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00:01 you saw this slide at the very , the very first lecture and today

00:08 you look at the images in this , you will realize how much more

00:14 understand. And also new material that will learn today too. So we

00:20 early on about the path of physiology neural infections in the central nervous system

00:28 COVID 19. And I said that going to update some material and so

00:32 dated some material. And it's interesting it is still an evolving story in

00:40 different respects is in the moment there's more research that is being

00:44 But if you look at pub med search for covid and central nervous system

00:51 neuron, you have about six or research articles and reviews that have been

00:56 . That's a lot in two But that doesn't solve a lot of

01:00 that this virus is presenting itself and new mutations variants as well. So

01:06 talked about the viral entry into the . Now I noticed some of this

01:13 not unique to Covid 19 but we talking about it with respect to covid

01:17 . You can have my Romeo when viruses in the blood that reaches

01:23 So now you understand that if you an infection through inhaling the virus or

01:28 touching the surfaces and somehow you have infection in the blood. Now it

01:35 breach the blood brain barrier. So understand how that happens to enter into

01:43 cns into the brain. We also this unique anatomy of the nasal cavity

01:53 in particular the bottom plates of the that contains the crib reform formation that

02:04 all of these minute administrations in the bound that allow for the whole factory

02:12 neurons to send their processes after the bind to the cilia from these receptor

02:23 to process that as a smell information the level of the factory evolved by

02:30 secondary order neurons and further on central projections. So if you inhale the

02:44 through the nose it can actually enter the surrounding olfactory epithelium and metal factory

02:55 and caused the infection of olfactory receptor . Hypoxia damage, compromise the blood

03:05 barrier. If you have infection in lungs and there's several things that could

03:11 happening now you're having less oxygen because lungs are infected. As you

03:18 neurons are exquisitely sensitive to loss of to hypoxia and so cutting them off

03:25 little bit can already impair neuronal cutting them off a lot depriving the

03:32 off the oxygen being on the ventilator has a significant effect on the brain

03:40 . Sars-Cov-2 which is abbreviated COVID-19 reaches stew receptors on neuronal tissues. Thanks

03:49 stew is a cell surface receptor which angiotensin converting enzyme two and it is

03:57 not just in the brain and different cells as you learn today but it's

04:03 present and other organs, not just the lungs but also in the kidneys

04:10 heart and of course in the cns PNS and potentially mesen enteric nervous system

04:18 another point of entry to these two . So if we look at what

04:26 learned about the factory system and we to understand what an oz mia is

04:34 is loss of smell. And we at the cellular mechanisms for it.

04:42 find some interesting things that we didn't . When we talked about the olfactory

04:49 , we talked about these primary olfactory neurons and their cilia that are projecting

04:57 the base of the skull into the cavity. And this is where the

05:02 molecules by. And then we talked how that signal gets transmitted to the

05:09 order neurons. And there you have Gomory lite structure in the olfactory

05:15 then onward projections to the central nervous areas in the cortex and sub cortical

05:22 . So these are our olfactory receptor . And it turns out that these

05:29 r olfactory receptor neurons Do not contain two receptors. So how does the

05:37 get into the brain? And how the virus lost sense of smell?

05:43 what is the loss of sense of losing sense of smell is actually losing

05:49 Sylvia? And this is unique for olfactory receptor neurons is that they can

05:55 and regrow the cilia as you regain sense of smell when you looked in

06:01 inner hair in the air circles and and outer hair cells, their cilia

06:07 regenerate but for the factory receptor neuron that actually do regenerate Now. So

06:19 the virus has to hang onto H2 , how does it infect the

06:27 It turns out that the cells that find in the olfactory epithelium that are

06:34 sussed intact ocular cell is sort of supporting role cell and progenitor ourselves are

06:42 responsible for clearing the utterance and enter the olfactory epithelium. So these cells

06:51 particular sussed intact ocular cell contains a receptors. So suss mm hmm.

07:05 based on results obtained from patients and animal models. This is what's going

07:11 right now. This is an evolving . Yeah. The sustain tacular cells

07:17 ace two and they seem to be first, impairment of such negatively effects

07:25 leading to the inhibition of odor The cascade and double lines is an

07:32 of outer perception, simultaneously rapid immune induced in the subset of ransom and

07:40 micro villi cells Michavila ourselves. This to activation of lymphocytes and macrophages and

07:49 infiltration into the O. E. or factory petroleum as well as secretion

07:57 pro inflammatory cytokines. So inflammatory processes on and this is going to be

08:02 common theme inflammatory cytokine cytokine storms that generated with covid infection, it is

08:12 known currently whether Stars Cove passes to Iran's as these neurons do not express

08:19 two and that's a question on the of infection of progenitor cells requires

08:26 So this is not clear if this there too. But they're in close

08:34 both of them with Justin tacular And so they proposed that there is

08:42 trans cellular infection essentially from the sustained selves and potentially progenitor ourselves onto the

08:49 Iran's. And when the Iran's get there is a loss of the

08:57 Okay. And there is no ability the voters to bind and so you

09:03 the perception of smell. This is necessarily unique to COVID-19 and its

09:10 It can also be some of these pathways and some of these symptomology is

09:15 an Oz Mia can be experienced with viruses flu like viruses, Common cold

09:22 sometimes too. I have experienced loss smell twice in the last five

09:29 The first time was maybe about five ago, the second time was about

09:34 weeks ago and I tested negative for and I lost the sense of smell

09:39 taste for one night and it then back. It was also it's very

09:47 but that's what happened And and when lose the sense of smell, the

09:53 becomes pretty monochrome when you lose the of smell and taste, it's really

10:03 and it's really just almost like I to say I have this like despair

10:10 almost like you said like never you know and you keep tasting things

10:16 then you're like, oh salt is , bitter is gone you know ah

10:21 is still there, it's like gone know cancel our coffee and it smells

10:28 gloves that's bad you know then you're spices still there then the spices going

10:35 and you're pouring pepper on your you're like this is bad you

10:39 So obviously the two are intricately We didn't talk about how we have

10:46 perception of taste which is you know sweet umami better ah and our perceptions

10:55 taste and things that we taste a of it is in hand enhanced by

11:00 sense of smell. So now let's we know this entry through the nose

11:07 we also understand the blood brain barrier . There are these two receptors in

11:13 endothelial cells and as you know this the end epithelial lining of the blood

11:19 barrier and once that blood brain barrier breached and neurons and glial cells express

11:25 two receptors and those cells can be . So essentially if you have a

11:33 breach of blood brain barrier and that happen not only because you have a

11:38 viral load in the blood but also of the inflammatory process is an infection

11:45 then the theory aligning now you have greater chance of this virus passing and

11:51 the brain cells in the cns Yes we're about to get to that very

12:01 question so we know this olfactory route . Right. And that would be

12:08 of you know the primary and the order neurons. How does this breach

12:14 with blood brain barrier? I also your convenience included some of the figure

12:21 . So we can look at the . There are three trans cellular

12:25 para cellular migration and trojan horse through microfiche invasion. These are the three

12:32 mechanisms and models of penetration of the from the blood into the brain

12:39 So then the epithelial cell infection is cellular infection from the blood and the

12:46 cells and then astra sides and then glial cells and then neurons. Okay

12:52 the entire neuron glial circuit gets You have paracel real migration where you

12:59 a breach and tight junction because of infection because of the inflammatory processes potentially

13:08 of the other factors forming in the like coagulated factors which may tighten the

13:15 brain barrier in some areas loosen it others have this parasite cellular migration and

13:20 microfiche enveloping it entering as a Children . Now the cells that are infected

13:31 they have microbial antigen, they release factor I. FM. Type

13:39 I then we'll look at it in subsequent slide. I just want to

13:42 you a general idea now and that for destruction of these cells infected

13:49 So this is a an immune response the cleanup response and you have the

13:55 glia involved in these processes and mediating inflammatory processes and responsible for injury and

14:03 and cleanup. So of course if have normal immune response, if that

14:10 response is compromised then you promote trans infection essential. And you promote these

14:21 instead of being killed and eliminated and . You promote them lingering around and

14:28 the infection. So this is We already discussed following a respiratory tract

14:37 may disseminate in the systemic circulatory So this is obviously in the blood

14:43 it reaches blood brain barrier, the may invade host and the ethereal cells

14:49 talked about this authoring tie junction programs psychosis by immune cells. The Children

14:59 in both in both of these Both of these MB waste cells infected

15:05 SARS released type one into for parents after neighboring and immune cells to the

15:10 of which alert sorry the neighboring and cells to the presence of the

15:17 So that the cells of microbes leah get activated and start taking care of

15:23 . And the cells themselves can induce processes to kill themselves programmed cell death

15:32 they may go necrosis. Non programmed death injury, trauma infection induced under

15:41 conditions. In fact that cells are by host immune cells to prevent further

15:46 on the spread of SARS covid So you have these COVID-19. He

15:55 the activation and the epithelial damage and have because of endothelial damage both in

16:01 blood. The release of the inter . I'll one interleukin six mon aside

16:08 protein serum interferon. These are all , pro inflammatory molecules that are referred

16:16 as side Akane storms. It's a reaction to clean up and engage some

16:22 the immune response inflammation. But with is unchecked. There's a balance as

16:28 learn to every system. There's a to gaba to gaba and glutamate glutamate

16:34 neurons and glia a certain balance. that inhibition. If that information is

16:42 , the neurons are in fact that a lot of information then that could

16:47 to significant or permanent damage In the . COVID-19. Apart from the breach

16:55 blood brain barrier can also cause problems causing problems and death. Brain vascular

17:03 infection can promote coagulant calculations of open these and trump was formation trump

17:12 trumpets formation. So clogging up the vessels, coagulating the blood, gathering

17:19 together. And then once it what can happen is when the small

17:24 vessels get blocked up. They can the pressure builds up and they can

17:29 and then you have bleeding. The in the brain you have the formation

17:35 edema and other complications binding of ace receptors. You have immune system

17:43 neuronal apoptosis and neuronal necrosis. And I included for you to look at

17:49 articles and I'll actually even show you to find these articles. Apart from

17:54 finding in the folder and in in few minutes. So this is a

18:01 that you're familiar with. But now going to walk through it in great

18:06 overview of C. N. And overview P. M.

18:10 Do you have a question a better to um activate the T.

18:19 Two receptors or to find a way Prevents 80 81? So can CB

18:27 receptors. I would suggest that this a good line of thinking. CB

18:32 receptors are widely expressed from Michael Greer they regulate the release of chrome parameter

18:39 upon. So I think that CB chapter agonists natural agonists would probably be

18:45 interesting solution to controlling some of the . So not just in the brain

18:51 in the body as well. So good question. Okay so how's it

19:01 the virus directly? Respiratory droplets. contact with infected individual indirectly format

19:09 We know that dr physiology theories violent into the brain adverse immune response,

19:16 response and respiratory stress. Hang onto three will review them in the subsequent

19:22 in greater detail. What's the histological hyper dense areas in ct scans?

19:30 the ct scan computer tomography? So sophisticated three dimensional x rays essential.

19:39 you will see hyper dense areas and brains that have infections with covid 19

19:45 symptom was the analysis, headache in that's not that bad on the

19:54 But if you get a major you may have a stroke or meningitis

20:04 goes to your question which is the essential of the brain in this

20:09 viral infection, which meningitis is the sequel of events too of inflammation and

20:17 into neurons. There's also this condition and e accurate necrotizing encephalopathy type

20:27 also known as susceptibility to infection accurate and so Phil op athena,

20:33 a rare type of brain disease. a philosophy that occurs following a viral

20:39 such as the flu but also following Covid infections. And when you talk

20:45 meningitis, you can also talk about of these men syphilitic the meningitis by

20:52 way, when you're talking about meningitis vaccines for meningitis, meningitis can be

21:02 by bacteria and viruses. Both bacterial viral meningitis. When you get vaccinations

21:08 meningitis, all of you probably You always say there's 16 variants.

21:15 13. Some of them get cycled . Why is that? Because there's

21:21 for the viruses that cause meningitis? , There's variants that are emerging for

21:28 on the chrome is knocking on our right now and it will be it's

21:32 here actually. So we'll see how last wave. Hopefully the last wave

21:38 the virus will treat us all. It's a constant evolutionary battle viruses trying

21:46 survive and kill us. We're trying survive and kill virus. We're probably

21:50 to win. It's not going to away the virus. So but we're

21:55 going to win the war and battle not going to be finished.

22:01 Uh huh. And why do you these different variants? Because the virus

22:06 smart and the virus wants to So the virus will adapt. Some

22:12 the vaccine stimulus may adapt to human and immune systems. It's very

22:22 It's blasted so hemorrhages and it's a by the way, it's a fill

22:29 inflammation of the brain can be also by for example viruses that are found

22:35 ticks. So in certain countries or parts of this country during the breeding

22:42 , which is typically in the People are very afraid to go out

22:47 certain areas. They get attacked by and get bitten the carrier viruses that

22:53 be so they called us a politic , actually hemorrhages. So bleeding

23:01 emerging problems, ruptured blood vessels, in certain areas of information of the

23:09 treatment. No conclusive treatment. one can say, how come there's

23:12 conclusive treatment? Well, okay, , recovered paracetamol, anything anti

23:18 anything that fights headache, vertigo without the symptoms. But is there conclusive

23:25 is many conclusive treatments. There's no treatment, meaning that there's many things

23:30 know will help with inflammation. But you have to be very careful.

23:33 is the cause? What is the ? Is it coagulation or is it

23:38 blood vessels then you need to give a coagulant because they don't have

23:44 Everybody will react differently to this virus it's variants. So that's why there's

23:49 conclusive treatment. There is many different in many different treatments and monoclonal antibody

23:56 . And people are consuming crazy things to treat themselves and seems to work

24:04 some instances directly. Now we're talking P. M. S. Peripheral

24:10 system. So directly respiratory droplets and direct contact with infected individual from our

24:16 . The path of physiology theories, sensory dysfunction. So we're talking about

24:21 of um taste receptor cells infection of olfactory receptor neurons, histological significance falling

24:31 of here like receptors and olfactory So you have a loss of these

24:39 parallel receptors, main symptoms of anosmia of smell. And you see a

24:45 of taste William Barr syndrome. Miller syndrome too. Some of the things

24:51 involved with pressure and some of the that are involved with balance. No

24:56 treatment for how do you regain the of smell the last meal? How

25:01 you treat her again? The sense well? Sense of taste uh nasal

25:08 potentially being delivered to medicate just these . Again this is about local

25:15 So that would be quite innovative, if you lost a sense of smell

25:20 maybe your load is primarily here. treated early on. For some people

25:27 of smell is the first signal that have covid before they have fever

25:33 For others it comes later again the and how it gets into the brain

25:39 . Whether it infects it very much . Um And are there ways for

25:47 if you lose a sense of we know that some people lose it

25:51 a day or two others for three and then it takes about three months

25:55 it to fully to come back. the things that you guys can think

26:00 as neuroscientists that would be potential programs which people could regain sense of

26:07 Maybe it's through olfactory stimulation of Turpin's letting people rebuild the specific maps for

26:15 Turpin's and then exposing them to complex . Which is the fruit of flour

26:22 will have many therapy means in a which will still have two or 3

26:28 in it. So is that is something that is in the future?

26:34 he said the virus may win. you know, we'll have this problem

26:38 back. Is that something that could plastic lee? Those nerve endings retrained

26:44 re grow faster and then people will wow instead of three weeks on average

26:49 takes me one week to regain my of smile. That would be significant

27:03 environment. I can't hear you. sorry, represent yourself nasal spray.

27:16 . Okay cool. So maybe that a nasal spray that I'm mentioning here

27:21 it's mentioned in that article. Okay, interesting. Also conducted.

27:27 the mandatory and so you need to the endocannabinoid system. That means you

27:34 to go for a long run I mean if you talk about what

27:41 talked about how and the cannabinoids get by stress and then we talked about

27:46 know if you do repeated physical long distance running, cycling,

27:52 whatever you know playing lifting. That's stress on the cells. It's continuous

27:57 . So that boosts into cannabinoid You know it also causes the runner's

28:02 if you if you have if you long distance. Ah So yeah those

28:09 all there interesting strategies and I think everybody's thinking of many different strategies and

28:15 that. I don't know if then cannabinoid system would be the first one

28:19 mind. I think people would fall on some of the common anti

28:24 common things that they've used for decades they can quickly apply with the exception

28:29 M. RNA technology which is brand and it seems to be like a

28:35 in a way for the vaccines. we'll see what else it can do

28:39 . But you also mentioned last and what Trevor comment. Yeah. Yeah

28:48 right. The circuit. The inhibitory could be potentially relieved with the CB

28:54 activation. Good. Alright. Unlike when you guys ask questions and

28:58 about previous lectures and how they relate this lecture because that's how I would

29:03 for you to remember things. So physiology, peripheral is the chemo dysfunction

29:09 reaches the nose reaches olfactory mucosa inflammatory . You have the Nazmi radusa manifesting

29:19 if you have in the C. . S. These are the three

29:24 that we talked about. Three ways enter into the brain, adverse immune

29:28 and respiratory stress or a viral entry the brain. You have leukemia.

29:34 a virus to cerebral circulation. Yes it's in the blood, it's in

29:39 Assyrian brah. Now you have undoubtedly with these three receptors. Get recognized

29:46 reaches the brain and the olfactory evolved the nasal passage. So maybe some

29:52 this component here is shared. So the nasal passage we also can be

29:58 some of these endothelial lining, some the neuronal and glial components. And

30:04 have opted emphasis on brain cells leading intracranial pressure and cerebral edema. If

30:11 have cerebral edema you have a compression the brain stem potentially and that can

30:16 your respiration. What does that That means if you have a swelling

30:22 the brain stem as you learn brain in different parts of the brain control

30:26 functions. Brain stem controls vital functions heart rate and breathing. So now

30:32 you have the pressure on the brain . Now you're also significantly complicating things

30:41 control of the heart rate and with breathing rate, desperation. So you

30:49 breakage of blood brain barrier causing cerebral possibility adverse immune responses to viral invasion

30:58 the cytokine release over abundant cytokine storms two receptors recognized by the virus and

31:06 cells causing the site of kind response normal response have apoptosis. Or you

31:14 the necrotic encephalopathy and hemorrhaging inside a of storms respiratory stress, loss of

31:23 in the lungs. If you lose in the lungs, you're in trouble

31:29 your brain because the brain consumes a of it and it needs it in

31:35 minutes without oxygen can kill your But other organs also need oxygen.

31:42 you may experience a multi system organ , possible neural injury in the brain

31:48 a consequence of hypoxia. And again necrotic and so Philip with the inflammatory

31:54 in the brain. So this is . N. S. And this

31:58 C. N. S. How does it happen? What data do

32:04 have there? This is from Probably needs to be updated and update

32:10 slide. But neurological abnormalities have been in about 30 percent of patients who

32:17 require hospitalization. So, if you up in the hospital, A 3rd

32:25 experience these neurological abnormalities from most common headaches to the most severe, most

32:36 their being death. Ah 45% of with severe respiratory illness and 85% of

32:46 with acute respiratory dysfunction. So the the worse off you are when you

32:57 to the hospital. The worst off your symptom ologists. The closer it

33:02 to act as respiratory failure. Active syndrome. The greater chance you have

33:09 the 85 chance of having these neurological with mild covid 19 neurological symptoms are

33:18 confined to non specific abnormalities such as , dizziness, headaches and loss.

33:23 taste routinely observed in respiratory virus infections as influenza. So your professor must

33:31 had an influenza virus, although I've had a flu shot. And the

33:39 and booster while serious neurological complications have reported In patients with otherwise model COVID-19

33:49 most severe complications occurring critically ill patients are associated with significantly higher mortality.

33:58 again, the severity of that depends many different fronts on the viral load

34:04 the variant of the virus entry Whereas it establishes itself if it establishes

34:12 the brain where in the brand's is . Is it affecting the blood?

34:17 is your immune state? How are reacting to immune stimulation, infection.

34:26 so philosophy and encephalitis. Ischemic So stroke, rupture of blood vessels

34:33 the brain. Post infectious neurological We have long haul covid 19 complications

34:41 they're not just psychological like depression. also physiological complications. Some of them

34:47 neuro physiological complications, intensive care related manifestations. How many people get off

34:56 ventilator once they get on the one in 4, one in

35:04 It depends on the immune state, age, but one in five is

35:08 good. 20%. Ah Sorry, in one in 41 in five.

35:18 get off the ventilator, they Okay, so 2020, no,

35:22 , 20-25% mortality rate. If you in the intensive care unit in your

35:29 with a severe SARS infection, one 4 people perish until later. So

35:37 happens if you get on ventilator and perish and you had a lack of

35:42 , you had so much stress, probably have ptsd you have issues with

35:49 brain circuits. It depends again, you have ruptured blood vessels. So

35:53 a whole slew of things that can also chronic problems. And I'm just

36:00 and not just long haul. But chronic and potentially terminal problems too.

36:07 this is all very important. And is the last lecture and it is

36:11 to scare you, but to just you know how things work and give

36:15 more insight and things that we looked . Like the nasal olfactory system.

36:20 now I understand how the virus uses system. What cells are there?

36:27 blood brain barrier, how the breach through blood brain barrier. This is

36:32 covid, 19. But now you think of all other things can do

36:38 . Okay, other viruses can do . You can think of what if

36:41 had a medication that can do that , who aren't these the three pathways

36:49 can potentially get the drug into the the brain to through the south Para

36:55 maybe a carrier. Maybe it's not , maybe it's not immune response,

36:59 it's something else. But so these all of the very relevant And timely

37:05 . And so I've posted of course material of COVID-19 that is there for

37:11 reviews for you to read. But the last thing on this course I

37:16 to tell you that and especially for students, you have to take advantage

37:25 the University of Houston and in this of the University of Houston Libraries and

37:32 of the things it can offer. so if you go to University of

37:36 libraries, you will say, well should I go there? I'm just

37:39 to go and do google search and my answers. Anytime you do a

37:45 search and get your answers, make it's not from and lily on google

37:52 somebody who is not a credible source information, be a credible source of

38:01 that has to be peer reviewed. has to be published. It has

38:06 be not only p reviewed and published peer reviewed and published. And something

38:11 is a real publication. That is real book, but there's a lot

38:16 self published stuff of course by specialists is also good as long as it

38:21 peer reviewed. As long as it serious information. So once you are

38:26 new age libraries you go to my and you can log in using your

38:33 nut I. D. So this my cougar nut I. D.

38:37 it is a stranger to that is same alias as everybody else. I'm

38:43 going to give you my password for . Do you have you around?

38:47 log in and now you're like oh a lot of fine things,

38:52 fines and fees blocks and messages. doesn't look very very welcome and sort

38:58 look above here it says new search search, citation search, journal

39:05 So you can search for journals specific health and biological sciences will give you

39:10 list of all of the journals. can search and go to databases.

39:15 is what I typically do. And you will see popular databases. A

39:20 bunch of databases but there's these popular that most of the people use.

39:25 if you do research and you're looking primary research articles or if you're looking

39:30 review articles and systematic review articles. go to pub man And once in

39:37 mad you do a search such as and CLS oh It's kind of a

39:53 tab here. Immediately shows you one these publications on COVID-19 starts About

40:01 2019. There's probably like a few know dating probably in the lab's research

40:06 years back or something. 214 What if we go to this

40:16 114 results. So you just want newest stuff, right, then you

40:21 these options here. You guys shop amazon. This is just the same

40:25 . It's like filters, you want something cheaper, expensive, good

40:29 , bad review free. You it's the same same thing. Full

40:33 . I just want abstract, but want both full text and Three full

40:38 . Let's say. I just want full tax because I want to see

40:41 entire article. That's what this That whatever publication is listed here under

40:46 114 results, we'll give you the pdf or other digital formats of that

40:55 . Let's say you just want If you don't do reviews, you

40:58 a lot more to look at. my suggestion for you, let's say

41:02 learned about some new field and you I'd like to learn more about

41:06 This is what I would do is would go and instead of trying to

41:10 all of the 359, I would for the most recent articles, maybe

41:14 year, I would look for a article or maybe a systematic review article

41:24 you know, and then you're down 126. Does that mean you have

41:28 read all of them now? Just on a few and then when you

41:32 on one of them, let's say one, you click on one of

41:35 and you have these full text links this item. Springer link. So

41:40 you have these links that says free tax, that means any one of

41:44 two click you get the entire article you can also download a pdf of

41:50 article. Uh huh. And then like, oh my God, what

41:54 heck is like shoot, there's a of words here. So one thing

42:04 you do is okay, don't get of a lot of words do

42:09 This is the abstract. Okay, the abstract, parse out the

42:13 This is not the best abstract. are the better abstract, abstract

42:19 I'll show you we're still sharing So it must be. So let's

42:36 to another abstract. Let's say we'll to this abstract. And uh this

42:42 is more manageable. Why? Because an introduction, objective methods. So

42:46 don't see it as a big blob you know, half a page,

42:50 know, like again, take your . And it's scary. And half

42:54 these words, I don't know. like no results was like, what

42:58 they want? Objective, comprehensive analysis the psychiatric neuropsychiatrist concluded can appear during

43:08 risks, gender and professional vascular distressing painting. Keywords. That's pretty

43:17 . Keywords are COVID-19 etiologies, psychiatric repercussions are still in the Indian city

43:25 . The kind of the key words speak. It's a very brief way

43:29 saying these are the five words that going to describe this article now these

43:33 the keywords. So you're looking at let's say you're here and now you're

43:37 my God there's a lot of words . So what I recommend for you

43:41 do is to scrawl until now. look at this, this is the

43:48 from your lecture and they were like what's going on here? Blood brain

43:54 ? Boom I understand this. Okay then look closer, what are these

43:59 ? Astrocytes? What's going on Read the figure legends. Now you

44:05 much understand a lot of times in review you'll have these two or three

44:10 and figure legends that really summarized graphically impala graphically what is going on?

44:17 pathways immune activation, coagulation, psycho . Mhm. So this is how

44:25 search for different articles and you can how much you can find out.

44:35 by searching in Parkman I'll give you example, covid 19 and th c

44:50 drug meeting the criteria. Mobile target to treatment using CBD. So we

44:58 something the normal noise CBD acts more Serotonin system and more through CB two

45:05 or CB one receptor. Okay when that begin these studies last year?

45:11 not surprising. How about if we C. N. S.

45:17 Th C. Oh that is How long ago did we go back

45:25 80s 90s but I will say give the whole range about Gaba seventies.

45:41 about Blue Demon sixties name a molecule july serotonin. Yeah sixties. What

45:56 before 60s? People didn't didn't like molecules. Aah PLC. High performance

46:04 chromatography, isolation of single active chemicals active ingredients from botanical extractions from everything

46:13 . Because No that over 80% of of the drugs have their origin and

46:20 and whatever mushrooms, flowers, things that. Okay and then they get

46:26 synthesized as pharmaceuticals and reformulated as pharmaceuticals lot of times and sometimes they remain

46:33 planned based drives. That's really interesting you a glimpse of when this began

46:38 these reviews began And reviews is an that reviews many articles. So it's

46:45 the primary literature, what we call literature is doctor So and so at

46:50 University of California has discovered that this causes plasticity in the amygdala. And

46:58 whole paper describes how he used some model, may be human model and

47:04 the plasticity. In the Mcdonald's. review paper will say okay this review

47:10 will address all of the plasticity ease have been studied in the amygdala.

47:17 . And then there are even systematic papers which will say let's say now

47:21 going to actually do a study. not just Gonna describe a review that

47:28 20 articles that deal with the subject . And these are the main themes

47:33 this is the future of these But it will say, Let's say

47:38 200 articles that proposed this treatment With drug for these two conditions. We're

47:46 to now compare the concentrations. We're to compare the regiments of that

47:50 We're going to compare if people in group had one disease and another

47:56 they were from another, maybe genetic that had a predisposition for another

48:01 Do this analysis, meta analysis and review analysis to communicate the information in

48:10 detail, summarizing it, but still that great detail. So finally,

48:18 you come to the end of the articles, you will see conclusions on

48:23 lot of times you will see challenges . So especially for graduate students,

48:29 you're looking for new areas to this is a section that will save

48:35 a lot of time. Instead of at individual primary research articles, hundreds

48:41 them go to the review articles written Sometimes 5, 4, 6 people

48:49 one of them is around 10-30 times five times 650 years of combined

48:57 on the subject matter, telling you maybe this is the future. And

49:01 doesn't mean you cannot question that or their conclusions. So there are suggestions

49:07 is often a really good place to new subject matter, new areas,

49:14 therapies, new challenges in the field well. So, I hope you

49:18 this tool When we come back on , we will Do a review for

49:26 whole section three. I will not today's material on Wednesday though because it

49:32 fairly fresh and it is also relatively lecture compared to some of our recent

49:40 . Thank you very much for being , being on zoom, we'll have

49:43 more meeting, I think it is to be in person on thursday and

49:50 you will subsequently take the exam. is no sample for certain parts of

49:56 material that I covered because it's new that I covered that I didn't cover

50:01 previous years to which makes it a bit more exciting for me. Makes

50:06 a little bit more challenging for Maybe at the same time there is

50:10 final sample exam in your folders that contain some of the questions from ah

50:16 factors that matter, sensory system and on. As well as your quizzes

50:20 released and you can view what questions got wrong and so bring any questions

50:25 you may have this thursday relating to of the material in this third section

50:30 the exam will cover this third Thank you. Thank

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