DIP Episode 413 - USMLE Step 2/3 Rapid Review Series 83

Welcome everyone, my name is Divine, this is episode 413 of the Divine Intervention Podcasts. In today's podcast we'll be continuing the rapid review series for Step 2, Step 3. This will be Series 83. For taking your USMEL exams anytime soon, I have a test against strategies class tomorrow. It's going to be from 5 to 7 30 PM Pacific Standard Time via Zoom. If you're interested, shoot me an email through the website and I'll give you some more information. Let's jump right into it. What if they give you a question about a 25-year-old female? They tell you that for the past three months she's been having some diarrhea, some constipation. They tell you that all the labs are normal. They tell you that the physical exam is completely fine. They tell you that the patient has not lost weight between visits. They tell you that the ESR CRP is completely normal. The person has a history of depression. You see stuff like this, what should you be thinking about? I really hope you're saying, oh, Divine. This sounds a lot like IBS, inflammatory bowel syndrome. IBS is something that many people screw up on exams. But the presentation many times is pretty consistent. It's going to be usually a female, young female, so not a person that is like middle aged or very old. It's going to be a young female with essentially almost like intermittent constipation, intermittent diarrhea, sometimes you can have both.

Many times when they poop, when they defy cake, when they have a bowel movement, they feel better. When you see stuff like this, think of IBS. Typically, when people have IBS, they don't have any physical exam findings. They've not lost weight. They don't have signs of my absorption. Usually, they also have no lab abnormalities. The ESR CRP, everything will be fine. When you see a person that has these kinds of symptoms, you start seeing lab abnormalities like anemia, signs of my absorption, hypocalcemia, weight loss. You need to be thinking about some organic GI disorder like inflammatory bowel disease. Remember, IBS is not the same thing as IBS. You also want to think along the lines of things like Crohn's UC, just some organic disorder. Just to reiterate, people that have IBS, they have no lab abnormalities. They have no physical exam abnormalities. They tend to have intermittent constipation on diarrhea. Most times, it gets better when they have a bowel movement. In fact, when you want to diagnose IBS, it's pretty high to know. They use the room criteria. Essentially, the thing that typically happens is, you will notice a person that will have abdominal pain. Usually, when they poop, it feels better. It literally gets better with the defecation. And they will also notice changes in their stool. How many times they poop or how the stool even looks. And the stool frequency is to the parents.

And another thing that you also notice, again, usually they have some kind of psychiatric history. It's not always the case, but it typically do have some kind of psychiatric history. So again, there are three things that are part of the room criteria for IBS diagnosis. The way those the way of stool look, as it changed, has the frequency with which you poop changed. And then the third thing, right, is abdominal pain that's relieved with a bowel movement with defecation. Really, if you meet like two out of those three criteria, and then obviously, if you meet all the impure, but you need to meet at least two out of those three criteria to be diagnosed with IBS. So how do we treat IBS? Well, the thing is, there are many kinds of IBS. You know, there's IBS constipation. We do have like constipation predominantly. There's IBS diarrhea, we do have diarrhea predominantly. And this is the mixed IBS M IBS mixed. We literally have both constipation and diarrhea. So typically the stuff you try to recommend for these people is typically the first thing that makes sense is lifestyle. Right, tell them to exercise, tell them to add fiber to your diet. That's usually like a smart thing to do for these people, holding exams. But many times our friends at the MBA meetings just straight up want you to know from our therapy. So just ask yourself, in the question that I just read, was the predominant symptom? Do they have a lot of constipation? They have a lot of constipation.

What makes sense that a treatment should be something that causes diarrhea. Right, so things like laxatives are pretty helpful in people that have IBS. So things like polyethylene, like all lactolose can literally be correct answers for IBS constipation. You can also use lube perstone. Right, lube perstone is a drug that can essentially promote GI motility. So it's very helpful in people that have IBS constipation. But if a person has IBS and the predominant symptom you read in the question is diarrhea, then obviously you need to kind of slow things down. Right, into slow things down. So you give them what we call an anti-spasmodic. Anti-spasmodics, and I'll kind of talk about the battlefield phase behind IBS in a bit. But anti-spasmodics are pretty helpful because there are essentially things that prevent your GI tract from being a little too antsy. So because that antsy GI tract causes diarrhea. So if you kind of make it less antsy, that would be helpful. So if you use drugs like dicyclo-min, you can use drugs like dicyclo-min. Dicyclo-min is essentially an anti-colonurgic drug. Because think about your parts and the athletic system makes you want to poop. So if you take an anti-colonurgic drug, it's going to make you not want to poop. And if you have a lot of diarrhea, you don't want to poop. So you take dicyclo-min. It's very helpful in those circumstances. I'll try to say that I'm anti-depressant. So I'm also really helpful. Especially for IBS diarrhea.

Because again, TC Es, as I've said many times on this podcast, have anti-harm side effects. So the H is for the harm, right? The H stands for anti-H1. So anti-Histamine. The H stands for anti-alpha one, right? And then the H stands for anti-muscorinic. So that's anti-colonurgic. So it's helpful for IBS diarrhea. But it's also helpful for treating some of the neurocyc symptoms like depression and anxiety that you may see a company inflammatory bowel syndrome. So those are just all things you kind of want to keep at the back of your mind on exams. Sometimes you may want to see an anti-histamine treatment for IBS. It's actually really helpful in people that have IBS just in general. Now let me explain the pathophys behind IBS. To be honest with you, there's not a lot of really great pathophys out there. But one of the simplest ways I would say you could understand IBS is think of it as asthma of the GI tract. If you've been that mental picture, it'll make things really helpful for you. Because think about it, right? Has a lot of parallels with asthma. People that have asthma, their airways are just very sensitive. They're like super, super, super sensitive, right? Especially the smoke muscles in their airways, super, super sensitive. That's pretty much the exact same thing that happens with IBS. The smoke muscle that constitutes those people's GI tract is just super sensitive. So it's almost like ANC and things like that. So it just kind of causes these weird bizarre symptoms.

But again, many times these people have a psychiatric history. So again, if you kind of know these things, I think you've been pretty good shape for exams. Now, what if they give you a question about a patient and they tell you that this patient has a history of, you know, Reynolds phenomenon, the GERD. And that now this person has been having for the last few months, chronic abdominal pain, if you've bloated all the time, things like that. When you see stuff like that, I would really hope you're thinking about a SIBO. SIBO means a small intestinal bacterial overgrowth. SIBO means small intestinal bacterial overgrowth, right? So it's something that typically happens. Like this person obviously has chryscular derma. Remember chrysct, the C-stance vocalcynosis, R-for-innotes phenomenon. So when those people step out in cold weather, their digital arteries begin to become visospastic and they begin to construct, right? So they don't produce their periphery and then they start getting hypoxia, right? So their digits get blue when they step out in the cold. And in the East Dance Facial Giotis motility, it's just voting to have GERD. The East Dance Facial Giotis is the T-stance Facial Giotis. Remember chryscular derma is associated with all five of those features, right? So these people sometimes they can literally, remember the essentially fibros, a lot of things. So they can fibros, they're GI tracks, right? And when you fibros, you're GI track.

It begins to have this phenomenon we call E-peristolsis. So it doesn't really pair with stols anymore. And when it goes in pair of stols anymore, then bacteria, I kind of think of it this way, right? Like you kind of know this, where when something is static, infection can build up behind it. That's literally like a concept that I'm sure you've probably learned starting for step one or something. When something is static, it's almost like you're kind of creating a set-to-man spot for bad things to happen, right? Like if you leave food open and it just settles, then bacteria is going to build up in it, right? You know, GI track literally pair stolsis has like, almost like antibacterial function, believe it or not, because it kind of keeps things going, keeps things going, keeps things going, right? It just comes in, it keeps those bacteria moving along. They never feel like completely comfortable so they don't have any time to overgrow. But when you have a pair stolsis for any reason, in the bacteria, they're like, okay, well, this looks like a place we're going to settle down. Looks like we've got in our visas and passports, so let's just chill here. A windy chill, well, that's not going to be a good situation for you, that's for sure. So this person that has crystal or derma they've literally fibroused the GI track and because they have fibroused the GI track, they have a pair stolsis, bacteria is going to build up, and they're going to get in trouble.

And as those bacteria builds up, you know, they elaborate all these gases, causes bloating, causes abdominal pain, literally gas in the GI track hurts. That's why you see all these people that have a small bowel obstruction, it just hurts a lot. So that bacterial overgrowth, the elaborate gases cause abdominal pain, causes the area, causes all these issues. So those are things that you can certainly find in scleroderma. Sometimes those people need antibiotics so you can kind of kill off those bacteria. And since we're going to talk about this whole, if something is static, you're getting trouble, business. This maybe makes some more integrations here, like you see what might that's pregnant? And you see I keep getting UT Is, well, it's kind of because of the progestin. Progestin is very good at relaxing the small bowel. Especially in many parts of your body, really like your relaxes, the small muscle of your blood vessels. That's why your average room is not pressure, it goes down a bit with pregnancy. And it also relaxes the small muscles of your uridors. So, your uridors are not going to be contracted as much as they should to kind of move the urine along. So the urine is going to stay, bacteria is going to build up, and if you're going to get a UTI from that. So that's literally the pathophys behind women, pregnant women having an increased risk of UT Is. If you think of a person that has obstruction, right? If you're looking at this, again, static things cause trouble.

You look at a person has like colliduclethiasis, where you're common bowel doctors obstruct it, or collisistitis for your cystic doctors obstruct it. And when those things obstruct it, your bile is not moving along. So bacteria is going to build up, either in the common bowel ducts that's the same in colinjitis, or in the cystic ducts, that's a kid colisistitis. Right? So again, your body really likes to kind of move things along so you don't get in trouble. And remember, just kind of jumping back to a crest where a derma business. Remember a crest where a derma is associated with anti-centrum here and T-buddies, right? So it's associated with anti-centrum here and T-buddies. That's something that's pretty high, you'll to know for exams. Now in terms of SIBO, small intestinal bacterial overgrowth, remember that's something that can also happen when you take PPI's. Because remember, those acids, the acids that you're making your stomach is not for fun, you know? It's pretty helpful for making things work as they should work. It has like anti-bacterial properties. But if for some bizarre reason, just that taking a lot of PPI as well, you're going to inhibit that hydrogen potassium pump that we find on the epical surface of the parietal cells. So you're not going to make acid anymore. Acid gone, anti-bacterial properties gone. So bacteria has gone over a girl, right?

So PPI's can paradoxically, if you see a person, having a lot of diarrhea with PPI therapy, a lot of blood in, a lot of abdominal pain, think of a SIBO, think of a small intestinal bacterial overgrowth. Or if you see a person that has had like gastric surgery, and you notice that, man, there's people having a lot of diarrhea, blood in and what not, can think of SIBO. Because sometimes when people have some gastric surgeries, especially gastric surgeries that involve vagotomies, right? So vagotomy. Remember, the vagus nerve is parasympathetic. It's one of the primary stimulants of acid secretion, your GI tract. If you grow vagotomy and mess up the vagus nerve, especially like a gastric surgery that involves a vagotomy, then you're not going to be able to make acid, and that's going to cause a SIBO. That's going to cause a small intestinal bacterial overgrowth. Or if you risk the part of the stomach that continues your parietal cells, then if those parietal cells are gone, then you're not going to be able to make acid. That can cause SIBO. Again, you'll see me make this big force about SIBO, SIBO, SIBO, SIBO, SIBO, SIBO, SIBO. I'm saying all these things, because it's a pretty high yield point too. It's a pretty high yield point to know, for example. And another high yield point I'll make in terms of exams. If you're taking your USMEL Es any time this month, the month of September, I have two courses that may be helpful to you, actually three.

In the beginning of this podcast, I talked about the test taking course, the sticking place on the second of September, which is tomorrow from 5 to 7 30 pm, specific standard time. You can still sign up. Lots of people have taken that course, don't extremely well on their exams. I get feedback from it almost every day. Then I have a four hour biostatistics bootcamp. It's going to be taking place on the 16th of September, from 5 to 9 pm, specific standard time via Zoom. Then I have a 20 hour course. It's going to be from the 19th to the 24th. Although we won't be on the 21st, so we'll meet that week Monday Tuesday Thursday Friday and Saturday, from 4 to 8 pm, specific standard time on all five days. You know, via Zoom, review a lot of stuff from IAM, surgery, PEE Ds, will be going neuropsych, bio-stats, ethics, communications, health care systems. You know, and you know, we review bio-stats, although you'll be on more of like a survey, right? But many people still find that bio-stats, review it to be helpful. But if you want a very deep dive into bio-stats, we are not just memorizing formulas, but you can understand how to navigate through problems that don't involve a lot of math. You definitely want to attend the bio-stats bootcamp. I don't know if people attended. I found these really profoundly helpful. I'm telling you that bio-stats course will help you significantly.

Because most of the NV Me questions these days, don't involve math at all, with bio-stats, it's just a lot of thinking and reasoning. So, I want to get you thinking and reasoning straight. You want to go ahead and attend the course. So, if you're interested in any of these courses, just shoot me an email and I'll give you some more, some more information. Now, the final thing I want to talk about today that I think kind of screws people up is differentiating obstructive sleep apnea from obesity, hypofintilation syndrome. I think that's one thing I want to delve deep into. Because the pathophysiology is very similar. But, they have some slight differences. So, in OSA, it's going to be a person. They feel tired during the day. They feel sleepy during the day. They snore. Many times they obese. And, you know, they feel tired during the day because their sleep is very interrupted. This sleep is very, very interrupted. And, typically, those people, right, the diagnosed, you know, you diagnosed, OSA, and also, I guess, narcolepsy, when a polysominogram, that's a sleep study, polysomnography. That's how you diagnose OSA. But, OHS is kind of like just a more severe form of OSA. People that have OHS, those people are usually like super obese, like their BMI's are like astronomical, like not like BMI's 27. Now, most times, their BMI's like 50 or higher. Although, it can be certainly less than 50, right? But, those people are obese. And so, by definition, so just, please be careful.

For persons BMI's on the 30, I would really hope you're not diagnosing them with OHS on exams. OSA, you can diagnose them. People that have BMI's on the 30, that's fine. Because, there are people that are normal with the Hav OSA. Whatever person that has obesity, hypofentilation syndrome, on NBM's, by definition, should be obese. Remember, the definition of obesity is that your BMI is over 30. So, for persons BMI is on the 30, they don't have OHS. That's, I think, that's a pretty simple role to follow there. And then, secondly, people that have OHS, they have hypoxia and hypercapnia during the day. That's one of the primary things that can help you differentiate OSA from OHS. People that have OSA, usually, they have problems or at night. People that have OHS, typically, they have problems at night and during the day. They have many of the very same symptoms as a person that has OSA. But, they have those nighttime symptoms as well during the day. So, during the day, when you check there are two sets, it will not be great. It will be low because they have a build-up of CO2. I mean, it will be like, wow, okay, the fine. So, how do we diagnose OHS? Really, the same way you diagnose OSA, polysumogram. And these people, typically, you recommend a bunch of stuff for them, right? I mean, the primary treatment is C-PAP or BIPAP. Typically, you do that at home.

After you've diagnosed them by polysumography, but it's also pretty high, you know, that these people should try to lose weight. When you lose weight, you'll, some of the fat that's going to put in your ear, it goes away. And that'll be really helpful for helping you just breathe better. And, you know, people that have OSA and OHS, they tend to have like very, sometimes some very strange symptoms. Like, you may see them, they're urinitine, like they, they notice that they have to wake up many times at night to urinit. The thing is, when you have OHS or OSA, again, you know, breathing in well, you're kind of hypoxic. Whenever you have hypoxia, right? Your pulmonary vessels, that causes them to constrict. That causes those pulmonary vessels to constrict. And also, if you think about it, people that have these conditions tend to have a lot of hypertension. So, logically, so this may not be scientifically accurate, but logically, it makes sense that if you're hypertensive, your body will try to get rid of some volume, you know? Because if you can get rid of some volume, you'll bring down your blood volume, you'll bring down the blood pressure. So, many times, people that have OSA OHS, especially OHS, they tend to have like a big time release of A and P, HL-nutriotic peptide, nutriasis. Because again, just think of it as a concept. When you're hypertensive, you want nutriasis. When you're hypertensive, you don't want your EDH to be high.

Because that's kind of counter to what your body is trying to achieve. When you're hypertensive, your body wants to lower the blood pressure. Your body doesn't want to be in viso-constricted, which is what it is. Because I'm going to think of EDH as, oh wow, anti-diarrhea, that's all it does. Yeah, it helps you reabsorb fluid from your kidneys. But it's also a very powerful viso-constrictor. I'm literally, when you hear people in the ICU get viso-person, what do you think it is? It's literally an EDH analog. It's a very powerful viso-constrictor. When you're hypertensive, you don't want EDH activity. Because it's kind of hitting you in two ways. One, it's making you reabsorb more water. That's raising your blood volume, raising your blood pressure. Two, it's causing a very powerful viso-constriction. That powerful viso-constriction is increasing your systemic vascular resistance. That's going to jack up your blood pressures. But if you're a natural retic peptide, it just comes into save the day. It pretty much downregulates EDH production. So you're beginning to lose a lot of blood volume in your kidneys. And you're not as constricted anymore. You're more diluted. So that's why it's, that's why AMP is, it's pretty helpful. It's pretty helpful. And again, if you think about all of this, you understand why drugs like sacubitra are used in heart failure. You know, they're providing inhibitors. They're providing inhibitors. They essentially prevent the breakdown of AMP and BMP.

Right? If you prevent the breakdown of those things, then you're going to persist more in the circulation. When they persist more in the circulation, they will cause a diorases. It's literally your body's own water pill. So you're going to be losing that volume, which is great for the person in the heart failure. Because if you have heart failure, you can't deal with it. You cannot really deal with extra volume. That's just the truth. So giving an inhibitor is very helpful. That's why actually there's these drugs that are RN As. Right? If you're afraid of the drugging, trace, dose, and RNA, it literally is an arb like Valsartan, and an inhibitor like sacubitra, combined together, they actually improve survival in heart failure. So that's something to keep in mind for, for example. Just keep those cluster of concepts. You see a lot of integrations, but it kind of explains many different things. So about the half OSA OHS, again, as we're saying, they tend to have like upper and related etioranotratic peptide. So they have more diorases. So that's important to know. You know, these people sometimes you may notice they have polycythemia. Because again, when you're hypoxic like that, your body's going to be like, this is not good. So let's make more EPO. When you make more EPO, you're going to stimulate your rib blood cell precursors and you'll be making more rib blood cells. So this will kind of have polycythemia, right?

It can develop pulmonary hypertension, it can cause right heart failure. Because again, that hypoxia causes viso-construction. Right? So there are just so many things. You may notice in these people. Right? Then again, that no sort of polysominogram, surely will see pap by pap. So I think I'm going to go ahead and stop here. And again, maybe I should say one more thing. Well, these people that have like OHS, for example, right? Again, you know, they have this hypoxia, right? That's going to build up the ap CO2. So they're going to be having a respiratory acid doses. Right? So the body's going to try to compensate by beefing up that bind carb with a monicaucalosis. Right? So just again, kind of keep, I just feel like all these things, these are classic concepts like, you may say, oh, divine, does this only apply to OSAOHS? No. They can literally make a COPD question from that. We're present at the House of Chronic COPD. You know, they'll have the respiratory acid doses for the metabolic ocalosis as compensation. These are just all things they can make as exam questions. So just going to keep it in mind. You know, don't over. And one thing I guess I will say here, I don't know why I just kind of have this burden in my heart to say it. Many people kind of over face to problems with exams. One, they don't have the understanding. So make sure that you understand it is right. I feel like this is something I've been saying quite a bit. I think my course is recently.

Many people, they're kind of struggling with these USML Es because they're very heavy on these flashcard tools. So they're very great memorizers or very poor understanders. You know, you don't want to be in that path. You see some people, they have no so much, but they still fail USMLE exams. They know so much. And they're still performing about average. You need to get your understanding up. I'm telling you this. This is something that I feel like has been more critical over the last few months, especially on the more recent USMLE exams. People that don't have understanding, people that lack understanding, they know all the facts, but they don't know the fiction behind the facts. They don't know the livenoclefection. They don't have the understanding behind the facts. They just really struggle on the exams because most of the exams these days, all those factoids, many of them don't show up as answers, it's more like a description, or answers that demand that you understand the factoid. And then the second thing is people just overcomplicate these exams. They just think that the Indian is trying to get them. That's something for very quickly dispel from your mind, but we're going to get of that so boxing conclude. So I don't want you to learn from all the exams. Step one, just step three, complex level one, two, three. I also help with shelf exams, preclinical medical exams. And then I also offer ERAS advising.

I know that this is something a lot of people are doing this month. So if you're preparing your ERAS application, and you need help with rec letters, like editing, rec letters, personal statements, ERAS applications, supplemental applications, or you need prep-like for specialized kinds of interviews, like just the regular mock interviews, but a lot of people also struggling with these Casper interviews. Those are all things I help with. Multiple many interviews. Those are all things I help with. Again, I've been on an admissions committee for a year. I've worked with tons of applicants that are resident. Some of the people I work with are actually attendants right now. Just reach out to me via through the website, through email, and I'll give you some more information. And then I also offer a view course. It's again a 20-hour view course for step two, step three, complex two, and three. I'll offer an MBA Me Test Ticking Strategy course for step two and step three, then I'll offer a four-hour biostatistics bootcamp for every USM and every complex exam. And by the way, the 20-hour view course, if you're a person that's in third year, and you want to kind of get a jumpstart on the knowledge that you will largely need for the year, the 20-hour view course is actually a very excellent review.

And then I'll also say is for people that are taking medicine shelf exams, or family medicine shelf exams that just test a lot of stuff across like so many different disciplines, the 20-hour view course is something that's a very sound, very solid review that can help you crush those exams. So again, if you're interested, just shoot me an email through the website. And I have this podcast, an Apple podcast, on Google podcast, and on Spotify. At least the most recent 150, if you want everything from a visual one to a visual four, 13, you have to check out the website, divineinterventionpodcast.com. And then I have a You Tube channel, divineintervention, USM and Lee podcast and videos. That's where I post all the videos that I make. And then finally, I have a new website called, divineinterventionlifelessens.com. And if you will have said, oh, divine, I love the life lessons you put at the end of your podcast. So, if you said it's that a new Bible Bees website, I'm divineinterventionlifelessens.com. There's actually an Apple podcast associated with it, it's called the divineintervention life lessons podcast. And literally, if you go on the website, we make like two podcasts a week. Most of them are about 10 or so minutes long. And I address the life lessons like, oh, come on, problem people face. And I address it from a biblical perspective. Even if it's not a Christian, it's something you probably benefit from. So, if you're interested, just check that out.

So thank you for listening to me today. I will see you in the next podcast. Have a wonderful rest of your day. God bless you. Bye.

In IBS, there are no objective signs of inflammation (normal ESR/CRP), weight loss, or malabsorption; these findings suggest an organic disorder like IBD.

1) Changes in stool frequency, 2) Changes in stool appearance, and 3) Abdominal pain relieved by defecation. (Meeting at least two is required).

Agents that promote bowel movement, such as polyethylene glycol (PEG) or Lubeperstone (a prokinetic agent).

1) PPI use (loss of gastric acid barrier), 2) Gastric surgery involving vagotomy, and 3) Impaired gut motility (e.g., scleroderma/pseudo-obstruction).

A BMI of $\ge 50 \text{ kg/m}^2$. Patients with a BMI between 30 and 50 are at risk but do not meet the definition.

OHSS patients exhibit both daytime hypoxemia AND hypercapnia ($\text{PCO}_2$ elevated), whereas typical OSA primarily causes nocturnal desaturation.

Changes in stool frequency, changes in stool appearance, and abdominal pain relieved by defecation.

Scleroderma/Systemic Sclerosis (due to vasculopathy affecting the GI tract).

Chronic hypoxia stimulates erythropoietin (EPO) release, leading to increased red blood cell production.

Stomach acid provides an anti-bacterial barrier; PP Is inhibit the hydrogen potassium pump, reducing acid and allowing bacterial overgrowth.

They promote vasodilation (reducing systemic vascular resistance) and act as diuretics, helping to reduce fluid volume overload.

Respiratory acidosis (due to retained $\text{CO}_2$) compensated by metabolic alkalosis.

Changes in stool frequency, changes in stool appearance, and abdominal pain relieved by defecation.

Scleroderma/Systemic Sclerosis (due to vasculopathy affecting the GI tract).

Chronic hypoxia stimulates erythropoietin (EPO) release, leading to increased red blood cell production.

Stomach acid provides an anti-bacterial barrier; PP Is inhibit the hydrogen potassium pump, reducing acid and allowing bacterial overgrowth.

They promote vasodilation (reducing systemic vascular resistance) and act as diuretics, helping to reduce fluid volume overload.

Respiratory acidosis (due to retained $\text{CO}_2$) compensated by metabolic alkalosis.