#really? really? wheres your prosthetic heart and lung and etc then?

[note-boom]

Okay. Quick thoughts after episode 3

Firstly. Something isn't computing with me. The thing of Dazai already having a plan for a new shin soukoku when he obviously wasn't going to leave the mafia or break up with Chuuya. Whatever you might say about Dazai's predictive genius powers, I do not for a moment believe that he really needed Akutagawa for something other than an unlikely backup, or that he thought he was ever going to leave the mafia, or that he really thought Chuuya was die or leave either. You know. For a suicidal guy, lots of plans sure hinge upon him staying alive, so maybe his little messed up plans and manipulations and contingency plans are just ways to give himself excuses to live even as he tries to kill himself but what do I know?

The reason I think Fukuchi and Fyodor get along so well is that they both have this weird thing where they think they have the right and the destiny to carry out heaven's will upon the earth. Fyodor "I am only doing the will of god" Dostoyevsky and Fukuchi "I wield this sword and want recognition from heavens, who will not let me rest" Ouchi are both living cycles of self-delusion

In my (probably wrong) opinion, Akutagawa telling Atsushi that he had lung disease was probably the hint to tell Atsu that he could trust Aku. "See. I'm telling you something I've never told anyone before. I'm trusting you. So trust me, idiot" Except Atsushi heard Dazai and was like "oh yeah, Akutagawa's not gonna turn me in dead." Oh, well...at least it worked

Fukuchi is basically Yoo Joonghyuk from ORV if Yoo Joonghyuk did actually defeat the end of the world, but only after dying for it several times before winning. And then if he had to witness another end of the world and go through it several times before beating it.

That ending. I am dead and so is Akutagawa. Send help

[flyonthewallmedstudent]

Q Fever

Aka, Query fever. What a weird name for a disease. Imagine telling people that's what you got.

in the 30s-40s, an Australian pathologist in QLD/Brisbane, came across an outbreak of the same or similar illness among abbatoir or slaughterhouse workers.

At the time, he called the disease "Q" fever or query as a temporary name until the pathogen could be identified. Unfortunately it stuck.

decades later, now nobel prize winner and virologist, MacFarlane Burnett isolated and identified the microbe responsible. I think this discovery contributed to his prize. i forget already.

Microbe responsible: Coxiella burnetti. Named for Burnett and HR Cox, the American bacteriologist who found the genus Coxiella where C burnetti falls under.

Initially they felt it was related to Rickettsia, responsible for Rocky Mountain Spotted Fever, but as science progressed, this was disproven.

Now for a Case Report

A 55 yo Italian man with a history of aortic valve replacement was diagnosed with pyrexia of unknown origin twice. Further signs included myalgias/splenomegaly/night sweats. The 2nd time he was admitted for PUO he deteriorated rather dramatically and was put on meropenem and teicoplanin.

A host of organisms was tested for on serological testing based on the man's travel and epidemiological history, all negative. Even a rheumatological panel was done, also less revealing. He also had a history of MGUS (a haem disoder), which is kind of a red herring here.

Cultures were negative, no vegetations were seen on a TTE - so they did consider IE. Which is an important differential for PUO.

Eventually a PET-CT was done (often favoured when investigations do not yield much for a sick patient with fevers), finally revealing a focus of infectious on his ascending aorta, where he'd also had previous surgery done. And in a round about way, they also further identified Coxiella Burnetti. He was treated doxycycline and hydroxychloroquine. As it's so rare in Italy, it wasn't really considered even though he mentioned rural travel.

Bottomline: Q Fever is an important consideration in the work up for culture negative IE. Further to this, always consider IE in the differentials for PUO particularly if they're at increased risk for IE (prosthetic valves, damaged valves, select congenital heart issues, previous IE). IE can present with night sweats, fevers, weight loss and splenomegaly. It can be insidious and chronic in nature. other risk factors can be more suggestive as we'll get into below.

Causative organism

Coxiella burnetti, it's a zoonoses - i.e. transmissible from animals. Special powers: very tough/hardy, can survive extreme environments (high temps and UV light etc.) over prolonged periods and is resistant to many common disinfectants/surface cleaners.

It's an intracellular pathogen and gram negative coccobacilli (PINK!)

name coccobaccili reminds me of cocopuffs.

it's mainly associated with farm animals, which the CDC so wholesomely displays on its website on Q fever (wtf).

goats, sheep, cattle typically (but many other animals, even birds, dogs and horses can be reservoirs)

in particular bodily fluids - amniotic fluid, placenta, faeces/urine, milk etc.

you can get it through unpasteurized milk and through inhaling it if it lands on dust in the area

ever visit a farm or petting zoo lately? OMG WASH YOU HANDS.

That said, it's typically inhaled in inorganic dust. You inhale it, it goes to the lungs, and then the bloodstream.

Increased risk for Coxiella burnetti (What to take on history of exposures and when to strongly consider it)

live on a farm or near one

exposure to a farm

work as a vet on a farm

farm worker, dairy workers, researchers on these animals/facilities

slaughterhouse/abbatoir

Also from CDC:

Clinical presentation

Most won't get sick after exposure and remain asymptomatic, a very small minority does. even though it is highly infectious.

incubation time is 2-3 weeks (consider this time in your history of exposure, did they work on the farm 2-3 weeks ago as opposed to yesterday).

Nonspecific acute infectious symptoms:

nonspecific systemic fevers/malaise/arthralgias/myalgias--> key is high fevers though and can be associated with headache and photophobia.

non specific GI - N/V/diarrhoea

respiratory ones - SOB or cough, consider it as atypical cause of community acquired pneumonia.

rare: hepatitis and jaundice (granulomatous) or encephalitis with neurological complications such as demyelinating disease or CN palsies, also haemolytic anaemia and HLH (yikes)

really it's the history of exposure that will lead you down the garden path to Q fever.

Chronic Q fever is perhaps worse, and can present as culture negative IE/PUO. Months/years later, as B symptoms as above above + LOW/LOA, night sweats. More likely to occur if you are predisposed for IE as above, have a weakened immune system for any reason, including pregnancy.

Chronic Q fever has a mortality of 10% if left untreated. About <5% of those with acute Q fever develop this if left untreated. Speculation is that it's more of an autoimmune process or abnormal immunological response to the bacteria.

To be honest, most who walk in the door with community acquired pneumonia get treated empirically for atypicals anyway, (standard course of doxycycline), so we hardly really ponder the question of Q fever in every patient. But if they present chronically and did not have atypical cover at the onset of acute symptoms, then it's something important to consider.

Other important conditions - can cause complications in pregnant women and 20% will get post Q fever syndrome. like chronic fatigue.

investigations

Serology! nice and easy. Look for IgG antibodies in the chronic presentation. Or PCR. Down side to serology - can take 2-3 days for the body to make said antibodies to the bacteria for detection. PCR can be done on any fluids/tissue sent.

Cultures useless, hence it fall under the umbrella of culture negative (hard to grow outside a host cell, it is an obligate intracellular pathogen).

Other hints on bloods (as serology/PCR takes time to return) - elevated or low platelet's, transaminitis with normal bili, opacities in CXR with hilar lymphadenopathy, CSF will show raised protein levels if done when encephalitis is suspected.

imaging can also support the diagnosis.. as illustrated by the case report.

Treatment

Acute disease - as standard for atypical bugs, doxycycline 100 mg BD for 14 days. Alternatives - TMP SMX or Clarithromycin.

Chronic Q fever or IE:

native valves: doxycycline and hydroxychloroquine (200 TDS) for 18 months

prosthetic: same but 24 months

why hydroxy: enhances the action of doxycycline (increases the pH of the phagolysosome)

Follow-up: look for 4 fold decrease in IGG

Sources:

CDC

Stat Pearls

Wiki as linked above

[insipid-drivel]

Your follow-up to the horse info post is just as good as the first one, and I offer a sincere thanks because those sorts of posts take forever, and are a lot of work.

But the reason I’m sending this is because of the joy of seeing the horsey prosthetics. I was aware that injury didn’t and doesn’t mean instant euthanasia, but I didn’t know what advances had been made and it’s a lovely thing to be able to help a friend live their best life.

For instances where euthanasia is the only course of action, would that be something like a horse has sustained a break that has gone septic in a time prior to antibiotics? So the horse would likely die anyway and it would be more humane to put it down than to let nature run its course, I’m thinking. Or is that completely wrong?

Thanks again for all of the hard work you put into these posts and answers!

Eugh, infections are a really horrible and scary part of horse health crisis management, because they can be very touch-and-go depending on where the actual infection is and how early it's treated with antibiotics. Once sepsis has taken hold, there usually isn't a lot modern medicine can do but try to provide comfort measures through medications, and pump the horse with large-bore doses of IV antibiotics, stress-reducing medications to keep them from panicking and their bodies from working too hard, and fluids while hoping the immune system is still strong enough to put the antibiotics to use and win against a case of sepsis. Sometimes, the bacterial load in the body is just too much or the infection has caused irreparable damage to a critical organ like the heart, and there isn't any other way to show the animal mercy but to euthanize. Most cases of sepsis, before death, result in a comatose state before the body completely shuts down from multiple organ failure, and it's an extremely miserable way to die. So yes, when euthanasia is discussed with horses, it's primarily when there is nothing else that can be done to make the horse's quality of life better while its suffering is only going to get worse (usually resulting in death) regardless of veterinary science or a limitless budget.

The problem with antibiotics in general is that they take time to work. If you've ever been miserable from something like a UTI or a chest infection, you know waiting 2-3 days for oral antibiotics to fully kick in sucks (IV antibiotics tend to work much faster, but still take a bit of time to reach full potency), because the infection is still there and causing intense pain and discomfort. The reason it takes so long is because antibiotics stimulate an immune system into going ham on an infection and destroying it. If there isn't enough time, or the immune system is already shot, then antibiotics may not be enough. End-stage or late-stage sepsis in pretty much any mammal is pretty much gonna be deadly, because sepsis is commonly called "blood poisoning" and kills by causing multiple essential organs to stop working in rapid succession - brain, heart, liver, lungs, etc. - like fairy lights on a string going out one by one after the first light fails. "Too far gone" happens, and that's when euthanasia becomes an open subject, because there's nothing left to anticipate for the animal but more suffering before they're going to die of their infection/injury.

Good vets will ALWAYS try to fight until the bitter end to provide options and other forms of intervention in saving an animal's life from disease or injury, but they also are specifically trained to know when a situation is just too beyond what they're capable of addressing and when continuing to try to treat an animal is only going to prolong its suffering before it inevitably succumbs to death. That's why prosthetics are becoming a thing for horses now! The cost of 3D printers have been going down, more designs for prosthetics are being published, and better materials are being employed for optimal horse comfort and recovery. Most injuries that result in a disabled leg in horses are caught and treated rapidly by owners and vet teams with no serious infections setting in, and so the main reason euthanasia has been employed for leg breaks and cases of amputation was more for preventing the horse from suffering without a mobility aid or prosthetic. Now, humans are catching up and figuring out what materials and structural designs work best in prostheses for horses, and we're seeing a huge increase in cases of horses surviving and living long, happy lives even after losing a leg!

[orangezinnia]

You seem to have lots of good ideas on how nastya's mechanisms works logistically, do you have any thoughts on how she respires? Cos oxygen and CO2 get round the body in red red blood cells, which she doesn't have.

Ashes, I assume, just has very thin, slightly porus areas that allow for gas exchange, but Nastua I am stumped on.

what's really funny about Nastya's mechanism, i think, is 1) how different it is from the others' mechanisms, and 2) how implausible it is to recreate in regards to the science that we currently have. (which is a pretty big dissonance from how her ARI / cybernetics are nearly reality!)

under the cut, because, hoo boy, this got Long!

i mean, think about it. their mechanisms are usually something solid that gets replaced- Jonny's heart, Ivy's brain, even Brian's body. but Nastya? hers is fluid, amorphous, unfettered. pretty strange, right?

and it's something that has to be Produced, too. not stable and grown like an organ or limb. i suppose this can happen in the same way that the mechs can "regenerate" whatever body parts they lose, but considering that the blood production system starts in the bone marrow, it's my personal headcanon that hers has been modified to make quicksilver, as my tags said.

regardless, that's point 1 over with. pretty short, but i'll bring us back to it later!

anyway, for the rest of the crew, their mechanisms are either something that science Has Already done, or is getting Very Close to accomplishing! like, for Jonny- there's no fully artificial hearts yet, but there's assistant devices, like the LVAD, that help it pump blood. there's even coronary stents made of metals like titanium, tungsten, cobalt, steel, etc.

with Marius and Raphaella, prosthetics are only getting more advanced with time, and as per my last Nastya cybernetics post, some even have haptic systems, i.e. Igor Spetic. for Ivy, MIT researchers have already put "tens of thousands of artificial brain synapses" on a computer chip "smaller than a piece of confetti", so who knows what advancements Carmilla could've made!

and with your mention of Ashes there- for a long time, the single implantation and subsequent long-term use of an artificial lung wasn't feasible, because our blood tends to clot when it runs over artificial surfaces, right? but in around... 2011? engineers started to focus on creating a biomimetic lung, with a structure that replicates the blood flow network and non-clotting surface of human capillaries.

and in a parallel experiment, there was an artificial lung (read: a small, flat, clear rectangle) made out of polydimethylsiloxane, a silicon rubber. it had a similar biomimetic structure, save that it was made for the purpose of air exchange instead of direct oxygenated blood delivery, featuring something close to what you guessed- a "gas exchange membrane" that oxygen and Co2 both diffused across.

to be fair, some of this IS just speculative, or else in a very limited testing phase, but a lot of it is based off of technology that we already have.

TLDR, everyone else has a mechanism where we can imagine how it might legitimately work, yeah? but for artificial blood, we've been stumped on that for a long time. and we still are!

from what i've read, the closest we've come to safely and commercially replicating blood is in one-time oxygenation injections... for dogs. with anemia. so, not quite what we're looking for, you know?

to answer your question, the most i can do is explain a bit about our closest-to-effective efforts for artificial blood, aka, PFCs (perfluorochemicals), and HBOCs (hemoglobin-based oxygen carriers)

ever seen that tumblr post about mice breathing in perfluorocarbon liquid? yeah, that's a PFC. they're very good at dissolving gases- both Co2 and oxygen. further experiments showed that long-term ventilation with it would require a sort of cycling system, instead of total submersion, but it's still pretty impressive, and that's why it's been looked into as a blood substitute.

PFCs aren't water soluble though, so they have to be combined with emulsifiers to work, which throws in a lot more issues to iron out- like severe side effects after transfusion from the emulsifying agents, and flocculation and Ostwald ripening giving them a poor shelf life. which means they're basically off the list.

not that this was an option anyway, since Nastya's blood is already quicksilver. i do headcanon perfluorocarbon to be what Aurora's blood is, though! since, as per the Who Killed Dr. Carmilla fiction, Aurora has veins that Nastya can be inside of! isn't that sweet? just like how a human can swim inside of a blue whale's arteries.

anyway, our current best bet for artificial blood is HBOCs, which are focused more on delivering oxygen than accomplishing any of our blood's other functions. since letting hemoglobin blunder around freely would wreck havoc on our bodies, they have to be either created or isolated from an external source, then packed up into a synthetic cell for delivery.

for example, in 2017, we got news of the testing phases of "erythromer", a "bagel-shaped artificial red blood cell", which is a cell made of purified hemoglobin, but safely coated in a synthetic polymer that is sensitive to changes in blood pH, picking up oxygen where pH is high and letting it go when pH is low. (there's also some talk of putting it in a transportable, just-add-water powder form. like a live-saving ramen flavour package.)

now, while that's likely our most scaleable method, i'd like to mention a June 2020 study which created artificial red blood cells, that apparently had "similar size, shape, charge and surface proteins to the real thing". they were made by coating real red blood cells with silica, layering on polymers, taking away the silica, then coating them with regular red blood cell membranes.

it's kind of a loaded procedure, and there was no proof that they could transfer any of their hemoglobin, drugs, and toxin sensor cargo, but in regards to the Mechanisms' futuristic setting, it's possible that Carmilla could have made something like this for Nastya!

Nastya seems to think that the healing factor of their mechanisms relies on nanobots anyway, saying that "They’re nanobot collectives, or biological agents, or something, that constantly remodel their hosts into their original programmed state". so nanobot red blood cells aren't out of the equation!

with all that said, this leaves us with 3 potential realities for Nastya's mechanism, going from least to most probable-

1) She is in a constant, lowkey state of dying-and-revival, with her blood unable to keep her living via basic red blood cell function, but unwilling to let her die. this is sad and i do not like it, nor is it very likely, or else her veins would have that constant self-regulating rainbow shimmer that we see in Drive The Cold Winter Away, for Jonny's heart, and in Cyberian Demons, for Nastya's veins.

2) She has a special sort of spquicksilver (space quicksilver) that has its own mock red blood cells. this isn't impossible, but since we never see anything in canon about her quicksilver being different from normal liquid mercury (beyond the healing factor), i can't say this is likely.

3) Similar to how nanobots might aid in the mechanims' regeneration, Carmilla had modified Nastya's bone marrow / blood itself to create 30 trillion artificial (or nanobot) red blood cells, and it continues to produce however many more she may need.

and say what you will about Carmilla, but for the efficacy of the mechs healing factor, she did a damn good job. i mean, look at all of the ways that Jonny's tried to get himself maimed and murdered! and he always came back at 100%! so i don't think it's a stretch that she could do something similar to give Nastya red blood cells.

anyway, remember when i said i'd bring us back to point 1? well, i'm doing that now. because mercury is a really heavy metal, and nothing in canon says that anything besides Nastya's blood was modified. it makes sense, too- her blood is that fluid, amorphous, unfettered thing, so it needs a lot of blood vessel passage ways to travel through her body.

100,000 miles worth of blood vessels, to be exact. with 10 billion capillaries that are only 0.0001 millimeters in size, and innumerable branches of arterioles and veinoles... yeeeah, i can't see Carmilla being too eager to replace all of that!

which means that Nastya's poor, normal human veins are trying to distribute liquid mercury. and if people with regular, non-metal blood can have their veins struggle to bring their blood back to their upper bodies (like in POTS), then i can only imagine what it's like trying to do that with, oh, you know. Literal Metal.

so while we may have figured out How she respires, it comes with the caveat that her lungs might not be getting good circulation anyway, from her potential spPOTS (space pots) :(

anyway, this was very fun to write, and i hope it answered your question!

[xadoheandterra]

SEP and how it Fucked Shit Up

Headcanons that play parts in Wanted and Salt and Sugar.

Jack:

So SEP did a number on its participants. Jack was part of “Wave 80″ (especially in Wanted as he joined SEP toward the end) which by that point the previous 79 “Waves” had been dwindled down to about 30 members. Each “Wave” contained about 15 subjects, so that should tell you the death rate I’m running with.

There were only 4 Waves after Jack’s, and then SEP ended because the Omnic Crisis went over hardcore. Every month the program pulled in new recruits, so a new set of 15 members joined SEP once a month, for 7 years.

(Gabriel was part of Wave 54)

The first few rounds of injections actually boosted the immune system and had beneficial boosts to overall traits. It’s in the latter half of injections that problems would crop up. By Jack’s time they figured out how to tune the cocktail to provide a mostly stable response. Jack get’s the increased stamina, healing factor, cell regeneration, boosted immune system, boosted nervous system, etc. Pretty much everything when you think ‘super soldier’ it was mostly hammered out by Jack’s wave.

The side effects for Jack thus were more minimal in their number. The biggest effect was nerve damage. They don’t know how or why, but after one round of injections Jack literally lost all feeling in his legs. He can move them, he can use them, but they’re completely numb. He can’t feel them. It’s like the worst version of your leg being asleep ever. It took him months to get walking again from the initial damage. He doesn’t need braces nowadays because he’s spent so long figuring out how to move without them, learning how to tell what might be a problem, judge his footing by his balance, etc.

But being numb in his legs comes with its own problems. Jack can’t tell when he’s injured in his legs, so 90% of the time if he can still move he assumes he’s fine. This has resulted in numerous instances of Jack breaking his legs and walking on them. Either because of stupid stunt a or stupid stunt b. Due to the amount of damage for a while during the Omnic Crisis he had to wear a sort of brace on the lower halves of his legs. Since Overwatch he has essentially prosthetic attachments to his feet to keep him walking. Permanent attachments. It was the hope that with these he’d stop breaking his damn ankles.

No dice, because it’s Jack.

The other big side effects that Jack tends to go through are really bad migraines, and some loss of bone density/strength. It’s essentially easier for him to break a damn bone than someone else. Because of this, and the nerve damage, Jack has to take specific supplements and keep a strict diet to ensure that shit doesn’t run the chance of getting worse.

Gabriel:

Being part of Wave 54 means that Gabe joined SEP right in the experimental phase. They’d been toying with the injection formulas like crazy at this point, so Gabe’s gotten all sorts fucked up. While he does have enhanced super soldier everything it came with so many drawbacks that there’s a question of is it worth it. For Gabe the problems started in the earlier injections. Due to the rapid cell growth Gabe suffered first from cancer. Nanites were introduced to mitigate the cell growth and curb it before cancerous cells could form, and to fight back cancerous cells that did.

The second problem formed out of the constant battle between the nanites, cancer, and rapid cell growth. Gabe started suffering from severe organ damage. Because of the nanites in his system, the cell regeneration/growth, and boosted healing the whole ‘death’ part of organ damage and failure never quite took. Gabe would reach the point of where he should probably die, and then hover there until he could bounce back.

Gabe will suffer heart attacks, his lungs will sometimes just collapse, his liver fails, his kidney’s go, his pancreas--it doesn’t matter what organ it is, it’ll fuck up at some point. Gabe is on a very fucking strict diet. He has to take more medicine than most people just to ensure his nanites get a proper helping boost. If he does something stupid like drinks a fuck ton he’ll probably end up in ICU for a while.

The nanites/healing factor/cell regeneration issue also compounds with sometimes his body just doesn’t know how to fix it when it breaks. So the nanites will pull from the people aroudn him to figure out what things are supposed to do, and then imprint that onto his cells.  This is what sets the stage for Reaper’s abilities.

(well, this and a really fucked up attempt at new-medicine healing combined with old as balls nanites)

Gabe doesn’t suffer any problems with his skeletal structure, although he will get the occasional seizure because of his nervous system freaking out. He’s also in a lot of pain a lot of the time, so he’ll hunt down ways to make him feel better. Angeal’s healing technology is actually one of the better pain relievers, but he has to be careful because it can mess with him something fierce. Something about the tech and his nanites not...getting along really well.

Oh, and both boys have a tattoo on the back of their neck. It’s to mark them as what subject, what wave, and which batches of SEP drugs they were placed in--5 batches total, 3 person per batch.

Jack’s is 801005 (Wave 80, Subject 10, Batch 5) Gabe’s is 540201 (Wave 54, Subject 2, Batch 1)