Nick Melia @arta_semita Twitter profile | Pikagi

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Nick Melia

@arta_semita

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Systems biochemist, researcher @RenegadeRes Studying the etiology and pathogenesis of Long COVID and Myalgic Encephalomyelitis (ME)

Joined September 2021

Don't wanna be here? Send us removal request.

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@arta_semita

Nick Melia

2 years

l've been suffering from #LongCovid since March 2020. A 3-day course of aprepitant has improved fatigue, neurological & inflammatory symptoms considerably (I'm not a doctor/this is not medical advice). Aprepitant needs to studied as a capable LC therapeutic - here's why;

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@arta_semita

Nick Melia

8 months

@drkeithsiau Teratoma?

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@arta_semita

Nick Melia

2 years

@simon_gordon_ @Supercox0521 Microclots are precipitated by a hypercoagulable state, which is itself brought about by SARS-CoV-2 spike protein (or EBV, VZV, enterovirus) superantigen - in these cases, the serpin alpha 2 antiplasmin is highly elevated. The research is already being done

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@arta_semita

Nick Melia

2 years

Here's a case study of a nurse who treated vascular Long Covid with aprepitant. Whilst this is only a single case study, there is evidence to support broader benefit for #pwLC ; /4

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Effectiveness of aprepitant in post‐acute COVID19 syndrome

Clinical Case Reports aims to improve global health outcomes by sharing clinical knowledge through the use of medical case reports, clinical images & procedural videos.

onlinelibrary.wiley.com

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@arta_semita

Nick Melia

2 years

Aprepitant has an excellent safety/side-effect tolerability profile, and there is a plethora of evidence from the literature and anecdotal evidence that it is effective treating different LC phenotypes. COVID-19 sets off inflammatory feedback loops. 2/

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@arta_semita

Nick Melia

2 years

Blocking the Neurokinin-1 receptor prevents this amplification of inflammatory processes. The NK-1R antagonist aprepitant is known for anti-emetic activity in CINV/PONV. However, at higher doses, it is a targeted anti-inflammatory & antiviral; 3/

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@arta_semita

Nick Melia

2 years

All viruses rely upon the on Warburg effect and pentose phosphate pathway for replication; aprepitant targets both at high enough doses /7

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Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of the Warburg Effect in...

The Warburg effect refers to a metabolic state in which cells preferentially use aerobic glycolysis rather than oxidative phosphorylation to generate ATP and macromolecules. A number of chronic...

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@arta_semita

Nick Melia

1 year

An update thread 🧵on aprepitant for Long COVID-19; I have taken another short course of aprepitant in an attempt to treat a recurrence of long COVID-19 after re-infection (in December). I took my first dose of 285mg on Friday morning.

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@arta_semita

Nick Melia

8 months

@tessfalor BDNF is highly overexpressed in ME/CFS and long COVID patients, but is unable to do it's job. Interference with autophagy or with PI3K/Akt/mTOR can lead to a loss of sensitivity to the neuroprotection provided by BDNF

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Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy through the...

Brain‑derived neurotrophic factor (BDNF) has been demonstrated to be a potent growth factor that is beneficial in neuronal functions following hypoxia‑ischemia (HI). Mature BDNF triggers three...

www.spandidos-publications.com

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@arta_semita

Nick Melia

2 years

Major inflammatory cytokines and RAAS dysfunction upregulate NK-1R and/or substance P production. RAAS dysfunction and viral protein interference (especially neprilysin and spike w/ACE2) can result in slower clearance of bradykinin and substance P, potentiating this effect. /5

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@arta_semita

Nick Melia

2 years

Thrombin -> Substance P -> NK-1R -> pro-inflammatory cytokines -> vascular damage -> thrombin could mediate continued vasculopathy. Aprepitant blocks this, reducing coagulation and vascular inflammation /8

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@arta_semita

Nick Melia

2 years

Potential for use for neurological symptoms of post-viral syndromes - excellent BBB permeability. Reduces viral load in above HIV study, is an excellent anxiolytic (anecdotally, anxiety and brain fog have improved significantly since using it myself) 13/

Pharmacologic rationale for the NK1R antagonist, aprepitant as adjunctive therapy in HIV - Journal...

Background Many HIV infected individuals with suppressed viral loads experience chronic immune activation frequently developing neurological impairment designated as HIV associated neurocognitive...

translational-medicine.biomedcentral.com

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@arta_semita

Nick Melia

2 years

@fitterhappierAJ Lupus EBV HIV MS COVID Most spondylopathies Activated PI3K delta syndrome Alzheimer's disease

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@arta_semita

Nick Melia

2 years

Chronic intermittent hypoxia downregulates NK-1R in cNTS - sleep apnea/LC/chronically hypoxic patients can become hypertensive as a result. Blocking NK-1R activation w/ aprepitant may restore NK-1R in cNTS and ameliorate cardiovascular symptoms. /10

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@arta_semita

Nick Melia

2 years

@lisa_iannattone @farid__jalali @BallouxFrancois I'm not sure if many Americans have been introduced to British libel law, but it is absolutely ruthless. Balloux should know better than to make defamatory statements; he really is losing the plot

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@arta_semita

Nick Melia

2 years

Ancedotally I have seen significant improvements in energy levels - I can put out 2x the physical energy I could 4 weeks ago, no PEM - although I am not quite back to 2019 baseline. Longer courses/higher doses (I used 285mg for 3 days with CYP3A4 inhibition) may be relevant. /18

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@arta_semita

Nick Melia

1 year

An update🧵on aprepitant for long COVID, ME and acute COVID infection; The current idea we are working with for Long COVID is that aprepitant has an appreciable anti-viral effect (which may take multiple courses to take effect).

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@arta_semita

Nick Melia

2 years

RAAS dysfunction provides substance P via Ang II -> AT1 -> Bradykinin -> B2 receptor -> SP. TLR activation by SCoV2, TNF-alpha, IL-1beta, LIF, IL-6 and many other cytokines upregulate NK-1R expression and/or increase substance P levels in acute and persistent infection models /6

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@arta_semita

Nick Melia

2 years

Aprepitant has an excellent safety and side-effect tolerability profile, there is a plethora of evidence from the literature (there is plenty more to be shared in due course) & anecdotal evidence of efficacy in different LC phenotypes. We must research this avenue further /end

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@arta_semita

Nick Melia

2 years

NK-1R is constitutively (always) expressed in microglia/astrocytes. Aprepitant switches M1 inflammatory microglia to an anti-inflammatory (M2) program. Hypoxia also activates/internalises NK-1R in CNTS (solitary tract) via SP release; /9

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@arta_semita

Nick Melia

1 year

"Sleeping in the lateral, or side position, as compared to sleeping on one's back or stomach, may more effectively remove brain waste and prove to be an important practice to help reduce the chances of developing Alzheimer's..."

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Could body posture during sleep affect how your brain clears waste?

Sleeping in the side position, as compared to on one’s back or stomach, may more effectively remove brain waste and prove to be an important practice to help reduce the chances of developing Alzhei...

www.sciencedaily.com

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@arta_semita

Nick Melia

2 years

(many thanks for the help with research & technological literacy, @Friesein )

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@arta_semita

Nick Melia

2 years

More on pro-thrombotic actions of NK-1R in literature; NK-1R is required for efficient Ca2+ flux in response to T cell receptor activation - - NK-1R could be useful to prevent continual TCR activation via superantigen /11

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Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent...

A number of types of non-neuronal cells including leukocytes have been confirmed to possess substance-P and its specific neurokinin-1 receptor (NK1R), while the pathophysiological roles of substanc...

pubmed.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

2 years

Mast cell activation; NK-1R activation upregulates substance P and hemokinin-1 expression due to the relationships explained above (RAAS/bradykinin, thrombin, etc.) - SP and HK-1 activate mast cells directly through MRGPRX2. /14

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@arta_semita

Nick Melia

2 years

@G_Commish @ysenussiMD This study on neurological LC (pre-print) found an increase in number of CD8+ memory T cells with a trend towards decreased activation. There are also increased polyfunctional and/or cytotoxic CD4+ T cells. SAg is seemingly the likely culprit

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T cell responses to SARS-CoV-2 in people with and without neurologic symptoms of long COVID

Many people experiencing long COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), suffer from debilitating neurologic symptoms (Neuro-PASC). However, whether virus-specific...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

2 years

Dermatological (& other) complications of LC are likely to be (in part) as a result of cortisol levels being insufficient to keep NK-1R signalling in check Synergises w/ increased CRH b/c of adrenal fatigue -> mast cells -> VEGF,

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@arta_semita

Nick Melia

2 years

In silico studies infer aprepitant binds to 3CLpro, PLpro, nsp15 and nsp13 with high affinity, in a manner which inhibits their protease/helicase functions; 16/

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@arta_semita

Nick Melia

2 years

Long COVID sufferers with neurological symptoms have demonstrable increase in TNFa+, Granzyme A/B and perforin+ CD4+ T cells @fitterhappierAJ @NoyesJHumphrey

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T cell responses to SARS-CoV-2 in people with and without neurologic symptoms of long COVID

Many people experiencing long COVID syndrome, or post-acute sequelae of SARS-CoV-2 infection (PASC), suffer from debilitating neurologic symptoms (Neuro-PASC). However, whether virus-specific...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

2 years

@fitterhappierAJ If they think this humour is dark, wait till they see how dark they'll want their bedrooms to be when sunlight hurts to look at

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@arta_semita

Nick Melia

2 years

SP and HK-1 also indirectly activate mast cells through NK-1R signalling -> NF-kB and MAPKs -> IgE and pro-inflammatory cytokines, and pro-viral effects -> increased TLR signalling Substance P inhibits natural killer cell cytotoxicity through NK-1R; 15/

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Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor

Ligation of neurokinin 1 receptor by substance P in NK cells can reduce calcium flux and cytotoxicity through interference with activation-induced ERK phosphorylation.SP is a potent neuroimmunomodu...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

2 years

Pro-viral effects of nuclear NK-1R in another persistent virus, VZV; - NK-1R is amongst a number of GPCRs (like AT1) which translocate to the nucleus and exert a pro-viral effect by interfering with transcription. Desperately needs further research 12/

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@arta_semita

Nick Melia

1 year

As such, I will periodically update you all over the coming weeks; hopefully there is a considerable increase to baseline. I will likely take another course once I assess what improvements stick around (or not) after a few weeks. Thanks for reading.

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@arta_semita

Nick Melia

2 years

@rubin_allergy There may be an exception to this - people with Ehlers-Danlos syndromes have an increased rate of hypersensitivity reactions, but also seem to sustain them far longer than what IgE sensitivity would suggest. You guess is as good as mine as to whether this is mediated by MRGPRX2

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@arta_semita

Nick Melia

2 years

@BallouxFrancois @farid_jalali @KashPrime "They advocate for people being sealed in their house and left to die. They want to cull all cats and dogs." Provides no evidence to support the claim... *is no evidence to support claim*... Are you asking to be sued for defamation, or are you completely mad?

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@arta_semita

Nick Melia

1 year

Yesterday, I experienced what @remissionbiome call a ‘level 2’ event; For about an hour, my mood was highly elevated, as if I could not access negative emotions. Colours were brighter, music sounds more crisp and defined; it was a remarkably immersive experience

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@arta_semita

Nick Melia

1 year

"Here, we show that 5-hydoxytryptophan (5-HTP), the first product of an alternative branch of Trp degradation and a serotonin precursor, is essential to protect virus growth against IDO in cell culture. We also show that the apparent antiviral effect..."

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5-hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replicat...

Interferon (IFN) exerts its antiviral effect by inducing a large family of cellular genes, named interferon (IFN)-stimulated genes (ISGs). An intriguing member of this family is indoleamine 2,3-dio...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

2 years

A short thread/update on the safety of aprepitant in Long COVID; (1/5)

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@arta_semita

Nick Melia

1 year

Aprepitant has come today! Will be updating you all soon as you how it goes - I'll be taking the first dose tomorrow morning.

Tweet media one

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@arta_semita

Nick Melia

6 months

@ErinMariLee If you crave sugar and salt/sugar is inducing a crash, it could be pathogens influencing this (most likely Candida; also Bacteroides, Helicobacter, Clostridium species)

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@arta_semita

Nick Melia

1 year

"Tachykinins and the potential causal factors for post-COVID-19 condition"

Tachykinins and the potential causal factors for post-COVID-19 condition

The most prevalent symptoms of post-COVID-19 condition are pulmonary dysfunction, fatigue and muscle weakness, anxiety, anosmia, dysgeusia, headaches, difficulty in concentrating, sexual dysfunction,...

www.thelancet.com

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@arta_semita

Nick Melia

2 years

@fitterhappierAJ "4 out of 5 primary school children found to have better risk assessment skills than loudmouth UK epidemiologist"

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@arta_semita

Nick Melia

9 months

Impairment of remyelination mediated by melatonin is rescued by PDK4 inhibition (dichloroacetate) @doc4care @lifeanalytics @renesugar @KatBoniface @angryhacademic @8Eevert

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PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination...

We recently showed that melatonin ameliorates the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, efficiency of melatonin therapy was associated with side...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

1 year

@microbeminded2 Deficiency of CD8+ response to EBV LCLs is likely a key factor in the genesis of autoimmunity There is such a response in MS, allowing for accumulation of LCLs in CNS;

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Decreased T cell reactivity to Epstein–Barr virus infected lymphoblastoid cell lines in multiple...

Objective: To investigate T cell and antibody immunity to Epstein–Barr virus (EBV) in multiple sclerosis (MS). Methods: Immunoglobulin G (IgG) immunity to EBV nuclear antigen 1 (EBNA1) and viral...

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@arta_semita

Nick Melia

2 years

@ms_simsimma @Friesein Thank you! I took the last dose three weeks ago Friday. I shall likely see if I can get any additional improvements from another (identical) course in the near future.

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@arta_semita

Nick Melia

2 years

I have unfortunately tested positive for COVID-19 after being exposed in circumstances beyond my control. Modeling suggests that aprepitant may be a capable COVID-19 antiviral and anti-inflammatory. I'm putting that hypothesis to the test in the acute setting. A thread 🧵

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@arta_semita

Nick Melia

1 year

Aprepitant modulates MAPK signalling and reduces aggregation of phosphorylated alpha synuclein to protect against dopaminergic neurodegeneration (in a rotenone model of Parkinsonism) @chydorina @tessfalor @renesugar @doc4care @lifeanalytics

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Novel trajectories of the NK1R antagonist aprepitant in rotenone-induced Parkinsonism-like symptoms...

Regulation of the interplay between autophagy and oxidative stress is vital in maintaining neuronal homeostasis during neurotoxicity. The interesting involvement of NK1 receptor (NK1R) in neurodege...

pubmed.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

1 year

This surge of serotonergic signalling seen during these remission events may signal restoration of GPCR signalling in the CNS – I believe this is due to restoration of normal levels of GPCR associated scaffold protein beta arrestin-2.

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@arta_semita

Nick Melia

1 year

@cjmaddison @BhupeshPrusty @scotjess3 P-selectin is highly upregulated in LC patients, as per this excellent study

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Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine...

Background Survivors of acute COVID-19 often suffer prolonged, diffuse symptoms post-infection, referred to as “Long-COVID”. A lack of Long-COVID biomarkers and pathophysiological mechanisms limits...

molmed.biomedcentral.com

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@arta_semita

Nick Melia

1 year

Although aprepitant is excellent for treating symptoms of COVID-19 infection, it has not prevented a return of long COVID after infection. However, PEM and major dysautonomic symptoms (reflex syncope, reflex anoxic seizures) did not make themselves apparent this time around.

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@arta_semita

Nick Melia

2 years

@EnemyInAState LC is an autoimmune disease that generally presents itself after viremic clearance. Viral load is less of a determining factor than we would like to believe - rather it is genetics and phenotypic presentation of the patient (those with hypermobility are far more likely to get LC)

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@arta_semita

Nick Melia

1 year

@cjmaddison P-selectin and Angiopoetin 1 are not discriminatory for LC - those with other forms of endothelial dysfunction or inflammatory disease could have highly raised P-selectin/ANGPT1. They do, however, signal that there is endothelial dysfunction that requires treatment

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@arta_semita

Nick Melia

11 months

@julierehmeyer @richardsima This premise is the foundation of much of my research. The substance P/TLR4 axis is activated by mental stressors, pain and pathogens alike

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@arta_semita

Nick Melia

2 years

@LongCovidComms So my major symptoms - reflex/neurocardiogenic syncope, vasovagal dysfunction (POTS-like), 2 instances of reflex anoxic seizure, brain fog/executive dysfunction, decreased mental processing speed, chest and abdominal pain, GI issues (mast cell activation inferred, 1/3

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@arta_semita

Nick Melia

2 years

@fitterhappierAJ Just came to the realization your Fast/Akt feed forward model explains the T cell exhaustion in activated PI3K delta syndrome. T cell pathology peaking after viremia signifies SARS-CoV-2 has means of neutralizing integrated stress response only during viremic stage @AMannanBaig

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@arta_semita

Nick Melia

1 year

Since the event I have felt physiologically tired, which is an excellent sign. The aprepitant is still in my system (last dose was taken 32 hours/about 2 half lifes ago); as it is leaving, I have felt hungry, and have felt satiated after eating a relatively small meal.

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@arta_semita

Nick Melia

2 years

@fitterhappierAJ @AMannanBaig Once virus is cleared from the bloodstream (or organ/organelle, eg beta islet cells), protection from pathogenic orf7a/orf8/N/S proteins activating NF-kB/NLRP3 inflammasome promoting integrated stress response is gone. Then T cell exhaustion (or T1 diabetes, respectively) set in

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@arta_semita

Nick Melia

1 year

Three of the major symptoms I was experiencing in the last few weeks were insomnia, lack of hunger and inability to feel ‘full’ or satiated after eating.

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@arta_semita

Nick Melia

1 year

I'll be taking a third course of aprepitant soon to target viral persistence. I will keep everyone informed as I evaluate the effect on the Long COVID symptoms that emerged after my second infection.

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@arta_semita

Nick Melia

1 year

@NBoydGibbins Aprepitant reversed my tinnitus/dysautonomia/PEM - I have documented my use of it in a few threads over the past 9 months. Feel free to give me a DM if you want to talk about it further

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@arta_semita

Nick Melia

10 months

@ahandvanish Are you perceiving an increase in mast cell activation or gut issues? Mast cells produce IL-10 and IL-13 upon stimulation with LPS

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@arta_semita

Nick Melia

2 years

Without lactate dehydrogenase, T cells and NK cells cannot produce interferon gamma - the Warburg effect determines Th1 development and anti-viral/anti-tumour activity of the immune system!?!

Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and...

Natural killer (NK) cells are cytotoxic lymphocytes capable of rapid cytotoxicity, cytokine secretion, and clonal expansion. To sustain such energetic…

www.sciencedirect.com

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@arta_semita

Nick Melia

2 years

@NoyesJHumphrey I have mentioned cannabinoids bind to spike protein/prevents viral entry to cells; Until Paxlovid becomes readily available, I will have tetrahydrocannabinolic acid to hand in case of infection. Even on indiamart, nirmatrelvir/ritonavir is 25k RS/330$

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@arta_semita

Nick Melia

1 year

@susan_mecfs @tessfalor @DiamonDie @nguyen_kevin By targeting TLR4 -> NF-kB, aprepitant can migitate almost all of the explosive pro-inflammatory capacity of bacterial LPS, fibronectin, hyaluronan fragments, fibrinogen, S-CoV-2 spike protein, Dengue NS1, RSV fusion protein, EBV gp350, HMGB1 & other TLR4 agonists

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@arta_semita

Nick Melia

2 years

@AlisaValdesRod1 @KunstJonas I can anecdotally vouch for Jonas here - the vast majority of my closer friends have ADHD diagnoses or executive dysfunction resembling ADHD, including myself - 6/8 of us know we have LC, one is in denial despite walking into rooms and forgetting why they were there

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@arta_semita

Nick Melia

2 years

@LongCovidComms I should add; I could be physically active 1hr a day maximum at my worst, 4/5 hours a day average with diet/medication improvements after two years, now I tolerate 8 hours a day moderate activity without having to pay a debt back. I will see if I am capable of more & let you know

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@arta_semita

Nick Melia

1 year

However, I have the tell-tale mark across my abdomen which I associate with mast cell mediated inflammation - this vanished last time and did not return. This time, it has returned about 28 hours after the final dose.

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@arta_semita

Nick Melia

9 months

@DavidAshleyDavi @fitterhappierAJ The widespread use of masks and Xocova (ensitrelvir) in Japan are likely to be very significant

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@arta_semita

Nick Melia

2 years

@EnemyInAState As T cell exhaustion/apoptosis and ROS (reactive oxygen species) are key drivers of LC pathology, it is important to mention that multiple infections are paving the way for LC in patients that recovered with little to no problems in their first/second/perhaps third infection

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@arta_semita

Nick Melia

1 year

@SplendidSpeseia @chydorina @remissionbiome @chyorina The longer that someone has a chronic inflammatory disease, the more likely it is that certain enzymes, chemicals or receptors are increased or reduced in amount/functionality.

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@arta_semita

Nick Melia

1 year

@chydorina @GeoEduOne Panic and impending sense of doom are evolutionary responses (you are vulnerable, get to a safe place) initiated by hypoperfusive or other highly stressing events - cortisol, serotonin and noradrenaline spike, leading to dizziness, nausea, tachycardia, panic/impending doom

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@arta_semita

Nick Melia

2 years

@NoyesJHumphrey @EnemyInAState Bartonella sp (B. henselae is the bacterium responsible for cat stratch fever) also persists intravascularly in humans, and has been thought to lead to post-covid sequelae Full blown Bartonellosis only usually appears in the severely immunosuppressed

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A case of Bartonellosis presenting as a puzzling multisystem disorder complicated by nosocomial...

The most commonly considered infection with a Bartonella species is cat-scratch disease caused by Bartonella henselae. Here, we discuss a unique case of a 60-year-old man who presented with Bartone...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

1 year

@exosome 🔥🔥🔥🔥🔥🔥🔥🔥 @ales_frost @chydorina @renesugar @lifeanalytics Insula dysfunction in ME/neuro-LC patients could contribute to systemic inflammatory state??? Perhaps context for Klimas et al. theory?

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Altered right anterior insular connectivity and loss of associated functions in adolescent chronic...

Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

2 years

@doctorsaluja @KunstJonas Zinc compounds are well known mast cell stabilisers, known when cromoglycate use was in it's infancy. MCs are being absolutely bombarded through CD34, c-KIT, NK-1, MRGPRX2 and other targets including complement, and their derangement constitutes a major phenotype of PASC

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@arta_semita

Nick Melia

1 year

Instead of taking a third dose, I have elected to see what changes to baseline will make themselves apparent after the event (I did not have the event until day 3 last time).

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@arta_semita

Nick Melia

1 year

@Bradgolf1216 @JoshuaPribanic @remissionbiome There are a small number of people I follow here who can demonstrate a systems understanding of post-viral disease. Two of those happen to run remission biome.

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@arta_semita

Nick Melia

2 years

@LongCovidComms moderate fatigue (severe for first 10/12 weeks), exercise intolerance with PEM, joint/muscle pain, poor circulation in extremities, intolerance to bright lights/loud noises/too much sensory stimulation, occasional migraine like headaches 3/3

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@arta_semita

Nick Melia

2 years

@DrDinaKulik This is somewhat within expected range of BA2. Coxsackies, like COVID, are responsible for Th1 autoimmune diseases, ME/CFS, POTS, MCAS, type 1 diabetes, autoimmune cardiomyopathy, aseptic meningitis. Unfortunately, that constellation includes a syndrome resembling polio paralysis

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@arta_semita

Nick Melia

9 months

@farid__jalali In a limited sense, S-CoV-2 has some of the weaponry of HIV/EBV (during lytic replication)/HCV. COVID spike, HIV gp120, EBV gp350, HCV NS5A (indirectly) all activate or boost toll like receptor 4/NF-kB axis.

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@arta_semita

Nick Melia

2 years

@enignosos @Friesein @AmbrosineShitr2 @AnnemiekeVoorn It seems to have broad anti-viral properties; there is much evidence to the inference EBV and SCoV2 combine to create 'long covid' in the vast majority of sufferers. So there is promise, but it requires research. Ancedotally, I was reminded of the nitric oxide/peroxynitrite 1/3

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@arta_semita

Nick Melia

8 months

@lugaresxcomunes @tessfalor Adenosine A1 antagonists can interfere with ketamine's ability to reduce glutamate release. Caffeine and theophylline are the most common A1A antagonists (and both are found in similar foodstuffs/tea/coffee). @chydorina

Ketamine decreases neuronally released glutamate via retrograde stimulation of presynaptic adenos...

Molecular Psychiatry - Ketamine decreases neuronally released glutamate via retrograde stimulation of presynaptic adenosine A1 receptors

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@arta_semita

Nick Melia

1 year

"Substance P is a key molecule in neuroimmune crosstalk; immune cells near the peripheral nerve endings can send signals to the brain with cytokines, which highlights the important role of tachykinins in neuroimmune communication." 👀

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@arta_semita

Nick Melia

2 years

@RobbieBryson14 I have not tried high dose niacin; I have reflex syncope, mast cell activation symptoms (improved since aprepitant) and an as of yet undetermined methylation profile, so 500-1000mg may trigger those. I might have to consider titrating if course 2 doesn't have the desired effect.

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@arta_semita

Nick Melia

11 months

@julierehmeyer @richardsima Outside of LC/ME/EDS research or mast cell immunology/neuroimmunology, I would say no, unfortunately

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@arta_semita

Nick Melia

2 years

@EnemyInAState When assessed in a simplistic manner is it easy to theorise why they could have a positive effect. Vaccines reduce viral load, reduced viral load may translate into less immune dysreg. and lung/heart/vascular damage. However this disregards reality

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@arta_semita

Nick Melia

8 months

@lugaresxcomunes @tessfalor Psychedelics (5-HT2A agonists) can mediate neurogenesis via BDNF, GDNF, enhancement of mitochondrial biogenesis (via SIRT1/PPAR-gamma/PGC-1alpha), inhibition of NF-kB activation by TNF-alpha & possibly other mechanisms. So they can still be useful (if respected).

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@arta_semita

Nick Melia

1 year

@cjmaddison @BhupeshPrusty @scotjess3 Microvascular vaso-occlusion seen in sickle cell anemia patients (P-selectin plays a key role) is treated with hydroxyurea and crizanlizumab;

Tweet card media

P-Selectin Blockade in the Treatment of Painful Vaso-Occlusive Crises in Sickle Cell Disease: A...

Microvascular vaso-occlusion driven pain crisis is the hallmark of sickle cell disease with profound morbidity and increased mortality. Selectins, most notably P-selectins have an integral role in...

www.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

1 year

It is very likely that gut dysbiosis and blood brain barrier damage should be targeted with pre-biotics and anti-inflammatories before attempting to use aprepitant, to protect patient/increase efficacy of treatment.

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@arta_semita

Nick Melia

2 years

@alltherobs Hi! It is good, thanks for asking - I still have a little GI trouble now and again (H. pylori/Candida still need to be kicked) and have had one pre-syncopal event since; however fatigue/energy, most neurological symptoms, sleep, pain are all still close to 2019 baseline

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@arta_semita

Nick Melia

1 year

We believe it can also help perform a similar immune system/HPA axis reset to the one described here by Nancy Klimas, once the offending innate immune activator is reduced to manageable levels;

Tweet card media

2022 SHIELD Conference - Dr. Nancy Klimas Presentation

Topic: State of the Science - Gulf War Illness - Moving Knowledge to TreatmentSpeaker: Nancy Klimas, M.D. Director, Institute for Neuro-Immune Medicine, Nova...

www.youtube.com

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@arta_semita

Nick Melia

2 years

@Supergravity @lisa_iannattone @farid__jalali @BallouxFrancois Perhaps so, but as Balloux et al. rely upon consensus rather than actual science to propagate ideas, they tactically choose to defame ideological opponents, to project their intellectual superiority to their audience. This is deliberate, he left it up

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@arta_semita

Nick Melia

5 months

"Aprepitant may have failed in Phase III because of an inadequate understanding of the relationship between brain NK1 receptor occupancy and clinical response. A validated and novel mechanistic approach to treat depression has been misperceived as..."

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@arta_semita

Nick Melia

1 year

@dbdugger @exosome BDNF is 22 fold higher in LC sufferers than healthy controls, as per the above study - supplemental file attached

Tweet media one

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@arta_semita

Nick Melia

1 year

@chydorina @ales_frost @renesugar @lifeanalytics Suramin as AIM2 inhibitor, context for Naviaux cell danger response theorem?

@drjackpgreen

Jack Green

1 year

Happy to share that our paper on the discovery of compounds that inhibit the AIM2 inflammasome is now published 🥳 – Check it out here

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@arta_semita

Nick Melia

1 year

@SplendidSpeseia @chydorina @remissionbiome @chyorina P.S. this is why testing MCAS patients for histamine metabolite levels during flares (and only during flares!) should be a common practice. Histamine levels in blood/sera are not a good prognostic indicator of MCAS.

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@arta_semita

Nick Melia

1 year

@ales_frost @chydorina There are several explanations for low TNF (and the constellation of other cytokine results seen by chydorina) Firstly - you have both been ill for considerable amount of time; TNF levels drop off over years in patients ME/CFS

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@arta_semita

Nick Melia

2 years

@ElianaUku was the best way to ensure that the aprepitant dose was sufficient for anti-viral effects. 125/80/80 is a good anti-inflammatory; however, the anti-viral effects may require 285mg a day with CYP3A4 inhibition (like I used), or about 400-500mg a day without.

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@arta_semita

Nick Melia

1 year

@ahandvanish LIFR (one half of leukemia inhibitory factor receptor, with IL-6 family receptor subunit gp130) is a super interesting one - existing literature points to the existence of autocrine loops which promote fibroblast activation (downloads pdf)

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@arta_semita

Nick Melia

2 years

@crwequine @_Mau_ME There is the same phenomenon in fibromyalgia

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Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia -...

The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by...

pubmed.ncbi.nlm.nih.gov

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@arta_semita

Nick Melia

1 year

@exosome

Aptamer blocking S-TLR4 interaction selectively inhibits SARS-CoV-2 induced inflammation

Signal Transduction and Targeted Therapy - Aptamer blocking S-TLR4 interaction selectively inhibits SARS-CoV-2 induced inflammation

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@arta_semita

Nick Melia

8 months

@lugaresxcomunes @tessfalor Ketamine's main mechanisms of action are NMDA receptor antagonism/adenosine A1 agonism and consequent reduction of glutamate signalling/release respectively. Induction of neurogenesis via BDNF/mTOR is likely to be impeded less as a result.

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