TruthArchive.ai - Tweets Saved By @a_kruschke
@a_kruschke - A.Kruschke
Here's the explanation related to the 👇thread. It's about air, lung anatomy, breathing problems, COVID and other structural illnesses... and about mice.
@a_kruschke - A.Kruschke
Lung Fibrosis Pulmonary Fibrosis Idiopathic, genetic, SARS-CoV-2 related. 🫁👀🧐🤔 svuhradiology.ie/case-study/pul… 🫁 https://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/symptoms-causes/syc-20353690
@a_kruschke - A.Kruschke
Let's start with the anatomy of the lung. When breathing, we bring the air into a system of airways, shaped like a tree.
@a_kruschke - A.Kruschke
At the end of each airway branch is a bundle of bubbles, the so-called alveoli.
@a_kruschke - A.Kruschke
When we have a closer look, we can see the bubbles are wrapped with elastic fibres (painted in green). A few muscle strings are present, but wrapped only around the "branches". [*) pictures from Netter anatomy atlas]
@a_kruschke - A.Kruschke
When we inhale, the bubbles (alveoli ) fill with air. The wall of the alveoli is very thin, and elastic. The elastic fibres wrapped around prevent the alveoli from bursting.
@a_kruschke - A.Kruschke
The alveoli are also wrapped in a net of blood vessels. The inhaled oxygen is then passed through the alveoli wall in the blood vessels, and transported by the red blood cells (erythrocytes).
@a_kruschke - A.Kruschke
This description is very simplified, as I only want to point out that the wall of the alveoli is smooth, thin, elastic and is able to move. Otherwise the passage of oxygen into the blood is hindered.
@a_kruschke - A.Kruschke
It is obvious that damage to the alveolar walls, the elastic fibers or the blood vessels that surround them would hinder proper air -> blood oxygen exchange. SARS-CoV-2 damages all three.
@a_kruschke - A.Kruschke
To fix the problem, the body has little choices but to make a scar out of the damaged tissue. The longer the damage of the lung lasts, the more scar fibers are produced. This is then called "lung fibrosis" or "pulmonary fibrosis".
@a_kruschke - A.Kruschke
Unfortunately a scar is not smooth, not thin, not elastic, and cannot move. Lung Fibrosis can be caused by everything that damages the lung tissues: infections, intoxication, asthma, ... https://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/symptoms-causes/syc-20353690
@a_kruschke - A.Kruschke
... hereditary illnesses, or unknown causes. In medicine "unknown" is called "idiopathic" (... that sounds much more scientific than "we have no clue"...).
@a_kruschke - A.Kruschke
Back to 2020... The COVID patients admitted to the ICU were treated for an infection causing severe lung damage, called ARDS (Acute Respiratory Distress Syndrome).
@a_kruschke - A.Kruschke
However the COVID patients didn't properly respond to the treatment. The most experienced pulmonologists were surprised. https://healthcare-mittelhessen.eu/ukgm-chef-ueber-corona-ueberraschend-ist-dass-das-lungenversagen-sich-so-lange-hinzieht
@a_kruschke - A.Kruschke
COVID reacted as there were supplementary factors causing the lung damages, besides the infectious compound.
@a_kruschke - A.Kruschke
Those "special effects" of SARS-CoV-2 infection are sometimes crazy.... High levels of oxygen are worsening COVID. https://www.monaldi-archives.org/index.php/macd/article/view/1916
@a_kruschke - A.Kruschke
As underlying cause it was discovered that high oxygen levels multiply the numbers of TMPRSS2-receptors*). High level of oxygen resulting in worsening COVID. ___ *)TMPRSS-receptors are the second important receptors SARS-CoV-2 uses to infect the cells. https://www.monaldi-archives.org/index.php/macd/article/view/1916
@a_kruschke - A.Kruschke
The next weird thing: SC2 is using a pathway called FOXO3 to induce lung fibrosis. But this pathway was known to be important for "idiopathic lung fibrosis". ___ (Links are just references, no need to read the papers.) https://www.medrxiv.org/content/10.1101/2022.09.02.22279542v1.full . https://www.researchgate.net/publication/321672416_FoxO3_an_important_player_in_fibrogenesis_and_therapeutic_target_for_idiopathic_pulmonary_fibrosis
@a_kruschke - A.Kruschke
Idiopathic fibrosis and cystic fibrosis both cause severe lung Fi, with quick progression. Both are unrelated to infections. So how could SC2 do that? ___ Cystic fibrosis is hereditary, and idiopathic fibrosis is "nobody knows".
@a_kruschke - A.Kruschke
What is idiopathic lung fibrosis?
@a_kruschke - A.Kruschke
🫁👀 特発性肺線維症とは？ What Is Idiopathic Pulmonary Fibrosis? https://www.nhlbi.nih.gov/health/idiopathic-pulmonary-fibrosis
@a_kruschke - A.Kruschke
🫁👀 特発性肺線維症とは？ What Is Idiopathic Pulmonary Fibrosis? https://www.nhlbi.nih.gov/health/idiopathic-pulmonary-fibrosis
@a_kruschke - A.Kruschke
Then, in 2020, the SARS-CoV-2 WT was "trained" by serial.passage to infect normal mice. (WT cannot infect mice.)
@a_kruschke - A.Kruschke
By coincidence, this new strain came out of the UNC lab. And just before the Alpha ("British variant"), Beta, Gamma variants appeared.
@a_kruschke - A.Kruschke
Here again the link to the short thread.
@a_kruschke - A.Kruschke
Lung Fibrosis Pulmonary Fibrosis Idiopathic, genetic, SARS-CoV-2 related. 🫁👀🧐🤔 svuhradiology.ie/case-study/pul… 🫁 https://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/symptoms-causes/syc-20353690
@a_kruschke - A.Kruschke
@reSeeIt save Thread @reSeeIt save conversation
@tommy_cleary - Tommy Cleary
Holmes attempted <
@tommy_cleary - Tommy Cleary
One more before I put the roast on for Australia Day dinner...
@GrahamPerrettMP is my local Federal MP and he has helped in the past, but last time I wrote to him he replied that I should check the Queensland State Library for more details...perhaps I should check back with him again too.
These issues of how to handle the dangerous side of science have been a problem since at least Iraq's @UN biological weapons inspections...with discussions of Mustard brought to the table by @R_H_Ebright thank you, @INTERPOL_CBRNE questions are important.
H/t @CharlesRixey @Ayjchan @Globalbiosec
Holmes attempted <
@tommy_cleary - Tommy Cleary
@Studio28nyc @McWLuke @PeterDaszak @WHO @SciDiplomacyUSA @BangXiao_ @POTUS After Australia Day roast lunch (which was fantastic) I sent another email this time to Zhengli Shi & @BangXiao_ Then me & the fam went to local barefoot lawn bowls.
@tommy_cleary - Tommy Cleary
Seeking No14 ORF8 omission...with some healthy distraction from @breakfast_dogs @harishseshadri2 @gdemaneuf
about the truisms of love...and knowing at all. @Rebecca21951651 @emilyakopp @a_kruschke @Ayjchan @VBruttel @BillyBostickson
Back to the data set.
Holmes attempted <
@VBruttel - Dr. rer. nat. Valentin Bruttel
Why SARS-CoV-2 was a lab manipulated virus in 10 key points https://vbruttel.substack.com/p/why-sars-cov-2-was-a-lab-manipulated The IMO most compelling molecular and circumstantial evidence regarding the origin of COVID-19. ➡️ Please share, retweet, and raise awareness to help prevent similar events from occurring again.
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@StoreEducation - EducationStore
Writing how to be more productive without procrastinating or bingeing UOW: University of Wollongong, Australia Speaker: Emeritus Prof. Brian Martin and members of PhD Candidates Date: 09/02/2020 Time: 11:30 AM Canberra, Melbourne, Sydney Register NOW: https://zoom.us/webinar/register/WN_aA-y9bEaQKKO4fTdu_oVxw
@tommy_cleary - Tommy Cleary
But there is poetry in these lethal paragraphs of RNA H/t @quay_dr @MartinaSisters Where have the poets of this world gone? Why have rhymes bent to reason and quills been put aside to crumble ? What feeble mind thinks yet does not imagine possibilities of other minds too? Minds seek minds within what we all wonder
@tommy_cleary - Tommy Cleary
The question of //Pathos// has disturbed the search for the next missing part of this data set.
Never a better reason to interrupt seeking is finding a question linked to the heart.
Knowing love is a perennial concern.
To leave souls behind has a sharp gravitas.
Back to the data.
In 2023 Holmes attempted <
@tommy_cleary - Tommy Cleary
@gdemaneuf There is a theory that Drosten changed his mind…or was more free to speak his mind…after Shi made it out of China recently…nice idea. People. People do what people do…they fall in love and do stupid and sometimes inspirational things.
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
In 2023 Holmes attempted <
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@CharlesRixey - Charles Rixey, MA MBA (c) 🐭
Linked below is an article written by LtCol Joseph Murphy, the person who leaked the DEFUSE proposal to me, which DRASTIC then analyzed and released on September 20th & 21st, 2021. 🧵 https://brownstone.org/articles/the-biodefense-oligarchy-and-its-demographic-defeats/
@tommy_cleary - Tommy Cleary
As science is very important...
https://journals.asm.org/doi/10.1128/jvi.01240-24methods
H/t @sciencecohen @hholdenthorp @ScienceMagazine
Holmes attempted
<
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
My application for SAGO at @WHO was rejected...but it was in volunteer capacity and so I simply continued to help where I can.
https://2012-2017.usaid.gov/sites/default/files/documents/2496/Combatting_Corruption_Among_Civil_Servants_-_Interdisciplinary_Perspectives_on_What_Works.pdf
My skill sets are listening...catching...and surprise...not simplicity
H/t @CharlesRixey
Umberto Eco said it well.
If it is too complicated, read more books.
But he wrote this type of thing in Italian, so don't see these ideas as complexity, see them as language.
Teaching a language takes time and repetition...about two years of immersion...or you can nowadays Gronk your way through?
The lived experience here is of an INCOMPLETE data set...so obviously I cannot fully explain the data...but you can join me on the journey.
Surprise!
Truth is important...but it takes a lot of listening to hear certain truths...trauma adds more layers of humanity and so our souls are stretched thinly as we listen to the person within the cyborg of text based embodiment twisting under the weight of the unknown...but knowable:
<
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
<
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
This is where I lost count!
Doh!
Next GI will have to start from here and be inserted into current tally.
GI 1769824546 restart count again here...and insert missing into tally
KISS Methods: basic GI series analysis this Xpost
GI is 1769824546 <
@tommy_cleary - Tommy Cleary
Next one?
<
@tommy_cleary - Tommy Cleary
Censorship of the nature deployed in the case of COVID had some obvious negative effects...but some were not so bad. @BiosafetyNow
https://biosafetynow.substack.com/p/censoring-virology
It was nice and quiet.
The people censored had to find ways to reach out to each other...the phenomenology was that we had to look at what we were looking through.
It also builds a compassion for a data set you are auditing during verification and for your own findings...a health doubt...need to double check and have peers that are brutal not lazy.
Fixing this mess is going to be fun!
Some wisdom always comes from a moment of stupidity and reflection.
KISS Methods: basic GI series analysis this Xpost
GI 1769824482 <
@a_kruschke - A.Kruschke
@tommy_cleary @JAHawk94684 @MartinaSisters @mlperk1 @MonaRahalkar @R_H_Ebright @quay_dr @BiosafetyNow @syd_health @SystemsVirology @NLM_NIH @POTUS @Sydney_Uni @DrJBhattacharya @FloDebarre @institutpasteur @thackerpd @Rebecca21951651 @capitolsheila @BillyBostickson @breakfast_dogs @Globalbiosec @gdemaneuf @RdeMaistre @dasher8090 @COVIDSelect @GrahamPerrettMP @harishseshadri2 @emilyakopp @Ayjchan @VBruttel @CharlesRixey @sciencecohen @hholdenthorp @ScienceMagazine @WHO @reSeeIt save Thread
@ScienceMagazine - Science Magazine
"Here at Science, we are making changes focused on strengthening the scientific record, helping authors submit papers with complete and robust data, and recognizing experts for their role in the peer review and publication process." Learn more in a new #ScienceEditorial: https://scim.ag/4a9qQP6
@a_kruschke - A.Kruschke
@takavet1 Dr Miyazawa, I tend to disagree. The construction of a new BSL-4 lab in the middle of a densely populated area with 1.5 million inhabitants is a thread for the whole world. https://web.archive.org/web/20241116115541/https://mainichi.jp/english/articles/20241116/p2g/00m/0sc/025000c
@a_kruschke - A.Kruschke
It is NOT a question of Nagasaki locals concerned. It's about the threat a lab leak could cause another pandemic. I'm pleased to help with the English translation, so overseas can join the discussion. The thread in translation:
@a_kruschke - A.Kruschke
Let's have a closer look at your comments. 1/ claim: A new BSL4 lab is necessary for national defence. You already mentioned it in an older thread.
@a_kruschke - A.Kruschke
Japan already has TWO BSL4 labs. In the middle of the highly dense populated Kanto area. Tokyo area, for foreigners. More than 40 million residents (2024), 15 million commuters. May I help you with the worldwide BSL-3+4 lab list? h/t DRASTIC
@BillyBostickson - Billy Bostickson 🏴👁&👁 🆓
Upgraded Biosafety Map (July 2024) Now Shows: 840 BLS3 Labs (in Orange) 87 BSL4 Laboratories (in Red) Click on the Pins to see details for each lab, Remember, Friends of DRASTIC, if you spot any errors or missing labs, please keep on informing us! https://www.google.com/maps/d/viewer?mid=1-I7wAGlqKCQ_UP14MqAHvBGwXavATtk&usp=sharing
@a_kruschke - A.Kruschke
Why should Japan's security be in danger without another BSL4 lab in Nagasaki?
@a_kruschke - A.Kruschke
2/ claim: ".. there has been no case (accident) of a virus leaking from BSL4 in the world." This is not true. Even Wikipedia knows about some. The underreporting yet not taken into account. https://en.m.wikipedia.org/wiki/List_of_laboratory_biosecurity_incidents
@a_kruschke - A.Kruschke
Are you sure? "However, it is unthinkable that the virus would physically leak from the facility, and there has never been a "physically" leak in the world."
@a_kruschke - A.Kruschke
3/ claim: " If the rules are followed, the experimenters will not be infected." Are all japanese scientists following the security rules? https://theintercept.com/2022/11/01/biosafety-avian-flu/
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
4/ "I really wish people would stop saying that all virus researchers are villains and descendants of Unit 731." Did you read the excellent comments from Dr Kakeya? h/t @hkakeya
@a_kruschke - A.Kruschke
For anyone who missed the discussion of whether SARS-CoV-2 came from a lab or not, I recommend this excellent summary from a Japanese perspective. https://zenodo.org/records/14741477 Thank you❣️@hkakeya
@a_kruschke - A.Kruschke
@hkakeya The history of Japanese laboratories and unit 731. h/t @hkakeya
@hkakeya - Hideki Kakeya, Dr.Eng.
薬害エイズを起こしたミドリ十字は旧日本軍の731部隊の流れを組む。731部隊の残党は東大伝染病研究所にも大量に流れ、それが国立予防衛生研（現・感染研）と東大医科研に分かれて現在に至る。これらの組織の非倫理性はその歴史を考えれば当然。組織の刷新が不可欠です。 https://www.hokeni.org/docs/2017040500122/
@a_kruschke - A.Kruschke
@hkakeya And for all japanese who still believe that unit 731 is a "racist US conspiracy theory" to suppress Japan: https://www.theguardian.com/world/2018/apr/17/japan-unit-731-imperial-army-second-world-war
@a_kruschke - A.Kruschke
@hkakeya 5/ claim: " Many of my students are also handling highly dangerous viruses. [..] They have no evil intentions. " It's not only the "evil intentions " that cause harm. Did you teach your students to discuss openly that lab accidents can happen? https://t.co/9IplSdXEYF
@a_kruschke - A.Kruschke
Organizing an international conference "preparing for the next pandemic", while ignoring the real-world threats? I would have expected a discussion block on improving laboratory safety, international oversight of GOF research and possible responses to bioweapons attacks. https://t.co/YvT2nBXWTN
@a_kruschke - A.Kruschke
Here's the original thread in japanese. To prevent a sudden loss. https://t.co/8vbgkuWX9V
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@a_kruschke - A.Kruschke
The "influenza season 2023/24" has been declared open in several European countries. Main strain is A(H1N1)pdm09, formerly known as "swine flu" (2009 pandemic). The current vaccines include this strain. Data from Austria 🇦🇹https://virologie.meduniwien.ac.at/wissenschaft-forschung/virus-epidemiologie/influenza-projekt-diagnostisches-influenzanetzwerk-oesterreich-dinoe/aktuelle-saison-20232024/
@a_kruschke - A.Kruschke
Last 🇩🇪 Influenza report (will be updated January 05th) https://www.rki.de/DE/Content/Infekt/Sentinel/Grippeweb/grippeweb_ergebnisse_node.html ARE weekly reports (PDF only) shows the current data 👇 https://influenza.rki.de/Wochenberichte.aspx
@a_kruschke - A.Kruschke
The press has already been informed https://www.sueddeutsche.de/gesundheit/gesundheit-grippewelle-in-deutschland-hat-begonnen-rki-raet-zur-impfung-dpa.urn-newsml-dpa-com-20090101-240103-99-483093
@a_kruschke - A.Kruschke
Santé France 🇨🇵 "Currently A(H1N1)pdm09 viruses are in the majority and the antigenic profile of the viruses allows us to anticipate good effectiveness of the vaccine." (translation from the linked PDF👇) https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-et-infections-respiratoires/grippe/documents/bulletin-national/infections-respiratoires-aigues-grippe-bronchiolite-covid-19-.-bulletin-du-3-janvier-2024
@a_kruschke - A.Kruschke
🇨🇭 lnfluenza Dashboard https://idd.bag.admin.ch/diseases/influenza/overview Also with wastewater tables for Influenza👇 https://idd.bag.admin.ch/diseases/influenza/statistic#waste-water-by-ara
@a_kruschke - A.Kruschke
Flu season with Influenza A(H1N1)pdm09. What could this mean for Europe in post-Covid times? It's a personal assessment. I may be wrong. Please consider it as a basis for discussions.
@a_kruschke - A.Kruschke
The "influenza season 2023/24" has been declared open in several European countries. Main strain is A(H1N1)pdm09, formerly known as "swine flu" (2009 pandemic). The current vaccines include this strain. Data from Austria 🇦🇹https://www.virologie.meduniwien.ac.at/wissenschaft-forschung/virus-epidemiologie/influenza-projekt-diagnostisches-influenzanetzwerk-oesterreich-dinoe/aktuelle-saison-20232024/
@a_kruschke - A.Kruschke
Let's compare it with Russia, which experienced the 2022/23 season with this strain. Assessing the Intense Influenza A(H1N1)pdm09 Epidemic and Vaccine Effectiveness in the Post-COVID Season in the Russian Federation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458445/
@a_kruschke - A.Kruschke
"PCR-testing of 220,067 clinical samples revealed that the influenza A(H1N1)pdm09 virus dominated, causing 56.4% of positive cases, while A(H3N2) influenza subtype accounted for only 0.6%, and influenza B of Victoria lineage—for 34.3%." (PCR, Russia, week 40.2022-20.2023)
@a_kruschke - A.Kruschke
"The comparative analysis of influenza activity [..] revealed an unprecedentedly rapid increase in both ILI incidence and the number of PCR-confirmed influenza cases [..]. The intensity of the epidemic surpassed the previously recorded “very high level” index, .." (Fig. 3)
@a_kruschke - A.Kruschke
"The effectiveness of influenza vaccines estimated in the sentinel surveillance system was evaluated as 92.7% in the prevention of SARI patient admissions and 54.7% in the prevention of influenza among outpatients with ILI/ARI (average 80%, Table 👇)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458445/table/viruses-15-01780-t001/?report=objectonly
@a_kruschke - A.Kruschke
*🤔 What does it mean for Europe in the current season? ▶️ The current influenza vaccines contain the Influenza A(H1N1) pdm09 strain. The protection of hospitalisation is probably very good. It doesn't prevent from infection, but infection rate is lower.
@a_kruschke - A.Kruschke
Influenza vaccine 2023/24 (Should be the same for whole EU), from PEI: https://www.pei.de/EN/medicinal-products/vaccines-human/influenza-flu/influenza-flu-node.html?cms_tabcounter=0
@a_kruschke - A.Kruschke
▶️ If you are not vaccinated yet, please discuss it with your family doctor. Different countries have different schemes who are eligible. This might be changed within the next few weeks, because of the current strain, follow the press release.
@a_kruschke - A.Kruschke
▶️ If you consider vaccination (and you are eligible), please do it as quick as possible. After every vaccination, it will take 2-3 weeks to establish the protection. During this period, you'll be even more susceptible to any infection. So it's useful to 😷 in populated areas.
@a_kruschke - A.Kruschke
▶️ IMO a combined Influenza vaccination with Covid vaccine is useless. Several recent studies showed low to no protection from the current variant (JN.1). And it's not useful to trouble your body even more in the current situation. Focus on Influenza !
@HarrySpoelstra - Harry Spoelstra
❗New recent work from @SystemsVirology needs your attention! ➡️Don't underestimate JN.1, your recent XBB.1.5 booster may even NOT protect you! 😷 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00813-7/fulltext
@a_kruschke - A.Kruschke
▶️ Children will probably be concerned in higher numbers as in "normal" Influenza waves. Reports from previous years with high A(H1N1)pdm09 prevalence 👇:
@a_kruschke - A.Kruschke
👀 Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11–2012/13 https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-015-1293-1
@a_kruschke - A.Kruschke
👀 Influenza A (H1N1)pdm09 viral clearance kinetics in hospitalized children (Spain, 2015–2016 flu season) https://www.analesdepediatria.org/en-influenza-a-h1n1-pdm09-viral-clearance-articulo-S2341287921000247
@a_kruschke - A.Kruschke
👀 Children under 10 years of age were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic in Canada: possible cohort effect following the 2009 influenza pandemic https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470369/
@a_kruschke - A.Kruschke
*🤔 What about co-infections with Covid? Do we have to fear a "Twindemic"? IMO (many may contest it), the Covid waves will soon crumble, assuming the A(H1N1)pdm09 strain stays dominant. There's known interference between this strain and SARS-CoV-2👇.
@a_kruschke - A.Kruschke
@UseBy2022 Disagree. It's a combined effect. Viral interference study by professor Y. Kawaoka, one of the leading Influenza specialists. "..viral interference between SARS-CoV-2 and influenza A(H1N1)pdm09, A(H3N2), or B/Victoria-lineage virus has been reported." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835431/
@a_kruschke - A.Kruschke
▶️ Please be aware that co-infections with other respiratory viruses/bacteria will probably happen. The recurring infections of everybody during the last two years has weakened our immune system. Please consider yourself as "vulnerable for Influenza". 😷😷😷😷😷😷😷😷😷😷
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@a_kruschke - A.Kruschke
💓💓💓 👀 SARS-CoV-2 スパイクタンパク質が心筋細胞に侵入する可能性のある経路👇 SARS-CoV-2 スパイク受容体結合ドメインは内部移行し、ヒト人工多能性幹細胞由来心筋細胞のタンパク質 ISGylation を促進する (大阪🇯🇵2023)
@a_kruschke - A.Kruschke
💓💓💓 👀 Possible pathway SARS-CoV-2 spike protein can enter heart muscle cells.👇 SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes (Osaka 🇯🇵2023) https://www.nature.com/articles/s41598-023-48084-7
@a_kruschke - A.Kruschke
「結論として、SARS-CoV-2 S-RBD は、エンドリソソーム経路を通じて ACE2 を介して取り込まれ、IFN 応答遺伝子を上方制御し、ヒト iPSC-CM の ISGylation を促進しました。」 https://t.co/C1ktnV7EEG
@a_kruschke - A.Kruschke
🤔▪️著者らは、心筋炎の問題に明確に取り組んでいます。 予防接種。 しかし、彼らが使用したスパイクタンパク質の量は、mRNA ワクチンから予想される量より 10,000 倍多かったです。
@a_kruschke - A.Kruschke
「イメージング実験と転写プロファイリングに使用された S-RBD の濃度 (> 600 ng/mL) は、推定される血清濃度よりも低かった SARS-CoV-2 感染後の S タンパク質濃度 (2500 ～ 17,500 ng/mL) ですが、mRNA ワクチン接種後の濃度 (20 ～ 100 pg/mL) よりも高かったです。」
@a_kruschke - A.Kruschke
🤔▪️この研究は、症候性心筋損傷に関して特に興味深いです。 SARS-CoV-2感染後。 ウイルスの複製がもはや起こっていないにもかかわらず、スパイクタンパク質が長期間検出され得ることは他のところで示されています。
@a_kruschke - A.Kruschke
この研究で使用されたスパイクタンパク質の量は感染時よりも 3 ～ 4 倍少ないため、スパイクに匹敵すると推定しています。 新型コロナウイルス感染症後の患者におけるタンパク質残基。
@a_kruschke - A.Kruschke
🤔🤔🤔 私の個人的な結論: 重要な基礎研究であり、感染後の晩期心臓症状を理解するための🧩確実な研究です。 mRNA の場合は、数桁の違いがあるため、これは困難です。
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
Lymphatic system... 🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼 ... has always been underestimated in medicine. I think it's worth treating LongCovid patients by keeping in mind their lymphatic drainage problems. Not every edema is cardiovascular.
@a_kruschke - A.Kruschke
Let me start with the simple, (because mechanics) part. As nearly all people are vaccinated, often repeatedly, it's worth to look at their effects first. Later I will focus on SARS-CoV-2 infection.
@a_kruschke - A.Kruschke
Lymphatic swelling is also a dilemma for radiologic diagnostics in cancer patients. Lymphnodes are essential in tumor staging for correct therapy.
@a_kruschke - A.Kruschke
This article recommended an increase in the follow-up imaging interval from 4–12 weeks to more than 12 weeks, as they found lymphadenopathy for several months after vaccination. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096715/#r5
@a_kruschke - A.Kruschke
An Israeli study, published in March 2021 measured hyper reactive lymph nodes by PET-CT, after BioNtech Pfizer vaccines. Their astonishing findings were hyperreactive supraclavicular lymphnodes in 9% of participants after the second injection. 💥 👇 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003894/
@a_kruschke - A.Kruschke
Hyperreactive lymph nodes means swelling, and also diminished the normal lymph flow. It's a mechanical problem. Similar to flooring, the transport of ugly substances will be hindered.
@a_kruschke - A.Kruschke
Supraclavicular, you'll also find "Virchow's node", last lymph nodes station of the main lymph vessel of our body (ductus thoracicus). Ductus thoracicus carries the lymph of the entire lower and upper left half of the body. (Red markings is supraclavicular lymph nodes)
@a_kruschke - A.Kruschke
👆 the picture is taken from this article. Lymphadenopathy (enlarged lymph nodes) https://aneskey.com/lymphadenopathy-2/
@a_kruschke - A.Kruschke
Very interesting details about the way of LNP-coated mRNA vaccines is found in this article, written by professor Miyazakia The lymphatic system and COVID-19 vaccines Masayuki Miyasaka (2022) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630830/
@a_kruschke - A.Kruschke
Due to their size, there is the "remarkable feature of the COVID-19 mRNA vaccines is that they can be readily incorporated into the lymphatic system" [..] as "particles with a size range of 10 to 100 nm readily enter into the lymphatics."
@a_kruschke - A.Kruschke
[..] "In the draining LNs, although most phagocytic cells can internalize the mRNA vaccine, macrophages within the subcapsular sinus and dendritic cells (DCs) within the interfollicular area are the main groups that abundantly take up specific antigens."
@a_kruschke - A.Kruschke
As professor Miyazaka concludes, "mRNA translation in muscle cells does not seem to play a major role in the induction of protective immune responses against SARS-CoV-2." So the reaction of lymph nodes are essential for mRNA's effective translation.
@a_kruschke - A.Kruschke
There's another, more critical problem, that apparently is linked to the spikeproteins, as also described for AstraZeneca vaccine. SARS-CoV-2 is not only targeting the epithelial cells, but also the inner layer of the lymphatic vessels.
@a_kruschke - A.Kruschke
Fibrin clots were also found in lymphatic vessels in lungs. It correlated with the presence of intralymphatic NETs. https://ashpublications.org/bloodadvances/article/6/24/6249/486280/Lymphatic-coagulation-and-neutrophil-extracellular
@a_kruschke - A.Kruschke
Researchers "...found abundant evidence of intravascular and interstitial coagulation, and interestingly, many intact lymphatic vessels also contained fibrin clots (Figure 1). " https://t.co/ofVe0zFIop
@a_kruschke - A.Kruschke
For explication of NETosis please refer to DR.DOGGIE's description 👇 in blood vessels. https://t.co/i4cGLqJDgj
@a_kruschke - A.Kruschke
For treatment of LongCovid patients, it will be useful to keep in mind that internal organs are also drained by the lymphatic system. Swelling of guts or ureter may lead to secondary effects like malassimilation of nutrition, obstruction and nephropathy.
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
この時点で、患者が診療所に行くべきであることは明らかです。 しかし、特によく訓練されたアスリートが注意すべき兆候はありますか? 私は心筋炎の経験からも話し、格闘技や競技スポーツを長年練習してきました。/..1
@a_kruschke - A.Kruschke
../私が言う「アスリート」とは、学生時代から厳しいトレーニングを積み、週5時間以上の集中トレーニングを行っている人を指します。 😅😅😅これらの人々は、特に成長期に集中的にトレーニングを行うと、心臓が肥大します💓. /..2 https://ja.m.wikipedia.org/wiki/%E3%82%B9%E3%83%9D%E3%83%BC%E3%83%84%E5%BF%83%E8%87%93
@a_kruschke - A.Kruschke
../ この心臓の肥大は、多くの場合、トレーニング セッションの終了後も後退しません。そのため、私は元アスリートにも話をしています。 残念ながら、これらのアスリートの心臓は、通常の心臓よりも心筋炎にかかりやすいのです。これはコロナウイルス以前から存在し、/..3
@a_kruschke - A.Kruschke
../同僚の心臓突然死を記憶しているアスリートも少なくない。コロナウイルスのワクチン接種によりリスクが大幅に上昇したため💉、アスリートが亡くなる前に心筋炎を見分ける方法を説明したいと思います。/..4
@a_kruschke - A.Kruschke
../ 心筋炎とは、心筋の炎症を意味します。 (-itis は最後の音節であり、炎症反応を意味します。) 心筋炎は、体内で炎症反応を引き起こす細菌、ウイルス、またはワクチンによって引き起こされる可能性があります。 場合によっては、実際の感染から数週間後まで体が反応しません。/..5
@a_kruschke - A.Kruschke
/..したがって、アスリートとして、感染後の心筋炎の可能性を常に考慮することが重要です。 一般に、危険が高まるこの段階は約 6 週間続きます。/..6 https://www.herzstiftung.de/infos-zu-herzerkrankungen/herzmuskelentzuendung/ursachen
@a_kruschke - A.Kruschke
/..心筋炎は診断が難しい。 MRI と生検のオプションが行われることはめったにないので、アスリートは「血液検査と超音波検査は正常です」という声明だけに頼るべきではないと思います。 アスリートは自分の体を知っているので、彼の話を聞いてください❗🫠/..7
@a_kruschke - A.Kruschke
/..心筋炎の徴候 (運動選手の場合): 💓 パフォーマンスが 10% 以上制限される、 💓 脈拍が異常に増加する、 💓 安静時の心拍数が 70/分を超える。 💓重要❗ 日中（通常の仕事）の気温は夕方（ベッド）よりも高い。 ...夕方の気温が 0.5°C 高くなる通常の 1 日のコースが逆転します! /..8
@a_kruschke - A.Kruschke
/..❗💓❗💓❗💓私が言ったように、これらは兆候であり、決定的な診断ではありません. 医師の診察を受け、それまですべてのスポーツ (サイクリングを含む) を中止してください。 医師が心筋炎を明確に診断していなくても、体の世話をしてください. 症状が続く場合は、/..9
@a_kruschke - A.Kruschke
/..スポーツを6週間完全に禁止することをお勧めします（自分の祖母であるかのように行動してください...） すでに傷ついた心筋細胞はもう修復できないので、なるべく数を減らすようにする。スポーツ禁止というのはそういうことです。/10. 💓💓💓💓💓💓💓💓
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
💓心筋炎 🇯🇵ワクチン接種（mRNA）を受けた2人対ワクチン接種を受けていない無症状の人々を対象とした研究。 無症候性 SARS-CoV-2 ワクチン接種済みおよび非ワクチン接種患者における PET/CT での心筋 18F-FDG 取り込みの評価 https://pubs.rsna.org/doi/10.1148/radiol.230743?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed…
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
Conclusion "Compared to nonvaccinated patients, asymptomatic patients who received their 2nd vaccination 1-180 days prior to imaging showed increased myocardial FDG uptake on PET/CT." https://t.co/HKKNB1KfsZ
@a_kruschke - A.Kruschke
朗報：リバーシブルです💓❣️ 「2回目の[..]ワクチン接種後1～180日後にPET/CTを受けた無症候性患者は、ワクチン接種を受けていない患者と比較して画像上の心筋[..]取り込みの増加が示されましたが、ワクチン接種後180日以上経過して画像化された患者ではそうではありませんでした。」
@a_kruschke - A.Kruschke
* 💓💓💓今回の研究は、無症状の人々のリスクが高まる期間について重要な情報を提供する。 もちろん症状のある患者にも。 これまでのところ、他のウイルス性心筋炎の例に基づいて、3か月で十分だと考えていました。 https://t.co/gy3gXnUNmu
@a_kruschke - A.Kruschke
‼️‼️💓💓どうやら、SARS-CoV-2の場合は、細菌性心筋炎の場合と同様に、丸6か月間（180日間）のスポーツ禁止が必要のようだ。🤔🤔🤔
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
💓 myocarditis 🇯🇵 study in x2 vaccinated (mRNA) vs unvaccinated asymptomatic people. Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2-vaccinated and Nonvaccinated Patients https://pubs.rsna.org/doi/10.1148/radiol.230743?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed…
@a_kruschke - A.Kruschke
@bioerorist
@SolidEvidence - Marc Johnson
Have there been any new surveillance reports about COVID in White Tailed Deer? I'm still waiting to learn whether @LongDesertTrain was right about a couple of patient lineages being from deer. We won't know until we find out what was circulating in the deer.
@a_kruschke - A.Kruschke
🐌 👀 Japanese site for LongCovid information. Different techniques for treatment are described, for doctors and patients. Very interesting approaches. Some videos in English, or can be translated by using the YouTube subtitles function. 🐌🐌🐌. http://longcovid.jp
@a_kruschke - A.Kruschke
@1goodtern @HarrySpoelstra @kasza_leslie
@a_kruschke - A.Kruschke
A response to Emmanuel @ejustin46, who doubts my statements.😊
@a_kruschke - A.Kruschke
First, let me introduce a paper, published in December 2022 by the inventors of BioNTech/Pfizer vaccine, with co-authors from the UK, Israel and Germany. I hope, nobody will suspect the authors being "anti-Vaxx".
@a_kruschke - A.Kruschke
Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T-cell recognition epitopes https://www.biorxiv.org/content/10.1101/2022.12.15.520569v1.full
@a_kruschke - A.Kruschke
The authors " investigated neutralizing activity of immune sera from individuals who received three or four doses [..] mRNA COVID-19 vaccines (BNT162b2/mRNA-1273 homologous or heterologous regimens) w/o subsequent breakthrough infection by different Omicron sublineages."
@a_kruschke - A.Kruschke
Findings: "Together these data show that [...] sublineages BA.2.75.2 and XBB have evolved to largely evade neutralizing antibody responses in vaccinated individuals and in those with breakthrough infections with previous and currently circulating Omicron sublineages."
@a_kruschke - A.Kruschke
"We found that B-cell epitopes [..] were altered [..] particularly [..] in BA.2.75.2 and XBB (≤12% conservation), .."
@a_kruschke - A.Kruschke
".. 80% of CD8+ and ~70% CD4+ T-cell epitopes were fully conserved in Omicron sublineages including [..], BQ.1.1, and XBB [..], suggesting that T-cell responses against Omicron sublineages may remain largely intact in individuals immunized with wild-type strain-based vaccines."
@a_kruschke - A.Kruschke
The second paper I will present is a study from China, published in Cell in May 2023 confirmed the findings of Miuk et al., investigating the sera of probands after triple vaccination with an inactivated vaccine.
@a_kruschke - A.Kruschke
Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00543-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124723005430%3Fshowall%3Dtrue "Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1."
@a_kruschke - A.Kruschke
"Structure analysis and functional verification reveal that N460K and F486V/S contribute to the increased neutralization resistances of BQ.1.1 and XBB.1[..]."
@a_kruschke - A.Kruschke
The third study I want to present, was published by Professor Yoshihiro Kawaoka's group (University of Tokyo), in Lancet, January 2023. Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00816-7/fulltext.
@a_kruschke - A.Kruschke
The authors "evaluated the neutralising ability of antibodies in plasma from three different groups against BQ.1.1 and XBB clinical isolates."
@a_kruschke - A.Kruschke
They compared individuals with (1.) three doses of the mRNA BNT162b2 and/or mRNA-1273. (2.) four doses of the mRNA BNT162b2 and/or mRNA-1273. (3.) three doses of monovalent BNT162b2 or mRNA-1273 before the BA.2 breakthrough infection.
@a_kruschke - A.Kruschke
They concluded "that the omicron sublineages BQ.1.1 and XBB effectively evade current humoral immunity induced by mRNA vaccines or natural infection." --- I will not summarize the characteristics of T-cells but leave this to others.
@a_kruschke - A.Kruschke
Now I'll focus on clinical outcome. As mentioned above, the effect of neutralizing antibodies is negligible for XBB. However, the T-cell response remains intact. Therefore, we tumbled back into a situation similar to pre-vaccine times. Let's look at some research from 2020.
@a_kruschke - A.Kruschke
First, I want to present a study of Mount Sinai, New York, published in Nature, August 2020. An inflammatory cytokine signature predicts COVID-19 severity and survival https://www.nature.com/articles/s41591-020-1051-9
@a_kruschke - A.Kruschke
The authors showed in hospitalized patients, "that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively)."
@a_kruschke - A.Kruschke
"Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death."
@a_kruschke - A.Kruschke
The authors also show the effect of different treatment on outcome and interleukin levels. The findings were confirmed by a smaller second group.
@a_kruschke - A.Kruschke
For involvement of interleukin in "white lung", I'll just leave two interesting papers . From Ghent University (Belgium): The pathophysiology of ‘happy’ hypoxemia in COVID-19 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-01462-5
@a_kruschke - A.Kruschke
And a case report: Happy hypoxia in critical COVID-19 patient: A case report in Tangerang, Indonesia https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.14619
@a_kruschke - A.Kruschke
I've focused on showing the similarities today and 2020. For me, that's the main message: XBB is equalizing the risk for the group of 30-60 years old people. Other effects look minor or interact with each other. Let's do more details later. Let's do Science, not Philosophy.
@a_kruschke - A.Kruschke
Next chapter. I will introduce some fictional characters. It will bring the explanation a little closer to everyday life. Let's start with two characters. I would like to emphasize that these are descriptions for illustration only, not criticism.
@a_kruschke - A.Kruschke
All persons acted according to their own or official rules and "did everything right". However, everyone finds themselves in a different situation. This is my starting point. Let's see what are the pros and cons.
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
Second is Maria Virginia (without any antigen contact) (You'll find a more detailed description in the 🔗 links above. )
@a_kruschke - A.Kruschke
Let's talk first about Maria Virginia. No vaccine, no infection. So no memory or plasmacells for SARS-CoV-2. Maria has an intact immune system. So, she's not unprotected.
@a_kruschke - A.Kruschke
She also owns some plasmacells for non-SARS-CoV-2 coronavirus (hCoV) she catches during her live. Some of these hCoV-memories might be crossreacting with SARS-CoV-2.
@a_kruschke - A.Kruschke
Lets compare to Pierre. Since both the infection with BA.2 and the vaccination with bivalent BA.5 are more than 6 months in the past, the neutralizing antibodies can no longer be detected. Let's say they don't exist anymore.
@a_kruschke - A.Kruschke
But Pierre got B-memory/plasma cells of Wuhan type (WT) from vaccination. These will remain for years or even lifelong. He also got memory T-cells.
@a_kruschke - A.Kruschke
The survival time of memory cells after a single antigen contact was previously assumed to be only a few months. However, a Canadian study could still detect memory cells of the different types after 8 months. https://www.science.org/doi/10.1126/science.abf4063
@a_kruschke - A.Kruschke
The study measured convalescents of WT, i.e. comparable to the memory cells induced by mRNA vaccine.
@a_kruschke - A.Kruschke
Back to our protagonist.... Due to his infection with Omicron BA.2, Pierre also has B-memory cells against N-protein. (Just keep it in mind, well see them again later...) Memory cells against S-protein-BA.5 were formed very little due to immune imprinting.
@a_kruschke - A.Kruschke
Today, let's be prepared for infection by XBB. Neutralizing antibodies don't play a rule any longer. More important now is the other immune reactions.
@a_kruschke - A.Kruschke
Let's skip the theme of cross reactivity of non- SARS-CoV-2 coronavirus. Pierre and Maria Virginia both live in Europe and have never been infected by SARS-CoV (2003) or MERS. The other hCoV-memories should be comparable for both protagonists.
@a_kruschke - A.Kruschke
It was shown that memory T-cell still fit on XBB.
@a_kruschke - A.Kruschke
".. 80% of CD8+ and ~70% CD4+ T-cell epitopes were fully conserved in Omicron sublineages including [..], BQ.1.1, and XBB [..], suggesting that T-cell responses against Omicron sublineages may remain largely intact in individuals immunized with wild-type strain-based vaccines."
@a_kruschke - A.Kruschke
Maria has none. Pierre's memory T-cells will react quicker and at higher level than Maria's naive tell population.
@a_kruschke - A.Kruschke
The following article published in April 2022, compared the response of naive (blue) vs. memory T-cell response. Pierre (red line) has a clear advantage in time, compared to Maria (blue line). The advantage consists in 2 weeks (CD4+) to 3 weeks (CD8+).
@a_kruschke - A.Kruschke
As CD4+ cells act on B-cells activation, Pierre will get neutralizing antibodies about 2 weeks earlier than Maria. This is important for the outcome in moderate to severe illness. Also, Pierre's cytotoxic T-cell activity against the virus is faster and higher than Maria's.
@a_kruschke - A.Kruschke
Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast? (April 2022). (Please keep in mind, article was published in the first phase of Omicron, where neutralizing antibodies still matched partly) https://www.nature.com/articles/s41577-022-00716-1
@a_kruschke - A.Kruschke
All good for Pierre? As presented above, the characteristics of SARS-CoV-2 acute infections consist in severe cytokinestorm during the first days. Cytokinstorm is expression of dysregulated T-cell response.
@a_kruschke - A.Kruschke
First, I want to present a study of Mount Sinai, New York, published in Nature, August 2020. An inflammatory cytokine signature predicts COVID-19 severity and survival https://www.nature.com/articles/s41591-020-1051-9
@a_kruschke - A.Kruschke
Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19 (November 2020, Norway) https://www.nature.com/articles/s41598-020-78710-7
@a_kruschke - A.Kruschke
"Severe SARS-CoV-2 infection cause a dysregulated immune response resulting in excessive production of inflammatory cytokines and chemokines that contributes to the pathogenesis. "
@a_kruschke - A.Kruschke
"Indeed, viral evasion of initial immune responses and a subsequent immunological misfiring causing collateral tissue injury in infected organs seem to play major roles in severe COVID-19. "
@a_kruschke - A.Kruschke
"Further, evidence suggests that a suboptimal or inappropriate T cell response producing pro-inflammatory cytokines may contribute to tissue damage in critically ill COVID-19 patients."
@a_kruschke - A.Kruschke
Finally, because of quicker and higher T-cell response, Pierre is at higher risk for cytokinestorm during the first 2 weeks.
@a_kruschke - A.Kruschke
The B-memory cell response lacking in XBB, this might bring a different risk profile in vaccinated /preinfected patients (Pierre), compared to naive patients (Maria Virginia). The risk of longer infection is certainly higher for Maria.
@a_kruschke - A.Kruschke
But it's necessary to be aware of "happy hypoxia" in vaccinated/preinfected patients. Are we aware of this?
@a_kruschke - A.Kruschke
Does everyone know the other symptoms of cytokinestorm? It's not to be scared, but to be prepared. https://my.clevelandclinic.org/health/diseases/22700-cytokine-release-syndrome
@a_kruschke - A.Kruschke
@reSeeIt save thread
@keisuke4713 - tune
水酸化AL誘発神経毒性にホウ砂の神経保護 魚🧠Nrf-2/BDNF/AChE経路? https://sciencedirect.com/science/article/abs/pii/S0006899323000112?via%3Dihub… 1-methyl-4-phenylpyridinium(MPP+)毒性Parkinson病model 窒化ホウ素ナノ粒子の神経保護効果 https://link.springer.com/article/10.1007/s11011-020-00559-6
@keisuke4713 - tune
ホウ素化合物 AL誘発性神経毒性・遺伝毒性に保護効果 https://www.mdpi.com/2305-6304/10/8/428 Alが血液と🧠酸化stressと遺伝損傷⬆️🧠深刻な組織病理・超微細構造の変化 ホウ素化合物単独はAl有害影響を除去、抗酸化・抗原毒性・細胞保護作用 ホウ素化合物(特にBA、BX、UX)で神経変性疾患/血液疾患を予防可能と示唆
@keisuke4713 - tune
Alzheimer病(AD)に薬物担体 窒化ホウ素ナノ粒子 https://www.mdpi.com/1422-0067/23/15/8249 抗酸化物質⬆️⬆️→酸化⬇️⬇️？ Amyloid β(Aβ)神経毒 六方晶窒化ホウ素ナノ粒子(hBN-NP)効果 https://www.mdpi.com/2079-4991/12/15/2690 細胞外Aβ沈着はAD特徴 神経芽細胞腫🧫 Aβ1-42神経毒性→生存細胞⬇️酸化⬆️apoptosis・necrosis死 hBN-NPで⬇️
@keisuke4713 - tune
神経膠芽腫 ホウ素化合物が有望？https://www.sciencedirect.com/science/article/abs/pii/S0197018621001832?via%3Dihub 銅誘発毒性ニジマス🧠 食物ホウ砂の神経保護効果 https://link.springer.com/article/10.1007/s10695-018-0530-0 抗菌・抗biofilm活性、細胞生存率 六方晶窒化ホウ素ナノ粒子の効果 https://www.sciencedirect.com/science/article/pii/S0928493117338419?via%3Dihub%20https://www.mdpi.com/1999-4923/15/1/149 ナノ材料の潜在riskと健康被害→生体適合性高く、細胞毒性ない物を探す
@keisuke4713 - tune
Borax(ホウ砂:Bx) ニジマスのferrocene(FcH)誘発性神経毒性に保護効果https://www.sciencedirect.com/science/article/abs/pii/S0946672X22000761?via%3Dihub FcHはMDA、MPO、BDNF、Nrf2、TNF-α、IL-6⬆️ BX 魚🧠組織FcHに重要な神経保護効果 BDNF/Nrf2経路⬆️、apoptosis阻害、DNA損傷⬇️ 神経損傷関連🧠障害の予防or治療に役立つ
@keisuke4713 - tune
食物BXがニジマス組織のCu(銅)毒性代謝に保護効果https://www.sciencedirect.com/science/article/abs/pii/S1532045618301972?via%3Dihub Cu併用/Cu単独と比べBX群・BX併用群で前処理・後処理で抗酸化酵素⬆️8-OHdG，Caspase-3、MDA⬇️ hsp70とcyp1a🧬発現もBX処理後⬇️ 結論 ホウ砂自体は抗酸化物質でなく、重金属で破壊された魚の抗酸化防御機構補助と示唆
@keisuke4713 - tune
ホウ砂補給はCu(銅)にさらされた ニジマスの血液毒性とDNA損傷⬇️ https://link.springer.com/article/10.1007/s12011-018-1399-6 Borax(ホウ砂:Bx)はニジマスのDNA損傷とapoptosis阻害→銅による腎障害⬇️ https://link.springer.com/article/10.1007/s12011-018-1622-5
@keisuke4713 - tune
ホウ酸塩は🐭酸化剤/抗酸化剤状態の調節→亜硝酸Na誘発酸化stress改善: Nrf2/HO-1/NF-κB経路👆https://link.springer.com/article/10.1007/s12011-021-02613-5 BoraxはapoptosisとNrf2 signal伝達経路調節 →ニジマスのacrylamide誘発性血液毒性、肝毒性、免疫毒性、遺伝毒性損傷⬇️ https://www.sciencedirect.com/science/article/abs/pii/S1532045622001314?via%3Dihub
@keisuke4713 - tune
eIF2α・Nrf2 ホウ酸活性化はPERK依存性 ホウ素がDNA損傷を防ぎ、抗酸化状態⬆️ https://link.springer.com/article/10.1007/s12011-018-1498-4 ホウ素は野菜、ナッツ、豆科植物、果物に豊富 摂取は癌やDNA損傷risk⬇️抗酸化状態⬆️
@keisuke4713 - tune
ニジマス🧠磁性ナノ粒子誘発神経毒性と酸化stress：抗酸化、抗炎症、抗apoptosis活性調節 →ulexite(UX)による緩和 https://www.sciencedirect.com/science/article/abs/pii/S0048969722028145?via%3Dihub 磁性ナノ粒子Fe3O4-MNPはニジマス🧠毒性 🧠組織AChE活性とBDNF⬇️ UXの治癒特性 ulexite:ホウ素の鉱石 https://www.britannica.com/science/ulexite
@keisuke4713 - tune
ニジマス ulexite補給 酸化鉄磁性ナノ粒子水毒性の中和https://www.tandfonline.com/doi/abs/10.1080/01480545.2022.2164298?journalCode=idct20 血液毒性/肝毒性の変化、酸化的損傷/遺伝的損傷⬇️ Zebrafish ulexiteが🩸・肝臓に有益 https://www.sciencedirect.com/science/article/pii/S1382668920301721?via%3Dihub ヒト🩸重金属毒性にホウ素化合物 https://www.sciencedirect.com/science/article/abs/pii/S0940299310001107?via%3Dihub%20https://journals.tubitak.gov.tr/medical/vol51/iss5/61/ 抗酸化酵素活性と総glutathione⬇️ 🧬毒性⬇️⬇️
@keisuke4713 - tune
スライム作りに必要なホウ砂って何？https://mamagirl.jp/0000210821?page=3 ホウ砂とは！？ https://belcy.jp/30299 四ホウ酸ナトリウム・Borax 重曹のように掃除や部屋のクリーンニングに活用できる 研磨剤:クレンザー 殺菌、防虫 👆機序が納得 ホウ酸（結膜嚢の洗浄・消毒、防腐剤） https://tourokuhanbaisha.com/archives/3399
@keisuke4713 - tune
ホウ素は求電子剤？求核剤？ https://www.chem-station.com/blog/2010/02/post-146.html 原子番号５番のホウ素(Ｂ)は耐熱ガラスやホウ酸ダンゴなどでおなじみ 有機合成化学で鈴木カップリング中枢を担う大事な元素 素晴らしい🧠💡
@keisuke4713 - tune
チェルノブイリ ホウ素と砂を何千t投棄https://www.livescience.com/65515-chernobyl-in-modern-times-nuclear-emergency.html ウランは中性子を放つ→他ウラン原子に激突→分裂 火が大量の煙・埃・破片を放出 原子分裂で様々な同位体:ヨウ素131 砂で原子炉を窒息、煙潰す ホウ素は核反応⬇️ 核連鎖反応 放射性同位体を近づけ中性子が激発火、他原子核に衝突→分裂
@keisuke4713 - tune
中性子が同位体と相互作用、原子核の構造により、中性子を吸収する可能性 ウラン235は中性子を吸収してすぐ分裂する傾向 ホウ素は中性子を吸収する傾向 その核構造→一種の中性子渇望 🚁投棄で強烈な放射線→数人👨✈️🙏 犠牲にも関わらず、中性子吸収体がコアに到達する事は殆どなく、失敗
@keisuke4713 - tune
原子力エネルギー中のホウ素https://www.borax.com/products/applications/nuclear-energy ホウ素は放射線を吸収する 軽水炉でホウ素が使用、原子力エネルギー運用の最も重要な段階で遮蔽、制御、安全性が強化 ホウ素は重要な核分裂段階で中性子を効果的に吸収 ホウ素は反応速度を制御、必要に応じて反応を遅らせ止めたりできる
@keisuke4713 - tune
骨と関節の健康にCaよりホウ素？ https://www.youtube.com/watch?v=K-sXgpygtso ホウ素 estrogen⬇️自然estrogen⬆️ 骨の健康⬆️ testosterone:筋肉成長・維持 testosteroneと相互作用、process制限 testosterone早期分解、testosterone⬆️ vit DとCa Mg影響 骨の適切な石灰化⬆️ ホウ素消費量の多地域:変形性関節症70%⬇️
@keisuke4713 - tune
♀骨、主要ミネラル・性ステロイド代謝 低ホウ素食・ホウ素補給の影響 https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/influence-of-a-lowboron-diet-and-boron-supplementation-on-bone-major-mineral-and-sex-steroid-metabolism-in-postmenopausal-women/709003425D7E65B6182AE8BB7DC29B09 B食 血漿estradiolとtestosterone⬆️閉経後尿Ca排泄⬇️ 低B食3週→3週Bサプリ ミネラルに影響無し 尿Ca排泄⬆️と組み合わせて正のCaバランス →低B食はCa過剰吸収を誘発？ この現象はB効果⬇️か不明瞭化？
@keisuke4713 - tune
食事中のホウ素補給 卵巣摘出🐭骨ミネラルバランスestrogen効果⬆️ https://idp.springer.com/authorize?response_type=cookie&client_id=springerlink&redirect_uri=https%3A%2F%2Flink.springer.com%2Farticle%2F10.1385%2FBTER%3A81%3A1%3A29 骨ミネラルのホメオスタシスに影響を与えず Ca・Mg ホメオスタシスに対する E2作用に 相乗的⬆️効果があるよう
@keisuke4713 - tune
変形性関節症:微量元素https://www.frontiersin.org/articles/10.3389/fmed.2021.771297/full B(ホウ素)やSeなど微量元素 抗炎症作用と抗酸化作用、軟骨matrix形成⬆️ 軟骨細胞増殖⬆️OA予防と治療をもたらす Cuなど過剰or不足は変形性関節症の危険因子 食事B補給 Ca、Mg、 活性酸素種、活性窒素など物質代謝に影響? B欠乏食はOA関連
@keisuke4713 - tune
https://ehp.niehs.nih.gov/doi/10.1289/ehp.94102s783 B摂取が1mg/日以下でOA発生率20~70% 3~10mgで発生率0～10% 🩸B濃度はOA患者で有意⬇️障害期間・重症度と負相関 OA患者の大腿骨頭・滑液中B含有量が健常者より⬇️ 29.6ppm対56ppm B経口か腹腔内💉はOA誘発🐭に有益 https://idp.springer.com/authorize?response_type=cookie&client_id=springerlink&redirect_uri=https%3A%2F%2Flink.springer.com%2Farticle%2F10.1007%2Fs12011-018-1381-3 🐭関節内💉→抗酸化特性に優れる
@a_kruschke - A.Kruschke
🌊🌊🌊🌊👀👀👀 https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000121431_00461.html
@a_kruschke - A.Kruschke
これらは7月12日に公開されたデータです。https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000121431_00461.html
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
👀🧐 ヒト PBMC [ヒト末梢血単核球] はスパイクタンパク質に応答して脂肪滴を形成する (🇩🇪🇨🇭2023) Human PBMCs [human peripheral blood mononuclear cells] Form Lipid Droplets in Response to Spike Proteins (🇩🇪🇨🇭2023) https://mdpi.com/2076-2607/11/11/2683
@ThailandMedicaX - Thailand Medical News
COVID-19 News: German And Swiss Study Finds That Human PBMCs Form Lipid Droplets In Response To SARS-CoV-2 Spike Proteins! https://www.thailandmedical.news/news/covid-19-news-german-and-swiss-study-finds-that-human-pbmcs-form-lipid-droplets-in-response-to-sars-cov-2-spike-proteins #COVID19 #News #Research #SARSCoV2 #PBMCs #USA #America #Germany #Switzerland #London #Thailand #Canada #France #Israel #Gaza #India
@a_kruschke - A.Kruschke
@bioerorist @HarrySpoelstra @DavidJoffe64 @keisuke4713 @gadboit @sabuchanhakoda1
@a_kruschke - A.Kruschke
💉👀. WHO: New initiative launched to advance mRNA vaccine development against human avian influenza (H5N1) 29 July 2024 https://who.int/news/item/29-07-2024-new-initiative-launched-to-advance-mrna-vaccine-development-against-human-avian-influenza-(h5n1)…
/mrna-vaccine-testing.tmb-1200v.jpg?sfvrsn=9b7e3e65_6)
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
The most dangerous animals in the world 🦇🦇🦇 🧐🤔👀
@CAPublicHealth - California Department of Public Health
CDPH is reminding Californians to be cautious around wild or unfamiliar animals after a Fresno County resident, suspected to have been bitten by a bat in Merced County, died from a rabies infection. Learn more: https://www.cdph.ca.gov/Programs/OPA/Pages/NR24-040.aspx
@a_kruschke - A.Kruschke
@reSeeIt save conversation
@a_kruschke - A.Kruschke
💉🧠👀 COVID-19ワクチン接種後の多巣性髄膜脳炎 (🇯🇵 2024) Multifocal meningoencephalitis after vaccination against COVID-19 (🇯🇵 2024) h/t @K9FCR @AaronOtsuka https://onlinelibrary.wiley.com/doi/10.1111/pin.13491
@a_kruschke - A.Kruschke
Interesting japanese discussion 👇 https://t.co/w60T0tnt1Z
@K9FCR - Stray
84歳日本人男性、４回目接種10週間後死亡。論文タイトルは 「コロナワクチン接種後の多巣性髄膜脳炎」 図4&5スパイクSとヌクレオカプシドNの免疫染色 a)d)は陽性対照（おそらくコロナ感染者の肺）でSもNも陽性 b)e)視床とc)d)橋と、図5 下垂体と副腎、いずれもS陽性、N陰性、つまりワクチン由来S！ https://t.co/ugajrthnDz
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG4 class switch was not observed following four doses of Novavax protein-based SARS-CoV-2 vaccine & IgG3 levels were 10x higher them after mRNA vaccines. https://www.journalofinfection.com/article/S0163-4453(24)00053-7/fulltext
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG3 produced by adenovirus vector vaccines and NVX protein subunit vaccines are 12% of total IgG antibodies but do 80% of the work neutralizing SARS-CoV-2. Natural infection also produce IgG3 predominantly.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 But mRNA vaccines class switch to IgG4 antibodies that lack certain FC related functions and are not as good at forming immune complexes. But they are also less inflammatory. If your first two doses were mRNA the class switch has already been fixed.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 Since the class switch involves genetic deletion of IgG1, IgG2 and IgG3 there is no way for a memory IgG4 B-cell to ever switch back from IgG4 to IgG3. So the only way to resolve this would be for these memory B-cells to wane entirely which they eventually will.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 mRNA vaccines induce memory B-cells but not long lived plasma cells (LLPCs). So they may only last a few years before new B-cells are recruited.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 Interestingly if we block IL-4 and IL-13 receptors & tumor necrosis factor this IgG4 class switching doesn't occur during mRNA vaccination. And it doesn't occur using any other vaccine platform. So it is mRNA specific. https://www.medrxiv.org/content/10.1101/2023.09.29.23296354v1
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 The class switch even occurs if you first have two vector vaccination and then to mRNA vaccinations. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1309997/full
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG4 only exists in certain primates and Fab arm exchange only exists in humans due to Arg409 (versus lysine). We simply lack a complete context of why this might be advantageous to humans.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 So it is clearly an issue with the mRNA vaccines but we don't know why specifically. Speculation includes elements of the LNP, pseudouridine use or simply elevated expression of spike for much longer than expected and longer than adenovirus. The last option seems plausible.
@a_kruschke - A.Kruschke
@RolandBakerIII @systematic_fun @newstart_2024 Missed the last one. It's intriguing that 2xAZ+2xmRNA show also the IgG4 effect. I would favor the third possibility: PEG-related. AZ contains no LNP, but the polysorbate80.
@gadboit - Guy Gadboit
in the wild. At low prevalence, but wide use of this antibody could soon change that... The "holy grail" for a broadly neutralizing antibody is: can you find a place to neutralize the virus that it *can't* mutate with destroying itself? The answer is still no. If it was that...
@gadboit - Guy Gadboit
easy the virus probably wouldn't have made it this far through evolution. Perhaps more interesting than news of yet another antibody therapy that won't work for long is the delivery mechanism. According to the reference for the new tech, antibody treatments are great because...
@gadboit - Guy Gadboit
they are safe and work at once. So why not deliver the abs instead via mRNA LNPs? This way the body's own cells make the antibodies, after a short delay, using far more complex biological pathways, with much greater potential for interesting side-effects? Although I think...
@gadboit - Guy Gadboit
mRNA vaccines have a lot to recommend them, including that they are a better emulation of a live infection than some other vaccine designs, resulting in the right immune response, using mRNA to create *antibodies* is completely different. Now we have other cells, mostly...
@gadboit - Guy Gadboit
monocytes producing antibodies, something they never usually do. LNPs have a strong adjuvant effect, so will we end up with the body making anti-idiotypic antibodies? We still have very limited knowledge of why mRNA vaccines have the side-effects that they do, but some may...
@gadboit - Guy Gadboit
be related to the LNPs, and therefore shared with this new therapy. The reason traditional antibody therapies are safe is because they are just antibodies. Obviously you can't assume this will still be the case if you completely change basically everything about the treatment...
@gadboit - Guy Gadboit
So what is the reason to use mRNA to create antibodies? My cynicism notwithstanding of course it isn't really to reduce safety. According to the reference, it's much cheaper. I trust those savings will be passed on to the consumer. END. h/t @a_kruschke
@a_kruschke - A.Kruschke
@gadboit Finding the "holy grail" by anticipating the future? That sounds more like Harry Potter to me than anything else. ..
@a_kruschke - A.Kruschke
@gadboit .. To be honest, antibodies are a very difficult therapeutic tool for COVID. Perhaps helping in very short time. But I also see it as very critical for the patient himself. Nobody can prevent reinfections. https://www.biorxiv.org/content/10.1101/2023.11.21.567575v1.full ..
@a_kruschke - A.Kruschke
@gadboit ... Pack this then as mRNA into LNP, which has now shown difficult in terms of BBB passing and myocarditis discussion? mRNA with or without frameshift potential by pseudouridine?
@a_kruschke - A.Kruschke
@gadboit .. mRNA technology still has no stop codons. Using this for a virus with known ADE (look at SARS-1 and MERS, too...)? Ongoing long-term production of an mRNA-coded antibody that will meet a mutated variant in some months? Any other ideas to kill patients more quickly 🙊🙊🙊?
@a_kruschke - A.Kruschke
コンブ Kombu Dietary Supplementation with Low-Molecular-Weight Fucoidan Enhances Innate and Adaptive Immune Responses and Protects against Mycoplasma pneumoniae Antigen Stimulation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471482/
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
How to make Dashi 😋 Soup stock from kelp (Kombu). https://www.justonecookbook.com/how-to-make-dashi-jiru/
@a_kruschke - A.Kruschke
Kelp/Kombu contains a lot of vitamins and minerals. (Translated from https://ja.m.wikipedia.org/wiki/%E3%82%B3%E3%83%B3%E3%83%96)
@a_kruschke - A.Kruschke
Thank you for the recipe @Salalalove. In different parts of Japan, different tastes.
@Salalalove - Salala
@a_kruschke マイコプラズマに！？本当ですか！😳 関西では特に、昆布を使った出汁が好まれます。 簡単なものなら、うどんが美味しいですね😋 https://www.kobayashi-foods.co.jp/washoku-no-umami/udon-dashi
@a_kruschke - A.Kruschke
Salmon cooked in kelp rolls. 😋
@Salalalove - Salala
@a_kruschke 昆布巻き😋 https://www.nissui.co.jp/recipe/00775.html
@a_kruschke - A.Kruschke
https://www.nissui.co.jp/recipe/00775.html
@a_kruschke - A.Kruschke
Cold rice balls with sour plums and seaweed.😋🙏
@momo61117806 - momo BH
@a_kruschke 梅干しと昆布のおにぎり。 簡単で美味しく作れると思います☺️https://www.kurashiru.com/recipes/2b247189-b641-474c-ad5a-f41a9cb7f880
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@keisuke4713 - tune
中医学 昆布は化痰軟硬 https://www.uchidawakanyaku.co.jp/tamatebako/shoyaku_s.html?page=241 痰飲(水毒)を去り、塊を柔らかくする
@a_kruschke - A.Kruschke
コンブ Kombu Dietary Supplementation with Low-Molecular-Weight Fucoidan Enhances Innate and Adaptive Immune Responses and Protects against Mycoplasma pneumoniae Antigen Stimulation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471482/
@keisuke4713 - tune
コロナも💉も甲状腺がやられるが ヨードが大切 https://t.co/4ccNsV7WM1
@keisuke4713 - tune
@NA19H5hHBdTdrDr @AichanwithKonan @sabuchanhakoda1 @a_kruschke 実はコロナ禍に昆布問題は繋がります マフィア薩摩藩(幕府に木曽川の泛濫工事で大借金させられた)返済計画に、昆布・沖縄の黒砂糖で清国(中国)と密貿易 昆布は北海道から北前船で本州に運ばれ、富山の売薬商人を介して薩摩にもたらされ、琉球、清国まで流通 中医学で軟堅化痰⇨甲状腺結節等を散らす https://t.co/1p7tADWT9T
@a_kruschke - A.Kruschke
@keisuke4713 いつもありがとうございます👏👏。 それは大きな宝箱です。 🤣 リストに何かがありません。 この時期に人々に希望を与える。 (国際グループはパンデミックのトラウマを利用して死の恐怖を煽っています。🤬🤬🤬) 昆布を使った料理は抗うつ薬です。 🤣すでに動き始めています。
@keisuke4713 - tune
@a_kruschke Frohes neues❗️ この絵の意味を簡単に教えていただけると有難いです 遠くの🇩🇪を身近に感じることができ、有難いです 🙇♂️🙏
@a_kruschke - A.Kruschke
@keisuke4713 🤣🤣🤣🤣🤣🤣🤣🤣🤣🤣🤣 多次元画像の意味を簡単に説明してください...運試しをします。
@a_kruschke - A.Kruschke
@keisuke4713 写真は、シュヴァルツヴァルトのフィリンゲン シュヴェニンゲンにある教会の内陣です。 少し違った方法で街の物語を写真で伝えます。 画像は、アジアのスクロール ペインティングに似た構造になっています。 部門を超えた部門で考えてください。 下の 4 分の 1 はフィリンゲンの街を表しており、...
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Counting 5 days of incubation time also for pat4, it's Dec 27th, where he was still in Shenzhen. The family was traveling on Dec 29th. Even a travel related (airport, taxi,...) infection is rather unlikely for pat4, as 3 days is a rather short incu time.
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf For the relatives other than rel1(baby at hospital), they all got I'll the same day, which points to a family meeting/evening meal with an infectious adult. The incubation time of the relatives matches best the infectious period of pat4 (yellow), less for pat3. https://t.co/F201CiYw1q
@Engineer2The - TheEngineer2 🇨🇦
@a_kruschke @BillyBostickson @gadboit @mbw61567742 @gdemaneuf There are other instances where onsets differ by 3 days. They mostly occur during husband/wife pairing like this from Li et al 2020. M49 and F48 are husband and wife. The increased exposure time likely shortens time to onset. https://t.co/1UgZsJVyZO
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Do you have a reference please? Unfortunately, the problem with many papers is the lack of sound experience from field work.
@Engineer2The - TheEngineer2 🇨🇦
@a_kruschke @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia DOI: 10.1056/NEJMoa2001316 https://www.nejm.org/doi/full/10.1056/NEJMoa2001316
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Thanks. I'll have a look.
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Nice study. I remember the figures. One of the first studies that provided useful epidemiological indicators despite the poor data situation. (Let's keep aside the affiliations of the authors.)
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Agreed, there's one of the clusters with an incubation time of 3 days, but it's in the cluster 4. https://t.co/eGUPurDd2D
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf The yellow cases could be infected at the Wet market, too. https://t.co/qPRhJ7lQjb
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf However, the authors calculated the mean incubation time even higher. "The duration from illness onset to first medical visit for 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days (95% CI, 4.3 to 7.5),.."
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf This of course doesn't exclude the possibility of 3 days incubation time, but it is outside their CI. Possible, but rare, and therefore questionable.
@a_kruschke - A.Kruschke
Oarfish 🧐 Oarfish keep washing ashore in California. https://www.npr.org/2024/11/19/nx-s1-5196630/oarfish-california-japan-folklore
@a_kruschke - A.Kruschke
Is Japanese Folklore Concerning Deep-Sea Fish Appearance a Real Precursor of Earthquakes? (🇯🇵 2019) "...it can be concluded that a deep-sea fish appearance is not useful for disaster mitigation." https://pubs.geoscienceworld.org/ssa/bssa/article-abstract/109/4/1556/571628/Is-Japanese-Folklore-Concerning-Deep-Sea-Fish
@a_kruschke - A.Kruschke
The Legend of Japan’s ‘Earthquake Fish’ https://www.atlasobscura.com/articles/long-fish-predicts-earthquake-legend
@a_kruschke - A.Kruschke
「地震魚」リュウグウノツカイが泳ぐ珍しい姿、台湾沖で撮影https://forbesjapan.com/articles/detail/64768?read_more=1
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
😋🍬👀 納豆、大豆が健常成人の食後血糖値に与える影響 Effect of Intake of Natto and Soybeans on Postprandial Blood Glucose Levels in Healthy Adults (🇯🇵 2009) https://www.jstage.jst.go.jp/article/seikatsueisei/53/4/53_4_257/_article
@a_kruschke - A.Kruschke
"..the natto meal, and not the soybean meal, significantly suppressed the rise in blood glucose level at 60 min compared to the control meal. Furthermore, the area under the glucose curve from 0 to 120 min after the natto meal was significantly smaller than for the control meal." https://t.co/jKmi5mo29L
@keisuke4713 - tune
@a_kruschke 生命は微生物🦠の影響を受け、 ある時は不治の病や痛い目に遭い、 ある時は不治の病や悩みが解決する ご先祖代々、何千年も何白万も続いている🤔 また、微生物🦠の力で 再起する❣️ 彼らの知恵を上手く利用❣️ 上手に付き合って共存💪👏
@a_kruschke - A.Kruschke
@keisuke4713 言いたいことはわかるんですけどね。 🦠❣️💪✨ 注目はミトコンドリア。ベッドが 🛏️🪶快適になってはじめて、残りの微生物は再び家にいるような気分になる。 化石から学ぶことは多いですね。 https://t.co/auC6Z16Vnn
@a_kruschke - A.Kruschke
@keisuke4713 🦊day 2 / 2日目。 効果や副作用は！ 皮下のびまん性浮腫はやや減少し、組織はより可動的になっている。特に、手、前足、胸骨の前に顕著に現れる。 全く良くない‼️著しい体積負荷、頚静脈の鬱血。RR 150/100 😳 => 利尿↗️（トラセミド＋🍌+塩分）。今日はナットウキナーゼの半量（1000FU）のみ。
@a_kruschke - A.Kruschke
@keisuke4713 3日目 ❌ ナットウキナーゼ
@a_kruschke - A.Kruschke
@keisuke4713 Thank you 😊 I thought about it. Did continue today. Smell and taste are important in healing. 🦊1000FU 1 h ago. Feels good. 🙏
@a_kruschke - A.Kruschke
@keisuke4713 ...✅マトリックスからの水の動員は、すでに説明したように周辺から起こります。 🤢 問題は溶解物の除去です。 ローカル リアクション (temporary 10min ) 検索中およびハンド中。 通過時の結腸の腫れ; その結果、便秘になりやすくなります。 排尿と発汗も局所的に刺激します。 全身アレルギーなし.
@a_kruschke - A.Kruschke
@keisuke4713 🦊day 12 /12日目：固定リンパ浮腫の解消が肘と中下腿に達している👍。1000FU+ Cuを継続（＋利尿＋PREDが必要）。
@a_kruschke - A.Kruschke
@keisuke4713 アイデア: 新しい堆積物を防ぎ、組織の圧力を高めます。 また、玉ねぎをたくさん食べる => 発汗 ↗️. RRは正常です。
@keisuke4713 - tune
@a_kruschke 玉葱で発汗するんだ⁉️ 辛味甘味で辛甘化陽⇒発汗 あり得ますが、考えた事無かった❗️ しかも、気圧絡み❗️
@a_kruschke - A.Kruschke
@keisuke4713 "Lauk" ( pronounce: lö:ok)北欧とアルプスでは神聖な植物です。 北欧神話 : laukは地球上の他のすべての植物よりも先に成長した. 薬には3つの異なる応用形態があり、季節に応じて使用されます. 夏☀️🌿タマネギ Zwiebel 生の形でのアプリケーション。 品質：スパイシー、ウォーター、クール。 ...
@a_kruschke - A.Kruschke
@keisuke4713 ..虫刺され、浮腫、発熱に対して。 秋、冬🍂❄️タマネギ Zwiebel 蒸したり焼いたりして使います。 品質：甘く、暖かく、水分を移動します。 効能：せき、肺炎、震え、虚弱・心臓によるむくみ。 😋秋に食べる：オニオンケーキ（温めて食べる）、若いワイン🍷と。https://www.chefkoch.de/rezepte/1716851280413039/Einfacher-Zwiebelkuchen.html ...
@a_kruschke - A.Kruschke
💉👀 小児におけるBNT162b2ワクチン接種から1年後に、非炎症性SARS-CoV-2スパイク特異的IgG4抗体の誘導が遅れて検出された Delayed Induction of Noninflammatory SARS-CoV-2 Spike-Specific IgG4 Antibodies Detected 1 Year After BNT162b2 Vaccination in Children(🇩🇪2024) https://journals.lww.com/pidj/fulltext/9900/delayed_induction_of_noninflammatory_sars_cov_2.959.aspx
@a_kruschke - A.Kruschke
The study included 14 healthy children, ages 5-11 years old. The authors measured IgG4 antibodies following two 💉BNT162b2 vaccination (= original Pfizer BioNTech vaccine).
@a_kruschke - A.Kruschke
Two children have been infected before the vaccination. None had more than mild postvaccination reactions. All children became infected with Omicron after the vaccination.
@a_kruschke - A.Kruschke
"The children’s antibody response 5 weeks after the second BNT162b2 vaccination was dominated by the IgG1 and IgG3 subclasses, which subsequently decreased over time."
@a_kruschke - A.Kruschke
" By contrast, IgG2 and IgG4 levels were relatively low at week 5 after the second vaccination and increased in frequency until the late follow-up for both S1 and RBD (Fig. 1A and B)" https://t.co/bOjHFi9gw7
@a_kruschke - A.Kruschke
" Specifically, S1- and RBD-specific IgG4 antibody levels increased significantly 1 year after the second vaccination compared to baseline (Fig. 1C and D)."
@a_kruschke - A.Kruschke
"In summary, we report on increased spike-specific IgG4 levels in children 1 year after BNT162b2 vaccination, such as the effect observed in adults."
@a_kruschke - A.Kruschke
The authors conclude: "IgG4 responses should gain more attention in health and disease, especially in the context of mRNA vaccination. Understanding the unusual mechanism triggering IgG4 production is crucial [..]."
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@keisuke4713 - tune
コロナが2020年春に突然何千人も🙏出したのはなぜ? https://dailysceptic.org/2022/10/06/why-did-the-coronavirus-suddenly-cause-thousands-of-deaths-in-spring-2020-when-it-had-been-hanging-around-quietly-all-winter/ コロナが遅くとも2019年秋までに世界中に検出されずに広がり始めた証拠多数 2019/9欧州で既に流行 2019/11🇧🇷25廃水から検出
@keisuke4713 - tune
茶番demic 2019/9欧州で既に流行 🇮🇹北部Lombardy州 2019年後半〜麻疹状eruption起こした患者サンプル コロナの分子的証拠https://www.sciencedirect.com/science/article/pii/S0013935122013068 156例435サンプル コロナ感染の分子証拠13人 陽性者2人はpandemic期(2/12、16.7%、2020/3～2021/3) 11人はpandemic前(11/44、25%、2019 /8～2020/2)
@keisuke4713 - tune
2019/11🇧🇷下水 SARS-CoV-2 RNA 存在 https://www.sciencedirect.com/science/article/pii/S0048969721012651?via%3Dihub
@keisuke4713 - tune
イングランド🏴とウェールズ🏴2019-20年の冬の目立たない終わりが左側（10週目前）にあり 春のサージ(その後の波)とのコントラストは明らか
@keisuke4713 - tune
なぜコロナは冬の間ずっと静か❓ 2020年春に多く🙏 コロナはインフルより深刻な🦠でない 過剰🙏は全て2020/2と3月にどう対応したかで起きた 2020年春🇮🇹北部 過剰🙏異常 https://www.eugyppius.com/p/jonathan-engler-on-anomalies-in-the 2019/8市中感染あった場合 →超過🙏率なかった理由 pandemic前の感染報告全ての論文で過剰🙏なしを無視
@a_kruschke - A.Kruschke
@keisuke4713 冬のコロナも静かではなかった。振り返ってみると、多くのケースを割り出すことができます。30代から50代の方が多かったですね。彼らは死ななかった。しかし、6週間も泪を流して...。症状について40℃以上の発熱が10日間続く、激しい咳が6週間以上続く、味覚・嗅覚の喪失、脳機能の低下（特に数学)/..1
@a_kruschke - A.Kruschke
@keisuke4713 /.. 北🇮🇹、／🇨🇭／西🇨🇵／、南🇩🇪。特に山間部。これらの地域の人々は、自分自身を治療します。医師はいない。/2.
@a_kruschke - A.Kruschke
@keisuke4713 多くの地方紙が報じている。そのうちの1つだけです。https://www.schwarzwaelder-bote.de/inhalt.colmar-noch-ein-frueher-corona-fall-im-elsass.61758b30-b80a-44fa-b18b-bd2c3659ddd3.html
@keisuke4713 - tune
@a_kruschke Elsass 🇩🇪語でエルザス 🇫🇷語でアルザス https://kotobank.jp/word/Elsass-1230550 面白い🙏
@a_kruschke - A.Kruschke
@keisuke4713 🇩🇪ELSASS 🇨🇵ALSACE ALSASS アルサス＝地元の方言。 意味：Alamannen アラマンニ（部族、地図年481）+ .から..SASS Sittingより。 現在でもスイスやドイツとの共通語になっている。 ELSASSは国🇹が変わることが多い🤣。 https://www.adalar.ch/pages/geschichte/blutgericht-zu-cannstatt.php 🟥= Alamannen アラマンニ
@a_kruschke - A.Kruschke
Molbio先生ありがとうございます 再接種をお考えの皆様へ、とても大切なツイート🧵👇です。 IgG4 の形成は、自己免疫疾患の発症に関して過小評価されるべきではありません。 コロナウイルスに関連するIgG4の研究は始まったばかりです。 今後数週間でさらに多くの結果が得られることを期待しています。
@a_kruschke - A.Kruschke
IgG4関連自己免疫疾患（オーモンド病、後腹膜線維症）に関する一般情報（シャリテ・ベルリンからの編集）https://nephrologie-intensivmedizin.charite.de/fuer_patienten/sprechstunden/igg4_assoziierte_autoimmunerkrankungen/#:~:text=Die%20IgG4%2Dassozierte%20Autoimmunerkrankung%20ist,Serumspiegeln%20die%20Krankheit%20identifiziert%20werden.
@a_kruschke - A.Kruschke
IgG4関連疾患 (IgG4-RD) https://www.msdmanuals.com/de-de/profi/erkrankungen-des-rheumatischen-formenkreises-und-des-bewegungsapparats/igg4-assoziierte-erkrankung/igg4-assoziierte-erkrankung
@a_kruschke - A.Kruschke
最初の症例報告では、後腹膜線維症とコロナウイルスワクチン接種との関係について議論しています。https://pubmed.ncbi.nlm.nih.gov/36814401/
@a_kruschke - A.Kruschke
後腹膜線維症は恐ろしい病気です。 これまでのところ非常にまれです。 腹部手術中に彼女を2回見ました。 組織は柔らかくはありませんが、貫通できない鎧に囲まれています。 冷凍カツレツを切ろうとしているようなものです。
@a_kruschke - A.Kruschke
🇯🇵 後腹膜線維症/骨膜炎の症例報告と治療。 ワクチン接種との関連は言及されていません。 ステロイド療法が奏効した広汎性後腹膜線維症の1例 A Case of Spreading Retroperitoneal Fibrosis Effectively Treated with Steroid Therapy https://www.jstage.jst.go.jp/article/ihj/advpub/0/advpub_22-470/_article
@a_kruschke - A.Kruschke
まれな後腹膜疾患のまとめ。 多くの場合、原因は不明です。 自己免疫/IgG4 の関与が議論されています。 後腹膜病変を伴う希少疾患 Seltene Erkrankungen mit retroperitonealer Beteiligung https://doi.org/10.1007/978-3-642-39940-4_114
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@APazyryk - Altai Pazyryk
@mrmickme @RolandBakerIII Is there any benefit to IgG3 class switch induced by Novavax?
@notquitegonzo - notquitegonzo עם ישראל חי
@mrmickme @APazyryk @RolandBakerIII Forgive me for my lack of clarity and therefore question Does this indicate a risk for developing auto-immune disorders from nvx booster?
@RolandBakerIII - Roland Baker
@notquitegonzo @mrmickme @APazyryk Antibodies against IL-4, IL-13 receptors& tumor necrosis factor circumvent the class switch to IgG4 with mRNA vaccines. Clearly this is specific to mRNA vax and not ad vector and protein sub-unit vax. https://www.medrxiv.org/content/10.1101/2023.09.29.23296354v1
@RolandBakerIII - Roland Baker
@notquitegonzo @mrmickme @APazyryk No these IgG4 antibodies are specific to the viral spike and don't cause autoimmune disease. The causal connection to IgG4-RD is that you first get an autoimmune disease and the class switch to IgG4 that binds "self" is to prevent damage caused by autoimmune disease.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Could these anti spike IgG4 trigger an immune reaction to the tissues where the spikeproteins are incorporated?
@RolandBakerIII - Roland Baker
@a_kruschke @notquitegonzo @mrmickme @APazyryk Do you mean like where SARS2 spikes are budding from mRNA vaccine or adenovirus vector vaccine transfected cells? Yes, you could see cross reactions to "self" on the cell. But in general IgG4 have less off a tool kit to cause immune reactions than IgG3.
@RolandBakerIII - Roland Baker
@a_kruschke @notquitegonzo @mrmickme @APazyryk If there is an antibody type we should all be worried about it's afucosylated antibodies. They can cause very severe disease.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Yes I meant the reaction to the "Spikeprotein presenting cells". The question was just scientific interest. The other antibodies you mentioned are certainly much more concerning in clinical practice.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Those IgG4 related illnesses are extremely rare. It became a bit less rare meanwhile. M. Ormond/retroperitoneal fibrosis, ... https://pubmed.ncbi.nlm.nih.gov/36814401/ ... mesenterial panniculitis. Pfizer even made a study about. https://www.ehealthme.com/vs/pfizer-biontech-covid-vaccine/mesenteric-panniculitis/
@a_kruschke - A.Kruschke
I want to try ❄️❄️❄️❄️❄️❄️https://t.co/z3xOoJE9fW
@komomo_Com - kom.com
@kakashi_tdn @maiti_86 19以下は自殺行為とまで言っているし、BMI24ぐらいでも筋肉が少ない方は危険だそうです。 糖質制限では脂質とタンパク質からATPを作るのに、アラニンが必要なので、痩せすぎてる方は食べていてもATP不足になるとはっきり書いています。
@komomo_Com - kom.com
@maiti_86 @kksft 糖質制限を薦める目安として【BMI25以上】というのは程よい目安ではないでしょうか？ https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1115333/full
@komomo_Com - kom.com
@kakashi_tdn @maiti_86 ある程度の臨床があればそのような結論に至るため安易に薦めないのだと思います。 リスキーな方が糖質制限をして筋トレしたらどうなるでしょう？ 肝グリコーゲン枯渇問題とケトン体が人間本来のエネルギー源説については、Kruschke先生にも聞いてみましたが、回答は【医学書の通り】とのことです。
@komomo_Com - kom.com
@kakashi_tdn @maiti_86 低炭水化物食につていては支持しているようですが【1/4 が炭水化物で構成される必要があり、日本の伝統的な食生活がこれにあたる】という考えのようです。 米国の低炭水化物食の研究では肥満に至る方も多いらしく問題に感じているようでした。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 引用していただきありがとうございます。 いろいろなことを分けて考えることが大切だと思います。 個人的には「低糖質」が賢いダイエットだと思っています。 ただし、過大評価すべきではありません。 それは常に健康な人を指します。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 重度の低体重の人、糖尿病、またはその他の代謝性疾患のある人は、医師に相談せずにこれを行うことはお勧めできません。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 「低炭水化物」と言うとき、私はこれを意味します。 各食事の 3 分の 1 は炭水化物で構成する必要があります。 同時に、脂肪を十分に摂取することが重要です。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 炭水化物を減らすにはさまざまな方法があります。この記事を使って説明してみます。 (Chrome ブラウザは非常に簡単に翻訳され、スマートフォンでもうまく動作します)。https://www.aerzteblatt.de/archiv/201673/Gegen-Diabetes-und-Adipositas-Dein-Freund-der-Ketonkoerper
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 炭水化物30％、脂肪35％、タンパク質35％のみを使用すべきだと思います。 https://t.co/tfQESiHzxR
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 残念なことに、炭水化物140gについてよく話題になります。 それは誤解を招きます。 560kcalに相当します。 人それぞれ必要なカロリーは異なります。 これは体重、スポーツ、仕事の活動によって異なります。 2000 kcalから12,000 kcalの間で変化します😱。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 要件の計算方法を知っていますか? これに基づいて、個人的にどのくらいのタンパク質を意味するかを計算できます。
@komomo_Com - kom.com
@a_kruschke @kakashi_tdn @maiti_86 Kruschke先生コメントありがとうございます！ こちらのコメントも大変参考になりました。 日本の伝統食を支持するのであれば、私はその意見に賛成です。 極端な低炭水化物で体調を崩している方も多いので、自己流でやる場合は注意が必要だと考えます。 https://t.co/qfdQcy2Lss
@a_kruschke - A.Kruschke
とても興味深い記事❣️❣️❣️ 研究者は、SARS-CoV-2 の 3D シミュレーションを作成しました。 写真や動画を見てください❣️ コロナウイルスはジャガイモ🥔のように見えます。可動 😱 Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling https://cell.com/structure/fulltext/S0969-2126(23)00040-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0969212623000400%3Fshowall%3Dtrue…
@a_kruschke - A.Kruschke
"...lack of symmetry, which is otherwise a typical feature of viral capsids." 対称性の欠如は、ウイルスでは珍しいことです。 ウイルスエンベロープは通常規則的です🤔. タンパク質は表面にパターン状に配置されています。 タンパク質の周りにはより強い電荷があります。 ..
@a_kruschke - A.Kruschke
..これにより、負に帯電した脂肪が引き付けられます。特にカルジオリピン。 "...enrichment of anionic lipids around the proteins, slightly so for POPS and most notably for the doubly charged cardiolipin." 甲羅は全体的に可動。 柄の配置も変わります。(動画は本文中)
@a_kruschke - A.Kruschke
💉👀 LNP 関連炎症はエンドソーム損傷の感知によって引き起こされる: 副作用のないエンドソーム脱出のエンジニアリング LNP-Associated Inflammation is Triggered by Sensing of Endosomal Damage: Engineering Endosomal Escape Without Side Effects ( 🇺🇸2024) https://www.biorxiv.org/content/10.1101/2024.04.16.589801v1.full
@a_kruschke - A.Kruschke
@keisuke4713
@sasabubucha - DR.DOGGIE
『SARS-CoV-2 mRNAワクチン接種後の糸球体毛細血管IgA沈着を伴うIgA腎症：3症例の報告』 慈恵医大からの症例報告。 考察:「SARS-CoV-2ワクチン接種はIgA腎症患者の体液性免疫を過度に活性化し、特徴的な異常であるガラクトース欠乏IgA1の産生を増加させる可能性がある。」 https://link.springer.com/article/10.1007/s13730-022-00707-0
@a_kruschke - A.Kruschke
@sasabubucha このレポートが発表されてから2年が経ちました。日常の臨床診療において、ワクチンやCOVID-19、あるいはその両方によるIgA腎炎の増加が見られますか?
@sasabubucha - DR.DOGGIE
@a_kruschke 疫学的にはよくわかりませんが、症例報告は非常に多いですね(特にワクチン関連)。日本腎臓学会東部学術大会2022はコロナワクチン接種後のIgA腎症・肉眼的血尿・ANCA関連腎炎・ネフローゼ症候群の報告の花盛りでした。 https://t.co/f5vMRPIfbW
@sasabubucha - DR.DOGGIE
日本腎臓学会東部学術大会2022のプログラム・抄録が掲載されています。コロナワクチン接種後の発症・増悪例が多数報告されています。https://cdn.jsn.or.jp/general/congress/journal/64_6-E.pdf https://t.co/GyAfdlzvVF
@a_kruschke - A.Kruschke
@sasabubucha それは私の懸念を裏付けています。 BioNTech の LNP に関する 2020 🐀年の研究では、腎臓の値が約 10% 増加していることがすでに示されています。
@a_kruschke - A.Kruschke
💓💓💓 👀 Possible pathway SARS-CoV-2 spike protein can enter heart muscle cells.👇 SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes (Osaka 🇯🇵2023) https://www.nature.com/articles/s41598-023-48084-7
@a_kruschke - A.Kruschke
Press release university of Osaka 🇯🇵 https://research-er.jp/articles/view/129809
@a_kruschke - A.Kruschke
From the homepage of Department of Cardiovascular Medicine Osaka University 🇯🇵 cardiology.med.osaka-u.ac.jp/?page_id=38131
@a_kruschke - A.Kruschke
💓 about the study: The authors used induced pluripotent stem cells (iPSCs) from a male patient with hypertrophic cardiomyopathy. The expression of ACE2 receptors showed similar distribution as previously described, and comparable to cells from female heart muscle cells.
@a_kruschke - A.Kruschke
"..the iPSC-CMs were incubated with purified His-tagged SARS-CoV-2 S-RBD protein, [..] for 48 h." " Immunostaining revealed that S-RBD accumulated at the periphery of the iPSC-CMs co-localized with ACE2 (Fig. 1d👇) .."
@a_kruschke - A.Kruschke
".. and was then internalized as the S-RBD/ACE2 complex in the subcellular space (Fig. 1e)."
@a_kruschke - A.Kruschke
" After treatment with S-RBD for 48 h, S-RBD signals were detected at the cell membrane and co-localized with ACE2 in ACE2-WT-iPSC-CMs (Fig. 1i) [..], suggesting that internalization of SARS-CoV-2 S-RBD depends on its binding to ACE2. "
@a_kruschke - A.Kruschke
Further experiments "suggested that S-RBD-sfGFP internalized into the iPSC-CMs co-localized with early endosome marker proteins and was then delivered from endosomes to lysosomes through the endolysosomal pathway in the iPSC-CMs." https://www.nature.com/articles/s41598-023-48084-7/figures/2
@a_kruschke - A.Kruschke
Live cell imaging (adeno-associated virus (AAV)) demonstrated the endocytosis of S-RBD bound to RAB5A in the iPSC-CMs (Fig 3 👇). https://t.co/LWQ0rxFkft
@a_kruschke - A.Kruschke
"S-RBD-sfGFP treatment significantly upregulated the IFN-responsive genes (IFI6, ISG15, and IFITM3) in mature cardiomyocytes, suggesting that S-RBD acts as a pathogen-associated molecule and promotes the expression of IFN-responsive genes."
@a_kruschke - A.Kruschke
The authors conclude: ".. S-RBD treatment dose-dependently increased ISG15 expression and promoted protein ISGylation in the human iPSC-CMs via ACE2. However, whether protein ISGylation in the cardiomyocytes is beneficial remains unknown and requires further investigation." https://t.co/hkYWtzqm80
@a_kruschke - A.Kruschke
" In conclusion, SARS-CoV-2 S-RBD was internalized via ACE2 through the endolysosomal pathway, upregulated the IFN-responsive genes, and promoted ISGylation in the human iPSC-CMs. "
@a_kruschke - A.Kruschke
🤔▪️The authors explicitly address the problem of myocarditis after vaccination. However, the amount of spike protein they used is 10.000x higher than the amount expected from mRNA vaccines.
@a_kruschke - A.Kruschke
"concentration of S-RBD used for imaging experiments and transcriptional profiling (> 600 ng/mL) was lower than the estimated serum concentration of S protein after SARS-CoV-2 infection (2500–17,500 ng/mL) but higher than the concentration after mRNA vaccination (20–100 pg/mL)."
@a_kruschke - A.Kruschke
🤔▪️This study is particularly interesting with regard to symptomatic myocardial damage, months after SARS-CoV-2 infection. It has been shown elsewhere, that spike protein can be detected for a long time even though virus replication no longer occurs.
@a_kruschke - A.Kruschke
The amount of spike proteins used in this study is 3-4x lower than in infection, so I estimate it's comparable to spike protein residues in post-Covid patients.
@a_kruschke - A.Kruschke
My personal conclusion: Important basic research, and certainly a 🧩 more to understand late cardial symptomatic after infection. In the context of mRNA it's difficult, in terms of several orders of magnitude difference.
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
Recently, this great paper was published by @SCOTTeHENSLEY. It will have an enormous impact on the vaccination concept against COVID (at least I hope so). It's difficult to understand when you never before heard about the "backboosting" concept. https://journals.aai.org/jimmunol/article/202/2/335/107289/Original-Antigenic-Sin-How-First-Exposure-Shapes
@a_kruschke - A.Kruschke
I'll try to explain the concept of BACKBOOSTING. ❣️Please note that this 🧵 has no impact on individual vaccination recommendations. Please follow the official guidelines. ❣️ This tweet is for MD and other science people who want to understand more.
@a_kruschke - A.Kruschke
During his life, everyone "collects" a series of antibody producing cell that recall ancestral infections. In case of reinfection, the immune system uses these plasma cells, stored in the bone marrow, to produce antibodies against the pathogen.
@a_kruschke - A.Kruschke
By this way, the immune response by antibodies is much quicker than in a primary infection. This memory function of the immune system is perfect for pathogens that do not mutate.
@a_kruschke - A.Kruschke
For defense against mutating pathogens, the immune system has developed some accessory skills. In the context of the backboosting concept, these two are important.
@a_kruschke - A.Kruschke
The first is "immune imprinting", which is also called "Original Antigenic Sin" (OAS). The second one is "somatic hypermutation", also called "immune maturation".
@a_kruschke - A.Kruschke
(Just for recalling.) B cell memory: building two walls of protection against pathogens https://www.nature.com/articles/s41577-019-0244-2 (fig.👇 )
@a_kruschke - A.Kruschke
The resulting antibodies of multiple contacts with e.g. influenza are difficult to predict, as everyone has a different history of life. Several studies for immunology and vaccines research were published, drawing maps of antibodies.
@a_kruschke - A.Kruschke
Most studies in context of backboosting were done on Influenza virus. Curiously, test subjects also showed "memory" to strains that were circulating only before their birth. This is explained by cross-reactivity and/or somatic hypermutation.
@a_kruschke - A.Kruschke
Antibody landscapes after influenza virus infection or vaccination (2014) https://www.science.org/doi/10.1126/science.1256427
@a_kruschke - A.Kruschke
"Titers were highest for influenza viruses that circulated when an individual was ~6 years old, corresponding with the time frame of first infection."
@a_kruschke - A.Kruschke
"Antibody levels against newly circulating viruses tended to be lower than those against strains circulating earlier in an individual’slifetime,.." "... each individual’s landscape shape was typically stable from one year to the next and had distinctive individual features.."
@a_kruschke - A.Kruschke
"Typically, the broad initial response was followed by a period of titer decay during which antibody titers stabilized to form an altered antibody landscape over the course of ~1year (fig.S24👇)" https://www.science.org/doi/suppl/10.1126/science.1256427/suppl_file/fonville.sm.pdf
@a_kruschke - A.Kruschke
As you can see in the figure, the pre-reinfection ab titers (first column, grey) are enhanced by reinfection (red). This process takes time, and some antibodies only rise after one year (lower part of fig.).
@a_kruschke - A.Kruschke
After this process, the titer was maintained higher than the initial one. These findings laid the foundation stone of the backboosting vaccination concept. Novel vaccine concept based on back-boost effect in viral infection (Kohler. 2015) https://www.sciencedirect.com/science/article/pii/S0264410X15006878?fr=RR-1&ref=cra_js_challenge
@a_kruschke - A.Kruschke
...to be continued... 😊
@a_kruschke - A.Kruschke
Let's continue BACK-BOOSTING... (chapter 2) The idea behind it is like a time machine. Recalling memory of old strains to fight the future.
@a_kruschke - A.Kruschke
The idea of using the Back-boosting mechanism to fight strains of virus that will come in the future . Sounds impossible?
@a_kruschke - A.Kruschke
The idea behind: We know that the "stored memory" in our immune system undergo some random mutation process. So, it will be helpful to have different "mother memory cell lines" to get a broad spectrum of random mutations.
@a_kruschke - A.Kruschke
Then, the chance of cross-reactivity with future mutations of the virus will be enhanced, just because of bigger choices. But is this not only theory? Let's have a look again at what happens in influenza.
@a_kruschke - A.Kruschke
Original Antigenic Sin: How First Exposure Shapes Lifelong Anti–Influenza Virus Immune Responses (2019) https://journals.aai.org/jimmunol/article/202/2/335/107289/Original-Antigenic-Sin-How-First-Exposure-Shapes
@a_kruschke - A.Kruschke
The authors collected "..serum samples [..] over a 20-year period from 40 individuals [..] and measured changes in their antibody titers against H1, H2, and H3 viruses in ∼5-y intervals."
@a_kruschke - A.Kruschke
The authors "observed that exposure to strains encountered later in life “back-boosted” the antibodies response to strains of the same subtype encountered earlier in life."
@a_kruschke - A.Kruschke
"Thus, the strains of a given subtype encountered earliest in life experienced the greatest number of back-boosting events, leading them to be consistently maintained at the highest antibody titers."
@a_kruschke - A.Kruschke
So, once again, the "immune imprinting " was confirmed. Looks like a trap nobody can escape?
@a_kruschke - A.Kruschke
But... "..severe infections, such as those caused by pandemic strains, might be capable of “reprogramming” the hierarchical antibody response caused by earlier imprinting with less virulent strains of the virus. ..
@a_kruschke - A.Kruschke
"..E.g., early serological studies showed that individuals born between ∼1863 and 1890 (the year of the H3Nx Russian Flu pandemic) all had high titers of antibodies against the virus that caused the 1968 H3N2 “Hong Kong Flu” and were roughly equally protected from mortality. ..
@a_kruschke - A.Kruschke
" This suggests that exposure to the 1890 H3Nx pandemic strain was able to “override” the imprint of earlier seasonal strains to which those born decades before the 1890 pandemic (i.e., from 1863 onwards) would have been exposed."
@a_kruschke - A.Kruschke
In sum, these findings tell us that it will be useful to look out for those "strong variants" that appear from time to time.
@a_kruschke - A.Kruschke
That's the principle of using the "backboost effects " for vaccines. Put these "strong variants" in the next vaccine, then you'll protect not only the already imprinted variant, but also the second one.
@a_kruschke - A.Kruschke
This was all about influenza. Also described in HIV and hepatitis C. But would it happen also in COVID? This was the big question.
@a_kruschke - A.Kruschke
Some in vitro or animal models, and also the Moderna's safety study for XBB.1.5 monovalent vaccine gave some hints that XBB.1.5 might be such a "strong variant".
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
PREPRINT ‼️‼️Moderna Safety study for monovalent-XBB 💉. Phase II/III study with 50+51 participants. Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines https://www.medrxiv.org/content/10.1101/2023.08.22.23293434v1.supplementary-material
@a_kruschke - A.Kruschke
Unfortunately, neither BioNTech/Pfizer nor Novavax published any safety study for the XBB.1.5 vaccines.
@a_kruschke - A.Kruschke
So we had to wait for the great study from Hensley Lab.
@SCOTTeHENSLEY - Hensley Lab
Check out our new manuscript on @medrxivpreprint. We show that ‘immune imprinting’ with ancestral SARS-CoV-2 mRNA vaccines is beneficial for priming neutralizing antibody responses against emerging SARS-CoV-2 variants. 1/n https://www.medrxiv.org/content/10.1101/2024.01.08.24301002v1
@a_kruschke - A.Kruschke
Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants (2024) https://www.medrxiv.org/content/10.1101/2024.01.08.24301002v1.full
@a_kruschke - A.Kruschke
The study confirms that the choice of XBB.1.5 for production of a monovalent vaccine was the right one.
@a_kruschke - A.Kruschke
The authors found "unlike BA.5, a single XBB exposure elicited low levels of XBB.1.5-specific antibodies and B cells in some individuals."
@a_kruschke - A.Kruschke
Their conclusion gives hope for the future: "The human immune landscape against SARS-CoV-2 is becoming more heterogenous as variants emerge and infection and vaccination histories become diverse among different individuals. ..
@a_kruschke - A.Kruschke
".. Most humans have been ‘immunologically imprinted’ with antigens from the ancestral SARS-CoV-2 strain, but that will inevitably change as time progresses. Most children born today will be first introduced to SARS-CoV-2 antigens in the form of a variant infection or variant ..
@a_kruschke - A.Kruschke
".. vaccination, leading to the formation of different memory B cell populations compared to individuals first exposed to ancestral SARS-CoV-2 antigens."
@a_kruschke - A.Kruschke
All pure theory? I think the advisor group of WHO takes this Back-boosting concept into account. In their statement from December 13, 2023 they maintain the XBB.1.5 as vaccine component. https://www.who.int/news/item/13-12-2023-statement-on-the-antigen-composition-of-covid-19-vaccines
@a_kruschke - A.Kruschke
NB: Sato Lab's hamsters 🐹 also predicted that two antigen contacts with XBB.1.5 would be necessary to establish a broader immune response. https://t.co/iZhkGpbsX0
@a_kruschke - A.Kruschke
This now published study is also very interesting in the context of backboost qualities of XBB.1.5. https://www.cell.com/immunity/fulltext/S1074-7613(24)00092-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS107476132400092X%3Fshowall%3Dtrue#secsectitle0035
@a_kruschke - A.Kruschke
"These data show that the updated XBB.1.5 S mRNA vaccine booster elicits greater neutralizing antibody responses against a panel of recently and currently circulating variants, including mismatched pseudoviruses,..."
@a_kruschke - A.Kruschke
A comment about the then preprint from @gadboit https://t.co/fTBFcApRvp
@gadboit - Guy Gadboit
Gigavaxxing doesn't work. This is a study of people who had had around 5, 6 or 7 vaccine doses altogether, the first 3 or 4 of which were Wuhan-Hu-1, and then either a bivalent, or a bivalent then the monovalent XBB.1.5 booster. They measured neutralization... https://t.co/rhPtXeUpN3
@a_kruschke - A.Kruschke
@gadboit @reSeeIt save thread
@a_kruschke - A.Kruschke
Did you see the HEADLINE ? There are 10 confirmed cases...🦟... of Dengue fever. A good opportunity to talk about ADE (antibody dependent enhancement) https://www.foxnews.com/health/dengue-virus-spreads-florida-counties-health-officials
@a_kruschke - A.Kruschke
Here's the explanation related to the 👇thread. It's about air, lung anatomy, breathing problems, COVID and other structural illnesses... and about mice.
@a_kruschke - A.Kruschke
Lung Fibrosis Pulmonary Fibrosis Idiopathic, genetic, SARS-CoV-2 related. 🫁👀🧐🤔 svuhradiology.ie/case-study/pul… 🫁 https://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/symptoms-causes/syc-20353690
@a_kruschke - A.Kruschke
Let's start with the anatomy of the lung. When breathing, we bring the air into a system of airways, shaped like a tree.
@a_kruschke - A.Kruschke
At the end of each airway branch is a bundle of bubbles, the so-called alveoli.
@a_kruschke - A.Kruschke
When we have a closer look, we can see the bubbles are wrapped with elastic fibres (painted in green). A few muscle strings are present, but wrapped only around the "branches". [*) pictures from Netter anatomy atlas]
@a_kruschke - A.Kruschke
When we inhale, the bubbles (alveoli ) fill with air. The wall of the alveoli is very thin, and elastic. The elastic fibres wrapped around prevent the alveoli from bursting.
@a_kruschke - A.Kruschke
The alveoli are also wrapped in a net of blood vessels. The inhaled oxygen is then passed through the alveoli wall in the blood vessels, and transported by the red blood cells (erythrocytes).
@a_kruschke - A.Kruschke
This description is very simplified, as I only want to point out that the wall of the alveoli is smooth, thin, elastic and is able to move. Otherwise the passage of oxygen into the blood is hindered.
@a_kruschke - A.Kruschke
It is obvious that damage to the alveolar walls, the elastic fibers or the blood vessels that surround them would hinder proper air -> blood oxygen exchange. SARS-CoV-2 damages all three.
@a_kruschke - A.Kruschke
To fix the problem, the body has little choices but to make a scar out of the damaged tissue. The longer the damage of the lung lasts, the more scar fibers are produced. This is then called "lung fibrosis" or "pulmonary fibrosis".
@a_kruschke - A.Kruschke
Unfortunately a scar is not smooth, not thin, not elastic, and cannot move. Lung Fibrosis can be caused by everything that damages the lung tissues: infections, intoxication, asthma, ... https://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/symptoms-causes/syc-20353690
@a_kruschke - A.Kruschke
... hereditary illnesses, or unknown causes. In medicine "unknown" is called "idiopathic" (... that sounds much more scientific than "we have no clue"...).
@a_kruschke - A.Kruschke
Back to 2020... The COVID patients admitted to the ICU were treated for an infection causing severe lung damage, called ARDS (Acute Respiratory Distress Syndrome).
@a_kruschke - A.Kruschke
However the COVID patients didn't properly respond to the treatment. The most experienced pulmonologists were surprised. https://healthcare-mittelhessen.eu/ukgm-chef-ueber-corona-ueberraschend-ist-dass-das-lungenversagen-sich-so-lange-hinzieht
@a_kruschke - A.Kruschke
COVID reacted as there were supplementary factors causing the lung damages, besides the infectious compound.
@a_kruschke - A.Kruschke
Those "special effects" of SARS-CoV-2 infection are sometimes crazy.... High levels of oxygen are worsening COVID. https://www.monaldi-archives.org/index.php/macd/article/view/1916
@a_kruschke - A.Kruschke
As underlying cause it was discovered that high oxygen levels multiply the numbers of TMPRSS2-receptors*). High level of oxygen resulting in worsening COVID. ___ *)TMPRSS-receptors are the second important receptors SARS-CoV-2 uses to infect the cells. https://www.monaldi-archives.org/index.php/macd/article/view/1916
@a_kruschke - A.Kruschke
The next weird thing: SC2 is using a pathway called FOXO3 to induce lung fibrosis. But this pathway was known to be important for "idiopathic lung fibrosis". ___ (Links are just references, no need to read the papers.) https://www.medrxiv.org/content/10.1101/2022.09.02.22279542v1.full . https://www.researchgate.net/publication/321672416_FoxO3_an_important_player_in_fibrogenesis_and_therapeutic_target_for_idiopathic_pulmonary_fibrosis
@a_kruschke - A.Kruschke
Idiopathic fibrosis and cystic fibrosis both cause severe lung Fi, with quick progression. Both are unrelated to infections. So how could SC2 do that? ___ Cystic fibrosis is hereditary, and idiopathic fibrosis is "nobody knows".
@a_kruschke - A.Kruschke
What is idiopathic lung fibrosis?
@a_kruschke - A.Kruschke
🫁👀 特発性肺線維症とは？ What Is Idiopathic Pulmonary Fibrosis? https://www.nhlbi.nih.gov/health/idiopathic-pulmonary-fibrosis
@a_kruschke - A.Kruschke
🫁👀 特発性肺線維症とは？ What Is Idiopathic Pulmonary Fibrosis? https://www.nhlbi.nih.gov/health/idiopathic-pulmonary-fibrosis
@a_kruschke - A.Kruschke
Then, in 2020, the SARS-CoV-2 WT was "trained" by serial.passage to infect normal mice. (WT cannot infect mice.)
@a_kruschke - A.Kruschke
By coincidence, this new strain came out of the UNC lab. And just before the Alpha ("British variant"), Beta, Gamma variants appeared.
@a_kruschke - A.Kruschke
Here again the link to the short thread.
@a_kruschke - A.Kruschke
Lung Fibrosis Pulmonary Fibrosis Idiopathic, genetic, SARS-CoV-2 related. 🫁👀🧐🤔 svuhradiology.ie/case-study/pul… 🫁 https://www.mayoclinic.org/diseases-conditions/pulmonary-fibrosis/symptoms-causes/syc-20353690
@a_kruschke - A.Kruschke
@reSeeIt save Thread @reSeeIt save conversation
@tommy_cleary - Tommy Cleary
Holmes attempted <
@tommy_cleary - Tommy Cleary
One more before I put the roast on for Australia Day dinner...
@GrahamPerrettMP is my local Federal MP and he has helped in the past, but last time I wrote to him he replied that I should check the Queensland State Library for more details...perhaps I should check back with him again too.
These issues of how to handle the dangerous side of science have been a problem since at least Iraq's @UN biological weapons inspections...with discussions of Mustard brought to the table by @R_H_Ebright thank you, @INTERPOL_CBRNE questions are important.
H/t @CharlesRixey @Ayjchan @Globalbiosec
Holmes attempted <
@tommy_cleary - Tommy Cleary
@Studio28nyc @McWLuke @PeterDaszak @WHO @SciDiplomacyUSA @BangXiao_ @POTUS After Australia Day roast lunch (which was fantastic) I sent another email this time to Zhengli Shi & @BangXiao_ Then me & the fam went to local barefoot lawn bowls.
@tommy_cleary - Tommy Cleary
Seeking No14 ORF8 omission...with some healthy distraction from @breakfast_dogs @harishseshadri2 @gdemaneuf
about the truisms of love...and knowing at all. @Rebecca21951651 @emilyakopp @a_kruschke @Ayjchan @VBruttel @BillyBostickson
Back to the data set.
Holmes attempted <
@VBruttel - Dr. rer. nat. Valentin Bruttel
Why SARS-CoV-2 was a lab manipulated virus in 10 key points https://vbruttel.substack.com/p/why-sars-cov-2-was-a-lab-manipulated The IMO most compelling molecular and circumstantial evidence regarding the origin of COVID-19. ➡️ Please share, retweet, and raise awareness to help prevent similar events from occurring again.
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@StoreEducation - EducationStore
Writing how to be more productive without procrastinating or bingeing UOW: University of Wollongong, Australia Speaker: Emeritus Prof. Brian Martin and members of PhD Candidates Date: 09/02/2020 Time: 11:30 AM Canberra, Melbourne, Sydney Register NOW: https://zoom.us/webinar/register/WN_aA-y9bEaQKKO4fTdu_oVxw
@tommy_cleary - Tommy Cleary
But there is poetry in these lethal paragraphs of RNA H/t @quay_dr @MartinaSisters Where have the poets of this world gone? Why have rhymes bent to reason and quills been put aside to crumble ? What feeble mind thinks yet does not imagine possibilities of other minds too? Minds seek minds within what we all wonder
@tommy_cleary - Tommy Cleary
The question of //Pathos// has disturbed the search for the next missing part of this data set.
Never a better reason to interrupt seeking is finding a question linked to the heart.
Knowing love is a perennial concern.
To leave souls behind has a sharp gravitas.
Back to the data.
In 2023 Holmes attempted <
@tommy_cleary - Tommy Cleary
@gdemaneuf There is a theory that Drosten changed his mind…or was more free to speak his mind…after Shi made it out of China recently…nice idea. People. People do what people do…they fall in love and do stupid and sometimes inspirational things.
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
In 2023 Holmes attempted <
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@CharlesRixey - Charles Rixey, MA MBA (c) 🐭
Linked below is an article written by LtCol Joseph Murphy, the person who leaked the DEFUSE proposal to me, which DRASTIC then analyzed and released on September 20th & 21st, 2021. 🧵 https://brownstone.org/articles/the-biodefense-oligarchy-and-its-demographic-defeats/
@tommy_cleary - Tommy Cleary
As science is very important...
https://journals.asm.org/doi/10.1128/jvi.01240-24methods
H/t @sciencecohen @hholdenthorp @ScienceMagazine
Holmes attempted
<
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
My application for SAGO at @WHO was rejected...but it was in volunteer capacity and so I simply continued to help where I can.
https://2012-2017.usaid.gov/sites/default/files/documents/2496/Combatting_Corruption_Among_Civil_Servants_-_Interdisciplinary_Perspectives_on_What_Works.pdf
My skill sets are listening...catching...and surprise...not simplicity
H/t @CharlesRixey
Umberto Eco said it well.
If it is too complicated, read more books.
But he wrote this type of thing in Italian, so don't see these ideas as complexity, see them as language.
Teaching a language takes time and repetition...about two years of immersion...or you can nowadays Gronk your way through?
The lived experience here is of an INCOMPLETE data set...so obviously I cannot fully explain the data...but you can join me on the journey.
Surprise!
Truth is important...but it takes a lot of listening to hear certain truths...trauma adds more layers of humanity and so our souls are stretched thinly as we listen to the person within the cyborg of text based embodiment twisting under the weight of the unknown...but knowable:
<
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
<
@tommy_cleary - Tommy Cleary
@R_H_Ebright @ScienceMagazine Further...as much as Holmes has stated that data from Jie Cui was not linked to WIV 162 of 163 submissions to GenBank remain suppressed or missing...with other serious data integrity issues and cyber biosecurity issues needing to be addressed... Disqualifying conflict of…
@tommy_cleary - Tommy Cleary
@_everythingism @AceBearstrom @hiltzikm STS studies regularly acknowledge and explore institutional limits to knowledge away from the political narratives you outline here. <<Undone Science Social Movements, Mobilized Publics, and Industrial Transitions By David J. Hess>> https://mitpress.mit.edu/9780262529495/undone-science/ Since this research…
@tommy_cleary - Tommy Cleary
This is where I lost count!
Doh!
Next GI will have to start from here and be inserted into current tally.
GI 1769824546 restart count again here...and insert missing into tally
KISS Methods: basic GI series analysis this Xpost
GI is 1769824546 <
@tommy_cleary - Tommy Cleary
Next one?
<
@tommy_cleary - Tommy Cleary
Censorship of the nature deployed in the case of COVID had some obvious negative effects...but some were not so bad. @BiosafetyNow
https://biosafetynow.substack.com/p/censoring-virology
It was nice and quiet.
The people censored had to find ways to reach out to each other...the phenomenology was that we had to look at what we were looking through.
It also builds a compassion for a data set you are auditing during verification and for your own findings...a health doubt...need to double check and have peers that are brutal not lazy.
Fixing this mess is going to be fun!
Some wisdom always comes from a moment of stupidity and reflection.
KISS Methods: basic GI series analysis this Xpost
GI 1769824482 <
@a_kruschke - A.Kruschke
@tommy_cleary @JAHawk94684 @MartinaSisters @mlperk1 @MonaRahalkar @R_H_Ebright @quay_dr @BiosafetyNow @syd_health @SystemsVirology @NLM_NIH @POTUS @Sydney_Uni @DrJBhattacharya @FloDebarre @institutpasteur @thackerpd @Rebecca21951651 @capitolsheila @BillyBostickson @breakfast_dogs @Globalbiosec @gdemaneuf @RdeMaistre @dasher8090 @COVIDSelect @GrahamPerrettMP @harishseshadri2 @emilyakopp @Ayjchan @VBruttel @CharlesRixey @sciencecohen @hholdenthorp @ScienceMagazine @WHO @reSeeIt save Thread
@a_kruschke - A.Kruschke
@takavet1 Dr Miyazawa, I tend to disagree. The construction of a new BSL-4 lab in the middle of a densely populated area with 1.5 million inhabitants is a thread for the whole world. https://web.archive.org/web/20241116115541/https://mainichi.jp/english/articles/20241116/p2g/00m/0sc/025000c
@a_kruschke - A.Kruschke
It is NOT a question of Nagasaki locals concerned. It's about the threat a lab leak could cause another pandemic. I'm pleased to help with the English translation, so overseas can join the discussion. The thread in translation:
@a_kruschke - A.Kruschke
Let's have a closer look at your comments. 1/ claim: A new BSL4 lab is necessary for national defence. You already mentioned it in an older thread.
@a_kruschke - A.Kruschke
Japan already has TWO BSL4 labs. In the middle of the highly dense populated Kanto area. Tokyo area, for foreigners. More than 40 million residents (2024), 15 million commuters. May I help you with the worldwide BSL-3+4 lab list? h/t DRASTIC
@BillyBostickson - Billy Bostickson 🏴👁&👁 🆓
Upgraded Biosafety Map (July 2024) Now Shows: 840 BLS3 Labs (in Orange) 87 BSL4 Laboratories (in Red) Click on the Pins to see details for each lab, Remember, Friends of DRASTIC, if you spot any errors or missing labs, please keep on informing us! https://www.google.com/maps/d/viewer?mid=1-I7wAGlqKCQ_UP14MqAHvBGwXavATtk&usp=sharing
@a_kruschke - A.Kruschke
Why should Japan's security be in danger without another BSL4 lab in Nagasaki?
@a_kruschke - A.Kruschke
2/ claim: ".. there has been no case (accident) of a virus leaking from BSL4 in the world." This is not true. Even Wikipedia knows about some. The underreporting yet not taken into account. https://en.m.wikipedia.org/wiki/List_of_laboratory_biosecurity_incidents
@a_kruschke - A.Kruschke
Are you sure? "However, it is unthinkable that the virus would physically leak from the facility, and there has never been a "physically" leak in the world."
@a_kruschke - A.Kruschke
3/ claim: " If the rules are followed, the experimenters will not be infected." Are all japanese scientists following the security rules? https://theintercept.com/2022/11/01/biosafety-avian-flu/
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
4/ "I really wish people would stop saying that all virus researchers are villains and descendants of Unit 731." Did you read the excellent comments from Dr Kakeya? h/t @hkakeya
@a_kruschke - A.Kruschke
For anyone who missed the discussion of whether SARS-CoV-2 came from a lab or not, I recommend this excellent summary from a Japanese perspective. https://zenodo.org/records/14741477 Thank you❣️@hkakeya
@a_kruschke - A.Kruschke
@hkakeya The history of Japanese laboratories and unit 731. h/t @hkakeya
@hkakeya - Hideki Kakeya, Dr.Eng.
薬害エイズを起こしたミドリ十字は旧日本軍の731部隊の流れを組む。731部隊の残党は東大伝染病研究所にも大量に流れ、それが国立予防衛生研（現・感染研）と東大医科研に分かれて現在に至る。これらの組織の非倫理性はその歴史を考えれば当然。組織の刷新が不可欠です。 https://www.hokeni.org/docs/2017040500122/
@a_kruschke - A.Kruschke
@hkakeya And for all japanese who still believe that unit 731 is a "racist US conspiracy theory" to suppress Japan: https://www.theguardian.com/world/2018/apr/17/japan-unit-731-imperial-army-second-world-war
@a_kruschke - A.Kruschke
@hkakeya 5/ claim: " Many of my students are also handling highly dangerous viruses. [..] They have no evil intentions. " It's not only the "evil intentions " that cause harm. Did you teach your students to discuss openly that lab accidents can happen? https://t.co/9IplSdXEYF
@a_kruschke - A.Kruschke
Organizing an international conference "preparing for the next pandemic", while ignoring the real-world threats? I would have expected a discussion block on improving laboratory safety, international oversight of GOF research and possible responses to bioweapons attacks. https://t.co/YvT2nBXWTN
@a_kruschke - A.Kruschke
Here's the original thread in japanese. To prevent a sudden loss. https://t.co/8vbgkuWX9V
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@a_kruschke - A.Kruschke
The "influenza season 2023/24" has been declared open in several European countries. Main strain is A(H1N1)pdm09, formerly known as "swine flu" (2009 pandemic). The current vaccines include this strain. Data from Austria 🇦🇹https://virologie.meduniwien.ac.at/wissenschaft-forschung/virus-epidemiologie/influenza-projekt-diagnostisches-influenzanetzwerk-oesterreich-dinoe/aktuelle-saison-20232024/
@a_kruschke - A.Kruschke
Last 🇩🇪 Influenza report (will be updated January 05th) https://www.rki.de/DE/Content/Infekt/Sentinel/Grippeweb/grippeweb_ergebnisse_node.html ARE weekly reports (PDF only) shows the current data 👇 https://influenza.rki.de/Wochenberichte.aspx
@a_kruschke - A.Kruschke
The press has already been informed https://www.sueddeutsche.de/gesundheit/gesundheit-grippewelle-in-deutschland-hat-begonnen-rki-raet-zur-impfung-dpa.urn-newsml-dpa-com-20090101-240103-99-483093
@a_kruschke - A.Kruschke
Santé France 🇨🇵 "Currently A(H1N1)pdm09 viruses are in the majority and the antigenic profile of the viruses allows us to anticipate good effectiveness of the vaccine." (translation from the linked PDF👇) https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-et-infections-respiratoires/grippe/documents/bulletin-national/infections-respiratoires-aigues-grippe-bronchiolite-covid-19-.-bulletin-du-3-janvier-2024
@a_kruschke - A.Kruschke
🇨🇭 lnfluenza Dashboard https://idd.bag.admin.ch/diseases/influenza/overview Also with wastewater tables for Influenza👇 https://idd.bag.admin.ch/diseases/influenza/statistic#waste-water-by-ara
@a_kruschke - A.Kruschke
Flu season with Influenza A(H1N1)pdm09. What could this mean for Europe in post-Covid times? It's a personal assessment. I may be wrong. Please consider it as a basis for discussions.
@a_kruschke - A.Kruschke
The "influenza season 2023/24" has been declared open in several European countries. Main strain is A(H1N1)pdm09, formerly known as "swine flu" (2009 pandemic). The current vaccines include this strain. Data from Austria 🇦🇹https://www.virologie.meduniwien.ac.at/wissenschaft-forschung/virus-epidemiologie/influenza-projekt-diagnostisches-influenzanetzwerk-oesterreich-dinoe/aktuelle-saison-20232024/
@a_kruschke - A.Kruschke
Let's compare it with Russia, which experienced the 2022/23 season with this strain. Assessing the Intense Influenza A(H1N1)pdm09 Epidemic and Vaccine Effectiveness in the Post-COVID Season in the Russian Federation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458445/
@a_kruschke - A.Kruschke
"PCR-testing of 220,067 clinical samples revealed that the influenza A(H1N1)pdm09 virus dominated, causing 56.4% of positive cases, while A(H3N2) influenza subtype accounted for only 0.6%, and influenza B of Victoria lineage—for 34.3%." (PCR, Russia, week 40.2022-20.2023)
@a_kruschke - A.Kruschke
"The comparative analysis of influenza activity [..] revealed an unprecedentedly rapid increase in both ILI incidence and the number of PCR-confirmed influenza cases [..]. The intensity of the epidemic surpassed the previously recorded “very high level” index, .." (Fig. 3)
@a_kruschke - A.Kruschke
"The effectiveness of influenza vaccines estimated in the sentinel surveillance system was evaluated as 92.7% in the prevention of SARI patient admissions and 54.7% in the prevention of influenza among outpatients with ILI/ARI (average 80%, Table 👇)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458445/table/viruses-15-01780-t001/?report=objectonly
@a_kruschke - A.Kruschke
*🤔 What does it mean for Europe in the current season? ▶️ The current influenza vaccines contain the Influenza A(H1N1) pdm09 strain. The protection of hospitalisation is probably very good. It doesn't prevent from infection, but infection rate is lower.
@a_kruschke - A.Kruschke
Influenza vaccine 2023/24 (Should be the same for whole EU), from PEI: https://www.pei.de/EN/medicinal-products/vaccines-human/influenza-flu/influenza-flu-node.html?cms_tabcounter=0
@a_kruschke - A.Kruschke
▶️ If you are not vaccinated yet, please discuss it with your family doctor. Different countries have different schemes who are eligible. This might be changed within the next few weeks, because of the current strain, follow the press release.
@a_kruschke - A.Kruschke
▶️ If you consider vaccination (and you are eligible), please do it as quick as possible. After every vaccination, it will take 2-3 weeks to establish the protection. During this period, you'll be even more susceptible to any infection. So it's useful to 😷 in populated areas.
@a_kruschke - A.Kruschke
▶️ IMO a combined Influenza vaccination with Covid vaccine is useless. Several recent studies showed low to no protection from the current variant (JN.1). And it's not useful to trouble your body even more in the current situation. Focus on Influenza !
@HarrySpoelstra - Harry Spoelstra
❗New recent work from @SystemsVirology needs your attention! ➡️Don't underestimate JN.1, your recent XBB.1.5 booster may even NOT protect you! 😷 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00813-7/fulltext
@a_kruschke - A.Kruschke
▶️ Children will probably be concerned in higher numbers as in "normal" Influenza waves. Reports from previous years with high A(H1N1)pdm09 prevalence 👇:
@a_kruschke - A.Kruschke
👀 Continued high incidence of children with severe influenza A(H1N1)pdm09 admitted to paediatric intensive care units in Germany during the first three post-pandemic influenza seasons, 2010/11–2012/13 https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-015-1293-1
@a_kruschke - A.Kruschke
👀 Influenza A (H1N1)pdm09 viral clearance kinetics in hospitalized children (Spain, 2015–2016 flu season) https://www.analesdepediatria.org/en-influenza-a-h1n1-pdm09-viral-clearance-articulo-S2341287921000247
@a_kruschke - A.Kruschke
👀 Children under 10 years of age were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic in Canada: possible cohort effect following the 2009 influenza pandemic https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470369/
@a_kruschke - A.Kruschke
*🤔 What about co-infections with Covid? Do we have to fear a "Twindemic"? IMO (many may contest it), the Covid waves will soon crumble, assuming the A(H1N1)pdm09 strain stays dominant. There's known interference between this strain and SARS-CoV-2👇.
@a_kruschke - A.Kruschke
@UseBy2022 Disagree. It's a combined effect. Viral interference study by professor Y. Kawaoka, one of the leading Influenza specialists. "..viral interference between SARS-CoV-2 and influenza A(H1N1)pdm09, A(H3N2), or B/Victoria-lineage virus has been reported." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835431/
@a_kruschke - A.Kruschke
▶️ Please be aware that co-infections with other respiratory viruses/bacteria will probably happen. The recurring infections of everybody during the last two years has weakened our immune system. Please consider yourself as "vulnerable for Influenza". 😷😷😷😷😷😷😷😷😷😷
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@a_kruschke - A.Kruschke
💓💓💓 👀 SARS-CoV-2 スパイクタンパク質が心筋細胞に侵入する可能性のある経路👇 SARS-CoV-2 スパイク受容体結合ドメインは内部移行し、ヒト人工多能性幹細胞由来心筋細胞のタンパク質 ISGylation を促進する (大阪🇯🇵2023)
@a_kruschke - A.Kruschke
💓💓💓 👀 Possible pathway SARS-CoV-2 spike protein can enter heart muscle cells.👇 SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes (Osaka 🇯🇵2023) https://www.nature.com/articles/s41598-023-48084-7
@a_kruschke - A.Kruschke
「結論として、SARS-CoV-2 S-RBD は、エンドリソソーム経路を通じて ACE2 を介して取り込まれ、IFN 応答遺伝子を上方制御し、ヒト iPSC-CM の ISGylation を促進しました。」 https://t.co/C1ktnV7EEG
@a_kruschke - A.Kruschke
🤔▪️著者らは、心筋炎の問題に明確に取り組んでいます。 予防接種。 しかし、彼らが使用したスパイクタンパク質の量は、mRNA ワクチンから予想される量より 10,000 倍多かったです。
@a_kruschke - A.Kruschke
「イメージング実験と転写プロファイリングに使用された S-RBD の濃度 (> 600 ng/mL) は、推定される血清濃度よりも低かった SARS-CoV-2 感染後の S タンパク質濃度 (2500 ～ 17,500 ng/mL) ですが、mRNA ワクチン接種後の濃度 (20 ～ 100 pg/mL) よりも高かったです。」
@a_kruschke - A.Kruschke
🤔▪️この研究は、症候性心筋損傷に関して特に興味深いです。 SARS-CoV-2感染後。 ウイルスの複製がもはや起こっていないにもかかわらず、スパイクタンパク質が長期間検出され得ることは他のところで示されています。
@a_kruschke - A.Kruschke
この研究で使用されたスパイクタンパク質の量は感染時よりも 3 ～ 4 倍少ないため、スパイクに匹敵すると推定しています。 新型コロナウイルス感染症後の患者におけるタンパク質残基。
@a_kruschke - A.Kruschke
🤔🤔🤔 私の個人的な結論: 重要な基礎研究であり、感染後の晩期心臓症状を理解するための🧩確実な研究です。 mRNA の場合は、数桁の違いがあるため、これは困難です。
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
Lymphatic system... 🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼🪼 ... has always been underestimated in medicine. I think it's worth treating LongCovid patients by keeping in mind their lymphatic drainage problems. Not every edema is cardiovascular.
@a_kruschke - A.Kruschke
Let me start with the simple, (because mechanics) part. As nearly all people are vaccinated, often repeatedly, it's worth to look at their effects first. Later I will focus on SARS-CoV-2 infection.
@a_kruschke - A.Kruschke
Lymphatic swelling is also a dilemma for radiologic diagnostics in cancer patients. Lymphnodes are essential in tumor staging for correct therapy.
@a_kruschke - A.Kruschke
This article recommended an increase in the follow-up imaging interval from 4–12 weeks to more than 12 weeks, as they found lymphadenopathy for several months after vaccination. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096715/#r5
@a_kruschke - A.Kruschke
An Israeli study, published in March 2021 measured hyper reactive lymph nodes by PET-CT, after BioNtech Pfizer vaccines. Their astonishing findings were hyperreactive supraclavicular lymphnodes in 9% of participants after the second injection. 💥 👇 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003894/
@a_kruschke - A.Kruschke
Hyperreactive lymph nodes means swelling, and also diminished the normal lymph flow. It's a mechanical problem. Similar to flooring, the transport of ugly substances will be hindered.
@a_kruschke - A.Kruschke
Supraclavicular, you'll also find "Virchow's node", last lymph nodes station of the main lymph vessel of our body (ductus thoracicus). Ductus thoracicus carries the lymph of the entire lower and upper left half of the body. (Red markings is supraclavicular lymph nodes)
@a_kruschke - A.Kruschke
👆 the picture is taken from this article. Lymphadenopathy (enlarged lymph nodes) https://aneskey.com/lymphadenopathy-2/
@a_kruschke - A.Kruschke
Very interesting details about the way of LNP-coated mRNA vaccines is found in this article, written by professor Miyazakia The lymphatic system and COVID-19 vaccines Masayuki Miyasaka (2022) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630830/
@a_kruschke - A.Kruschke
Due to their size, there is the "remarkable feature of the COVID-19 mRNA vaccines is that they can be readily incorporated into the lymphatic system" [..] as "particles with a size range of 10 to 100 nm readily enter into the lymphatics."
@a_kruschke - A.Kruschke
[..] "In the draining LNs, although most phagocytic cells can internalize the mRNA vaccine, macrophages within the subcapsular sinus and dendritic cells (DCs) within the interfollicular area are the main groups that abundantly take up specific antigens."
@a_kruschke - A.Kruschke
As professor Miyazaka concludes, "mRNA translation in muscle cells does not seem to play a major role in the induction of protective immune responses against SARS-CoV-2." So the reaction of lymph nodes are essential for mRNA's effective translation.
@a_kruschke - A.Kruschke
There's another, more critical problem, that apparently is linked to the spikeproteins, as also described for AstraZeneca vaccine. SARS-CoV-2 is not only targeting the epithelial cells, but also the inner layer of the lymphatic vessels.
@a_kruschke - A.Kruschke
Fibrin clots were also found in lymphatic vessels in lungs. It correlated with the presence of intralymphatic NETs. https://ashpublications.org/bloodadvances/article/6/24/6249/486280/Lymphatic-coagulation-and-neutrophil-extracellular
@a_kruschke - A.Kruschke
Researchers "...found abundant evidence of intravascular and interstitial coagulation, and interestingly, many intact lymphatic vessels also contained fibrin clots (Figure 1). " https://t.co/ofVe0zFIop
@a_kruschke - A.Kruschke
For explication of NETosis please refer to DR.DOGGIE's description 👇 in blood vessels. https://t.co/i4cGLqJDgj
@a_kruschke - A.Kruschke
For treatment of LongCovid patients, it will be useful to keep in mind that internal organs are also drained by the lymphatic system. Swelling of guts or ureter may lead to secondary effects like malassimilation of nutrition, obstruction and nephropathy.
@a_kruschke - A.Kruschke
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@a_kruschke - A.Kruschke
この時点で、患者が診療所に行くべきであることは明らかです。 しかし、特によく訓練されたアスリートが注意すべき兆候はありますか? 私は心筋炎の経験からも話し、格闘技や競技スポーツを長年練習してきました。/..1
@a_kruschke - A.Kruschke
../私が言う「アスリート」とは、学生時代から厳しいトレーニングを積み、週5時間以上の集中トレーニングを行っている人を指します。 😅😅😅これらの人々は、特に成長期に集中的にトレーニングを行うと、心臓が肥大します💓. /..2 https://ja.m.wikipedia.org/wiki/%E3%82%B9%E3%83%9D%E3%83%BC%E3%83%84%E5%BF%83%E8%87%93
@a_kruschke - A.Kruschke
../ この心臓の肥大は、多くの場合、トレーニング セッションの終了後も後退しません。そのため、私は元アスリートにも話をしています。 残念ながら、これらのアスリートの心臓は、通常の心臓よりも心筋炎にかかりやすいのです。これはコロナウイルス以前から存在し、/..3
@a_kruschke - A.Kruschke
../同僚の心臓突然死を記憶しているアスリートも少なくない。コロナウイルスのワクチン接種によりリスクが大幅に上昇したため💉、アスリートが亡くなる前に心筋炎を見分ける方法を説明したいと思います。/..4
@a_kruschke - A.Kruschke
../ 心筋炎とは、心筋の炎症を意味します。 (-itis は最後の音節であり、炎症反応を意味します。) 心筋炎は、体内で炎症反応を引き起こす細菌、ウイルス、またはワクチンによって引き起こされる可能性があります。 場合によっては、実際の感染から数週間後まで体が反応しません。/..5
@a_kruschke - A.Kruschke
/..したがって、アスリートとして、感染後の心筋炎の可能性を常に考慮することが重要です。 一般に、危険が高まるこの段階は約 6 週間続きます。/..6 https://www.herzstiftung.de/infos-zu-herzerkrankungen/herzmuskelentzuendung/ursachen
@a_kruschke - A.Kruschke
/..心筋炎は診断が難しい。 MRI と生検のオプションが行われることはめったにないので、アスリートは「血液検査と超音波検査は正常です」という声明だけに頼るべきではないと思います。 アスリートは自分の体を知っているので、彼の話を聞いてください❗🫠/..7
@a_kruschke - A.Kruschke
/..心筋炎の徴候 (運動選手の場合): 💓 パフォーマンスが 10% 以上制限される、 💓 脈拍が異常に増加する、 💓 安静時の心拍数が 70/分を超える。 💓重要❗ 日中（通常の仕事）の気温は夕方（ベッド）よりも高い。 ...夕方の気温が 0.5°C 高くなる通常の 1 日のコースが逆転します! /..8
@a_kruschke - A.Kruschke
/..❗💓❗💓❗💓私が言ったように、これらは兆候であり、決定的な診断ではありません. 医師の診察を受け、それまですべてのスポーツ (サイクリングを含む) を中止してください。 医師が心筋炎を明確に診断していなくても、体の世話をしてください. 症状が続く場合は、/..9
@a_kruschke - A.Kruschke
/..スポーツを6週間完全に禁止することをお勧めします（自分の祖母であるかのように行動してください...） すでに傷ついた心筋細胞はもう修復できないので、なるべく数を減らすようにする。スポーツ禁止というのはそういうことです。/10. 💓💓💓💓💓💓💓💓
@a_kruschke - A.Kruschke
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@a_kruschke - A.Kruschke
💓心筋炎 🇯🇵ワクチン接種（mRNA）を受けた2人対ワクチン接種を受けていない無症状の人々を対象とした研究。 無症候性 SARS-CoV-2 ワクチン接種済みおよび非ワクチン接種患者における PET/CT での心筋 18F-FDG 取り込みの評価 https://pubs.rsna.org/doi/10.1148/radiol.230743?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed…
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
Conclusion "Compared to nonvaccinated patients, asymptomatic patients who received their 2nd vaccination 1-180 days prior to imaging showed increased myocardial FDG uptake on PET/CT." https://t.co/HKKNB1KfsZ
@a_kruschke - A.Kruschke
朗報：リバーシブルです💓❣️ 「2回目の[..]ワクチン接種後1～180日後にPET/CTを受けた無症候性患者は、ワクチン接種を受けていない患者と比較して画像上の心筋[..]取り込みの増加が示されましたが、ワクチン接種後180日以上経過して画像化された患者ではそうではありませんでした。」
@a_kruschke - A.Kruschke
* 💓💓💓今回の研究は、無症状の人々のリスクが高まる期間について重要な情報を提供する。 もちろん症状のある患者にも。 これまでのところ、他のウイルス性心筋炎の例に基づいて、3か月で十分だと考えていました。 https://t.co/gy3gXnUNmu
@a_kruschke - A.Kruschke
‼️‼️💓💓どうやら、SARS-CoV-2の場合は、細菌性心筋炎の場合と同様に、丸6か月間（180日間）のスポーツ禁止が必要のようだ。🤔🤔🤔
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
💓 myocarditis 🇯🇵 study in x2 vaccinated (mRNA) vs unvaccinated asymptomatic people. Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2-vaccinated and Nonvaccinated Patients https://pubs.rsna.org/doi/10.1148/radiol.230743?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed…
@a_kruschke - A.Kruschke
@bioerorist
@a_kruschke - A.Kruschke
🐌 👀 Japanese site for LongCovid information. Different techniques for treatment are described, for doctors and patients. Very interesting approaches. Some videos in English, or can be translated by using the YouTube subtitles function. 🐌🐌🐌. http://longcovid.jp
@a_kruschke - A.Kruschke
@1goodtern @HarrySpoelstra @kasza_leslie
@a_kruschke - A.Kruschke
A response to Emmanuel @ejustin46, who doubts my statements.😊
@a_kruschke - A.Kruschke
First, let me introduce a paper, published in December 2022 by the inventors of BioNTech/Pfizer vaccine, with co-authors from the UK, Israel and Germany. I hope, nobody will suspect the authors being "anti-Vaxx".
@a_kruschke - A.Kruschke
Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T-cell recognition epitopes https://www.biorxiv.org/content/10.1101/2022.12.15.520569v1.full
@a_kruschke - A.Kruschke
The authors " investigated neutralizing activity of immune sera from individuals who received three or four doses [..] mRNA COVID-19 vaccines (BNT162b2/mRNA-1273 homologous or heterologous regimens) w/o subsequent breakthrough infection by different Omicron sublineages."
@a_kruschke - A.Kruschke
Findings: "Together these data show that [...] sublineages BA.2.75.2 and XBB have evolved to largely evade neutralizing antibody responses in vaccinated individuals and in those with breakthrough infections with previous and currently circulating Omicron sublineages."
@a_kruschke - A.Kruschke
"We found that B-cell epitopes [..] were altered [..] particularly [..] in BA.2.75.2 and XBB (≤12% conservation), .."
@a_kruschke - A.Kruschke
".. 80% of CD8+ and ~70% CD4+ T-cell epitopes were fully conserved in Omicron sublineages including [..], BQ.1.1, and XBB [..], suggesting that T-cell responses against Omicron sublineages may remain largely intact in individuals immunized with wild-type strain-based vaccines."
@a_kruschke - A.Kruschke
The second paper I will present is a study from China, published in Cell in May 2023 confirmed the findings of Miuk et al., investigating the sera of probands after triple vaccination with an inactivated vaccine.
@a_kruschke - A.Kruschke
Omicron BQ.1.1 and XBB.1 unprecedentedly escape broadly neutralizing antibodies elicited by prototype vaccination https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00543-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124723005430%3Fshowall%3Dtrue "Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1."
@a_kruschke - A.Kruschke
"Structure analysis and functional verification reveal that N460K and F486V/S contribute to the increased neutralization resistances of BQ.1.1 and XBB.1[..]."
@a_kruschke - A.Kruschke
The third study I want to present, was published by Professor Yoshihiro Kawaoka's group (University of Tokyo), in Lancet, January 2023. Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00816-7/fulltext.
@a_kruschke - A.Kruschke
The authors "evaluated the neutralising ability of antibodies in plasma from three different groups against BQ.1.1 and XBB clinical isolates."
@a_kruschke - A.Kruschke
They compared individuals with (1.) three doses of the mRNA BNT162b2 and/or mRNA-1273. (2.) four doses of the mRNA BNT162b2 and/or mRNA-1273. (3.) three doses of monovalent BNT162b2 or mRNA-1273 before the BA.2 breakthrough infection.
@a_kruschke - A.Kruschke
They concluded "that the omicron sublineages BQ.1.1 and XBB effectively evade current humoral immunity induced by mRNA vaccines or natural infection." --- I will not summarize the characteristics of T-cells but leave this to others.
@a_kruschke - A.Kruschke
Now I'll focus on clinical outcome. As mentioned above, the effect of neutralizing antibodies is negligible for XBB. However, the T-cell response remains intact. Therefore, we tumbled back into a situation similar to pre-vaccine times. Let's look at some research from 2020.
@a_kruschke - A.Kruschke
First, I want to present a study of Mount Sinai, New York, published in Nature, August 2020. An inflammatory cytokine signature predicts COVID-19 severity and survival https://www.nature.com/articles/s41591-020-1051-9
@a_kruschke - A.Kruschke
The authors showed in hospitalized patients, "that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively)."
@a_kruschke - A.Kruschke
"Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death."
@a_kruschke - A.Kruschke
The authors also show the effect of different treatment on outcome and interleukin levels. The findings were confirmed by a smaller second group.
@a_kruschke - A.Kruschke
For involvement of interleukin in "white lung", I'll just leave two interesting papers . From Ghent University (Belgium): The pathophysiology of ‘happy’ hypoxemia in COVID-19 https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-020-01462-5
@a_kruschke - A.Kruschke
And a case report: Happy hypoxia in critical COVID-19 patient: A case report in Tangerang, Indonesia https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.14619
@a_kruschke - A.Kruschke
I've focused on showing the similarities today and 2020. For me, that's the main message: XBB is equalizing the risk for the group of 30-60 years old people. Other effects look minor or interact with each other. Let's do more details later. Let's do Science, not Philosophy.
@a_kruschke - A.Kruschke
Next chapter. I will introduce some fictional characters. It will bring the explanation a little closer to everyday life. Let's start with two characters. I would like to emphasize that these are descriptions for illustration only, not criticism.
@a_kruschke - A.Kruschke
All persons acted according to their own or official rules and "did everything right". However, everyone finds themselves in a different situation. This is my starting point. Let's see what are the pros and cons.
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
Second is Maria Virginia (without any antigen contact) (You'll find a more detailed description in the 🔗 links above. )
@a_kruschke - A.Kruschke
Let's talk first about Maria Virginia. No vaccine, no infection. So no memory or plasmacells for SARS-CoV-2. Maria has an intact immune system. So, she's not unprotected.
@a_kruschke - A.Kruschke
She also owns some plasmacells for non-SARS-CoV-2 coronavirus (hCoV) she catches during her live. Some of these hCoV-memories might be crossreacting with SARS-CoV-2.
@a_kruschke - A.Kruschke
Lets compare to Pierre. Since both the infection with BA.2 and the vaccination with bivalent BA.5 are more than 6 months in the past, the neutralizing antibodies can no longer be detected. Let's say they don't exist anymore.
@a_kruschke - A.Kruschke
But Pierre got B-memory/plasma cells of Wuhan type (WT) from vaccination. These will remain for years or even lifelong. He also got memory T-cells.
@a_kruschke - A.Kruschke
The survival time of memory cells after a single antigen contact was previously assumed to be only a few months. However, a Canadian study could still detect memory cells of the different types after 8 months. https://www.science.org/doi/10.1126/science.abf4063
@a_kruschke - A.Kruschke
The study measured convalescents of WT, i.e. comparable to the memory cells induced by mRNA vaccine.
@a_kruschke - A.Kruschke
Back to our protagonist.... Due to his infection with Omicron BA.2, Pierre also has B-memory cells against N-protein. (Just keep it in mind, well see them again later...) Memory cells against S-protein-BA.5 were formed very little due to immune imprinting.
@a_kruschke - A.Kruschke
Today, let's be prepared for infection by XBB. Neutralizing antibodies don't play a rule any longer. More important now is the other immune reactions.
@a_kruschke - A.Kruschke
Let's skip the theme of cross reactivity of non- SARS-CoV-2 coronavirus. Pierre and Maria Virginia both live in Europe and have never been infected by SARS-CoV (2003) or MERS. The other hCoV-memories should be comparable for both protagonists.
@a_kruschke - A.Kruschke
It was shown that memory T-cell still fit on XBB.
@a_kruschke - A.Kruschke
".. 80% of CD8+ and ~70% CD4+ T-cell epitopes were fully conserved in Omicron sublineages including [..], BQ.1.1, and XBB [..], suggesting that T-cell responses against Omicron sublineages may remain largely intact in individuals immunized with wild-type strain-based vaccines."
@a_kruschke - A.Kruschke
Maria has none. Pierre's memory T-cells will react quicker and at higher level than Maria's naive tell population.
@a_kruschke - A.Kruschke
The following article published in April 2022, compared the response of naive (blue) vs. memory T-cell response. Pierre (red line) has a clear advantage in time, compared to Maria (blue line). The advantage consists in 2 weeks (CD4+) to 3 weeks (CD8+).
@a_kruschke - A.Kruschke
As CD4+ cells act on B-cells activation, Pierre will get neutralizing antibodies about 2 weeks earlier than Maria. This is important for the outcome in moderate to severe illness. Also, Pierre's cytotoxic T-cell activity against the virus is faster and higher than Maria's.
@a_kruschke - A.Kruschke
Disentangling the relative importance of T cell responses in COVID-19: leading actors or supporting cast? (April 2022). (Please keep in mind, article was published in the first phase of Omicron, where neutralizing antibodies still matched partly) https://www.nature.com/articles/s41577-022-00716-1
@a_kruschke - A.Kruschke
All good for Pierre? As presented above, the characteristics of SARS-CoV-2 acute infections consist in severe cytokinestorm during the first days. Cytokinstorm is expression of dysregulated T-cell response.
@a_kruschke - A.Kruschke
First, I want to present a study of Mount Sinai, New York, published in Nature, August 2020. An inflammatory cytokine signature predicts COVID-19 severity and survival https://www.nature.com/articles/s41591-020-1051-9
@a_kruschke - A.Kruschke
Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19 (November 2020, Norway) https://www.nature.com/articles/s41598-020-78710-7
@a_kruschke - A.Kruschke
"Severe SARS-CoV-2 infection cause a dysregulated immune response resulting in excessive production of inflammatory cytokines and chemokines that contributes to the pathogenesis. "
@a_kruschke - A.Kruschke
"Indeed, viral evasion of initial immune responses and a subsequent immunological misfiring causing collateral tissue injury in infected organs seem to play major roles in severe COVID-19. "
@a_kruschke - A.Kruschke
"Further, evidence suggests that a suboptimal or inappropriate T cell response producing pro-inflammatory cytokines may contribute to tissue damage in critically ill COVID-19 patients."
@a_kruschke - A.Kruschke
Finally, because of quicker and higher T-cell response, Pierre is at higher risk for cytokinestorm during the first 2 weeks.
@a_kruschke - A.Kruschke
The B-memory cell response lacking in XBB, this might bring a different risk profile in vaccinated /preinfected patients (Pierre), compared to naive patients (Maria Virginia). The risk of longer infection is certainly higher for Maria.
@a_kruschke - A.Kruschke
But it's necessary to be aware of "happy hypoxia" in vaccinated/preinfected patients. Are we aware of this?
@a_kruschke - A.Kruschke
Does everyone know the other symptoms of cytokinestorm? It's not to be scared, but to be prepared. https://my.clevelandclinic.org/health/diseases/22700-cytokine-release-syndrome
@a_kruschke - A.Kruschke
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@a_kruschke - A.Kruschke
🌊🌊🌊🌊👀👀👀 https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000121431_00461.html
@a_kruschke - A.Kruschke
これらは7月12日に公開されたデータです。https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000121431_00461.html
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
👀🧐 ヒト PBMC [ヒト末梢血単核球] はスパイクタンパク質に応答して脂肪滴を形成する (🇩🇪🇨🇭2023) Human PBMCs [human peripheral blood mononuclear cells] Form Lipid Droplets in Response to Spike Proteins (🇩🇪🇨🇭2023) https://mdpi.com/2076-2607/11/11/2683
@ThailandMedicaX - Thailand Medical News
COVID-19 News: German And Swiss Study Finds That Human PBMCs Form Lipid Droplets In Response To SARS-CoV-2 Spike Proteins! https://www.thailandmedical.news/news/covid-19-news-german-and-swiss-study-finds-that-human-pbmcs-form-lipid-droplets-in-response-to-sars-cov-2-spike-proteins #COVID19 #News #Research #SARSCoV2 #PBMCs #USA #America #Germany #Switzerland #London #Thailand #Canada #France #Israel #Gaza #India
@a_kruschke - A.Kruschke
@bioerorist @HarrySpoelstra @DavidJoffe64 @keisuke4713 @gadboit @sabuchanhakoda1
@a_kruschke - A.Kruschke
💉👀. WHO: New initiative launched to advance mRNA vaccine development against human avian influenza (H5N1) 29 July 2024 https://who.int/news/item/29-07-2024-new-initiative-launched-to-advance-mrna-vaccine-development-against-human-avian-influenza-(h5n1)…
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
The most dangerous animals in the world 🦇🦇🦇 🧐🤔👀
@CAPublicHealth - California Department of Public Health
CDPH is reminding Californians to be cautious around wild or unfamiliar animals after a Fresno County resident, suspected to have been bitten by a bat in Merced County, died from a rabies infection. Learn more: https://www.cdph.ca.gov/Programs/OPA/Pages/NR24-040.aspx
@a_kruschke - A.Kruschke
@reSeeIt save conversation
@a_kruschke - A.Kruschke
💉🧠👀 COVID-19ワクチン接種後の多巣性髄膜脳炎 (🇯🇵 2024) Multifocal meningoencephalitis after vaccination against COVID-19 (🇯🇵 2024) h/t @K9FCR @AaronOtsuka https://onlinelibrary.wiley.com/doi/10.1111/pin.13491
@a_kruschke - A.Kruschke
Interesting japanese discussion 👇 https://t.co/w60T0tnt1Z
@K9FCR - Stray
84歳日本人男性、４回目接種10週間後死亡。論文タイトルは 「コロナワクチン接種後の多巣性髄膜脳炎」 図4&5スパイクSとヌクレオカプシドNの免疫染色 a)d)は陽性対照（おそらくコロナ感染者の肺）でSもNも陽性 b)e)視床とc)d)橋と、図5 下垂体と副腎、いずれもS陽性、N陰性、つまりワクチン由来S！ https://t.co/ugajrthnDz
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG4 class switch was not observed following four doses of Novavax protein-based SARS-CoV-2 vaccine & IgG3 levels were 10x higher them after mRNA vaccines. https://www.journalofinfection.com/article/S0163-4453(24)00053-7/fulltext
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG3 produced by adenovirus vector vaccines and NVX protein subunit vaccines are 12% of total IgG antibodies but do 80% of the work neutralizing SARS-CoV-2. Natural infection also produce IgG3 predominantly.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 But mRNA vaccines class switch to IgG4 antibodies that lack certain FC related functions and are not as good at forming immune complexes. But they are also less inflammatory. If your first two doses were mRNA the class switch has already been fixed.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 Since the class switch involves genetic deletion of IgG1, IgG2 and IgG3 there is no way for a memory IgG4 B-cell to ever switch back from IgG4 to IgG3. So the only way to resolve this would be for these memory B-cells to wane entirely which they eventually will.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 mRNA vaccines induce memory B-cells but not long lived plasma cells (LLPCs). So they may only last a few years before new B-cells are recruited.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 Interestingly if we block IL-4 and IL-13 receptors & tumor necrosis factor this IgG4 class switching doesn't occur during mRNA vaccination. And it doesn't occur using any other vaccine platform. So it is mRNA specific. https://www.medrxiv.org/content/10.1101/2023.09.29.23296354v1
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 The class switch even occurs if you first have two vector vaccination and then to mRNA vaccinations. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1309997/full
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 IgG4 only exists in certain primates and Fab arm exchange only exists in humans due to Arg409 (versus lysine). We simply lack a complete context of why this might be advantageous to humans.
@RolandBakerIII - Roland Baker
@systematic_fun @a_kruschke @newstart_2024 So it is clearly an issue with the mRNA vaccines but we don't know why specifically. Speculation includes elements of the LNP, pseudouridine use or simply elevated expression of spike for much longer than expected and longer than adenovirus. The last option seems plausible.
@a_kruschke - A.Kruschke
@RolandBakerIII @systematic_fun @newstart_2024 Missed the last one. It's intriguing that 2xAZ+2xmRNA show also the IgG4 effect. I would favor the third possibility: PEG-related. AZ contains no LNP, but the polysorbate80.
@gadboit - Guy Gadboit
in the wild. At low prevalence, but wide use of this antibody could soon change that... The "holy grail" for a broadly neutralizing antibody is: can you find a place to neutralize the virus that it *can't* mutate with destroying itself? The answer is still no. If it was that...
@gadboit - Guy Gadboit
easy the virus probably wouldn't have made it this far through evolution. Perhaps more interesting than news of yet another antibody therapy that won't work for long is the delivery mechanism. According to the reference for the new tech, antibody treatments are great because...
@gadboit - Guy Gadboit
they are safe and work at once. So why not deliver the abs instead via mRNA LNPs? This way the body's own cells make the antibodies, after a short delay, using far more complex biological pathways, with much greater potential for interesting side-effects? Although I think...
@gadboit - Guy Gadboit
mRNA vaccines have a lot to recommend them, including that they are a better emulation of a live infection than some other vaccine designs, resulting in the right immune response, using mRNA to create *antibodies* is completely different. Now we have other cells, mostly...
@gadboit - Guy Gadboit
monocytes producing antibodies, something they never usually do. LNPs have a strong adjuvant effect, so will we end up with the body making anti-idiotypic antibodies? We still have very limited knowledge of why mRNA vaccines have the side-effects that they do, but some may...
@gadboit - Guy Gadboit
be related to the LNPs, and therefore shared with this new therapy. The reason traditional antibody therapies are safe is because they are just antibodies. Obviously you can't assume this will still be the case if you completely change basically everything about the treatment...
@gadboit - Guy Gadboit
So what is the reason to use mRNA to create antibodies? My cynicism notwithstanding of course it isn't really to reduce safety. According to the reference, it's much cheaper. I trust those savings will be passed on to the consumer. END. h/t @a_kruschke
@a_kruschke - A.Kruschke
@gadboit Finding the "holy grail" by anticipating the future? That sounds more like Harry Potter to me than anything else. ..
@a_kruschke - A.Kruschke
@gadboit .. To be honest, antibodies are a very difficult therapeutic tool for COVID. Perhaps helping in very short time. But I also see it as very critical for the patient himself. Nobody can prevent reinfections. https://www.biorxiv.org/content/10.1101/2023.11.21.567575v1.full ..
@a_kruschke - A.Kruschke
@gadboit ... Pack this then as mRNA into LNP, which has now shown difficult in terms of BBB passing and myocarditis discussion? mRNA with or without frameshift potential by pseudouridine?
@a_kruschke - A.Kruschke
@gadboit .. mRNA technology still has no stop codons. Using this for a virus with known ADE (look at SARS-1 and MERS, too...)? Ongoing long-term production of an mRNA-coded antibody that will meet a mutated variant in some months? Any other ideas to kill patients more quickly 🙊🙊🙊?
@a_kruschke - A.Kruschke
コンブ Kombu Dietary Supplementation with Low-Molecular-Weight Fucoidan Enhances Innate and Adaptive Immune Responses and Protects against Mycoplasma pneumoniae Antigen Stimulation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471482/
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
How to make Dashi 😋 Soup stock from kelp (Kombu). https://www.justonecookbook.com/how-to-make-dashi-jiru/
@a_kruschke - A.Kruschke
Kelp/Kombu contains a lot of vitamins and minerals. (Translated from https://ja.m.wikipedia.org/wiki/%E3%82%B3%E3%83%B3%E3%83%96)
@a_kruschke - A.Kruschke
Thank you for the recipe @Salalalove. In different parts of Japan, different tastes.
@Salalalove - Salala
@a_kruschke マイコプラズマに！？本当ですか！😳 関西では特に、昆布を使った出汁が好まれます。 簡単なものなら、うどんが美味しいですね😋 https://www.kobayashi-foods.co.jp/washoku-no-umami/udon-dashi
@a_kruschke - A.Kruschke
Salmon cooked in kelp rolls. 😋
@Salalalove - Salala
@a_kruschke 昆布巻き😋 https://www.nissui.co.jp/recipe/00775.html
@a_kruschke - A.Kruschke
https://www.nissui.co.jp/recipe/00775.html
@a_kruschke - A.Kruschke
Cold rice balls with sour plums and seaweed.😋🙏
@momo61117806 - momo BH
@a_kruschke 梅干しと昆布のおにぎり。 簡単で美味しく作れると思います☺️https://www.kurashiru.com/recipes/2b247189-b641-474c-ad5a-f41a9cb7f880
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@keisuke4713 - tune
中医学 昆布は化痰軟硬 https://www.uchidawakanyaku.co.jp/tamatebako/shoyaku_s.html?page=241 痰飲(水毒)を去り、塊を柔らかくする
@a_kruschke - A.Kruschke
コンブ Kombu Dietary Supplementation with Low-Molecular-Weight Fucoidan Enhances Innate and Adaptive Immune Responses and Protects against Mycoplasma pneumoniae Antigen Stimulation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471482/
@keisuke4713 - tune
コロナも💉も甲状腺がやられるが ヨードが大切 https://t.co/4ccNsV7WM1
@keisuke4713 - tune
@NA19H5hHBdTdrDr @AichanwithKonan @sabuchanhakoda1 @a_kruschke 実はコロナ禍に昆布問題は繋がります マフィア薩摩藩(幕府に木曽川の泛濫工事で大借金させられた)返済計画に、昆布・沖縄の黒砂糖で清国(中国)と密貿易 昆布は北海道から北前船で本州に運ばれ、富山の売薬商人を介して薩摩にもたらされ、琉球、清国まで流通 中医学で軟堅化痰⇨甲状腺結節等を散らす https://t.co/1p7tADWT9T
@a_kruschke - A.Kruschke
@keisuke4713 いつもありがとうございます👏👏。 それは大きな宝箱です。 🤣 リストに何かがありません。 この時期に人々に希望を与える。 (国際グループはパンデミックのトラウマを利用して死の恐怖を煽っています。🤬🤬🤬) 昆布を使った料理は抗うつ薬です。 🤣すでに動き始めています。
@keisuke4713 - tune
@a_kruschke Frohes neues❗️ この絵の意味を簡単に教えていただけると有難いです 遠くの🇩🇪を身近に感じることができ、有難いです 🙇♂️🙏
@a_kruschke - A.Kruschke
@keisuke4713 🤣🤣🤣🤣🤣🤣🤣🤣🤣🤣🤣 多次元画像の意味を簡単に説明してください...運試しをします。
@a_kruschke - A.Kruschke
@keisuke4713 写真は、シュヴァルツヴァルトのフィリンゲン シュヴェニンゲンにある教会の内陣です。 少し違った方法で街の物語を写真で伝えます。 画像は、アジアのスクロール ペインティングに似た構造になっています。 部門を超えた部門で考えてください。 下の 4 分の 1 はフィリンゲンの街を表しており、...
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Counting 5 days of incubation time also for pat4, it's Dec 27th, where he was still in Shenzhen. The family was traveling on Dec 29th. Even a travel related (airport, taxi,...) infection is rather unlikely for pat4, as 3 days is a rather short incu time.
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf For the relatives other than rel1(baby at hospital), they all got I'll the same day, which points to a family meeting/evening meal with an infectious adult. The incubation time of the relatives matches best the infectious period of pat4 (yellow), less for pat3. https://t.co/F201CiYw1q
@Engineer2The - TheEngineer2 🇨🇦
@a_kruschke @BillyBostickson @gadboit @mbw61567742 @gdemaneuf There are other instances where onsets differ by 3 days. They mostly occur during husband/wife pairing like this from Li et al 2020. M49 and F48 are husband and wife. The increased exposure time likely shortens time to onset. https://t.co/1UgZsJVyZO
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Do you have a reference please? Unfortunately, the problem with many papers is the lack of sound experience from field work.
@Engineer2The - TheEngineer2 🇨🇦
@a_kruschke @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia DOI: 10.1056/NEJMoa2001316 https://www.nejm.org/doi/full/10.1056/NEJMoa2001316
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Thanks. I'll have a look.
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Nice study. I remember the figures. One of the first studies that provided useful epidemiological indicators despite the poor data situation. (Let's keep aside the affiliations of the authors.)
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf Agreed, there's one of the clusters with an incubation time of 3 days, but it's in the cluster 4. https://t.co/eGUPurDd2D
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf The yellow cases could be infected at the Wet market, too. https://t.co/qPRhJ7lQjb
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf However, the authors calculated the mean incubation time even higher. "The duration from illness onset to first medical visit for 45 patients with illness onset before January 1 was estimated to have a mean of 5.8 days (95% CI, 4.3 to 7.5),.."
@a_kruschke - A.Kruschke
@Engineer2The @BillyBostickson @gadboit @mbw61567742 @gdemaneuf This of course doesn't exclude the possibility of 3 days incubation time, but it is outside their CI. Possible, but rare, and therefore questionable.
@a_kruschke - A.Kruschke
Oarfish 🧐 Oarfish keep washing ashore in California. https://www.npr.org/2024/11/19/nx-s1-5196630/oarfish-california-japan-folklore
@a_kruschke - A.Kruschke
Is Japanese Folklore Concerning Deep-Sea Fish Appearance a Real Precursor of Earthquakes? (🇯🇵 2019) "...it can be concluded that a deep-sea fish appearance is not useful for disaster mitigation." https://pubs.geoscienceworld.org/ssa/bssa/article-abstract/109/4/1556/571628/Is-Japanese-Folklore-Concerning-Deep-Sea-Fish
@a_kruschke - A.Kruschke
The Legend of Japan’s ‘Earthquake Fish’ https://www.atlasobscura.com/articles/long-fish-predicts-earthquake-legend
@a_kruschke - A.Kruschke
「地震魚」リュウグウノツカイが泳ぐ珍しい姿、台湾沖で撮影https://forbesjapan.com/articles/detail/64768?read_more=1
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
😋🍬👀 納豆、大豆が健常成人の食後血糖値に与える影響 Effect of Intake of Natto and Soybeans on Postprandial Blood Glucose Levels in Healthy Adults (🇯🇵 2009) https://www.jstage.jst.go.jp/article/seikatsueisei/53/4/53_4_257/_article
@a_kruschke - A.Kruschke
"..the natto meal, and not the soybean meal, significantly suppressed the rise in blood glucose level at 60 min compared to the control meal. Furthermore, the area under the glucose curve from 0 to 120 min after the natto meal was significantly smaller than for the control meal." https://t.co/jKmi5mo29L
@keisuke4713 - tune
@a_kruschke 生命は微生物🦠の影響を受け、 ある時は不治の病や痛い目に遭い、 ある時は不治の病や悩みが解決する ご先祖代々、何千年も何白万も続いている🤔 また、微生物🦠の力で 再起する❣️ 彼らの知恵を上手く利用❣️ 上手に付き合って共存💪👏
@a_kruschke - A.Kruschke
@keisuke4713 言いたいことはわかるんですけどね。 🦠❣️💪✨ 注目はミトコンドリア。ベッドが 🛏️🪶快適になってはじめて、残りの微生物は再び家にいるような気分になる。 化石から学ぶことは多いですね。 https://t.co/auC6Z16Vnn
@a_kruschke - A.Kruschke
@keisuke4713 🦊day 2 / 2日目。 効果や副作用は！ 皮下のびまん性浮腫はやや減少し、組織はより可動的になっている。特に、手、前足、胸骨の前に顕著に現れる。 全く良くない‼️著しい体積負荷、頚静脈の鬱血。RR 150/100 😳 => 利尿↗️（トラセミド＋🍌+塩分）。今日はナットウキナーゼの半量（1000FU）のみ。
@a_kruschke - A.Kruschke
@keisuke4713 3日目 ❌ ナットウキナーゼ
@a_kruschke - A.Kruschke
@keisuke4713 Thank you 😊 I thought about it. Did continue today. Smell and taste are important in healing. 🦊1000FU 1 h ago. Feels good. 🙏
@a_kruschke - A.Kruschke
@keisuke4713 ...✅マトリックスからの水の動員は、すでに説明したように周辺から起こります。 🤢 問題は溶解物の除去です。 ローカル リアクション (temporary 10min ) 検索中およびハンド中。 通過時の結腸の腫れ; その結果、便秘になりやすくなります。 排尿と発汗も局所的に刺激します。 全身アレルギーなし.
@a_kruschke - A.Kruschke
@keisuke4713 🦊day 12 /12日目：固定リンパ浮腫の解消が肘と中下腿に達している👍。1000FU+ Cuを継続（＋利尿＋PREDが必要）。
@a_kruschke - A.Kruschke
@keisuke4713 アイデア: 新しい堆積物を防ぎ、組織の圧力を高めます。 また、玉ねぎをたくさん食べる => 発汗 ↗️. RRは正常です。
@keisuke4713 - tune
@a_kruschke 玉葱で発汗するんだ⁉️ 辛味甘味で辛甘化陽⇒発汗 あり得ますが、考えた事無かった❗️ しかも、気圧絡み❗️
@a_kruschke - A.Kruschke
@keisuke4713 "Lauk" ( pronounce: lö:ok)北欧とアルプスでは神聖な植物です。 北欧神話 : laukは地球上の他のすべての植物よりも先に成長した. 薬には3つの異なる応用形態があり、季節に応じて使用されます. 夏☀️🌿タマネギ Zwiebel 生の形でのアプリケーション。 品質：スパイシー、ウォーター、クール。 ...
@a_kruschke - A.Kruschke
@keisuke4713 ..虫刺され、浮腫、発熱に対して。 秋、冬🍂❄️タマネギ Zwiebel 蒸したり焼いたりして使います。 品質：甘く、暖かく、水分を移動します。 効能：せき、肺炎、震え、虚弱・心臓によるむくみ。 😋秋に食べる：オニオンケーキ（温めて食べる）、若いワイン🍷と。https://www.chefkoch.de/rezepte/1716851280413039/Einfacher-Zwiebelkuchen.html ...
@a_kruschke - A.Kruschke
💉👀 小児におけるBNT162b2ワクチン接種から1年後に、非炎症性SARS-CoV-2スパイク特異的IgG4抗体の誘導が遅れて検出された Delayed Induction of Noninflammatory SARS-CoV-2 Spike-Specific IgG4 Antibodies Detected 1 Year After BNT162b2 Vaccination in Children(🇩🇪2024) https://journals.lww.com/pidj/fulltext/9900/delayed_induction_of_noninflammatory_sars_cov_2.959.aspx
@a_kruschke - A.Kruschke
The study included 14 healthy children, ages 5-11 years old. The authors measured IgG4 antibodies following two 💉BNT162b2 vaccination (= original Pfizer BioNTech vaccine).
@a_kruschke - A.Kruschke
Two children have been infected before the vaccination. None had more than mild postvaccination reactions. All children became infected with Omicron after the vaccination.
@a_kruschke - A.Kruschke
"The children’s antibody response 5 weeks after the second BNT162b2 vaccination was dominated by the IgG1 and IgG3 subclasses, which subsequently decreased over time."
@a_kruschke - A.Kruschke
" By contrast, IgG2 and IgG4 levels were relatively low at week 5 after the second vaccination and increased in frequency until the late follow-up for both S1 and RBD (Fig. 1A and B)" https://t.co/bOjHFi9gw7
@a_kruschke - A.Kruschke
" Specifically, S1- and RBD-specific IgG4 antibody levels increased significantly 1 year after the second vaccination compared to baseline (Fig. 1C and D)."
@a_kruschke - A.Kruschke
"In summary, we report on increased spike-specific IgG4 levels in children 1 year after BNT162b2 vaccination, such as the effect observed in adults."
@a_kruschke - A.Kruschke
The authors conclude: "IgG4 responses should gain more attention in health and disease, especially in the context of mRNA vaccination. Understanding the unusual mechanism triggering IgG4 production is crucial [..]."
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@keisuke4713 - tune
コロナが2020年春に突然何千人も🙏出したのはなぜ? https://dailysceptic.org/2022/10/06/why-did-the-coronavirus-suddenly-cause-thousands-of-deaths-in-spring-2020-when-it-had-been-hanging-around-quietly-all-winter/ コロナが遅くとも2019年秋までに世界中に検出されずに広がり始めた証拠多数 2019/9欧州で既に流行 2019/11🇧🇷25廃水から検出
@keisuke4713 - tune
茶番demic 2019/9欧州で既に流行 🇮🇹北部Lombardy州 2019年後半〜麻疹状eruption起こした患者サンプル コロナの分子的証拠https://www.sciencedirect.com/science/article/pii/S0013935122013068 156例435サンプル コロナ感染の分子証拠13人 陽性者2人はpandemic期(2/12、16.7%、2020/3～2021/3) 11人はpandemic前(11/44、25%、2019 /8～2020/2)
@keisuke4713 - tune
2019/11🇧🇷下水 SARS-CoV-2 RNA 存在 https://www.sciencedirect.com/science/article/pii/S0048969721012651?via%3Dihub
@keisuke4713 - tune
イングランド🏴とウェールズ🏴2019-20年の冬の目立たない終わりが左側（10週目前）にあり 春のサージ(その後の波)とのコントラストは明らか
@keisuke4713 - tune
なぜコロナは冬の間ずっと静か❓ 2020年春に多く🙏 コロナはインフルより深刻な🦠でない 過剰🙏は全て2020/2と3月にどう対応したかで起きた 2020年春🇮🇹北部 過剰🙏異常 https://www.eugyppius.com/p/jonathan-engler-on-anomalies-in-the 2019/8市中感染あった場合 →超過🙏率なかった理由 pandemic前の感染報告全ての論文で過剰🙏なしを無視
@a_kruschke - A.Kruschke
@keisuke4713 冬のコロナも静かではなかった。振り返ってみると、多くのケースを割り出すことができます。30代から50代の方が多かったですね。彼らは死ななかった。しかし、6週間も泪を流して...。症状について40℃以上の発熱が10日間続く、激しい咳が6週間以上続く、味覚・嗅覚の喪失、脳機能の低下（特に数学)/..1
@a_kruschke - A.Kruschke
@keisuke4713 /.. 北🇮🇹、／🇨🇭／西🇨🇵／、南🇩🇪。特に山間部。これらの地域の人々は、自分自身を治療します。医師はいない。/2.
@a_kruschke - A.Kruschke
@keisuke4713 多くの地方紙が報じている。そのうちの1つだけです。https://www.schwarzwaelder-bote.de/inhalt.colmar-noch-ein-frueher-corona-fall-im-elsass.61758b30-b80a-44fa-b18b-bd2c3659ddd3.html
@keisuke4713 - tune
@a_kruschke Elsass 🇩🇪語でエルザス 🇫🇷語でアルザス https://kotobank.jp/word/Elsass-1230550 面白い🙏
@a_kruschke - A.Kruschke
@keisuke4713 🇩🇪ELSASS 🇨🇵ALSACE ALSASS アルサス＝地元の方言。 意味：Alamannen アラマンニ（部族、地図年481）+ .から..SASS Sittingより。 現在でもスイスやドイツとの共通語になっている。 ELSASSは国🇹が変わることが多い🤣。 https://www.adalar.ch/pages/geschichte/blutgericht-zu-cannstatt.php 🟥= Alamannen アラマンニ
@a_kruschke - A.Kruschke
Molbio先生ありがとうございます 再接種をお考えの皆様へ、とても大切なツイート🧵👇です。 IgG4 の形成は、自己免疫疾患の発症に関して過小評価されるべきではありません。 コロナウイルスに関連するIgG4の研究は始まったばかりです。 今後数週間でさらに多くの結果が得られることを期待しています。
@a_kruschke - A.Kruschke
IgG4関連自己免疫疾患（オーモンド病、後腹膜線維症）に関する一般情報（シャリテ・ベルリンからの編集）https://nephrologie-intensivmedizin.charite.de/fuer_patienten/sprechstunden/igg4_assoziierte_autoimmunerkrankungen/#:~:text=Die%20IgG4%2Dassozierte%20Autoimmunerkrankung%20ist,Serumspiegeln%20die%20Krankheit%20identifiziert%20werden.
@a_kruschke - A.Kruschke
IgG4関連疾患 (IgG4-RD) https://www.msdmanuals.com/de-de/profi/erkrankungen-des-rheumatischen-formenkreises-und-des-bewegungsapparats/igg4-assoziierte-erkrankung/igg4-assoziierte-erkrankung
@a_kruschke - A.Kruschke
最初の症例報告では、後腹膜線維症とコロナウイルスワクチン接種との関係について議論しています。https://pubmed.ncbi.nlm.nih.gov/36814401/
@a_kruschke - A.Kruschke
後腹膜線維症は恐ろしい病気です。 これまでのところ非常にまれです。 腹部手術中に彼女を2回見ました。 組織は柔らかくはありませんが、貫通できない鎧に囲まれています。 冷凍カツレツを切ろうとしているようなものです。
@a_kruschke - A.Kruschke
🇯🇵 後腹膜線維症/骨膜炎の症例報告と治療。 ワクチン接種との関連は言及されていません。 ステロイド療法が奏効した広汎性後腹膜線維症の1例 A Case of Spreading Retroperitoneal Fibrosis Effectively Treated with Steroid Therapy https://www.jstage.jst.go.jp/article/ihj/advpub/0/advpub_22-470/_article
@a_kruschke - A.Kruschke
まれな後腹膜疾患のまとめ。 多くの場合、原因は不明です。 自己免疫/IgG4 の関与が議論されています。 後腹膜病変を伴う希少疾患 Seltene Erkrankungen mit retroperitonealer Beteiligung https://doi.org/10.1007/978-3-642-39940-4_114
@a_kruschke - A.Kruschke
@reSeeIt save Thread
@APazyryk - Altai Pazyryk
@mrmickme @RolandBakerIII Is there any benefit to IgG3 class switch induced by Novavax?
@notquitegonzo - notquitegonzo עם ישראל חי
@mrmickme @APazyryk @RolandBakerIII Forgive me for my lack of clarity and therefore question Does this indicate a risk for developing auto-immune disorders from nvx booster?
@RolandBakerIII - Roland Baker
@notquitegonzo @mrmickme @APazyryk Antibodies against IL-4, IL-13 receptors& tumor necrosis factor circumvent the class switch to IgG4 with mRNA vaccines. Clearly this is specific to mRNA vax and not ad vector and protein sub-unit vax. https://www.medrxiv.org/content/10.1101/2023.09.29.23296354v1
@RolandBakerIII - Roland Baker
@notquitegonzo @mrmickme @APazyryk No these IgG4 antibodies are specific to the viral spike and don't cause autoimmune disease. The causal connection to IgG4-RD is that you first get an autoimmune disease and the class switch to IgG4 that binds "self" is to prevent damage caused by autoimmune disease.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Could these anti spike IgG4 trigger an immune reaction to the tissues where the spikeproteins are incorporated?
@RolandBakerIII - Roland Baker
@a_kruschke @notquitegonzo @mrmickme @APazyryk Do you mean like where SARS2 spikes are budding from mRNA vaccine or adenovirus vector vaccine transfected cells? Yes, you could see cross reactions to "self" on the cell. But in general IgG4 have less off a tool kit to cause immune reactions than IgG3.
@RolandBakerIII - Roland Baker
@a_kruschke @notquitegonzo @mrmickme @APazyryk If there is an antibody type we should all be worried about it's afucosylated antibodies. They can cause very severe disease.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Yes I meant the reaction to the "Spikeprotein presenting cells". The question was just scientific interest. The other antibodies you mentioned are certainly much more concerning in clinical practice.
@a_kruschke - A.Kruschke
@RolandBakerIII @notquitegonzo @mrmickme @APazyryk Those IgG4 related illnesses are extremely rare. It became a bit less rare meanwhile. M. Ormond/retroperitoneal fibrosis, ... https://pubmed.ncbi.nlm.nih.gov/36814401/ ... mesenterial panniculitis. Pfizer even made a study about. https://www.ehealthme.com/vs/pfizer-biontech-covid-vaccine/mesenteric-panniculitis/
@a_kruschke - A.Kruschke
I want to try ❄️❄️❄️❄️❄️❄️https://t.co/z3xOoJE9fW
@komomo_Com - kom.com
@kakashi_tdn @maiti_86 19以下は自殺行為とまで言っているし、BMI24ぐらいでも筋肉が少ない方は危険だそうです。 糖質制限では脂質とタンパク質からATPを作るのに、アラニンが必要なので、痩せすぎてる方は食べていてもATP不足になるとはっきり書いています。
@komomo_Com - kom.com
@maiti_86 @kksft 糖質制限を薦める目安として【BMI25以上】というのは程よい目安ではないでしょうか？ https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1115333/full
@komomo_Com - kom.com
@kakashi_tdn @maiti_86 ある程度の臨床があればそのような結論に至るため安易に薦めないのだと思います。 リスキーな方が糖質制限をして筋トレしたらどうなるでしょう？ 肝グリコーゲン枯渇問題とケトン体が人間本来のエネルギー源説については、Kruschke先生にも聞いてみましたが、回答は【医学書の通り】とのことです。
@komomo_Com - kom.com
@kakashi_tdn @maiti_86 低炭水化物食につていては支持しているようですが【1/4 が炭水化物で構成される必要があり、日本の伝統的な食生活がこれにあたる】という考えのようです。 米国の低炭水化物食の研究では肥満に至る方も多いらしく問題に感じているようでした。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 引用していただきありがとうございます。 いろいろなことを分けて考えることが大切だと思います。 個人的には「低糖質」が賢いダイエットだと思っています。 ただし、過大評価すべきではありません。 それは常に健康な人を指します。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 重度の低体重の人、糖尿病、またはその他の代謝性疾患のある人は、医師に相談せずにこれを行うことはお勧めできません。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 「低炭水化物」と言うとき、私はこれを意味します。 各食事の 3 分の 1 は炭水化物で構成する必要があります。 同時に、脂肪を十分に摂取することが重要です。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 炭水化物を減らすにはさまざまな方法があります。この記事を使って説明してみます。 (Chrome ブラウザは非常に簡単に翻訳され、スマートフォンでもうまく動作します)。https://www.aerzteblatt.de/archiv/201673/Gegen-Diabetes-und-Adipositas-Dein-Freund-der-Ketonkoerper
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 炭水化物30％、脂肪35％、タンパク質35％のみを使用すべきだと思います。 https://t.co/tfQESiHzxR
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 残念なことに、炭水化物140gについてよく話題になります。 それは誤解を招きます。 560kcalに相当します。 人それぞれ必要なカロリーは異なります。 これは体重、スポーツ、仕事の活動によって異なります。 2000 kcalから12,000 kcalの間で変化します😱。
@a_kruschke - A.Kruschke
@komomo_Com @kakashi_tdn @maiti_86 要件の計算方法を知っていますか? これに基づいて、個人的にどのくらいのタンパク質を意味するかを計算できます。
@komomo_Com - kom.com
@a_kruschke @kakashi_tdn @maiti_86 Kruschke先生コメントありがとうございます！ こちらのコメントも大変参考になりました。 日本の伝統食を支持するのであれば、私はその意見に賛成です。 極端な低炭水化物で体調を崩している方も多いので、自己流でやる場合は注意が必要だと考えます。 https://t.co/qfdQcy2Lss
@a_kruschke - A.Kruschke
とても興味深い記事❣️❣️❣️ 研究者は、SARS-CoV-2 の 3D シミュレーションを作成しました。 写真や動画を見てください❣️ コロナウイルスはジャガイモ🥔のように見えます。可動 😱 Molecular architecture and dynamics of SARS-CoV-2 envelope by integrative modeling https://cell.com/structure/fulltext/S0969-2126(23)00040-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0969212623000400%3Fshowall%3Dtrue…
@a_kruschke - A.Kruschke
"...lack of symmetry, which is otherwise a typical feature of viral capsids." 対称性の欠如は、ウイルスでは珍しいことです。 ウイルスエンベロープは通常規則的です🤔. タンパク質は表面にパターン状に配置されています。 タンパク質の周りにはより強い電荷があります。 ..
@a_kruschke - A.Kruschke
..これにより、負に帯電した脂肪が引き付けられます。特にカルジオリピン。 "...enrichment of anionic lipids around the proteins, slightly so for POPS and most notably for the doubly charged cardiolipin." 甲羅は全体的に可動。 柄の配置も変わります。(動画は本文中)
@a_kruschke - A.Kruschke
💉👀 LNP 関連炎症はエンドソーム損傷の感知によって引き起こされる: 副作用のないエンドソーム脱出のエンジニアリング LNP-Associated Inflammation is Triggered by Sensing of Endosomal Damage: Engineering Endosomal Escape Without Side Effects ( 🇺🇸2024) https://www.biorxiv.org/content/10.1101/2024.04.16.589801v1.full
@a_kruschke - A.Kruschke
@keisuke4713
@sasabubucha - DR.DOGGIE
『SARS-CoV-2 mRNAワクチン接種後の糸球体毛細血管IgA沈着を伴うIgA腎症：3症例の報告』 慈恵医大からの症例報告。 考察:「SARS-CoV-2ワクチン接種はIgA腎症患者の体液性免疫を過度に活性化し、特徴的な異常であるガラクトース欠乏IgA1の産生を増加させる可能性がある。」 https://link.springer.com/article/10.1007/s13730-022-00707-0
@a_kruschke - A.Kruschke
@sasabubucha このレポートが発表されてから2年が経ちました。日常の臨床診療において、ワクチンやCOVID-19、あるいはその両方によるIgA腎炎の増加が見られますか?
@sasabubucha - DR.DOGGIE
@a_kruschke 疫学的にはよくわかりませんが、症例報告は非常に多いですね(特にワクチン関連)。日本腎臓学会東部学術大会2022はコロナワクチン接種後のIgA腎症・肉眼的血尿・ANCA関連腎炎・ネフローゼ症候群の報告の花盛りでした。 https://t.co/f5vMRPIfbW
@sasabubucha - DR.DOGGIE
日本腎臓学会東部学術大会2022のプログラム・抄録が掲載されています。コロナワクチン接種後の発症・増悪例が多数報告されています。https://cdn.jsn.or.jp/general/congress/journal/64_6-E.pdf https://t.co/GyAfdlzvVF
@a_kruschke - A.Kruschke
@sasabubucha それは私の懸念を裏付けています。 BioNTech の LNP に関する 2020 🐀年の研究では、腎臓の値が約 10% 増加していることがすでに示されています。
@a_kruschke - A.Kruschke
💓💓💓 👀 Possible pathway SARS-CoV-2 spike protein can enter heart muscle cells.👇 SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes (Osaka 🇯🇵2023) https://www.nature.com/articles/s41598-023-48084-7
@a_kruschke - A.Kruschke
Press release university of Osaka 🇯🇵 https://research-er.jp/articles/view/129809
@a_kruschke - A.Kruschke
From the homepage of Department of Cardiovascular Medicine Osaka University 🇯🇵 cardiology.med.osaka-u.ac.jp/?page_id=38131
@a_kruschke - A.Kruschke
💓 about the study: The authors used induced pluripotent stem cells (iPSCs) from a male patient with hypertrophic cardiomyopathy. The expression of ACE2 receptors showed similar distribution as previously described, and comparable to cells from female heart muscle cells.
@a_kruschke - A.Kruschke
"..the iPSC-CMs were incubated with purified His-tagged SARS-CoV-2 S-RBD protein, [..] for 48 h." " Immunostaining revealed that S-RBD accumulated at the periphery of the iPSC-CMs co-localized with ACE2 (Fig. 1d👇) .."
@a_kruschke - A.Kruschke
".. and was then internalized as the S-RBD/ACE2 complex in the subcellular space (Fig. 1e)."
@a_kruschke - A.Kruschke
" After treatment with S-RBD for 48 h, S-RBD signals were detected at the cell membrane and co-localized with ACE2 in ACE2-WT-iPSC-CMs (Fig. 1i) [..], suggesting that internalization of SARS-CoV-2 S-RBD depends on its binding to ACE2. "
@a_kruschke - A.Kruschke
Further experiments "suggested that S-RBD-sfGFP internalized into the iPSC-CMs co-localized with early endosome marker proteins and was then delivered from endosomes to lysosomes through the endolysosomal pathway in the iPSC-CMs." https://www.nature.com/articles/s41598-023-48084-7/figures/2
@a_kruschke - A.Kruschke
Live cell imaging (adeno-associated virus (AAV)) demonstrated the endocytosis of S-RBD bound to RAB5A in the iPSC-CMs (Fig 3 👇). https://t.co/LWQ0rxFkft
@a_kruschke - A.Kruschke
"S-RBD-sfGFP treatment significantly upregulated the IFN-responsive genes (IFI6, ISG15, and IFITM3) in mature cardiomyocytes, suggesting that S-RBD acts as a pathogen-associated molecule and promotes the expression of IFN-responsive genes."
@a_kruschke - A.Kruschke
The authors conclude: ".. S-RBD treatment dose-dependently increased ISG15 expression and promoted protein ISGylation in the human iPSC-CMs via ACE2. However, whether protein ISGylation in the cardiomyocytes is beneficial remains unknown and requires further investigation." https://t.co/hkYWtzqm80
@a_kruschke - A.Kruschke
" In conclusion, SARS-CoV-2 S-RBD was internalized via ACE2 through the endolysosomal pathway, upregulated the IFN-responsive genes, and promoted ISGylation in the human iPSC-CMs. "
@a_kruschke - A.Kruschke
🤔▪️The authors explicitly address the problem of myocarditis after vaccination. However, the amount of spike protein they used is 10.000x higher than the amount expected from mRNA vaccines.
@a_kruschke - A.Kruschke
"concentration of S-RBD used for imaging experiments and transcriptional profiling (> 600 ng/mL) was lower than the estimated serum concentration of S protein after SARS-CoV-2 infection (2500–17,500 ng/mL) but higher than the concentration after mRNA vaccination (20–100 pg/mL)."
@a_kruschke - A.Kruschke
🤔▪️This study is particularly interesting with regard to symptomatic myocardial damage, months after SARS-CoV-2 infection. It has been shown elsewhere, that spike protein can be detected for a long time even though virus replication no longer occurs.
@a_kruschke - A.Kruschke
The amount of spike proteins used in this study is 3-4x lower than in infection, so I estimate it's comparable to spike protein residues in post-Covid patients.
@a_kruschke - A.Kruschke
My personal conclusion: Important basic research, and certainly a 🧩 more to understand late cardial symptomatic after infection. In the context of mRNA it's difficult, in terms of several orders of magnitude difference.
@a_kruschke - A.Kruschke
@reSeeIt save thread
@a_kruschke - A.Kruschke
Recently, this great paper was published by @SCOTTeHENSLEY. It will have an enormous impact on the vaccination concept against COVID (at least I hope so). It's difficult to understand when you never before heard about the "backboosting" concept. https://journals.aai.org/jimmunol/article/202/2/335/107289/Original-Antigenic-Sin-How-First-Exposure-Shapes
@a_kruschke - A.Kruschke
I'll try to explain the concept of BACKBOOSTING. ❣️Please note that this 🧵 has no impact on individual vaccination recommendations. Please follow the official guidelines. ❣️ This tweet is for MD and other science people who want to understand more.
@a_kruschke - A.Kruschke
During his life, everyone "collects" a series of antibody producing cell that recall ancestral infections. In case of reinfection, the immune system uses these plasma cells, stored in the bone marrow, to produce antibodies against the pathogen.
@a_kruschke - A.Kruschke
By this way, the immune response by antibodies is much quicker than in a primary infection. This memory function of the immune system is perfect for pathogens that do not mutate.
@a_kruschke - A.Kruschke
For defense against mutating pathogens, the immune system has developed some accessory skills. In the context of the backboosting concept, these two are important.
@a_kruschke - A.Kruschke
The first is "immune imprinting", which is also called "Original Antigenic Sin" (OAS). The second one is "somatic hypermutation", also called "immune maturation".
@a_kruschke - A.Kruschke
(Just for recalling.) B cell memory: building two walls of protection against pathogens https://www.nature.com/articles/s41577-019-0244-2 (fig.👇 )
@a_kruschke - A.Kruschke
The resulting antibodies of multiple contacts with e.g. influenza are difficult to predict, as everyone has a different history of life. Several studies for immunology and vaccines research were published, drawing maps of antibodies.
@a_kruschke - A.Kruschke
Most studies in context of backboosting were done on Influenza virus. Curiously, test subjects also showed "memory" to strains that were circulating only before their birth. This is explained by cross-reactivity and/or somatic hypermutation.
@a_kruschke - A.Kruschke
Antibody landscapes after influenza virus infection or vaccination (2014) https://www.science.org/doi/10.1126/science.1256427
@a_kruschke - A.Kruschke
"Titers were highest for influenza viruses that circulated when an individual was ~6 years old, corresponding with the time frame of first infection."
@a_kruschke - A.Kruschke
"Antibody levels against newly circulating viruses tended to be lower than those against strains circulating earlier in an individual’slifetime,.." "... each individual’s landscape shape was typically stable from one year to the next and had distinctive individual features.."
@a_kruschke - A.Kruschke
"Typically, the broad initial response was followed by a period of titer decay during which antibody titers stabilized to form an altered antibody landscape over the course of ~1year (fig.S24👇)" https://www.science.org/doi/suppl/10.1126/science.1256427/suppl_file/fonville.sm.pdf
@a_kruschke - A.Kruschke
As you can see in the figure, the pre-reinfection ab titers (first column, grey) are enhanced by reinfection (red). This process takes time, and some antibodies only rise after one year (lower part of fig.).
@a_kruschke - A.Kruschke
After this process, the titer was maintained higher than the initial one. These findings laid the foundation stone of the backboosting vaccination concept. Novel vaccine concept based on back-boost effect in viral infection (Kohler. 2015) https://www.sciencedirect.com/science/article/pii/S0264410X15006878?fr=RR-1&ref=cra_js_challenge
@a_kruschke - A.Kruschke
...to be continued... 😊
@a_kruschke - A.Kruschke
Let's continue BACK-BOOSTING... (chapter 2) The idea behind it is like a time machine. Recalling memory of old strains to fight the future.
@a_kruschke - A.Kruschke
The idea of using the Back-boosting mechanism to fight strains of virus that will come in the future . Sounds impossible?
@a_kruschke - A.Kruschke
The idea behind: We know that the "stored memory" in our immune system undergo some random mutation process. So, it will be helpful to have different "mother memory cell lines" to get a broad spectrum of random mutations.
@a_kruschke - A.Kruschke
Then, the chance of cross-reactivity with future mutations of the virus will be enhanced, just because of bigger choices. But is this not only theory? Let's have a look again at what happens in influenza.
@a_kruschke - A.Kruschke
Original Antigenic Sin: How First Exposure Shapes Lifelong Anti–Influenza Virus Immune Responses (2019) https://journals.aai.org/jimmunol/article/202/2/335/107289/Original-Antigenic-Sin-How-First-Exposure-Shapes
@a_kruschke - A.Kruschke
The authors collected "..serum samples [..] over a 20-year period from 40 individuals [..] and measured changes in their antibody titers against H1, H2, and H3 viruses in ∼5-y intervals."
@a_kruschke - A.Kruschke
The authors "observed that exposure to strains encountered later in life “back-boosted” the antibodies response to strains of the same subtype encountered earlier in life."
@a_kruschke - A.Kruschke
"Thus, the strains of a given subtype encountered earliest in life experienced the greatest number of back-boosting events, leading them to be consistently maintained at the highest antibody titers."
@a_kruschke - A.Kruschke
So, once again, the "immune imprinting " was confirmed. Looks like a trap nobody can escape?
@a_kruschke - A.Kruschke
But... "..severe infections, such as those caused by pandemic strains, might be capable of “reprogramming” the hierarchical antibody response caused by earlier imprinting with less virulent strains of the virus. ..
@a_kruschke - A.Kruschke
"..E.g., early serological studies showed that individuals born between ∼1863 and 1890 (the year of the H3Nx Russian Flu pandemic) all had high titers of antibodies against the virus that caused the 1968 H3N2 “Hong Kong Flu” and were roughly equally protected from mortality. ..
@a_kruschke - A.Kruschke
" This suggests that exposure to the 1890 H3Nx pandemic strain was able to “override” the imprint of earlier seasonal strains to which those born decades before the 1890 pandemic (i.e., from 1863 onwards) would have been exposed."
@a_kruschke - A.Kruschke
In sum, these findings tell us that it will be useful to look out for those "strong variants" that appear from time to time.
@a_kruschke - A.Kruschke
That's the principle of using the "backboost effects " for vaccines. Put these "strong variants" in the next vaccine, then you'll protect not only the already imprinted variant, but also the second one.
@a_kruschke - A.Kruschke
This was all about influenza. Also described in HIV and hepatitis C. But would it happen also in COVID? This was the big question.
@a_kruschke - A.Kruschke
Some in vitro or animal models, and also the Moderna's safety study for XBB.1.5 monovalent vaccine gave some hints that XBB.1.5 might be such a "strong variant".
@a_kruschke - A.Kruschke
@a_kruschke - A.Kruschke
PREPRINT ‼️‼️Moderna Safety study for monovalent-XBB 💉. Phase II/III study with 50+51 participants. Safety and Immunogenicity of XBB.1.5-Containing mRNA Vaccines https://www.medrxiv.org/content/10.1101/2023.08.22.23293434v1.supplementary-material
@a_kruschke - A.Kruschke
Unfortunately, neither BioNTech/Pfizer nor Novavax published any safety study for the XBB.1.5 vaccines.
@a_kruschke - A.Kruschke
So we had to wait for the great study from Hensley Lab.
@SCOTTeHENSLEY - Hensley Lab
Check out our new manuscript on @medrxivpreprint. We show that ‘immune imprinting’ with ancestral SARS-CoV-2 mRNA vaccines is beneficial for priming neutralizing antibody responses against emerging SARS-CoV-2 variants. 1/n https://www.medrxiv.org/content/10.1101/2024.01.08.24301002v1
@a_kruschke - A.Kruschke
Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants (2024) https://www.medrxiv.org/content/10.1101/2024.01.08.24301002v1.full
@a_kruschke - A.Kruschke
The study confirms that the choice of XBB.1.5 for production of a monovalent vaccine was the right one.
@a_kruschke - A.Kruschke
The authors found "unlike BA.5, a single XBB exposure elicited low levels of XBB.1.5-specific antibodies and B cells in some individuals."
@a_kruschke - A.Kruschke
Their conclusion gives hope for the future: "The human immune landscape against SARS-CoV-2 is becoming more heterogenous as variants emerge and infection and vaccination histories become diverse among different individuals. ..
@a_kruschke - A.Kruschke
".. Most humans have been ‘immunologically imprinted’ with antigens from the ancestral SARS-CoV-2 strain, but that will inevitably change as time progresses. Most children born today will be first introduced to SARS-CoV-2 antigens in the form of a variant infection or variant ..
@a_kruschke - A.Kruschke
".. vaccination, leading to the formation of different memory B cell populations compared to individuals first exposed to ancestral SARS-CoV-2 antigens."
@a_kruschke - A.Kruschke
All pure theory? I think the advisor group of WHO takes this Back-boosting concept into account. In their statement from December 13, 2023 they maintain the XBB.1.5 as vaccine component. https://www.who.int/news/item/13-12-2023-statement-on-the-antigen-composition-of-covid-19-vaccines
@a_kruschke - A.Kruschke
NB: Sato Lab's hamsters 🐹 also predicted that two antigen contacts with XBB.1.5 would be necessary to establish a broader immune response. https://t.co/iZhkGpbsX0
@a_kruschke - A.Kruschke
This now published study is also very interesting in the context of backboost qualities of XBB.1.5. https://www.cell.com/immunity/fulltext/S1074-7613(24)00092-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS107476132400092X%3Fshowall%3Dtrue#secsectitle0035
@a_kruschke - A.Kruschke
"These data show that the updated XBB.1.5 S mRNA vaccine booster elicits greater neutralizing antibody responses against a panel of recently and currently circulating variants, including mismatched pseudoviruses,..."
@a_kruschke - A.Kruschke
A comment about the then preprint from @gadboit https://t.co/fTBFcApRvp
@gadboit - Guy Gadboit
Gigavaxxing doesn't work. This is a study of people who had had around 5, 6 or 7 vaccine doses altogether, the first 3 or 4 of which were Wuhan-Hu-1, and then either a bivalent, or a bivalent then the monovalent XBB.1.5 booster. They measured neutralization... https://t.co/rhPtXeUpN3
@a_kruschke - A.Kruschke
@gadboit @reSeeIt save thread
@a_kruschke - A.Kruschke
Did you see the HEADLINE ? There are 10 confirmed cases...🦟... of Dengue fever. A good opportunity to talk about ADE (antibody dependent enhancement) https://www.foxnews.com/health/dengue-virus-spreads-florida-counties-health-officials