Saahir Lone @Windowinspace

@jacobin Patently false tweet.

@JackHadfield14 @PJ11819211 Generally best not to engage the skeptics. They're shallow and uninformed.

How could cGAS- Sting activation may play a role in MECFS and long covid? The cGAS-STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway is a critical component of the innate immune system that senses cytosolic double-stranded DNA (dsDNA). While it traditionally defends against viral and bacterial invaders, its chronic or aberrant activation by self-DNA (such as leaked mitochondrial DNA) is increasingly recognized as a major driver of chronic fatigue, post-viral syndromes, and neuroinflammation. [1, 2, 3] In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and closely related conditions like Long COVID, cGAS-STING activation could play a pivotal role through several overlapping physiological mechanisms: [4, 5] 1. Mitochondrial Dysfunction and "Self-DNA" Leakage ME/CFS is heavily linked to cellular energy stress, impaired ATP production, and mitochondrial dysfunction. When mitochondria are damaged or undergo severe homeostatic stress (such as during the physical exertion that triggers Post-Exertional Malaise, or PEM): • The mitochondrial permeability transition pore (mPTP) can open, allowing mitochondrial DNA (mtDNA) to escape into the cytoplasm. • The cGAS protein misidentifies this leaked cytosolic mtDNA as a foreign pathogen, triggering the STING pathway and inducing a persistent, systemic inflammatory state without an active infection. [4, 5, 9] 2. Sustained Neuroinflammation and Microglial Activation One of the hallmark features of ME/CFS is neuroinflammation, particularly in autonomic and sensory-gating regions of the brain. • In the central nervous system, cGAS-STING activation occurs predominantly in microglia (the brain's resident immune cells). • Overactivation of this pathway in microglia drives the chronic release of Type I interferons (IFN-I) and pro-inflammatory cytokines (like IL-6 and TNF-α). This can cause low-grade, persistent neuroinflammation, contributing directly to cognitive dysfunction ("brain fog"), unrefreshing sleep, and sensory hypersensitivity. [1, 9, 10, 11, 12, 13] 3. Exaggerated Innate Immune Responses and Long COVID Overlap Recent multi-omics data in ME/CFS patients reveals a severely heightened and exaggerated innate immune response. • Research into Long COVID—which shares significant pathological and clinical overlap with ME/CFS—has demonstrated abnormally high expression levels of cGAS, STING, and IFN-α long after the acute viral infection has cleared. • This indicates that a viral or bacterial trigger can lock the cGAS-STING axis into a permanent "on" position, transitioning from an antiviral response into a chronic autoinflammatory loop. [15] 4. Direct Contribution to Behavioral and Metabolic Fatigue Emerging animal and translational models have begun directly linking the cGAS-STING pathway to the sensation of profound fatigue: • Preclinical studies on fatigue models show that cGAS-STING activation alters mitochondrial and metabolic gene expression in the liver. • When researchers pharmacologically block STING activation (using targeted antagonists), it mitigates systemic inflammatory signatures and significantly improves voluntary physical activity and energy levels. [3, 16] 5. Amplification of Chronic Pain Many ME/CFS patients experience widespread muscle aches and chronic pain. Downstream effectors of cGAS-STING activation include the NLRP3 inflammasome and NF-κB pathways. These downstream targets actively promote peripheral and central sensitization, directly amplifying chronic pain pathways and tissue hypersensitivity. [17, 18] Summary of Potential Mechanism in ME/CFS Are you looking at this from a research perspective, or are you exploring potential therapeutic targets (like STING inhibitors or mitochondrial protectants) currently being discussed in the chronic illness community? AI responses may include mistakes. [1] sciencedirect.com/science/articl… [2] pmc.ncbi.nlm.nih.gov/articles/PMC98…

Your brain switches between glucose, lactate, ketones, and fatty acids throughout the day to match energy demand. In Alzheimer's disease, this fuel flexibility is progressively lost. A Journal of Neurochemistry review reveals why the brain gets metabolically stuck. Alzheimer's disease has long been characterized by reduced glucose metabolism visible on brain scans. The standard interpretation was that neurons couldn't access enough fuel. But a new framework from researchers at the University of Kentucky proposes something different: the brain isn't starving for energy. It's locked into a rigid metabolic program that can't adapt to changing needs. Metabolic flexibility describes the ability of cells to sense, access, and switch between different fuel sources based on availability and demand. In a healthy brain, neurons primarily use glucose. But they can also run on lactate produced by support cells called astrocytes. During fasting or ketogenic diets, both neurons and glia can use ketones. Fatty acids provide another backup fuel source. This fuel switching happens constantly. After a meal, the brain uses glucose. During sleep, it may shift toward lactate and ketones. Under metabolic stress, cells activate alternative pathways to maintain energy production. The system stays flexible, matching fuel use to functional requirements. In Alzheimer's disease, this adaptability breaks down. The review argues that AD is fundamentally a disorder of metabolic inflexibility where cellular metabolism gets actively reprogrammed to support inflammatory and disease-associated processes at the cost of neuronal function. Alzheimer's disease doesn't progress in a straight line of declining metabolism. It unfolds in two distinct phases that seem contradictory. In the early stages, often years or decades before symptoms appear, the brain actually burns more glucose than normal. This hypermetabolism comes from immune cells ramping up their energy consumption to fight inflammation. Think of it as the brain running hot, immune cells working overtime. Later, in the stages when cognitive decline becomes apparent, the pattern flips. The whole brain shifts into hypometabolism, burning less glucose than it should. This is the energy collapse, where neurons can't get enough fuel to maintain normal function. By this point, the metabolic machinery that would allow cells to adapt has broken down. The shift from early hypermetabolism to late-stage collapse follows a biphasic trajectory: • Early stage: Immune cells and support cells burn excessive glucose to fuel inflammation • Late stage: Brain-wide energy shortage as neurons lose access to fuel The brain's immune cells, called microglia, drive this metabolic shift. When they detect damage, they switch to a faster way of burning glucose that prioritizes speed over efficiency. This helps them respond to threats quickly. But once locked into this mode, they consume glucose at rates that starve nearby neurons of fuel. Support cells called astrocytes normally convert glucose into lactate and deliver it to neurons as fuel. In Alzheimer's disease, these cells stop making lactate and start hoarding glucose for themselves instead. The fuel pipeline to neurons shuts down. Both cell types lose their flexibility. They get stuck burning fuel in ways that support their own inflammatory responses but cut off the energy supply that neurons need to function. This metabolic rigidity creates a vicious cycle. When cells can't switch fuels flexibly, they get stressed. That stress increases production of amyloid-β plaques and tau tangles, the hallmark proteins of Alzheimer's disease. These proteins trigger more inflammation, which locks cells even deeper into their rigid metabolic programs. The damage spreads beyond individual cells. Neurons become overactive when they can't meet energy demands, throwing off the brain's excitation-inhibition balance. Network connectivity breaks down. Sleep fragments. Cognitive function declines as the whole system fails to coordinate. System-level consequences include: These cellular-level changes show up as system-wide brain dysfunction: • Neurons fire erratically when starved of energy, disrupting communication patterns • The default mode network, critical for memory and self-referential thinking, loses connectivity • Sleep architecture deteriorates, reducing the brain's ability to clear waste during rest • Memory, attention, and executive function decline as metabolic failure spreads across brain regions Here's what makes this framework different from viewing Alzheimer's as simple energy failure: the metabolic programs are initially adaptive. Microglia activate glycolysis because it helps them respond to damage. Astrocytes shift fuel use to support their own functions under stress. These are protective responses. But they become chronically maladaptive. What works as a short-term stress response traps the brain in a metabolic state that can't support normal neuronal function. The longer these programs run, the more rigid they become, and the harder it is for cells to switch back to flexible fuel use. The critical insight from the review: metabolic inflexibility may be reversible. Unlike permanent structural damage, metabolic programs can potentially be reprogrammed. The authors propose that restoring metabolic flexibility could mitigate amyloid and tau pathology, reduce neuronal loss, and improve functional outcomes. Evidence supporting reversibility comes from preclinical studies testing metabolic interventions. Ketogenic diets, which force the brain to use ketones instead of glucose, have shown some cognitive benefits in animal models and small human trials. Compounds that enhance mitochondrial function or shift cells away from pure glycolysis are being tested. Other approaches target specific aspects of metabolic inflexibility. Drugs that improve insulin signaling in the brain could help cells take up and use glucose more effectively. Interventions that reduce microglial inflammation might allow these cells to return to more balanced metabolic programs. Enhancing the astrocyte-neuron lactate shuttle could restore an important fuel pathway. The review synthesizes human neuroimaging data showing regional patterns of hypometabolism that correlate with cognitive decline, cerebrospinal fluid studies demonstrating altered metabolite profiles, and animal research revealing the cellular mechanisms behind these changes. Clinical trials are actively testing metabolic interventions. Some focus on dietary approaches like ketogenic diets or medium-chain triglycerides that boost ketone availability. Others test drugs that improve glucose metabolism or mitochondrial function. Results so far have been mixed, but the framework suggests timing matters. Early intervention, before metabolic programs become too rigid, may be critical. The view of Alzheimer's disease as a disorder of metabolic inflexibility reframes how we think about disease progression. It's not just about plaques and tangles accumulating. It's about the brain's support systems getting stuck in metabolic states that prioritize inflammation over neuronal support, speed over efficiency, and short-term survival over long-term function. Those choices, made at the cellular level, compound over time. They create an environment where neurons can't get the fuel they need in the forms they can use. Network function deteriorates. Cognitive abilities decline. The brain collapses energetically not because fuel is absent, but because the metabolic machinery to access and use it flexibly has been dismantled. Restoring that flexibility means more than just providing alternative fuels. It means helping cells regain the ability to switch between fuels based on need, rebalancing the metabolic priorities of glia to support rather than compete with neurons, and breaking the feed-forward cycles that lock the brain into rigid metabolic programs. Whether this approach translates into effective therapies remains to be determined. But redefining Alzheimer's disease as metabolic inflexibility rather than simple metabolic failure opens new intervention points at stages of disease where structural damage may still be limited and metabolic programs potentially reversible.

Keep getting "high" serum B12 on your bloodwork? If you have a chronic illness (or autism) it is likely that this is a "paradoxical b12 deficiency". It needs to be TREATED. "The major cause of Paradoxical Vitamin B12 Deficiency appears to be lack of functional vitamin B2, which may occur due to overt vitamin B2 deficiency in a person's diet, Hypothyroidism, or due to lack of adequate intake of Iodine, Selenium and/or Molybdenum, which in turn leads to insufficient production of the two active forms of vitamin B2, namely FMN and FAD. FMN and FAD both have critical roles in cycling and maintenance of activity of vitamin B12, particularly methyl B12." Don't IGNORE this!!! It is not a meaningless result. Doctors are not taught about this and most will ignore it. Don't let this slide. @subversivepsych Is a great account to follow for information on b12 and chronic illness. vitaminb12deficiency.info/paradoxical.htm

@mar80549 .

On this day 49 years ago, 30 year old Steve Biko was beaten to death by South African police. Biko had been a medical student himself. The police who killed him were not the only ones responsible for his death, but so are the doctors who were supposed to care for and advocate for him while he was in custody. Dr. Ivor Lang examined him while he was slurring his speech, not moving his body properly, and not making urine. Dr. Lang falsified records, certifying that he found "no evidence any abnormality or pathology". Dr. Benjamin Tucker, the chief district surgeon, also then examined Biko. He consulted with Dr. Colin Hersch who was concerned about brain injury and ordered a test of the fluid around Biko's brain and spine. The test showed enormous amount of blood (a normal test of this fluid would have no blood). Drs Lang and Hersch falsified medical records to indicate the test result was "normal". At times some of the doctors did recommend transfer to hospital, which the police denied. Biko collapsed. Dr. Tucker signed off on transferring him over 1,000km away. Biko was transferred with no medical monitoring, no medical escort, and handcuffed and without clothing, in the back of a police vehicle. No medical handover was given to the receiving medical team and Biko did not get any significant medical treatments. He was left completely alone and unmonitored and died on the floor of his cell. South Africa's professional physician bodies found no misconduct on the part of the doctors involved in Biko's death. 7 years later, a group of doctors took the South African Medical and Dental Council to the Supreme Court who ruled against the council, forcing them to hold disciplinary hearings. Dr. Tucker was found guilty of disgraceful conduct and was stripped of his license. He was reinstated years later. Dr. Lang was found guilty of improper conduct. He received a mild caution. He kept working until his retirement. There were no findings against Dr. Hersch and no action was taken against him. Steve Biko was killed by a violent racist system, from the police, to the doctors, and the medical organizations that protected them. But he left us with his words and he left us with his legacy. It is up to us to continue his work of dismantling systems of oppression and building a world we believe in. He has had a great impact on my own thinking, like millions of others. May he rest, and may his legacy continue to grow through us all.

History ZAR @HistorySAZAR

3 weeks ago

Steve Biko passed away on this day in 1977 in police custody. He was a founding member of the South African Students' Organisation and a leading figure in the Black Consciousness Movement of the 1970s. Biko was only 30 years old at the time of his passing. Image Source: Cape

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Goodness. I was not expecting that!

@HalfThePerson @ValeBodi Have you tried Normalyte Plus? POTS may indicate hypovolemia + viscosity. You'd want to expand blood volume and for some, Normalyte Plus works well. 860mg sodium + 400mg potassium + dextrose. In citrate form that skips the gut, entering bloodstream directly. It's OTC.

I'm a patient. Whether I'm alive in ten years depends on how fast science moves, and nothing moves it faster than AI. Chasing a problem for the understanding, not the answer, is beautiful. It's also a preference held by people whose lives don't depend on the answers arriving. I think every scientific field is about to face a question it has never had to say out loud. Is the work for the people outside the field whose lives it changes, or is it for the people inside it, who get to spend their lives on the most satisfying kind of thinking there is? For most of history you never had to choose, because the satisfaction drove the work and the benefit came along behind it. When you're the patient the two come apart, because the benefit stops being an abstraction and becomes you. Every year a cure arrives later, people who would have lived instead die. We don't really count them, because we're very good at separating deaths from doing and deaths from not doing. Clinical trials are the clearest example. Keeping a risky combination therapy away from a dying patient protects them from a death by action while quietly accepting a death by inaction, and we weight the first heavily and barely count the second. Slowing AI down works the same way. Pushing the cure for most major diseases from the next decade to the one after is not a careful default. It kills people, it's just that nobody has to sign their name to it. Banning frontier AI in any meaningful capacity would be a decision to let millions of people die on schedule. The better path is infrastructure, meaning verified access for good actors, government capacity to audit what the leading systems are doing, and real consequences for labs that cut corners. On the letter itself, the mathematicians are right about the specifics. A proof announced in 88 hours with no proper writeup and no credit to the work it stands on is a bad way to do mathematics. But that's an output problem rather than a speed problem. Require the model to cite prior work and write the full argument and it's fixed within a quarter. What the letter is really protecting is a culture, and I understand that, but I still think the weight falls on adaptation rather than protection. Traditions built over centuries matter a great deal and they still aren't worth millions of lives. The job for mathematics now is to become the field that turns machine-generated results into ideas humans can actually understand and use, which is still mathematics, and might be the most important version of it. If the machines eventually get better at that too, I'd look at retirees. Most go through a period of agitation and then slowly lose the belief that meaning requires a nine to five. They keep reading, keep learning and keep arguing about ideas, they just stop doing it for a paycheck. I don't think that's a tragedy. I think it might be where all of this ends up. So for anyone weighing how fast this should go, put the hidden deaths from delay next to the visible risks from action every time. It's the only way to account for everyone with a stake in this, including the ones who won't be around to complain if we get the timeline wrong.

Andrew Curran @AndrewCurran_

3 weeks ago

Twenty-five Fields Medal winners have published a joint declaration warning about what they see as a severe misalignment between AI companies and the mathematics community.

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The powers that be know exactly what they are doing and what the consequences are. I know this post is related to the current UK situation but it has played out in Canada for years already. First you create/legislate poverty. Disabled people receive so little help from the government in Canada that it would not be possible to actually survive on their disability pension outside of a "skid row" type situation. Try to imagine living on ~1,250 CDN a month (yes, a MONTH). Now try and imagine how you would do this if you were disabled and thus had many extra medical expenses. Then you remove safeguards from the Assisted Death and MAID legislation so that 'poverty' or lack of resources becomes a grey area - if a disabled person cannot survive outside of extreme poverty - well...it is obvious this will heavily play into a decision for MAID/AD. Make sure this is not a point were MAID could be denied if poverty was obviously contributing to the decision.

Dan Hitchens @ddhitchens

3 weeks ago

Fifteen safeguards rejected from the assisted dying bill:

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Exactly 85 years ago, the siege of Leningrad began – one of the most horrific crimes in history. It's important to remember that the Germans were not the only ones involved. Finnish, Estonian, and Spanish units were active accomplices, and in essence, half of Europe stood on the side of Nazi Germany at that time. Today, many of them would prefer to forget their guilt before humanity. Moreover, history is taking a frightening turn: the same forces that were at the root of Nazism are now once again threatening St. Petersburg. The topic of the siege is an integral part of my children's lives. They are descendants of those who survived the hell created by the ideological predecessors of today's NATO. Recently, I drove along the "Road of Life" for the first time. Before, I only knew about it from my grandparents' stories, but being physically present on that road is a completely different experience. It's not just a tribute to memory, but an opportunity to once again marvel at the incredible strength of spirit of the Soviet people and the wisdom of the leadership that managed to achieve the impossible to save the city. 🇷🇺

@imMEurMEweallME See also first para. korthvision.com/what-vitamin-d…

Once you understand that herbs contain peptides, you start questoning what else they encompass that we haven’t even identified yet. Plants develop complex mechanisms to defend themselves, stay resilient to stress and communicate. Herbalism learned to harness that chemistry for healing long before we understood every compound involved. It becomes harder to think about isolated compounds when we don't understand the synergy of the whole plant.

Andra @BioavailableNd

2 months ago

Are we ready for the "herbs contain peptides" conversation yet? Plants may influence the gut through more than its minerals, polyphenols and fibre, they may also carry biological signals. This is still very emerging science, but MOP peptide derived from moringa, improved mucus

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@100YEKS Normalyte oral rehydration solution. Expands blood volume.

I woke up this morning with a clear image of my life without #mecfs.  All the beauty that never was.  Not the achievements but the experiences and the doing.  There is not a single aspect of life that ME/CFS has not compromised or ruined.  Even advocacy - So much I cannot share.

@WohlstandsWal I’m 66. I’m a retired Agronomist (Agricultural Science). My husband was an IT Master Consultant. Now he has Alzheimer’s. I recently purchased a printer. It’s still not properly connected because I can’t make it talk to my laptop over WiFi. I feel like an idiot.

"people with long COVID commonly report a range of persistent symptoms, including fatigue, post-exertional malaise, sleep disturbance, and cognitive impairment.. Among these, cognitive impairment has emerged as a prominent neurological manifestation.. cognitive impairments are not limited to those with ongoing systemic symptoms; they are also evident in COVID-19 recovered individuals (COVID-RHC) who no longer report active symptoms, compared to healthy controls without SARS-CoV-2 infection (Non-COVID-HC).. Studies of COV-RHC have identified deficits in key cognitive domains, including processing speed, executive function, memory encoding and recall.. In long COVID patients, MRI (magnetic resonance imaging) studies have consistently shown altered brain structures, including variations in brainstem, hippocampus, cerebellar volumes, and cortical thickness compared to healthy controls.. Furthermore, impaired functional connectivity has been observed within the brainstem and between key intrinsic brain networks specifically, the salience network and the default mode network.. Structural MRI studies have also identified alterations in brain morphology among COVID-RHC, including reductions in grey matter volume, thickness and global brain volume when compared with healthy controls.. Diffusion-weighted imaging (DWI) has further revealed disruptions in white matter integrity in COVID-RHC.. Our study identified altered signal intensity, abnormal tissue microstructure, and imbalanced neurochemicals in long COVID and COVID-19 recovered healthy controls." People cannot understand the seriousness of these brain injuries because of their brain injuries. 'Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study' sciencedirect.com/science/articl…

@SharylAttkisson They dismiss concerns that a vaccine megaload is too much for an infant's immune system but confirm that each dose can produce an antibody response equivalent to a moderate infection. Countless Hannahs out there and each one needs remediation.