Blood Transfusion Basics with Ryan Breuer

Join us for a discussion about a study that looks at using bovine blood as an alternative to caprine blood when goats need a blood transfusion. 

In this episode we discuss a 2021 paper looking at xenotransfusion between bovines and caprines. This paper is titled Preliminary Investigation of Bovine Whole Blood Xenotransfusion as a Therapeutic Modality fo the Treatment of Anemia in Goats and can be found at 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969644/

Questions can be sent to Dr. Breuer at rmbreuer@wisc.edu


If your company or organization would like to sponsor an episode or if you have questions about today's show, email Office@AASRP.org

Transcript

0:40

Hello. Welcome to our next episode of Boz and Bleats, the AASRP podcast. Today, we are talking with Dr. Ryan Breyer, a faculty member at the University of Wisconsin Madison. Hello. It is so good to chat with you today. Great to be here, Sarah. Thanks for inviting me. Pleasure to be here on today's show. So Ryan and I actually went to vet school together. We were one year apart, right? We were in the food animal club together. So it's very exciting for me to have a fellow badger on the show today. So let's just start with a little bit of history, a little bit of how you got to be. Where you are today, where you went to school, all that good stuff. Yeah. Like Sarah said, I am an alumnus from UW and I, I have ventured back to my old stomping grounds, but I have I have an appointment here, both at the vet school, as well as the Wisconsin Veterinary Diagnostic Lab or WVDL as a client case and outreach coordinator. And what that means is basically I work with veterinarians Who send in samples for animals that may be having health issues or need something diagnosed. And if that kind of troubles them or have kind of stumps them, then I help with investigating or providing some information to help them investigate those disease incidences a little bit further. So, like I said I'm, I work at the WVDL, but I also work at the, the vet school. I'm a clinical assistant professor. In large animal internal medicine and that's kind of my role here at the, the UW. But going as far back as my background I'm from a diversified rural farm back rural farming community and background in Southeastern Wisconsin with an upbringing in agriculture and And large animals. I completed my vet school at UW in 2012, and then I practiced in large animal practice general practice for about two and a half years, and then found that I wasn't being challenged enough, and I wanted to venture on to, into other things. Venues and then I went to Northwest Iowa where I was a dairy field extension specialist with ISU Extension and Outreach and was there for a year or so and then was offered the opportunity to do a large animal or food animal residency at Iowa State which I did. I did that training program for about three years. It was a three year program and then after that, I was accepted back to my position currently here. At UW so at UW, I have a special focus in consulting with veterinarians, as well as teaching veterinary students and areas of my interest include Animal internal or large animal internal medicine, small ruminant medicine, concepts of AVMA approved humane euthanasia for large animal species, as well as herd health investigations and diagnostic and infectious disease consultations. So, long list there, but I enjoy doing all of the things here that UW allows me to do with all the different hats I wear. And Ryan is also super helpful with AASRP. We sit on a number of committees together. He helps with the student stuff. Basically my takeaway from all that you just said is if you have a case and you don't know what's going on, you're the person to call. You better believe it. Yes. All right. So ASRP members, Ryan's out there for you. Give him a call at the, at the diagnostic lab in Wisconsin, even though I live in New York and I I do consult Cornell, I tend to call Wisconsin still on a regular basis. I still feel like it's my comfort zone to call back to Wisconsin if I have questions. No problem. No problem. And we have no bias. So if we don't have the answers, we certainly send those diagnostic cases or testing that we'd have. don't have here. We refer that to other diagnostic cases to different diagnostic labs. And Cornell is on our list too. So, yeah, yeah, they do. So today we are talking to Dr. Breyer about his 2021 paper entitled Transcripts Preliminary investigation of bovine whole blood xenotransfusion as a therapeutic modality for the treatment of anemic goats. As we all know, barber pole worms or harmonicas are such a huge problem across the country. This is a nationwide issue, and then we can even say that it's a worldwide issue too, especially with humongous contortist resistance. So yes, it is found in all parts of the country as well as the world. All right. So along with all the other causes that animals get anemia, right? Like they might have a bad kidding you know, lots of disease processes, but really we, we watched the anemia with the worm and the resistance. I'm lucky. That and probably you too, Ryan, we live north where we don't have quite as much resistance. I won't not zero for sure, but less we're not the South. So it's not as big an issue up here, but I see anemic goats every day. I saw two today. We'll even see anemic animals from copper toxicity as well. So they go into that hemo hemolytic crisis too. So there's a lot of diseases that cause these animals to. Go anemic. So that's why we had this paper and focused on ways that can help us deal with anemia and small ruminants. So it was kind of our focus to look at how we might think about address anemia in small room, and it's specifically goats on this on this paper. And when we did not have the ability to have a donor animal for, for that transfusion as you may or may not know in the large animal realm, there's not a lot of, and a lot of times there are no commercially available blood transfusion products out there. So we have to rely on blood donors, whether that, That is from a herd member within your herd or flock, or from a hospital setting. At the University of Wisconsin, we do have some blood donor cows and blood donor horses. Unfortunately, we don't have any blood donor camelids or blood donor small ruminants. So in those circumstances we ask for producers or pet owners small ruminant owners to bring in a buddy to provide a transfusion. And sometimes they may not have a buddy that can be a donor to the animal that needs a a transfusion. Sometimes anemia is a herd wide issue as well. So taking blood from an animal that appears non anemic may not be a, a non anemic animal also when we're taking blood from animals, we're looking for animals that are typically larger in size than the animals that need a transfusion and then also animals that don't don't have a very high demand for blood. for the normal blood volume. So that is animals that might be in gestation or are in peak lactation. And this is a lot of times difficult, especially coming from the dairy state that we have goats from goat dairies or ewes from sheep dairies that are in lactation. So that kind of reduces the, the pool of blood donors. So that kind of spurred us to thinking, well, Can we run a pilot study that looks at this xenotransfusion? So, xenotransfusion might be a new concept or a new term to many people, and I just want to kind of explain that. It basically means, xenotransfusion, it's a process of transferring blood from one species to a different species. So, in this study, we are transferring blood from cattle, our donor, to goats. And then. seeing how those animals respond to this, this mixing of different species, blood which is not uncommon in the realm of veterinary medicine. So we knew that this was a possibility because it has worked in other small animal species, particularly dog, transfusion, blood transfusions to cats. And it works well because dogs are typically larger in size and can donate blood to our smaller cats. Now, with that being said, this is not typically done on a regular basis. It's usually done in more emergent or emergency type of basis, where either, you know, the blood stores in small animal, small animal, dog and cat hospitals. They're deficient in maybe a supply or there's agglutination issues or they, they have an instance where the blood cells coagulate or agglutinate to one another and, and clot and do not help that animal in that transfusion issue. So that's kind of where, where we came from with this idea of, let's see if we can use an animal with a larger blood volume, cattle, and use that in, in a species that potentially doesn't have a good donor. Right. So this study was basically two parts. So one was two goats that actually got the transfusion and then there was another section that was lab work. Yeah, so there was a, there was a live animal part, portion of this study, and then there was the lab portion. The live animal, we had a very small kind of shoestring budget. So we just did a very pilot kind of study on two animals that we provided a blood transfusion. Now these animals had lower PCVs, not low that I would say are in the severe category of anemia. And that's where I would say when animals need a blood transfusion typically I'm looking at pack cell volumes of 10 to 12. Now goats do great jobs of, of not showing their need for a blood transfusion. They can be at a PCV of 10 or 12 percent for a pretty extended period of time because their disease process typically intestinal parasites is a more of a chronic issue than an acute issue. When that 10 or 12 percent PCV becomes more of an emergent type of issue is when we have acute blood loss or hemorrhage, that kind of thing, or a hemolytic crisis because of a copper toxicity. That, that's when it's more emergent and this would kind of help those animals if a donor wouldn't be available. So the live animal proof of concept is that Can we do this? Will these animals respond positively or negatively to a xenotransfusion from a a cow? In this case, it was a nine year old Angus cow. She was healthy, no history of drug administration, and was non lactating and not pregnant. So, a great animal to take also blood from as well. And the laboratory phase was then to do our major and minor cross cross shoot across matching to see the compatibility of bovine and Kapron or, Goat cow and goat blood combinations. So we looked at how they, how red blood cells reacted to being put in serum or plasma and from a different species and then vice versa. So do the major and minor cross matching. And we found some promising information out of those animals. And I believe we had 15 cross matches. Between the recipient and the donor, the recipient was the, the small ruminant or goat in this case. And the donor was a cattle species. So we didn't we did not what's the term I'm looking for? They were both beef and dairy species that we used for our cattle. Same, same with our goats. Oh, right. So there were both. Yeah. Yeah. So boar, boar goats and toggenbergs were there and alpines. So back to the, the two goats that got the cow blood. So those of you have ever done a, you know, cow to cow or dog to dog or any sort of blood transfusion, the protocol is very similar. You know, you give it really slow and then you, as you see, they're not reacting, you go a little quicker. It was very, you're very typical kind of protocol. The goats did get some banamine ahead of time, which a lot of us will give anti inflammatories. I'm never sure if I should give. Benadryl or Banamine or what dose? So you guys chose Banamine at kind of a lower than normal dose. What, what, what was the decision making there? Yeah, I'm glad you asked this question. It's a good question, Sarah. We give an anti inflammatory or antihistamine because these animals anaphylactic disorder. phylactic reaction with blood products, especially when they're coming from other animals. So when I say blood products, it's not only blood transfusions, but plasma transfusions as well. And an antihistamine does exactly that. It's it restricts histamine response. So Unfortunately, I mean, we see antihistamines being provided such as diphenhydramine or what we call in the store, Benadryl, to small animals, so dogs and cats, but unfortunately, we can't really use that as a comparison to our small ruminants or large animals, first of all, because it's given injectably in those animals, and there might be some cost prohibitive to that. Prohibitive restraints that we may have giving an antihistamine I. V. to, to our large animals. Again there is also the worry of hypotension and I was doing a little bit more reading prior to this podcast as well when looking at the pharmacokinetics of diphenhydramine in other species. And there was a paper which we do reference here our paper to camelids and horses and the use of Diphenhydramine and they, they can cause some issues and what we've, what they found in that particular study was the diphenhydramine stayed around a lot longer. So the distribution was different as well in Camelot. So there's, There are species difference differences, and hypotension can certainly be a risk. I think it's quite low that that thought process comes from humans. So another kind of interesting study that I quick looked up to in humans is that You can cause, at toxic doses, cause hypotension, but also hallucinations and some other really bad effects. So it's, oh, hypnotic effects too. So there is a, there is a study out there that look at pigs with diphenhydramine toxicity as a controlled kind of pilot study as well. But The reason we, we don't use Benadryl or diethanhydramine is because there, there are some more contraindications there. And we know that flunixameglamine or banamine is, is used as an antipyretic or reduces fever. And that's one of the first things that we may see in a anaphylactic reaction is fever to An anaphylactic reaction after a transfusion. So, and, and that can really be detrimental to an animal too. So we're trying to suppress that and just be proactive and giving that at a lower dose. They don't have to have the higher dose, especially when we're thinking about an animal that might be feeling Not very well being anemic. These animals probably aren't eating and consuming water as readily. And we know that a side effect of banamine is renal damage as well as abomasal ulcers. So if we know that the. The kidneys are taxed because there's some dehydration there already. We don't want to give a, a very large dose of, of Banamine or Flunixin to cause further issues. And we will monitor kidney values before and after a blood transfusion because there can also be some Azotemia or issues with giving or providing a blood transfusion because when we provide blood transfusions, it's basically a bandaid to allow the bone marrow to produce more red blood cells. And that, that blood transfusion sometimes can only last about four days at minimum, but as long as seven to 10 days. And the more often you give blood transfusions, the likelihood of that transfusion lasting longer is pretty reduced. It typically is along that line of five or less days. With more, more concurrent transfusions. Also, it seems with the Benadryl and the Flunixin, you guys are looking to see what happens, right? You're looking to see how the animals respond. So if you do a bunch of stuff to mask it, you know, you're not gonna, you're not gonna, I mean, obviously you don't want to cause harm to these animals, but you do want to see, like, what does this blood do? How does the animal respond to this? Exactly. And even without xenotransfusions, when we're giving transfusions from one goat to another, or one sheep to another, even one calf to another, even plasma, doesn't have to be blood transfusions, we're monitoring these animals incrementally. So every 5, 10, 15 minutes, 30 That concurrently to make sure that if we're seeing any adverse reactions, such as increased heart rate, increased respiratory rate, increased temperature, if we have urticaria, which is hives or hair standing on, on, and those are all reactions that the animal is potentially having anaphylactic reaction so that we can stop the transfusion and provide some more antiphylactic medications so that these animals don't go into a crisis. Yeah, and that's not just in the vet hospital. Those of us who do it in the field, I mean, primarily the blood products that I give are plasma to CREAs. And yeah, it's scary. Even when you're giving something like, Plasma from another camelid and you know, it's like this or die. I swear, I just keep my stethoscope on their heart the whole time. I'm so paranoid and you have all your little syringes lined up. So yes, it's not just something they do with a vet hospital. We all do that whenever we do this. Yeah, it's really, it's really important to keep those parameters in mind and see if there's a trending up or trending down because that will help you get ahead of what, what could potentially be a dangerous situation for those animals that are potentially already critical when you're, when you're providing this therapy. Yeah, because at least in the field, a lot of times these are last ditch efforts. I just want to step back. Ryan had said one of the things that this can cause is azotemia, and I just want to define that quickly. It's just a term we use for basically when there's a buildup of nitrogen in the blood. So if the BUN and creatinine are the, the kidney values that we, monitor through the blood. And so if the BUN is elevated we know that the kidneys are not filtering out the nitrogen like they're supposed to. And that, that's a symptom, it's not a disease, so it can be caused by many things. Is that a good definition, Ryan? Yes. And, and I will say that in, in both of our animals here, so we did see a little bit of, of reaction. Unfortunately we did not have the, the laboratory phase completed before the live animal phase. So we did not have the compatibilities of the bovine transfusion or bovine donor to the recipients before we did the trial here on the two animals and there was a little bit reaction. They did fine. They, we stopped the transfusion on one and the other one we completed and we did look at blood values and there was some mild elevation for the creatinine on the one. And then there was a little bit more, I would say above mild, but not so much that we would call it severe. So probably about moderate acetamia and BUN and creatinine on the other though but after some, IV fluid therapy. We had no issue. Okay, so when you were giving the blood, you did see reactions in the animals. Can you talk to us about that? Yeah, so we we did see some mild issues come up on on these girls. Sometimes we do see that see this, but Not as significant from a standpoint of we start seeing elevated heart rates and elevated respiratory rates and elevated temperatures. So, for the first doe we, we were able to administer about 300 mLs of bovine whole blood. And we did start seeing a little bit of hyperemia around the vulva, some urticaria. So, again, that's kind of your that's your Like rash of the ears and then some pilo erection of the hairs over the animal. And then they developed some loose stool. And this transfusion lasted 105 minutes but we saw resolution of these signs after that transfusion about 20 minutes. So this animal did not have significant anaphylaxis, but she did have some, some reaction. The, the second doe she only received a little bit more 319 mils of whole blood and At about 75 minutes into the transfusion we did know some agitated animal. She was restless and she would kind of get up and lay down. And then we said, okay, stop. We have to, we have to stop this transfusion. She also developed some pyorection of the hair and then swelling along the muscle, which did go away but some of that swelling around the muscle did last into the, into the next day, but after 24 hours, she was back to normal. We did do some blood work on them and noticed that they did have one had slight azithemia, one had a little bit more azithemia than the other, which was seen as an increase in the creatinine. But then this had resolved again within the 24 hours after some fluid therapy in these animals went back to normal behavior within 30 minutes of the transfusion. So we were quite impressed in how well it How well they responded now I will say that that second dough just because of her behavior. We did provide a little bit of epinephrine, for support and she developed that normal behavior after 30 minutes. So just wanted to clarify that, that we did not let her suffer or anything. We were under IACUC protocols, so we have certain things to follow to make sure that no harm is done and we make sure that the patient's well being is, is first and foremost held up. So even though, even though there was reactions, we still consider this a successful transfusion, right? I mean, I, I feel like I've never given a blood transfusion where there was zero reaction. You know, there's always some mild kind of reaction. Pyloerection is basically furred animal goosebumps is how I explain it. Yes. When their hair stands on end. Perfect. Yeah. Right. And so So even though those reactions occurred, we still would consider this a successful Yeah, and like I said with, with the information we knew after, with the laboratory phases and doing major cross matches and a minor cross match matches we did not have that set up until after the live animal proof of concept. So we have that information later because not always do we have the capability of doing major and minor cross matches, especially in the field. Right. Correct. Correct. And a lot of times because of the different type of the different blood types, and I do have a great like supplementary paper that is, is great for those who have not done blood transfusions. It's in the Vet Clinics of America. There's a great Chapter on the use of blood and blood products and ruminants and they go through how much you should take, how you should prepare the animals for blood transfusion and then they also mentioned that there is not We don't have those capabilities to do my major and minor cross matches, but they also talk about cattle who have 11 genetic systems of blood groups and sheep have Eight blood group systems and goats have six blood group systems and camelids have not so much studied about them But they do have identified six blood group systems, but there certainly could be more What's interesting to know is that there's factors or glycolipid antigens that cause reactions. And for what we know in goat blood is that they don't have these These factors as of what I know from these studies which make them great recipients for decreased reactions to blood transfusions. So we will say that we wish we had maybe some better and like compatibility and wish we had to have the ability to do the cross matching before we had the live animals. But we use this as more of a. in the fields type of approach that not all the time will there be cross matching available, and a lot of times small ruminants will accept blood transfusions without that cross matching and have no issues. Right, right. All right. For the cross matching it was a group of animals. That donated blood as far as donor donor blood and recipient blood. And then they went through a couple of different processes. I won't go into that. I I'll let you read on about how we cross matched there, but then we looked at their compatibility and there were there were some criteria that looked at macroscopic agglutination. And then we had a scoring system. So a score of four plus was incompatible reaction. It had one or two major solid clumps with clear plasma down to three, two, and one incompatible reaction, which was numerous small clumps and barely visible macroscopic agglutinations. And then we had an incompatible. So there's one plus, and then incompatible, which was, red blood cells aggregates observed on the microscope evaluation. Now, we know in small ruminants and cattle, we don't have a lot of that agglutination like horses and dogs and cats do, where their blood, red blood cells kind of stick together a little bit easier. But in our ruminant species, we don't typically see that. So when we do see that, we know that there may be some incompatibility. And then we also looked at compatible. So when there was no macroscopic or microscopic agglutination detected when we processed these samples. And we talk about how we washed the red blood cells and we took the serum from one of species and the red blood cells from the different species and mix them together to see how the red blood cells responded. And all in all we only, We only had four incompatible reactors or cross matches on a macroscopic agglutination scoring system. And then all of our minor cross matches were compatible. So this, this makes us more intrigued to see, hey, can we use bovine blood with the, our small small ruminant species, particularly goats in this study? For this blood transfusion process. So, and if we can have the ability to do cross matching, this would make us more comfortable to say, all right, this is a good match from, from a cow to, to a goat. And we, we have less fear of it causing some anaphylactic reaction. Yeah. And can any lab do that? Or is that like a specific thing that only certain labs would be able to do? A lot of times, now in an emergency situation, which typically this would be, we wouldn't We wouldn't probably have the opportunity to, and a lot of times we're doing this at 10 o'clock at night or after because they are hemolytic crises. But when we do have that, that our lab here at the W sorry, at the, not at the WVDL, but at the vet school, they have the the ability and the staffing to do cross matching. And it takes the special reagents that they rinse and wash the red blood cells. It's a saline solution, base solution, and they have to centrifuge them down and create a red blood cell pellet. And then have the people that have the education to evaluate whether there's a glutination occurring or not to do this. So it's more or less Done in, in a lab setting to see if there's that reaction or not. There's not a particular test, not that I know of. It certainly could be out there for other species, but I don't know if that's out there available for small ruminants at this time. I did try to Google to see if you could buy goat blood or cow blood online. Yeah. Have you done this before? You can buy bovine blood, but it's for research. So it comes in these tiny little like 120 mil vials. I don't know what people do research for them, but and it, and for like this little thing was like over a hundred dollars. Yeah, it's, it's quite expensive and blood transfusions are, are expensive. It's a life saving. Treatment or therapy. So it's going to be a little bit more expensive. And, and the reason why it's expensive is because either you have to have a donor and you take blood from that donor right there and right then or if you do have the opportunity, like we do here at the, at UW, we do have cow blood donors and horse blood donors. We can draw blood from them and then store it, but similar to small animals, cats and dogs. There's only a certain length of time for a shelf life of blood and in blood transfusions or blood transfusions that we store blood from cows, we go back to our, our small animal. colleagues. And typically, depending on the bag that they're collected into and the reagent that allows for those red blood cells not to die off, because they do need glucose and energy, basically ATP, to survive on the shelf, it typically has anywhere from a 21 day to 42 day shelf life for those blood products. Oh, wow. That's really short. Correct. Correct. I mean, plasma, we can freeze and that's Has a much longer shelf life, but and we can and we can freeze or keep at very low temperatures we don't want to refrigerate that blood because there's always a chance for bacterial contamination so we want to freeze that and we do freeze that and we have to thaw it out very slowly because again there can be some denaturation of proteins on the thawing process end one other thing that we should be cognizant about when providing blood transfusions, even from the same species, is disease status. Now this is the diagnostician coming out in me, because that's all I do every day is look for disease or look for infectious disease. And, Providing blood product or blood transfusions is by no means no risk. So what that means is there certainly can be animals that are not clinically ill, they're clinically healthy but can can be carrying infectious diseases. So in the, in our study we did look at or we do know of bovine animals or cows providing blood transfusions and they are able to transfer bovine lucosis virus in that blood transfusion. Now, we should keep that in mind because yonis can be transmitted that way. So a lot of times when we're purchasing plasma products from a commercial entity, they screen their animals for these infectious diseases to reduce the chances of Of cross contaminating or cross infecting an animal who's receiving a blood transfusion this with this being said, we can certainly do our best in in looking for those diseases, but they certainly can be there and they're certainly a risk. I know during my residency, I remember this as a very good learning. opportunity for myself is when we did a blood transfusion from one camelid to another camelid we found out that the recipient of the blood transfusion also received a hemoparasite known as mycoplasma hemolame. And it was because the animal that was donating that blood also had mycoplasma hemolame. So we had to treat the, the recipient with oxytectocycline. And, and everything went well, but it's certainly important to screen for infectious diseases that can be carried in the blood from asymptomatic carriers. So that's just one other thing I want to make sure that's well understood is that blood transfusions don't go without risk, but it's really important for us to also monitor for those risks and look for infectious diseases in anyone that's going to be a blood blood donor. And I know at the University of Wisconsin we do do that screening, especially for if you don't have buddy donor to come along with your goat or sheep. We have a program at the UW where we encourage people to have their animals be donor animals, and then we will cover some of that infectious disease testing costs. Nice. Yeah. That's a great point for sure. Unfortunately, like everything else when you're in the field, it's going to be last minute probably. So, hopefully, hopefully your vet knows, like. Oh, I have this herd of cows that I know is really clean and well tested. You know what I mean? So correct, correct. On your own farm or something or enough goats or goats that aren't lactating or gestating, so. All right, great. So Dr. Brewer's email will be in the notes of the podcast if anybody has any questions and would like to reach out to him. So as with all of our podcasts, I have my final wrap up question that hopefully you've been thinking about. What do you see as the next problem that researchers need to think about and address in small ruminant medicine? It can be in your own field, outside of your field reach for the stars. Yeah, this is a great question. And unfortunately, I don't have a particular disease that might be up and coming, but coming from a diagnostic lab perspective I guess I would, say I think it's important to send in samples to diagnostic labs for further investigation. We might not have a slam dunk diagnosis on some of those samples. And a lot of Sometimes those samples may be a post mortem or after death sample. Sometimes we don't know what caused a disease and why an animal fell ill and died. But over time, we collect this data, and we sit on mountains of information here at the Diagnostic Lab, and I wish I could split myself into four so that I could go back retrospectively to look at the data. different species and different disease entities like abortions or respiratory disease or enteric disease so dealing with the GI tract. And then see if there's any trends particular age groups or breeds or male versus female kind of issues. And we can gain a lot of information. So I do encourage The listeners to understand that even though if an animal passes away it is good to send in samples if we don't have a, a strong feeling of why this animal passed away, because it's important to kind of look at those infectious diseases and to see why this is happening and is there a possibility to, to further investigate what, this is happening. What cause, what causes this, or why is there, why there is a higher incidence in, in one particular animal over the other. So I don't have anything that's up and coming right at the moment, but just kind of keep that in mind that diagnostics are good for learning and investigation, and hopefully it gives us better understanding in the future for the people that come and the animals that come. Right. It's a little bit of help us help you, right? If the vets out in the field and the producers are willing to send in samples and help diseases get diagnosed. You guys can help us better in the future. Yeah, and that's what helps us with creating these ideas. Investigators are, what we call it, clinical medicine and more of a scientific based clinical medicine so that we can utilize those samples to help us create new diagnostics, to create new treatments and therapies or management practices. Great. All right. Well, this was a super interesting study. I love the studies that are so applicable to, you know, day to day life for all of us out in the field. Thank you for doing it. And I'm sure there'll be more on this in the future, I'm guessing. Yes, yes, we'd hope to have that opportunity to do more studies into this kind of topic. And if there are questions, they can certainly reach out to me. Unfortunately, I'm not one of the social media aficionados. But I do have an email address that they can send to me. Any questions, it's rmbrier at wisc. edu. And that's just my email at the university here. Perfect. Thank you so much for sitting down with me today, Ryan!