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Gene expression alterations at baseline and following moderate exercise

Discussion in 'Latest ME/CFS Research' started by Bob, May 30, 2011.

  1. Bob

    Bob

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    Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome.

    Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC

    J Intern Med. 2011 May 26. doi: 10.1111/j.1365-2796.2011.02405.x. [Epub ahead of print]

    26 May 2011

    http://www.ncbi.nlm.nih.gov/pubmed/21615807




    (Department of Anesthesiology, University of Utah, Salt Lake City, UT The Brain Institute, University of Utah, Salt Lake City, UT Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT Department of Exercise and Sprt Science, University of Utah, Salt Lake City, UT.)
     
    Last edited: Nov 7, 2014
  2. redo

    redo Senior Member

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    Very good find bob.
     
  3. Dolphin

    Dolphin Senior Member

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    One important typo and two less important typos (I think)

    One important typo and two less important typos (I think)
     
  4. Dolphin

    Dolphin Senior Member

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    I'd recommend anyone who can gets a chance reads this paper, as it's very good. Also, the graphs again are very impressive.

    Information on cohort:
    Interesting point about the exercise test to use (although I'm not sure if it's that clear cut):
    Some basic confounders were ruled out as being important to differences:
    Results:
    This is interesting. Generally I think "CFS trumps FMS" i.e. if you have CFS and FMS, follow the CFS advice (for exercise anyway) - this suggests this could be a fair assessment:
    Baseline gene expression doesn't tell us much about CFS/help us distinguish with controls (for these genes):
    The discussion section I think is very good overall - too many points to post I think.
     
  5. mellster

    mellster Marco

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    Nice find! That is consistent with my observations as well that - being a mild(er) CFS/FM case - continued moderate-to-high aerobic exercise beyond a certain time threshold (~ 30 mins depending on conditioning) without enough time to recuperate will increase the likelyhood for PEM in the aftermath. Obviously the time and intensity thresholds are fluid and dependent on the individual but I bet that the trend they found will be validated by other studies. It might be somehow related to faster depletion of aerobic fiber for CFS patients due to lack of oxygenation, mehtylation and malabsorption And I still think like redo that a lot of the patients could be bettered by fixing the gut cause I have the hunch that nutrient malabsorption together with viral/adrenal fatigue causes that consistent state of maloxygenation. The genetic expressions have to play a part in this.
     
  6. Esther12

    Esther12 Senior Member

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    I've only read the abstract, and doubt I'd understand the full thing properly, but it would have been nice to get sedentary controls, to make sure these differences aren't just related to lower fitness/activity levels. Could that be a plausible or partial explanation at this point?
     
  7. Dolphin

    Dolphin Senior Member

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    (has this post long lines and short lines?)

    Abstracts I find can be harder to read often - they're very dense and things aren't explained. For what it's worth, I was able to understand this paper even though my knowledge of exercise physiology and biochemistry is minimal - I still couldn't tell you exactly what each individual chemical does exactly but one doesn't need to know.

    They do say:
    Also they tested if Ratings of Perceived Exertion could explain the differences:
    and

     
  8. mellster

    mellster Marco

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    Hi Esther,

    I know one person is not statistically significant, but I scored high (for my age group) on the CV fitness treadmill test, which is basically 10-15 minutes high impact increasing incline and speed on the treadmill. I was feeling unwell and fatigued before taking the test and had no PEM whatsoever afterwards. I am also fairly active when doing well so I doubt that I am deconditioned by traditional understanding. I see this as 80% of a recovery and depletion problem and think that the genes might play a role in this as I have always had minor recovery problems all my life (but far form the extent since CFS onset). I think that people can be fairly athletic or strong but weakness might show mostly during aerobic endurance and moreso during the recovery period. Add lack of sleep, stress and gut problems plus viral stressors to the mix and you have the perfect setup for a crash. That's why I think graded exercise is wrong without specific modification, i.e. only increase time and intensity when you feel good and rested and decrease/modify as soon as you begin feeling depleted or having other stressors in your life that could aid to a crash. Since the common nature of doctors is not to stay with you throughout all the stages of health in your life and not knowing about possible current co-factors, I think scientists and doctors should be left with finding the best treatment options - drugs and supplements - for the cause(s) of CFS while you have to become either your own personal trainer/nutritionalist or find one to spend that important journey to betterment in your life with you (money is obviously a big issue), but as much as I would like to wake up and pop a newly discovered pill and have it all gone I think it will require at least a 2-pronged approach and take time and determination (and money).
     
  9. Esther12

    Esther12 Senior Member

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    Oh excellent. Thanks Dolphin.

    lol - it seems like an obvious point, but I'm so used to CFS papers with obvious flaws! I got a genuine shiver of excitement upon reading how well they'd dealt with that concern. Maybe I will try to read the whole thing - it would be nice to read a paper that might be helpful for us, rather than only reading the ones by people I least respect.
     
  10. Esther12

    Esther12 Senior Member

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    Ta mellster. It's a pain. Magic pill sounds more fun imo.
     
  11. Dolphin

    Dolphin Senior Member

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    This graph from a previous paper might motivate some people to consider reading it (I'm not saying it's essential):

    [​IMG]
     
  12. mellster

    mellster Marco

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    Thanks Dolphin - very revealing! A must read slide for every doc out there learning about CFS/FM.
     
  13. Bob

    Bob

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    Thanks Dolphin.

    I haven't read it all yet, but it looks like a very helpful and interesting study.
    The gene expression changes due to exertion seem to be very helpful for us to demonstrate that post-exertional-malaise is a real and physical feature of ME.
     
  14. oceanblue

    oceanblue Senior Member

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    Fascinating indeed. That MS data might just persuade me to read 44 page of the full article posted in the library, when I have time...
     
  15. ukxmrv

    ukxmrv Senior Member

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    Remember that the pro-CBT brigade claim that they can change (i.e. fix ) gene expression (From the UK Gibson Inquiry on ME, by Lord Turnberg at one meeting)
     
  16. Dolphin

    Dolphin Senior Member

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    Not sure the relevance of this? Should we run away from it because they suggest they can change it (without evidence)? There is a huge amount of different "gene expression" that could be tested so even if they might change one thing, they might not change another such as the abnormalities found here.
     
  17. ukxmrv

    ukxmrv Senior Member

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    Thanks Dolphin,

    It would probably cost us UK5 million to find out anyway (the evidence).

    Certainly should not run away from it. Just be aware of the propoganda that will be used to try and discredit these findings.
     
  18. Dolphin

    Dolphin Senior Member

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    Asked in the duplicate thread which will hopefully get locked:
     
  19. oceanblue

    oceanblue Senior Member

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    Promising, but not there yet

    I really like what the authors are trying to do here - look at how gene expression in CFS patients differes from controls after moderate exercise - but I think the results are compromised by the fact that the exercise was not always moderate for CFS patients. Here's what they tried to do:
    The problem with this approach is that for the most severely affected patients (bedbound/housebound) 70% of max heart rate for 25 mins is way, way more than moderate exercise and is vastly more than "natural exercise experiences reported to exacerbate CFS symptoms in patients daily lives". I would be in the second most severe category, 'could live alone with occasional help' and know from trying in the past that I could only manage 70% of max heart rate for a few minutes - my problems are caused by activity way below this.

    The mean score for self-rated exertion for the control group was 3.1, which is just right as a score of 3 equates to moderate exertion. For the CFS group the mean was 5.0 ('hard' exertion) but would have been substantially higher than this for some patients. [from other data given, the exertion for the 21 most exhausted patients can be calculated as 6.5, equivalent to 'very hard' exertion]

    This matters, because the genes chosen for study have increased expression for strenous exercise in healthy controls:
    Worryingly, figure 3 shows that the biggest increases by far for gene expression are in the two most severely affected groups whose exercise level is likely to be far above moderate. It could be argued this is exactly as expected for individuals exercising very hard, not evidence for a specific disease process.

    Now, as Dolphin noted, the authors do address this point by an analysis that only looked at patients and controls with similar exertion levels:
    This is an important finding. However, the statistical significance is much less impressive than for the full study (no doubt due to losing the patients with the biggest differences, as well as the inevitably smaller sample size) and the sample size is small. We don't know if the alpha-2a subgroup exists in this smaller sample.

    What this leaves us with is effectively a pilot-study type result (15 controls/27 patients vs 49/48 in the full study), rather than a confirmatory result. It's still very interesting, but it's not nearly as convincing.

    Well, that's my take. I'm happy for anyone to point out flaws in my logic. Otherwise, to be convinced I'd like to see rersults for a much larger study and ensure that exertion/exercise levels are appropriate for the level of severity experienced by each CFS patient.
     
  20. Dolphin

    Dolphin Senior Member

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