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like Nick has had to just pop up, so I wasn't expecting to do this in my brain box will be kicking in. So next week dot doctor Jessica Escort levels. Who is going to be talking to us about brain fog on pots and long covitz? The cause is on. The management checked about mind later. Hello, everyone. My name is Jessica Rectals on I Am a Chemical, a senior lecturer of Brightened and Suspects Medical School, where I haven't interest in brain body interactions. Particulars. They relate to ice cream ability, which several people have already mentioned earlier today on. But I I have Teo give a bit of a disclaimer that essentially, I am going to talk to you about learning from research that we've already conducted on autonomic and implement tree influences on mental fatigue from studies that I did before coverted in terms of how that might be relevant to some of the patients that we have been talking about today. Because off this overlap between long whole bed parts, post viral fatigue, M cast, etcetera, etcetera and in fact the bulk of mine theater vice is actually order the advice that people have already given about how to treat pots and m cast and things like that. So, um uh, this is an outline of off of what we're going to talk about on, but I'm going to introduce you to my interest in chronic pain and fatigue. And basically, this is pre probably chronic pain and fatigue, but essentially think they're many things going on, including the for two pneumonia, a connective tissue variant small probe in Europe with being Marcel activation Onda dysregulated intraseptal processes. All of which could, ah be multi disciplinary treatment targets on I'm just I lighted from this some paper that we wrote about growing interest in dysautonomia in on day how pots on orthostatic intolerance frequently found in fibromyalgia and every CFS. So some years ago, I I secured to money from, uh, colleague tonight from versus arthritis to look into autonomic with inflammatory mechanisms or pain and fatigue and fibromyalgia on. We were including patients with CF s as a control, but I will not as controlled, but is a comparisons as fatigue patients. Rather than paying patients on we thes participants underwent a autonomic challenge which was tilt table on an implement to challenge which was tight for vaccination on Do they have various tests and on the way, including, uh, gene expression in trouble Cheese sites. Mine's on, um, mobility assessments. So, um, what we found was a third of the patients came to us with the diagnosis of fibromyalgia and the flare with the diagnosis of any CFS, but in third with a jeweled diagnosis. But in fact, and actually those the results of this paper available on the on the QR code on we were hoping that we will be able to compare the fiber miles of patients with the M. E C. F s patients. But in fact, off this group of patients, 90% of them met diagnostic criteria for fibromyalgia, and nearly 100% met diagnostic criteria for any CFS indicating how difficult on research criteria it is to tease a part of patients with chronic pain and fatigue. But they're most interestingly for me, interested in hopes of ability that actually 81% off. These patients met the old writing criteria for joint hypermobility syndrome. Um, Andi nearly 20 and sent the hcts criteria. This is very high proportion on interestingly, hyper mobility, hokum, ability and characteristics correlated with fatigue. And we talked about mental fatigue. Here is, well, mental clutter on a pain on Palin disease. So it's been traditionally thought that M. E. C F s and fibromyalgia non inflammatory that there's a growing There's a growing evidence to suggest this is not the case. And we found even correcting probably, um, I which you haven't effect of the implant you, Marcus, that both, um ah, yes. So and crp were raised in patients competitive trans. But for the evil eye amongst you, you can see the basically the patients of the lower level of normal on the controls our way below What we think all that's normal. But why? Why is this relevant to brain fog? I'm going to tell you in a minute, Um uh, what we found was that baseline. Yes, I level. And we excluded any patient that we thought on the keep phase response. You had a white cell count greater than 10 way eat. Baseline s are significantly predicted Fatigue, severity on pain level, including a mental pretty brain for a mental platter. CRP significantly projects the teeth severity and pain level on. Really interestingly. Yes. I mediates so it's a mechanistic factor. The mechanistic factor, so I have recently covered will pay for it and struggling the between being a patient on having your cognitive fatigue so you're more likely to have higher levels of publishing fatigue If you're a patient on this is explained mathematically by your baseline inflammation. So what the the tilt table, which, um, we'll talk to us about. We've heard of all sorts of ingenious ways of mimicking a tilt table. We put patients on a tilt table on. We got them. Teo do some tests before and after, and what I want to show you is supine and whilst after the meal, until for eight minutes is that a self reported pain increased on tilt in the patient. But not that controls. But there was no change in pain thresholds induced by tilts, so this is really interesting, So tilt is not making you more sensitive to pay. It is increasing Onda, a fatigue level also impatience, and this is exactly the same result for brain fog for mental fatigue, which we also measured is induced by tilt in patients with any CFS and fibromyalgia and not controls. So that's that's interesting, but it's it's just an observation. What could be the mechanisms behind this? And this is this is where that's really exciting. So this news doing something? Put a haze Mediation, Alice. On day three, these findings are actually available. It's an abstract online, but we hope to submit them for Is a pre print in the next couple of weeks is that tilt induced pain is mediated to the mechanistic practice is the number of collective tissue features in the I probability Diagnostic criteria on tilt induced, the T mediated by baseline levels off inflammation on what is, um what is interesting is I told you that we gave the patient's a type of vaccinations and the plumbing challenge. We find very similar findings in terms or inflammation in June mental tea. So I mean, people time waste doing well the time, um, said it. We also did something quite exciting, Which is Jeanette suppression. Eso This is typical transplant. Thomas is where you left. Messages are in a and you're not looking at what genes people have. But you're looking at what proteins are being translated by the jeans at any one moment. So as a while, not. That's not necessarily particularly informative. But after the inflammatory challenge on between the groups of patients could be quite revealing about some of the disease process is the biological mechanisms that are going on in these conflicts in drinks. So we've found that this is thanks to my our PhD student, Marissa Amato. We found it that at baseline between patients with chronic pain and fatigue controls the genes expression was completely different. 90% over differential upregulated genes in patients prepared to controls on day, some down regulate it so the biological processes are different on. But, uh, this some of this has come up before one of the interesting biologicals systems seem to be different between patients and controls. This is before doing any intervention mitochondrion metabolic posts. Um, then we gave a looked at the difference between patients and controls, Um, after the tight wood vaccination, which was the inflammatory challenge on there with differences in as you might expect well, way across the group immune process is particularly, but patients were pet controls correcting for first placebo. This Nick NF happen be signal part with which I'm afraid I am. I am not an expert in That is to do with immune process. Um, okay, so I said, how much time do I have? You Both was on That was a chat. You did fine. Oh, okay. In summary, in terms of the the new data with, um putting together and hooked up the sheets is that there are biologicals mechanisms that relate. Um, these complex conditions, like EDS on do any cfs and fibromyalgia, uh, to, um, uh, altered responsive itty teo autonomic factors and inflammatory factors on this will interplay with m cast on long coded in some some patients. And I think that the lessons that we can learn in terms of what this means for mental fatigue brain full ah, are are the same as we have been hearing earlier in terms of manage what you contribute. So if you suspect it'll to know yet So if if if If unauthentic challenge is inducing rainfall treat underlying autonomic symptoms. If brain fog is perhaps being caused by muscle activation, try um, ourselves mediated or low dose. Now fax it on. Do sink. Think because it's so like to me, obviously so important thing. Does this patient have high probability and I'm interested in the broader spectrum of hyper mobility than 80 s. Uh, because it, um it could be so impactful in in terms off, um, you know, musculoskeletal recovery. I mean, I think that there's an association with mobility aspect. There's and gastro problems and likely with them casts. And so I think if there are any people in the room you have long ago did research over what I'd love to talk to you about measuring lots of quite probability related a phenomenal because I think on deck really did mention as the Bethan How many of these patients have? Some of them have died next, hyper mobility in in our only one in fight or patients who we found to be hyper Mobil have ever been told they were High Mobil or thought they live. So it is. It is massively over lift. And I think it be a a a reason for some of the things that are going on and why I might have a s o. This, um, this elliptically and this'll is a lower body negative pressure chamber. Onda. Probably most people were thinking what the earth is a little body negative pressure chamber but it's a way has a way off inducing what it's like to be on a tilt table but in the brain scanner, and clearly we can't tilt on MRI machine. So this is very relatively straightforward device. Being models by an Italian engineer who has made it, uh, is, um is for our brains gonna where we have money from disorder nor any international to look at multimodal neural coral. It's a brain fog in postural tachycardia syndrome. On that Nick had this fantastic slight. I think it was Nick or it might have been. Let's see, someone did earlier about But, um, with the blood in the wrong part of the body, we thought of taught at medical school that brain auto regulates and that cerebral profusion should be should be, um, constant, regardless of your posture. But a group of people through puberty, great imaging center and whales. They made one of these chambers, and they put healthy controls and standard and showed that using arterial spin labeling, cerebral cerebral profusion was reduced the water static stress. It is probably inducing, um, lack of blood flow to the brain, which may well be involved in brain full but that that's possibly just one mechanism. We did, in fact try in the early days off long kind of it. I was part of a consortium, Uh, we were in a large, long paid it did to do this in a nonprofit, including the covered patients, unfortunately, but that this is an exciting new study, which will We will combine the lower body to brush chamber with the brain imaging techniques that looks at arterials. Been labeling with the e G a swell at same time on the infrared spectroscopy so that we can really get a good handle on what's happening in the brain with a Norden status challenge. It isn't necessarily just orthostatic challenged. A. There's a small boat when your oxy other things going on, but it potentially lead to some of these. So I've actually sort of talked about this. So the implications the management of brain fog and long age related condition is each patient is different. I think a personalized approach is required. But if you suspect ah, disorder Nemea Oh M cast or hyper mobility. Um, please do asthma, uh, cheese you can to treat the underlying these treatable, well manageable treatments are gets to improve. Uh, strength quite bring you because I was an earlier doctor. Now everybody's doing their code status. I I was in March 2020 Jaar Super Spreader. Something like that. That was it. There was no way I could have done this thing. So it's huge. Thank you. Any questions in the audience? I mean, we know we've been asking you for a lot of questions today. Otherwise I couldn't go to So it does look like we're chatting away. I mean, we are looking to cats and ordinating I'm not just, you know, chatting to wait. So this one that's coming in, it's talking about what we're talking about. Long Holmes's about posted desertion. Elaine's is not clearly explained on, um, including the Nets necessity to screen for it. I'm not sure you wear the right time thinking. Bring my well, what because a long time patient that management, because it changes mansion shooting. People been looking for the things. I think we absolutely should be looking for malaise, but I think we shouldn't necessarily think that there aren't things that we could g to help the laser because of the overlap between any CFS m cast as this alternaria. Think about treating disorder. Know? Yeah. On M cast. In addition to your standard, A commission, fatigue services any more any more, we'll give you just a little bit. That's okay.