Jessina Graham

@ZebraLoveCo @PneumaNeura @AndrewG76201347 Interesting, thanks. There is some data that beyond modulating upstream inflammatory signaling, it may shift intracellular signaling like cAMP and improve metabolic dynamics. That’s likely part of how you see effects on insulin resistance and possibly tissue-level function.

@PotsyNP @PneumaNeura @AndrewG76201347 I think it may most likely be a vascular/immune. They were tight and wouldn't release but also they literally were physically shortened from damage that would heal if I gave it enough time. I also may have an iliac vein compression which is contributing. I have an MPO of 5300

An old drug I’d love some feedback on, Amlexanox. Old asthma drug, but now we know it stabilizes mast cells upstream and reduces insulin resistance. It’s available off label/compounded in the US, and in some European areas. Anyone have any experience with it? #MCAS #pots #hEDS

@HalfThePerson @PutrinoLab I suspect you would see more than 2 subgroups emerge, but there’s some extrapolation happening in my modeling.

@PotsyNP @PutrinoLab Yes, and hemodynamic abnormalities=>tissue hypoperfusion could be dysautomia-specific, while oxygen utilization abnormalities downstream to it could be ME-specific? Ofc oversimplifying this now, X posts are not the right format to get into intricacies

Shame, but I’ve not found the work around two day CPET to be compelling as a biomarker or even feasible as a test for many who are more severe. Interested in Systrom’s work on invasive CPET to understand the physiology and Wust’s work on muscle biopsy as a biomarker. Onward!

@HalfThePerson @PutrinoLab You’re narrowing in on exactly why I want to see ocular testing vs global flow dynamics. These tests don’t reflect all pathology. SPECT and similar imaging assume blood flow ≈ oxygen/utilization, but they don’t capture how well tissue responds to demand.

@PotsyNP @PutrinoLab Study I posted above found that dysautonomia pts have reduced cBF even while supine

@KimJDay12 @PutrinoLab symptoms that concern me and other providers, but they haven’t gotten many clear answers despite how disabling the visual patterns can be. Also some of the options on the table for them are invasive and life altering, so I tread carefully.

@KimJDay12 @PutrinoLab So sorry you experienced such a devastating loss. I saw that you were tracking some of your lactate levels. May I ask if you had any visual snow symptoms, or other visual symptoms that presented before your loss, and how that progressed? I ask because I have several pts with

@amyrochlin @PutrinoLab Right now so much of MCAS/POTS management is empiric, and without better functional stratification it’s hard to know which pathways are actually driving symptoms in a given patient.

@amyrochlin @PutrinoLab That’s why I keep coming back to downstream physiology. If we can’t reliably measure the signal, we may need to focus on how it’s expressing.

@PutrinoLab That alone would start to break patients into groups we currently lump together and make treatment responses easier to interpret. Not exactly Twitter-friendly to unpack, but it’s where I’d start.

@PutrinoLab For feasibility, stratification, and treatment relevance, I’d pair TCD with flicker-induced vasodilation. You capture global flow and local response, something we’re not separating well right now.

@ZebraLoveCo @PneumaNeura @AndrewG76201347 Trying to understand if this was more tone, perfusion, or neuromuscular.

@ZebraLoveCo @PneumaNeura @AndrewG76201347 Thanks for sharing, that’s really helpful. When you say you couldn’t straighten your legs, was it like: •tight/resistant (almost like they wouldn’t release) •true weakness •or more of a pressure/pain limitation? And did it fluctuate at all or stay pretty constant?

@NZJennings @PrzemekPWr @MacrinePhD Makes sense. I don’t exactly learn theories by rote memorization. I tend to bottom up mechanisms across diseases and if the theory speaks to what I see in bodies I’ll align with it. I see utility in both.

@PotsyNP @PrzemekPWr @MacrinePhD 2/2 ... unstable due to physical substrate issues the problem is upstream of the modes entirely and the theory doesn't speak to it.

Does the body really keep the score? A new paper by Steven Kotler & Karl Friston argues trauma isn’t stored in tissues. It’s a prediction error—the brain gets stuck in rigid threat expectations. The key to healing is updating these predictive models, and Flow states are one of the best ways to rewire that flexibility! #share" target="_blank" rel="nofollow noopener">frontiersin.org/journals/syste… @KarlFristonNews #Neuroscience #Trauma #PredictiveCoding #PTSD #FlowState #ActiveInference #MentalHealthResearch #Metastability

@NZJennings @PrzemekPWr @MacrinePhD An either/or argument is beautiful in theory, but dissolves in messy bodies. The body does keep score, and top down prediction errors occur as well. You can’t silo either one away from the other. Dominance varies and interaction is constant.

@NZJennings @PrzemekPWr @MacrinePhD This framework makes sense when prediction error is driven by misweighted priors. In some patients, the signal itself is unstable, e.g., mechanotransduction/Piezo-mediated afferent noise. In that case, the brain may be modeling accurately, and recalibration alone won’t resolve it

@J__Doh @ChrisMasterjohn 2/2 TLR or interferon signaling amplification. A few other genetic predispositions, but I’ve noted those groupings circling around.

@J__Doh @ChrisMasterjohn 1/2 Yes, reactive viruses. And no, not all reactivate. A good percentage can, but many stay latent as well. I suspect due to increased innate immune signaling in hypermobility most struggle with latency, but reactivation seems to live in genetic predisposition to

What do astronauts have in common with gymnasts, pole vaulters, cancer patients, and Crohn's patients? They all offer support to my hypothesis that optimal pressure is fundamental to health and especially to immune function. As I covered in "The Biomechanics of Immune Dysfunction: This is the elephant in the autoimmunity and cancer room that EVERYONE IS IGNORING," T cells use the pressure of their extracellular environment to push off with internal "muscle power" that drives the capture of kinetic energy to invest into the energy-hungry reactions involved in their activation. Cancer modifies its external environment to make it more difficult for T cells to perform this maneuver. In Crohn's patients, 1) liquid diets made of trash (Ensure) are as effective as high-end biologics in inducing remission because 2) they reduce the internal pressure in the intestinal segment proximal to the site of inflammation with 3) animal experiments showing that internal pressure is the very cause of that inflammation, and 4) one of the major risk factors for a flare is a trip to altitude of 5000 or more feet and 5) simply putting Crohn's patients in a hypobaric chamber for 3 hours experimentally induces a flare in 33% of them and 6) PIEZO1 is a gene for a pressure sensor and mutations in it are strongly associated with Crohn's. This shows that Crohn's flares involve a high ratio of internal to external pressure in the section proximal to the inflamed section. Liquid diets reduce internal pressure but altitude and hypobaric chambers reduce external pressure. I suspect this interacts with poor biomechanics in the pelvis and lower spine to cause intestines smooshing into their environment in a way that generates the inflammation. Astronauts get reactivation of viruses in space because space causes dramatic reduction in external pressure. A space suit corrects for this, but the correction is incomplete and wearing a space suit in space is like being at 30,000 feet altitude. So the low pressure destroys their immune function. I believe the reason that elite male gymnasts and pole vaulters live eight years longer than the general population, whereas athletes that have excellent cardiorespiratory fitness like cyclists only have two years on the general population is because their sports require excellent biomechanics, and excellent biomechanics leads to optimal pressure in body spaces and around body tissues, which leads to optimal immune function.

@Catinmyfamily It’s hard. Mast cells are so broad, and where they’re getting activated from matters whether it’s genetic predisposition or cellular environment dynamics. Medication failures at least give us some information, even if it’s crossing things off the current list.

@PotsyNP Mast cells are definitely a key issue for me but the specifics may not be.

@Catinmyfamily Thanks! Just for your own knowledge, what this would reduce is interferon signaling, NF-kB signaling and mast cell calcium signaling. That doesn’t mean those aren’t involved, but they may not be your primary drivers of disease.

@PotsyNP I tried it and it appeared to do exactly nothing positive or negative for me