A Supercomputer Analyzed COVID-19, and an Interesting New Hypothesis Has Emerged (medium.com) 251
Thelasko shares a report from Medium: Earlier this summer, the Summit supercomputer at Oak Ridge National Lab in Tennessee set about crunching data on more than 40,000 genes from 17,000 genetic samples in an effort to better understand Covid-19. Summit is the second-fastest computer in the world, but the process -- which involved analyzing 2.5 billion genetic combinations -- still took more than a week. When Summit was done, researchers analyzed the results. It was, in the words of Dr. Daniel Jacobson, lead researcher and chief scientist for computational systems biology at Oak Ridge, a 'eureka moment.' The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis. The hypothesis provides a model that explains many aspects of Covid-19, including some of its most bizarre symptoms. It also suggests 10-plus potential treatments, many of which are already FDA approved. Jacobson's group published their results in a paper in the journal eLife in early July.
According to the team's findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease's cardiac and GI symptoms. But once Covid-19 has established itself in the body, things start to get really interesting. According to Jacobson's group, the data Summit analyzed shows that Covid-19 isn't content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body's own systems, tricking it into upregulating ACE2 receptors in places where they're usually expressed at low or medium levels, including the lungs.
The renin-angiotensin system (RAS) controls many aspects of the circulatory system, including the body's levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team's analysis, when the virus tweaks the RAS, it causes the body's mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin. (ACE normally degrades bradykinin, but when the virus downregulates it, it can't do this as effectively.) The end result, the researchers say, is to release a bradykinin storm -- a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it's this storm that is ultimately responsible for many of Covid-19's deadly effects. Several drugs target aspects of the RAS and are already FDA approved, including danazol, stanozolol, and ecallantide, which reduce bradykinin production and could potentially stop a deadly bradykinin storm.
Interestingly, the researchers suggest vitamin D as a potentially useful Covid-19 drug. "The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN," the report says. "Again, this could stop potentially deadly bradykinin storms from forming." Other compounds could treat symptoms associated with bradykinin storms, such as Hymecromone and timbetasin.
According to the team's findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease's cardiac and GI symptoms. But once Covid-19 has established itself in the body, things start to get really interesting. According to Jacobson's group, the data Summit analyzed shows that Covid-19 isn't content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body's own systems, tricking it into upregulating ACE2 receptors in places where they're usually expressed at low or medium levels, including the lungs.
The renin-angiotensin system (RAS) controls many aspects of the circulatory system, including the body's levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team's analysis, when the virus tweaks the RAS, it causes the body's mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin. (ACE normally degrades bradykinin, but when the virus downregulates it, it can't do this as effectively.) The end result, the researchers say, is to release a bradykinin storm -- a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it's this storm that is ultimately responsible for many of Covid-19's deadly effects. Several drugs target aspects of the RAS and are already FDA approved, including danazol, stanozolol, and ecallantide, which reduce bradykinin production and could potentially stop a deadly bradykinin storm.
Interestingly, the researchers suggest vitamin D as a potentially useful Covid-19 drug. "The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN," the report says. "Again, this could stop potentially deadly bradykinin storms from forming." Other compounds could treat symptoms associated with bradykinin storms, such as Hymecromone and timbetasin.
Prevention not treatment (Score:5, Informative)
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Re:Prevention not treatment (Score:5, Funny)
Re:Prevention not treatment (Score:5, Insightful)
> Do not leave your house unless you must.
Sorry, this is deadly advice.
Get outside, develop a tan before winter comes, and do whatever else is necessary to build up endogenous stores of Vitamin D.
The virus hasn't yet evolved UV-resistance and there are no documented cases of people outside, who stay six feet apart, transmitting the virus. Wear a mask if you're going to be close, but don't be silly and wear a mask while riding a bike or hiking a mountain, except when other people are nearby. There is only negative impact on reducing airflow in the absence of others - nuance matters.
Be smart, not afraid.
Re:Prevention not treatment (Score:4, Insightful)
I could be wrong, but I think vitamin D is one of those things that's mostly stored in your blood - which is to say you can't really store more than a few days worth, so you need a steady supply.
Meanwhile, by blocking sunlight a tan actually reduces the rate at which your body can produce vitamin D - the darker your skin, the longer you have to stay in the sun to produce the same amount of D.
Re:Prevention not treatment (Score:5, Informative)
I'm VitD deficient - or more accurately, at risk of - due to side effects of some chronic meds, and take a tablet with 50 000 IU every two weeks. 50 000 IU represents the upper daily tolerable limit in some official recommendations, which in this case means taking that much EVERY DAY may result in toxicity in about 4 months or so. (Obviously general figures, which will differ from person to person. And unfortunately the tablets look similar to purple M&Ms...)
It wasn't nice when I was VitD deficient, but the upside is that I now undergo blood tests every 3 months to check the levels and get prescription meds (albeit cheap) to keep it in the acceptable range since way before 2020.
Wikipedia states 5-30 minutes moderate exposure of face, arms, and legs, twice a week, for light-skinned people, as sufficient. But yeah, darker people have to stay longer. Also, not wear sunscreen or sit behind window glass.
Ergocalciferol (D2 - typically from food and supplements) and Cholecalciferol (D3 - produced in the skin) are not biologically active. These are converted in the liver to 25-hydroxycholecalciferol (calcifediol or 25(OH)D), which is the form that blood tests measure in blood serum. Which however needs to be converted in the kidneys to 1,25-dihydroxycholecalciferol (calcitriol or 1,25(OH)2D) before being biologically active - it binds to a specific protein for transport through the blood to its final sites. So the whole tanning/supplementing thing is only half the issue, you still need adequate liver and kidney health too.
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The tan also is not healthy, the 50s were wrong about that. Tanning increases the aging effects on skin (wrinkles) and can cause skin cancer. If you are outside in the sun then use suncreen with a high SPF number.
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Except that the vitamin D does not protect you from covid-19, it only helps with the bradykinin storm. And it's unknown if the amount of vitamin D you get from an hour in the sun is enough to matter, or even the amount you get from a multivitamin tablet. My guess is that this really is only going to matter for people who are bad enough to be hospitalized, and there will be enough other symptoms to deal with that the hospitalization won't become unnecessary. It definitely won't prevent people from being inf
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Almost none of what you said is true.
Vitamin-D is a well known contributor to upper respiratory resistance to infection. We also know from existing COVID literature that there is a clear correlation between severity of symptoms and serum levels of Vitamin D. Consequently, Vitamin D is best taken as a preventative, as high serum levels of Vitamin D will mitigate COVID 19's hijacking of the RAS system.
Also, Vitamin D can be found in fatty fish such as salmon, in addition to
You know you can just take a supplement right? (Score:5, Funny)
That said, GP isn't entirely wrong. If everybody would just stay home and pick up their groceries for a month or two this would all be under control. One of the things that really, really pisses me off is that I put a ton of effort into containing the virus and made a bunch of sacrifices only to have yahoos blow my work to hell going to the beach and bars and shit...
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Re:You know you can just take a supplement right? (Score:5, Insightful)
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Well we have experts that make dangerously premature statements and policy the decisions the ruin lives, so sounds like the public has learned their lesson well.
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The beach is fine. Part of the problem that we're getting here is mixed messages from the government and the media.
Go to the beach. The sun will cause you to produce vitamin D (mentioned in the article as a possible partial treatment), and the volume of air and presence of UV light degrading the virus make it *extremely* unlikely that's where you'll catch it.
But governments are telling people to stay out of parks and off the beach, and allowing hair salons and cafes and bars to open, which is insane. And th
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It's the complete and utter lack of social distancing which tends to happen at a crowded beach. Yes, the UV and the open air reduces the chance of transmission. It REDUCES it; it doesn't eliminate it. All the screaming and yelling from people running around at the crowded beach increases the chance of transmission. Remember, there was choir practice at a church which turned into a superspreader event. They were
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I think that saying "Outdoor transmission is nearly non-existent," is grossly overstating the case, but it certainly is a lot lower than indoor areas with recirculating air flow. Especially where people are densely packed. Hair salons might be reasonably opened, as the people there are usually not densely packed, and they often have good air circulation. Similarly cafes, though there's a lot of variation in the design of those places. Bars, though, generally encourage close packing of people...and alcoh
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Uhm, who do you think delivers the groceries? And stocks the stores? And distributes the food to the stores? And makes the food?
Robots? Maybe in 20 years. What you describe has clear and obvious flaws.
Note, just because someone is wrong, does not mean the opposing theory is right.
We are just a bunch of primates throwing crap at each, we can ALL be WRONG together.
Re:You know you can just take a supplement right? (Score:4, Insightful)
You mean like the 4-6 week quarantine we should have done back in February/March but instead were told by dear leader, who had been warned in January action needed to be taken [nytimes.com], we have it totally under control [cnbc.com], it's only one person from China, it will magically go away [cbsnews.com], then went golfing [snopes.com] before announcing, "The world was blindsided [youtube.com]. No one saw this coming."
Re:Prevention not treatment (Score:5, Insightful)
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"the time required for the virus to eventually mutate into something less deadly on its own": IIUC, that isn't what happens (at least not in less than millennia). The virus can mutate all it wants, but what that means is that somewhere an individual virus--one out of a trillion individual viruses--has mutated, and maybe that mutation makes it less deadly. That doesn't mean the other 999,999,999,999 viruses share that mutation, so they're still as dangerous as ever. (Of course, many of those other viruses
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Re:Prevention not treatment (Score:5, Insightful)
Well...you said "might", so OK. But do remember the study that showed heart problems two months after the virus was cleared even in asymptomatic cases. Perhaps it's transient, perhaps it isn't. And one of the effects of the virus is small circulating blood clots. These can easily cause problems, e.g. micro-strokes, that aren't easily noticed, but have a long term cumulative effect. (They can also cause problems in the kidneys, which aren't repairable, but which also aren't noticed because we're born with slightly more than twice the kidney capacity that we need. This, however, often degrades as we get older.)
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Well, no, they're both important. Prevention is important because it buys time for more effective and less drastic means of prevention (vaccines) and new treatments. But the amount of coordination and stoppage of commerce required from every person and nation on Earth to actually eliminate the virus is so improbable that you may as well treat it as impossible. Therefore, people WILL contract the virus. Probably even some of the ones who are being careful. Knowing that, it's important to understand the
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Indeed, and also helps explain why it affects black people more than whites (other than being a racist virus, of course).
So I guess its about time that the governemnt issues advice to all blacks, if you want to live in the cold, wet northern climate, then you must take vitamin D supplements.
As should all us basement dwellers.
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I am baffled as to why this is considered flamebait. The science supports it.
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Going to sun-bathe in a park is safe if you keep a good distance if you don't have a garden and vitamin D supplements are cheap if you shop around.
Re: Prevention not treatment (Score:5, Informative)
Masks are there to prevent the mask wearer from infecting other people - not the other way around. Even if *you* don't have COVID, how do you know the next guy doesn't have it? Masks work when everybody wears them. They don't prevent YOU from getting it - unless the guy standing next to you is wearing his mask.
They're not there to prevent the virus from getting in - they're there to prevent it from getting out.
Update: It also reduces your chance of getting it (Score:5, Informative)
There is an update to that. Studies have found that wearing a mask ALSO reduces the chance that the wearer catches it. Which is consistent with what doctors and nurses have been doing for decades - wearing a mask with appropriate patients so that a patient doesn't cough directly into your mouth while you're working on them.
Just common sense. If you have your mouth open and I cough in your direction, wouldn't you rather have a piece of paper blocking my cough from spraying directly into your mouth?
Of course nothing is 100% foolproof. It reduces your risk. Kinda like opening your eyes while driving doesn't guarantee you won't get in a wreck, it reduces the chance that you will.
Additionally, there is the second-order effect. Humans are irrational and highly influenced by social norms. Seeing everyone else wear a mask, Joe is more likely to wear his than of Joe sees nobody else is wearing one. Joe doesn't know he has covid. One reason I put my mask in is to encourage Joe to put his on, because I don't want to catch covid from Joe.
Re:Update: It also reduces your chance of getting (Score:5, Informative)
There is an update to that. Studies have found that wearing a mask ALSO reduces the chance that the wearer catches it.
Yes, there are experiments [thelancet.com] as well as anecdotal reports [bloomberg.com] that indicate some protection to the wearer.
Re:Update: It also reduces your chance of getting (Score:4, Informative)
It depends on the pathogen. There are experiments with airborne bacteria and viruses that show masks, and especially cloth masks, are pretty much ineffective. The larger the droplets required, the more likely a mask is going to help. It looks like COVID, especially with fairly brief contact, requires substantial droplets, so even cloth masks are worthwhile.
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FWIW, there's a recent study that indicates wearing a mask may protect you, too: https://www.msn.com/en-us/heal... [msn.com] (wish I could find a better URL).
Re: Prevention not treatment (Score:2)
The most effective way to slow the spread of any contagious disease is to limit large gatherings. We can't do that completely without crippling our economy and fomenting violent rebellion (see last few months) but we can limit large gatherings for leisure activities. Indoor (and probably outdoor) sit down dining is on that list of things that we can both do without for a while and that limit the spread, unfortunately.
You gotta wo
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Yeah, how the fuck is referencing the summary seen as offtopic!? Hahaha. Oh Slashdot, may ye never change.
Vitamin D (Score:5, Informative)
This explains a number of things.
It's been known for a while now that patients with Vitamin D deficiencies have a harder time with COVID, with much worse outcomes.
Of course, one way to make sure you have a D deficiency is to spend all of your time indoors.
So if you're stuck inside, take D3 supplements.
Re:Vitamin D (Score:5, Funny)
Well the user base here is certainly doomed.
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Re:Vitamin D (Score:5, Funny)
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That'd require interacting with someone in person so I think we'll be ok
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> Well the user base here is certainly doomed.
Not really. We might be low on vitamin D due to the lack of sunlight, but the fact that we've all been sheltering in place and social distancing for our entire lives will keep us from getting it to begin with.
People talk about all this "effort" to not go anywhere or do anything, but I've been taking most of the precautions since way before Covid was a thing. Half the time I'd hear of a new idea, I'd laugh because we were already doing it pre-Covid.
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So if you're stuck inside, take D3 supplements.
But what if I'm not a JavaScript programmer?
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You forgot vitamin K2... It is essential for the absorption of Vitamin D.
Taking one without the outher makes little sense.
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Except Vitamin K2 is not something that you should just take lightly and has its own pretty severe issues if you get to toxicity levels...
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Or just walk out your door or onto your balcony for literally 10 minutes a day in the sunlight. But as winter is coming, definitely stock up on D3 supplements now.
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Or we can get some sunlight.
The body is very good at making vitamin D using sunlight. An exposure at midday of 20-30 minutes 3 times a week while wearing shorts and a t-shirt will meet your needs. Dark skinned people need more exposure.
Re: Vitamin D (Score:3)
The Vitamin D connection to COVID severity has been known since March. It also explains why dark skinned people suffer more severe effects from COVID. If we had leaders that cared, there would be a huge campaign to encourage Vitamin D supplements, especially for dark skinned people. It would be a lot safer and more effective than hydroxycloroquine.
It almost looks like our âoeleadersâ donâ(TM)t care ?
Silver Lining? (Score:5, Interesting)
If there's one bright side to this whole pandemic, it's been fascinating watching the world's scientists start to piece together the puzzle on SARS-CoV2.
Re:Silver Lining? (Score:5, Informative)
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When we have an effective vaccine, the American people will declare they do not trust the scientists and this must be some nefarious plot, so no takee vaccine.
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wait a sec (Score:2)
So your telling me we spent all this time and money just for an "electronic brain" to "hoover up" data and all it came back with was "you're an asshole"?
Bill .... I don't think there's a future in this Computationalizer nonsense, lets go have a martini and a pack of redwoods
Vitamin D advantages (Score:4, Informative)
So if you are black, or otherwise dark skinned, living in the US or Europe, you should definitely take some, especially in the winter.
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Umnh...maybe. I understand that there's some evidence that dark skin color is associated with a different metabolism of vitamin D. So *perhaps* the blood serum value associated with deficiency isn't the same. IIUC, the answer is "we don't know".
Still, AFAICT, it's reasonable advice until more evidence comes in.
OTOH, I'm no expert in the field.
Vitamin D? (Score:2)
Why only hypothesize and not measure? (Score:2)
How much money and time would it take to get a couple dozen blood samples from diseased victims through a chromotographer?
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Depends on how many hurdles the ethics committee makes them jump through. And, without looking at their CVs, authors of a simulation paper might not be trained to work in biosafety level 2 labs.
Get it while supply lasts (Score:2)
Re:Get it while supply lasts (Score:5, Funny)
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Sorry but there is a lot of evidence that the Vitamin D you stuff into your face isn't available for many benefits. You're going to need a proper UV-B lamp if you can't get into sunlight, which are VERY hard to find now, the companies that made the good ones were forced to nerf their products.
So this is a... computer model? (Score:2)
Does the phrase "computer model" ring a bell with anyone? As with Imperial clusterfuck, someone wrote a program and loaded a lot of data into it.
And from this they get all the conclusions described in TFA?
I would have hoped that, if nothing else, Slashdotters would be alert to the risks of computer models.
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"The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis".
So... "the computer... revealed a new theory". Did it wave its arms and talk loudly while chalking up incomprehensible equations on a blackboard?
Come on. It's just a very fast adding machine.
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I have yet to see anybody criticizing that model point out anything substantially wrong with it.
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science (Score:2)
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"Several drugs target aspects of the RAS and are already FDA approved, including danazol, stanozolol, and ecallantide, which reduce bradykinin production and could potentially stop a deadly bradykinin storm."
So the next step is to have a double-blind test using some of those drugs.
This is good science here.
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First of all, it is not a "computer model", it is a computational analysis of gene expression data from Covid-19 patients.
Second, there is no supercomputer involved in the findings. This appears to be something completely made up by one of the journalists. The medium.com article, which references a Forbes article and an ieee.org article, claims they did a large scale GWAS analysis, but that is not what was published. The actual paper is a rather ordinary gene expression study. They had a cohort of ~50 patie
Peer review (Score:2)
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Ya, could you please lend them your supercomputer to recheck them findings?
Re:Peer review (Score:4, Interesting)
It was peer reviewed, but only on presentation level because of the desire to fast-track COVID-19 related research.
You can see the review correspondence on the journal website.
https://elifesciences.org/arti... [elifesciences.org]
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Explains the curves (Score:2)
When the whole thing began, death rates were very high. Granted, part of that was a lot of deadly treatment and the culling of the weakes that was likely to happen... but it was also winter.
Might explain why death rates in Switzerland have been constant and very low (0-2 individuals per day on a pop of 8million) in the last few months. Seems to me now that fall is coming, they might rise again as exposure to sunshine gets rarer.
Nose (Score:2)
TFS states the virus enters the body mainly through ACE2 receptors in the nose. So, is mouth breathing safer, or might the virus still get up into the nose if it gets into person's mouth?
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Vitamin D (Score:2)
What do today's bums and 1918 sailors have in common? [wnycstudios.org]
Hypothesis? (Score:2)
Now I understand (Score:2)
"the virus enters the body through ACE2 receptors in the nose, "
That's why the covidiot mouth-breathers don't catch it.
Discussion in the weeds (Score:5, Interesting)
The entire discussion here has been about the most minor findings about Vit. D. While vit. D may be helpful, the other findings are quite interesting.
For one, it suggests anyone on an ACE inhibitor should stop taking it if they get COVID. Perhaps that even partially explains why older people are more vulnerable since older people are more likely to have hypertension and so are more likely to be prescribed an ABE inhibitor. Note that hypertension is known to be a risk factor in COVID. Perhaps the prescribed ACE inhibitors is why.
There are several already approved medications that reduce bradykinin levels that are worth considering for COVID treatment.
This is not medical advice, I am not a doctor and I have never played one on TV. Discuss any change of medication with your doctor, etc. etc. etc.
Re:as usual governments are wrong and dangerous (Score:5, Informative)
This study suggests that vitamin D stops the storm that causes damage and death. This vitamin is produced by exposing your skin to the Sun.
The major natural source of the vitamin is synthesis of cholecalciferol in the lower layers of skin epidermis through a chemical reaction that is dependent onÂsun exposureÂ(specificallyÂUVB radiation
Governments around the world have forced people to stay indoors and to avoid going outside, to avoid outdoors activities and to cover yourself while in the open...
As per usual the governments are wrong, stupid and dangerous to the people.
My state and local government have been very much recommending people get out and be in nature, just try to socially distant from those who don't live with you. The CDC has often pointed out that outdoor spaces are generally safer than their indoor counterparts.
I'm not sure what non-US oriented governments have been advising their citizens (I seem to recall most of the lockdowns had clauses permitting outdoor activity for exercise and such, many with area restrictions such as 500 meter radius of your residence), but it seems everyone that has any say in my area (with the exception of POTUS) has encouraged venturing outdoors.
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ya same, there's even radio advertisements going nuts for various parks to visit (city state and one national) just in my area. Specifically because they dont want a bunch of stir crazy nutjubs getting all riled up on the internet and becoming dangerous asshats like our OP friend here
Re:as usual governments are wrong and dangerous (Score:4, Informative)
Meanwhile, california is closing their beaches AGAIN in advance of labor day. Most outdoor areas were closed until about a month ago. Not just state parks ( rivers/lakes ), but as petty as the local playgrounds.
If they can get something so basic wrong ( and we knew it was wrong back in march ), what else do you think they screwed up?
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Re:as usual governments are wrong and dangerous (Score:4, Insightful)
My state and local government have been very much recommending people get out and be in nature, just try to socially distant from those who don't live with you. The CDC has often pointed out that outdoor spaces are generally safer than their indoor counterparts
roman_mir isn't one to let facts get in the way of a good story, and is desperately trying to spin it to be the fault of government. Which it often is, just not the way it would be in his libertarian fantasy world.
Personally, I got way more time outside this year than usual. I'm lucky enough to be working from home and can take a break in the garden in the middle of the day or walk in the country.
Re:as usual governments are wrong and dangerous (Score:5, Informative)
I think you need to re-read what they are saying. They are encouraging social distancing, which is NOT the same as staying indoors. It is that people are choosing to stay indoors in order to conform to the guidance, but this is a secondary effect of the guidance, not the guidance itself.
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Where I live the trails I run and ride on, and the picnic areas where I take my family, have all been annoyingly busy all through the pandemic. And I think that's very typical, because sales of bicycles etc. are through the roof.
Re:So, ignore the doctors (Score:5, Insightful)
insofar as "stay inside" was the shorthand people got from "don't go to the store or bars or restaurants or gather with groups of people" .. but nobody explicitly said "do not go outside" you dingdong
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Actually, many government proclamations said some version of "stay at home". This wasn't quite what the doctors had said, but it's wrong to say 'nobody explicitly said "do not go outside"'. In Britain some people have been fined for sitting in their own yards.
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Well, lack of selenium causes "milky white disease" in sheep. OTOH, over most of the surface of the earth that's not a likely think to happen. (It occurs in New Zealand, or possibly Australia. In Nevada you're more likely to get Selenium poisoning.)
I'm less certain about Magnesium, though I'm fairly sure we need some.
And we definitely need *some* Zinc. The problem with Zinc, though, is that too much is as bad as too little. Both are hard on the immune system. IIUC, there's a fairly wide range of toler