only genes with very minor effects have been uncovered (summarised in Manolio et al 2009; Dermitzakis and Clark 2009). In other words, the genetic variation confidently expected by medical geneticists to explain common diseases, cannot be found.

There are, nevertheless, certain exceptions to this blanket statement. One group are the single gene, mostly rare, genetic disorders whose discovery predated GWA studies2. These include cystic fibrosis, sickle cell anaemia and Huntington’s disease. … With these exceptions duly noted, however, we can reiterate that according to the best available data, genetic predispositions (i.e. causes) have a negligible role in heart disease, cancer, stroke, autoimmune diseases, obesity, autism, Parkinson’s disease, depression, schizophrenia and many other common mental and physical illnesses that are the major killers in Western countries.
…
This dearth of disease-causing genes is without question a scientific discovery of tremendous significance. It is comparable in stature to the discovery of vaccination, of antibiotics, or of the nature of infectious diseases, because it tells us that most disease, most of the time, is essentially environmental in origin.

Firstly, in my view, common diseases can not have its origin in genetic problems. And secondly, who says that common diseases (chronic, with presumably gradual onset and/or gradual build-up, like e.g. type 2 diabetes) can't have a infectious origin? I think nutrition is far more likley to be the culprit, but hey.

In a rare public sign of the struggle to come to terms with this genetically impoverished world-view, the authors of a brief review in Science magazine, Andrew Clark of Cornell University and Emmanouil Dermitzakis of the University of Geneva Medical School, Switzerland have been alone in stating the case even partly straightforwardly. According to them, the GWA studies tell us that “the magnitude of genetic effects is uniformly very small” and therefore “common variants provide little help in predicting risk” (Dermitzakis and Clark 2009). Consequently, the likelihood that personalised genomics will ever predict the occurrence of common diseases is “bleak”. This aim, they believe, will have to be abandoned altogether.

The first conclusion to be drawn from these quotes is that such directness implies that if the GWA findings are not finding their way to the front page the reason is not ambiguity in the results themselves. From a scientific perspective the GWA results, though negative, are robust and clear.

Most human geneticists view the GWA results somewhat differently, however. An invited workshop, convened by Collins and others, discussed the then-accumulating results in February 2009. The most visible outcome of this workshop was a lengthy review published in Nature and titled: “Finding the Missing Heritability of Complex Diseases.” (Manolio et al. 2009).

For a review paper that does not lay out any new concepts or directions, 27 senior scientists as coauthors might be considered overkill. “Finding the Missing Heritability”, however, should be understood not so much as a scientific contribution but as an effort to conceal the gaping hole in the science of medical genetics.

In their Science article, which was published almost simultaneously, Dermitzakis and Clark paused only briefly to consider whether so many genes could have been overlooked. Apparently, they thought it an unlikely possibility. Manolio et al., however, frame this as the central issue. According to them, since heritability measurements suggest that genes for disease must exist, they must be hiding under some as-yet-unturned genetic rock. They list several possible hiding places: there may be very many genes with exceedingly small effects; genes for disease may be highly represented by rare variants with large effects; disease genes may have complex genetic architectures; or they may exist as gene Copy Number Variants (CNVs). Since Manolio et al. presented their list, the scientific literature has seen further suggestions for where disease genes might be hiding. These include in mitochondrial DNA, epigenetics and in statistical anomalies (e.g. Eichler et al. 2010; Petronis 2010).

It is sad to see scientists working in the field genetics have so little grasp of evolution that they fail to see the evolutionary interdependence of genes and environment...

Farming causes crowded and crooked teeth

Parents going broke to pay for their offspring’s braces and orthodontistry can finally blame somebody besides their mildly malformed children: our farmer ancestors. A study published this week in the Proceedings of the National Academy of Sciences found that people living in subsistence farming communities around the world have shorter, wider jaws than those in hunting and gathering societies. This leaves less room for teeth, which have changed little in size or abundance over human history—and may help explain why crooked choppers and a need for orthodontia are so common, study author Noreen von Cramon-Taubadel tells the BBC.

So is it a genetic trait, or is it the environmental factor (as in consumption of grains)? I would say the latter.

Previous studies have shown that differences in the length of jawbones seem to arise relatively quickly after a change in subsistence economy, suggesting the shift to a shorter jawbone in agricultural groups could reflect a selective pressure for downsizing.

Or it suggests that it is environmental (as in consumption of grains).

Changes in jawbone size can also arise within a single generation due to phenotypic plasticity, wherein environmental differences lead to anatomical changes. For example, a 2004 study found that the mandibles of hyraxes (a small rodent-like mammal) given soft, processed food grew to be 10 percent shorter than those fed a heartier unprocessed diet.

Or it could be that is the consumption of grains.

Perhaps one day this “mismatch” will correct itself. Until then, were stuck with braces.

Or we could try changing our diet and see if we are really "stuck" with this.

CDC versus the rest

Among U.S. scientists who work primarily on this disease, essentially no one argues for a psychosomatic cause. Nor do any researchers use the 2005 definition, besides the ones whose work is paid for by the CDC. Nevertheless, the agency has had a huge influence on the opinion of doctors and the general public, creating an attitude of skepticism and even condescension toward the disease. Rather than focusing on treatments, the majority of research has gone toward providing evidence, in one form or another, that patients had some kind of psychological problem long before they developed the syndrome.