So I guess it's time to start. Oh, let's see here. I'm sorry. I'm trying to Get my slide projection going here. Okay. This is just a slide to show Yes, I was buggering it up To show the anatomy that we're going to be discussing we have the Oral cavity here. That's the tongue teeth and appendages floor mouth and the pharynx Begins at the interior pillar of falsies. I guess in this particular Slide they're indicating the Palatine tonsil, which is a typical thing that it's taken out in tonsillectomy as This yellowish blob there on the side They seem to be pointing that is oh, I guess here. This is what they're trying to say is Palatine tonsil This is my neighborhood in a way and I Think this slide is it's hard to depict this kind of thing. There is a structure, which is worth knowing about Nicole wall Dire's ring It's an anatomical Histological Regulation of lymphoid tissue that Circles the pharynx and the nasal pharynx Is above the soft palate and behind the exterior aspect of the septum Also known as the epi pharynx off the roof is a clump of adenoid lymphoid tissue called the adenoid or epi pharyngeal tonsil and Then the oral pharyngeal tonsils include the Palatine tonsil and on the back third of the tongue is a mass Tissue which is called the lingual tonsil. This is pertinent to my discussion and There's Some lateral strands and the nasal pharynx which kind of complete the ring then The oral pharynx think of the oral pharynx is what you can see when you look with a tongue depressor Pushing the at the very back of the throat the nasal pharynx is above the soft palate and the hypo pharynx is the part of the throat intimately associated with The larynx if you take a plane. There's a cricoid cartilage here, which is really important Ever had to open your way you have thyroid cartilage and the Adam's apple is the prominent in the junction and in front of the two thyroid cartilage ala and Below it is this little bump Just a cricoid cartilage if you absolutely had to you could enter the airway through this Thyroid cricoid membrane in the very front with a pen With a knife and a ballpoint pen take the ballpoint out and you could put a tubular thing in there and blow into it to get air But normally you make a tracheostomy down here in the like the second ring if you take a plane Right below the cricoid cartilage and thyroid cartilage there This portion below would be esophagus and be cervical esophagus and this portion above that would be the hypo pharynx or lower pharynx and If you do a laryngectomy where someone has cancer the larynx and has to have the larynx removed And you take away all this structure including the entire Cricoid cartilage it's sort of signet ring shaped. That's the back part of it right there It's tall in the back and the Ritnoid cartilage is sit on top of it Take that away. The pharynx is wide open and close it in a tee sutures and Let it heal for a week 10 days at any rate It helps to understand nasal cavity oral cavity pharynx and larynx pharynx and larynx and oral cavity and nasal cavity make the arrow digestive tract So that's where we're going to be Looking at slides from that area. I wanted to talk about a couple of other things real quickly One is the age old question. What is life? Living organisms are cellular Basically, they are cellular they're contained structures and have a defining membrane membranes can vary Within those membranes they maintain their own little environment Which is called homeostasis that maintain balance of all the biochemical processes carry out metabolism in which they seek out energy find energy opportunistically analyze it and grow and Do what is required to have a life cycle and and Of course of it they evolve and I threw this in just to For heuristic purposes really the Pneumonic device you might want to use if you never memorized one is What I would suggest is deum King Philip came over from Great Spain and and G for great and s for Spain is the genus species designation that is typically used in describing organisms the genus being capitalized and Normally both are either Underlined or italics Deum D stands for domain. There's three domains This is represent this slide is representing periodic cells or Organisms that have cells that have organelles and a nuclear membrane This guy is Carl wos both But they would have said woes This is from 1982 in the Charlie Voss Frank was kind enough to allow me to use this slide and it Chose a man who has been Under Noticed in my opinion. He never won the Nobel Prize. I think he got the MacArthur Prize what he did was Out of the box and it was absolute heresy at the time The ideas he came up with people considered there were two basic Tree branches in the Tree of Life there were prokaryotes and eukaryotes and He realized based on sequencing RNA in Replicative machinery she thought would be similar between Related species Which was quite a good guess Educated guess He Associated organisms and develop phylogeny based on similarity of sequencing similarity of replicated replicative Strategies and RNA sequences and ribosomes now there are bacteria of a sort called archaea Which are quite ancient probably the first forms of life on earth as everyone is thinking these days This is I thought was a nice picture locus castle Where research is being done to try to find Samples of archaea which might be the Missing link in a sense Luca the last universal common ancestor You look at the Tree of Life That was Archaotite bacteria which then had bacteria branch off of bacteria meaning prokaryotes which Have distinctions from the archaea They both have Chromosomes floating in the Side cytoplasm and such but and neither have organelles, but the ribosomes in the archaea are much more closely related to eukaryotes Which Of course have cellular membranes and we're later. We are all eukaryotes with our organelles and Chromatin and in a nucleus that's bound by a membrane on except in mitosis and Something that's really interesting in this is that there is This goes a bit beyond Darwin in a sense. I think of woes is a bit like Darwin There is this Indosymbiotic evolution Some but endosymbiotic revolutionary evolutionary process in which it's felt that maybe larger Archaea swallowed up smaller bacteria or Archaea and and for food and Likely and as it turned out that was Symbiotic or mutualistic relationship and those ingested bacteria and became organelles that is where your mitochondria and Where chlorophylls and plants are felt to originate and this is I just like this slide it shows size relations and down one micrometer is Bacteria with similar sized mitochondria which have a double membrane and chrystae and a membrane bound enzymes and Intermembrane space and then space in between the chrystae Share these little septae or divisions in the mitochondria They have their own DNA and they have their own ribosomes And they divide you get all your mitochondria from your mother and so it's the source of Eternal language It's also as interesting it shows that the naked eye can Only see to about a tenth of a millimeter Or a hundredth of them I guess but With a light microscope you can see down to a hundred nanometers not very well in my experience, but Maybe someone with super sharp eyes could and Flu viruses for instance or viral particles are tending to get into that area seems to me that to be back on mosaic virus is Potentially visible by a light microscope, but it's definitely seen in On microscopy which can go down to atomic levels This is myself indulgence slide This is just a picture from a book chapter I wrote in 1993 for a medical textbook and it shows Variety of viruses that can affect the arrow digestive tract arrow digestive tract being the nasal cavity and Where air and food go? Once you get to the esophagus, it's digestive tract and once you get to the trachea, it's respiratory tract Another aspect of this that's really interesting is you look at how technology comes along following discovery of pure physics or like rink and discovering x-rays in 1895 led to x-ray diffraction being quite applicable by 1912 and Rosalind Franklin employed it for figuring out that the DNA Crystallinized as well as it could be was a double helix Which Watson and Crick didn't understand squat about what she said except that hey, it's a double helix So they took that and made their model with a few Guesses playing with paper Nuclear magnetic resonance as a quantum property of matter and be exploited with Algorithms for positioning and in scanning with a gradated magnetic field to make images which can be quite detailed and It's used for figuring out molecules as well, but the first electron microscope was produced in 1933 in Germany Interestingly it Followed this period of to 1925 to 1927 when Heisenberg was thinking about possibility of the gamma microscope as a thought experiment So it was actually invented I guess 31 and then started to be used to after that and They started trying to make that was a transmission electron microscope that tried to make scanning electron microscopes after that still in wartime interestingly and In 1981 a scanning tunneling microscope Emerged and I Think the I Was thinking it was 93, but it's a 1986 that the Inventors of that got the Nobel Prize it opened up immense opportunities and learning new things to image Small things Better than Transmission or scanning electron microscopy could do now a new Technologies emerged in 2017 It led to the Nobel Prize for three Individuals that helped develop its cryo electron microscopy and in that you super cool Samples so the water doesn't freeze but becomes vitrified You think of vitrification you think of clay being fired and turned into glassy substance Anyway, it was a marvelous way to examine specimens and not destroy them It's the conditions for which one has to expose samples to Visualize them in electron microscopy traditionally had been really harsh and destructive tail-to-vacuum and other things and this preserves the structure and Pretty much exactly what molecules are doing at the time. They are I'll just say frozen frozen in place So This has opened up a Great line of research. I really I wanted when I was young to build my own electron microscope Actually, I didn't do it, but I was thinking of it and If someone is interested or you have a student who's interested this is the micro Or the molecular biology age since DNA was Defined in terms of structure and all the discoveries since the Greatest things that are going to happen in medicine in this century are going to be based on molecular biology and if you want to be in something be in something that's a happening field and encourage your students or young people to Learn everything they can about molecular biology and if they got and and or cell biology They're really inseparable at one point. I wanted to put medicine and just go work getting a PhD in virology Which would be related to cell biology and molecular biology but At any rate that would be a really cool thing to do you know, I guess Enormous advances are being made with optics in all fields Now David Baltimore is an professor emeritus at the California Institute of Technology. He's a remarkable Quiet individual who Was a co discoverer independently of reverse transcriptase or RNA transcriptase so that retroviruses can convert their RNA to DNA which was Considered heresy at the time it was proposed Somewhat the way Carl wos was considered to be heretical in what he was proposing and he was ignored by a lot of people But at any rate, I will make this Balable and I meant to put this out at the very beginning. I kind of forgot Here is a link of all my slides. It's a shareable link and so Anyone's welcome to take all this and I'm gonna pass through some of this quickly, but if you want to go back and look at it Well, it's an interesting point and you know how science becomes dogmatic, you know And Boltzmann committed I don't like to say committed suicide because that's you commit crimes and you End yourself by suicide He took his own life because he felt always lost because Mach and others were scornful of his arguments of the atomic theory and Maybe had it pinching for depression without being able to fight it Whatever any one person Embraces can become like a religion to them overall science as a consensus observation based Human progress progressive process should not be religious At any rate what I want to point out is that Baltimore certainly like waltz looked at replic of it replic of Strategies for replication of organisms and the similarities in the RNA in ribosomes To organize a phylogeny a tree of life into three domains Baltimore classified viruses and Seven classes and the class I want to focus on today is class one human papillomavirus is a class one double strand DNA virus and It's not too pretty. Let's see There's my link again. I meant to I had to I have to put in the command for My slide to advance. Oh, I'm sorry. I did it wrong Sorry Okay So this is just a summary slide to describe some aspects of human papillomavirus HPV They're small Viruses they have basically eight Reading frames and in a sense they can produce a couple of extra products, but sort of by Reading in the middle of a frame and some splicing and they have special functions, but the main ones I'm going to talk about I'm not going to get into the other two, but eight reading frames about 8,000 base pairs and They bind to histones or these pro-naceous spools for DNA in the nucleus of Eukaryotes that they attack Which they target? They don't have an envelope. They are like a postcard you might think Viruses that have an envelope There are viruses with single strand DNA and double-stranded RNA But anyway viruses that have an envelope Don't produce those themselves. They they basically borrow those as they extrude from a cell They take a piece of these cell membrane wrap wrap it around themselves Like a cloak and they have these little spicula spires it's of Ends of proteins that Stick through by which they can find their next host Cell or by which immune cells might find them and destroy them at any rate The human peplum virus basically has eight genes There are 50% of the genome is in these six early viral viral genes the e genes e for early e1 2 4 5 6 7 and And These People that write these papers don't know how to count and An important aspect of this oncogenic Products are made from e5 e6 and e7 viral oncogenes which can get taken up by the host DNA and Alter them so they become immortal a transform Sometimes to malignant cells Good example of that sort of malignant transformation is you might have heard of a cell from a Deceased patient named Henrietta Lake called the HeLa cell which is in thousands of laboratories across the world Since At least 70 years It's a lot of research has been based on what the HeLa cells were Doing in cooperation with a researcher about 40% of the genome is in The production or involves in production of two late Proteins or proteins that go into making the capsid now virus is a Latin word or comes from a Latin word for poison And the capsid is like a container box and capsaomers are subunits of capsids the L1 and L2 proteins are eight products L1 is 70% of what is formed and it forms the outside of the capsid and therefore it's the one that's important Imogenically when these That's something you do make Recombinant DNA Strategies of taking the DNA from virus that that snippet that would make L1 proteins Introducing it into the genome of yeast the yeast will make L1 proteins You sacrifice the yeast and harvest all these L1 Proteins and fairly pure form. They will self-assemble 72 capsum box and Which is pretty cool. I think that I've also read about they Have potential energy by which they spring open That they kind of steal from the cell. I don't understand the energetics of that and I I Just mentioned it But Something would have to reverse it to let the genome out these boxes contain the bad stuff that really gets you sick this is an example of What can be displayed by using cryo electron microscopy and Imaging techniques and algorithms on the data used to Produce digital images they're far better and Considered are more valid than any images that can be obtained by analog Procedures like transmission electron microscopy These are not really Icazahedrons that always confuse me they would show these and I'm a mathematical and I think of Icazahedrons is a Icazahedrons Icazahedro like If you look here That is surrounded by six units Do you look here? That's surrounded by five units. It's not it. It's not a uniform Perfect Icazahedron and made me think of a soccer ball, but it's I think it's distinct from that as well, but Because it has ends up with 72 cap smears so I Wanted to review quickly the Early prototype early virus viral genes And I want to go into too much detail about this, but just to let you know what they do E1 proteins they find to DNA and they in The virus and and assemble into hexameric helicases with the of the second viral protein Now I think when this starts off it it's using the cells equipment the HPV virus Replication takes place in the nucleus the virus gets into the cell and the genome of the virus gets to the nucleus and It starts off Slowly and then after a point the virus itself is able to take off but these helicases a helicase is an enzyme or active enzyme that will unravel DNA and Once you have E1 and E2 proteins being Produced you can make these helicases that will speed up the production of the HPV virus Now the E4 gene it really is taken out of a central portion of The E2 gene it it's an open reading frame within that That portion of the gene and it gets spliced with Some of the beginning of the E1 so you have this E1 splice E4 String that Really starts to increase when the virus is getting amplified and Starting to produce on its own having kind of borrowed from the cells resources at first the Fact that it grows and its quantity at this point Means that it becomes a molecular marker for HPV infection I'm gonna have some pictures before long so don't Tune out That's all I go. There's and there's only six of these early genes and I've talked a little bit about the L1 and L2 So anyway the E1 and E4 is most but abundantly expressed viral protein when HPV virus is up and running and getting itself going now Talks some in a bit about how skin matures from basal cells to keratin and In the skin Ordinary word combined to this cyto keratin, which is a keratin is like the same kind of made of By what a repellent aspect of your skin is due to keratin Osa in your throat and the vagina and such do not have And or in the cervix anyway Anyway, it can collapse the cyto keratin network it really disrupts the cell and there's Interesting aspect it locks it into G2 phase of The cell cycle and it also can prolong the S phase of the cell cycle So and it combined to proteins in the mitochondria in one Particle now, I'm not sure what the significance of that is but it's it is interesting it that Stuff's all over the cell. This is a slide I found on the street It was a Work of art I must say Interface I want to read just mention here and this will be available Through that link I gave it has a lot of information if you had all the information of this in your mind You have a pretty good Perspective on cell cycle but the G2, you know cells grow that's one of the aspects of life and G1 and G2 phases are both growth phases G1 phase after after you have the separation of the DNA nuclear division you have cytokinesis where the cytoplasm divides and Have Energy molecules pull a waste in just like it Starts to look like a figure eight and the cell begins to constrict with a cleavage for all and two cells finally are Created after completion of that process, so that's the cytokinesis part of cell division Then you got two smaller cells that have their fair share of Golgi processes and Plasmic reticulum Another interesting thing is when the nuclear membrane breaks down at a Ciculate it forms little bubbles and these all get separated evenly and then Contribute to forming new nuclear membranes in each new cell It's really absolutely fascinating process M-phase of mitosis But at any rate in the G1 phase these little cells that just got their daughter cells They start to grow the S phase is where chromosomes are S for synthesis that means the cells gonna go But funny at times they go into a G zero phase while or G zero cells Examples of cells that go permanently in G zero phases are red blood cells which are Denucleate mature red blood cells don't have nuclei It's G zero phase neurons are Stable cells that no longer divide and cardiac muscle is another one Start to Damage your cardiac muscle You gotta be careful you'd be screwed You don't get any more of it unless you get lucky Get an expensive operation. I'm not sure it's lucky Anyway the viral genes e5 e6 and e7 are really important in terms of Serious disease because those can become Taken up by the genome of the host and change it forever The e5 I was saying slows the differentiation of Skin cells from basal cells to the corny cells, which I'll show you in a minute Which benefits the virus by giving it more time to produce more virons? and If it's going into a lysogeny, which means it's producing virons. It's gonna kill the cell and spew them out Or the lysis stage rather Lysogenes when it's sitting with the virus in it but At any rate them there's an e3 Spliced type of product that I'm not going to get into but it has something to do with controlling Number of viron Particles that are in the cell and how the cell proceeds Once it's been taken over I Made a little joke before the virus once it gets in there and gets a hold of the DNA. It's like emoluments It starts to manipulate the cell for its own good its own Future and wealth rather than for the good of the so Funny how everything's sort of like anything else Anyway, these early viral genes continuing e6 and e7 stimulate production of proteins that require for synthesis and Get it get the cells into S phase and then able to proliferate but more ominously they can and activate Tumor repress a tumor suppressor p53 and the retinoblastoma p rb retinoblastoma tumor suppressor proteins so they can Subvert I'm going to show in the end of this talk how they do this in a sense. They subvert the Justice system of the cell that is intended to keep them from taking over Dictating what happens in the cell? And it's the best interests of the cell oh What metaphors? Okay, I Want to talk some about vaccines This was a slide from the NIH or National Institutes of Health which I Urge everyone to look to as a quality source one of the great achievements of Government in the world for the good of humanity at DNA vaccine efforts were Pushed by people at Johns Hopkins. I mentioned the researchers here. They focused on HPV 16 There were over 150 strand strains or types of HPV virus Known 16 and 18 are two types that are responsible for 70 percent of cervical Rowan not just 16 and 18 but also type 31 you're talking about 90 percent of cervical cancers are Caused by those viruses Like the HeLa cell Offhand I can't tell you which which one the HeLa cell was from but Probably one of those It was quite an aggressive tumor. She had a day-rate I Wanted to mention this there was a lot of work also done and by people in Australia the United States and England to develop vaccines in 2006 the amount of 20 of development discovery Abled this including ways to do Dominant DNA whereby you take the gene and Corporate it just the single gene not the whole genome that is responsible for something that would be antigenic and and put it in the yeast genome and The yeast will produce L1 proteins for you and you isolate those by purification methods from the yeast and Which can be quite pure And you're not having to remove any viruses you're just removing it from cellular components and those L1 Products Will and have this done for each time. You don't have the same L1 Section from all these types into the same batch you do some different batches So it's so it's nice and neat For any one of those you isolate the L1 proteins and they self-assemble self-assemble to virus like particles the LP it's called and using this kind of approach Merrick It's the first to market And get a get approved and market of Gardasil which had these four types of HPV virus covered now type 6 and type 11 are They can cause malignant transformation, but more commonly they're associated with genital warts and condoloma mulata which is word in the Pretty gross in the cervix vagina vulva and also rectum and anus and Penile cancers and anal rectal cancers have a high association with HPV virus 16 and 18 or two of the big Problems for causing cervical cancer and they also can cause head neck cancer because of Basically direct contact and exposure Yeah, I'm letting people's imagination run wild with my presentation just as a historic note in 2009 a server X Blacksau Smith Klein produced server X which was a Bit different from Gardasil So they weren't equivalent interchangeable meaning if you're giving you know normally when like with the current Gardasil 9 it's a known abalent or nine different antigenic types are Covered by the current only available Gardasil 9 which is Merrick But you give the you give a dose and then six months or so you give the second dose and third dose at about a year and There is Some potential strategy for giving two doses, but if you give it less than six months apart you have to do something more Let's see a question if the virus inserts itself in the DNA doesn't tend to do so in active areas do they stimulate transcription? Yes, they well they have to expose they have to have exposed DNA to they they I think that they would have to get inserted where the DNA is not wrapped around a histone and Yes, then that stretch of virus gets actively transcribed and it gets transcribed as to make messenger RNA just as the and Reading the negative sense Strand of DNA after gets unwound just like ordinary DNA and Yes, I'm talking basically about Faryngeal laryngeal cancers, and I'm talking about head and neck cancers Not skin cancers there Thank you for the questions So Anyway, server X Went to a lot of trouble GSK went to a lot of trouble producing server X competitive field Expensive to do research and develop this and then to go through all these trials and it was effective And it didn't catch on and they gave up in 2016. They they sacked it Which I thought was kind of interesting yet. So I Wanted to add in 2010 Gardasil was approved by the FDA or federal drug administration in the United States for prevention of anal cancer and associated pre-cancerous lesions due to HPV 611 16 and 18 sorry, I just hit my microphone I Waving my arms around I'll let you just imagine that At any rate For anal cancers and pre-cancerous lesions due to these four types of viruses that Gardasil original Gardasil covered in Patients nine to 26 years now currently the Recommendations are for nine to 49 years old to 45 years old to Get the vaccination and Usually three or complete Coverage as well as it's going to be there's no guarantee that any one person getting any vaccine is going to be safe completely from the Agent that's being Worked on because there's a lot of things that could could go wrong and for some reason the specimen the sample the Substances that sat too long and become inactive or if they don't shake it up It's a suspension. You got to shake it up and get it mixed up nicely to get the mixture right and If the person's own immune system doesn't respond to it and So it's not an agent that works by itself. It works by It's a heads up for your immune system for here's what's coming So this is one reason why they're recommending this be given to children age 11 before they're sexually active and Chained in the earlier discussion. I think it's worth saying is From my experience, I think there's so many cases where children are abused sexually by someone in the household Sometimes a boyfriend or Someone who's not a blood relative but predatory and It's Probably worth considering that Children younger than 11 be given this kind of protection because it If you get it before you get exposure and it works if enough people get the Get the vaccine so that the virus doesn't have any place to leap to person person Herd immunity. Yes now Artisal 9 it's a non-availant or 9 different antigenic Types are covered these these these 9 different types of HPV again 6 and 11 are for genital and anal warts and Condoloma cumulata of the vulva and that sort of thing the vulva being part of the vagina and I've 16 and 18 and 31 are treacherous Associated 90% of the cervical cancers in women 400 I think 400 Million die yearly of that I Believe that's about right and then there's also other 3345 52 58 all those are associated with Kansas and I took this NIH poster, which I thought was quite interesting and might be Something to keep in mind that people that just receive one dose are Of HPV vaccine have 88% lower infection with HPV in the oral laryngeal cavity About 150 types of HPV are known actually a bit more than that, but they're not all human hosts for that there are HPV in the zoonoses there you find them in mammals like rabbits that have HPV viruses over there and things like that hanging down Okay So now Gardasil since 2017 is the only show in town and I Think it's Interesting to note that there appears to be some cross coverage there is some protection against suggested by research Against Viruses of other types based over based on maybe Molecular similarity I Guess that's right Well, there's peplum of viruses in the animals I think there are a hundred and fifty human via HPV so I'm glad you point that out. I think that there's there's a lot more out there But I think there's a great number of variants that attack humans or that use humans as hosts So People who shouldn't get it someone who's ever had Anaphylaxis to a vaccine just not common, but it's life threatening if it occurs and Anyone giving a vaccine should be able to administer Countermeasures in the case of anaphylaxis which is basically epinephrine and redness own injected Pregnancy I told a long story. I won't go back through now About a guy getting into a potential ruckus with some Other guys that thought they were tough and he went up to him and I Said you wanted all at once or one at a time and these guys who have been provoking the problems said we don't want no trouble, man and Basically, that's probably a good philosophy of life if you've got somebody who's pregnant they've got enough going on and anything you do if Anything changes or any Unexpected outcomes Happen everybody would be wondering if it were the vaccine. So basically you just don't give it to the vaccine it To a pregnant female It's not expected. It would have any effect Particularly but It It's no reason to take a chance somebody who's who's already ill with something their immune systems probably challenged a bit so Shouldn't have it Exception might be HP HIV or something like that when they're in between or someone with leukemia now there have been all kinds of oh There's local reactions to the shot and there's fainting and I don't know a lot of Typical stuff. I told a story this morning. I had a big brawny guy one time and my office and I examined his ear under the microscope operating a you know clinical microscope like a field microscope and Afterwards I was sitting there looking at him talking and he got glazed over this was within a couple minutes after finishing looking at his ear I hadn't done much and I thought this guy's not there and he's had a Glassy look and he suddenly started to fall forward like a tree falling in a forest so I dove under him and Landed on the knee and caught him on my shoulder. So he didn't smash onto the floor and Called for help As I couldn't get out. I was in a position where I couldn't easily stand up without possibly dropping them. I Mean people faint all the damn time When they're they get basal vagal responses, you don't know who's going to do it and So getting that in response to a shot doesn't surprise me but This slide just describes a couple of issues that had been brought up as potential claims against as as reactions to the vaccine and basically The EMA or European Medic medicines Agency Concluded that the casual there's no casual link between these vaccines any of them and the development of these Swords of conditions. This is kind of typical I Will go on about that particularly. I want to talk a bit about Wow, I need to Speed up. I looked at the time Some the five layers of the skin the basal layers where it all starts those are the cells that replicate to Reproduce cells that are being going through differentiation and sloughing finally at the layer, which is at the bottom here This spiny layer is Where the cells go from being sort of cuboidal and plump to being Sort of speculated and stretched out and that's Probably strongest layer of any of these then this granulosa layer is Our granular layer is where the Keratin granules are being formed and it's that's where those get disrupted by those early genes And the whole network of them and it tends to arrest development so that this the virus gets to produce itself longer then you get a loss of nucleus and They Cells or start to look lucid or clear and then finally you have this Keratin Hacked dead cells and keratin is what makes hair for instance Keratin makes the outside of the skin impermeable to water Lipid soluble stuff will tend to get through acetone will get through The petal toxins line neurotoxins can get through the skin so You know you're not off scot-free, but your skin does a quite a good job for being the largest organ But it gets little micro breaks all the time and has to repair itself it repairs itself There's a basement membrane here that separates the dermis from this layer of basal cells right there and Then you have the Spiny layer Which is the strength layer and then this little darker band is the granular layer We start to have keratin formed and it gets clear and then you got these stratified Keratin filled layers of dead skin. I think the integument meaning the Skin as an organ is considered the largest is what I've always understood This is just to illustrate The layers of the skin. This is not HPV. It's just a nice slide of skin. These are called ready pegs They are sort of like anchors going down into the dermis. You have blood vessels and also fine Nerves tactile nerves that are myelinated and autonomic nerves to the blood vessels that are Unmyelinated down here in the dermis. You don't have any of those in the skin and You get thickened keratin layers and a thickened granular layer But this kind of condition, but I just wanted to show it because it was a nice slide of skin showing another example and albeit Normal skin condition, but not a good. It's it's an annoyance. It's itchy Most of my slides now are going to be clinical type slides This is a close-up of that one. I just showed So I'll keep going here Okay Don't shake hands bump elbows Also shaking hands is the best way to get a cold High efficiency Transmission you can have cold viruses active still after three hours of dry dryness That's not that wasn't that was a wart what I just showed you CNN disagrees with me. Oh, well, that's fake news, I guess And I'll have to check that out anyway This is a common wart Veruca's vulgaris and you get a lot of the hyperkeratosis or a lot of this Corny layer it's real thickened and the granular layer right there it gets thicker and more active and But long ready Pegs and they interlock which is kind of interesting it helps to anchor the skin and cause it to be Let's see Well, I think that the realization that viruses were associated with cervical cancer May date back to the 70s I'd have to look that up to be sure This is just a close-up of the common wart and the ready pegs here and there's the granular layer lucidum layer and The spiny layer This is where the virus is really taken off It gets into the basal layer and it depends on cell maturation for its development And if it can slow it down in this middle zone, it gets to the virus gets to do more Here's the endo layer endo cervix. This is the ecto cervix and the endo cervix This is the junction of those two cell types and that is Felt to be the most vulnerable area or HPV to get started Hot spot I guess and you get it started and you get dysplasia and then Further changes that lead to cancer. Okay, these are some clinical slides.  It has sort of dilated blood vessels, but Chittin's too unusual, but this is all papillomavirus here and here and here and There are different ways I always took these off mechanically. I didn't like using laser on them Yeah, you get a plume you here. This is the endotracheal tube. This is an operative Endoscopic view of the endo larynx. That's part of the endoscope the steel endoscope right there But if you use a laser you have to have a guarded tube you don't You can end up with the tube catching on fire and Endotracheal fires were common particularly in early laser surgery You have to have a laser nurse in the room. You have to have all this extra equipment it takes a lot of space and It's a lot more complex and the more complex it is more likely something's gonna go wrong also, you get reflections of the Laser beam off metal or off the metal here if it's not aimed, right? You calibrated at the first and it can scatter and burn some stray area So there's a lot more to worry about when you do laser extraction Yeah, if that happens you extra you pull the tube out But you have a high level of oxygen going through these endotracheal tubes when people are asleep. This is more Apolloma virus caused tumor of the endo larynx. That's benign There as well right there all that that's fairly normal looking cord that Looks polypoid it might have virus in it and eventually would look like this It's hard to tell without testing it sometimes unless sometimes it's blatant like this In this case, this is the front and that's the posterior commissure of the endo larynx kind of an interspace between the Structures associated with the arytenoid cartilages which move the cords Or close them. So it's kind of messy and if this gets really advanced it can obstruct the airway and Here's another It's really could be polypoid cords. I Think that often a person with this appearance if there was no history would go to the operating room with thought it was polypoid cords and Then you my hospital tests all these for HPV now other things have been tried like ultrasound which was bogus and I was going to tell you that Using the laser there was with the plume of smoke. It can have viral particles It was one guy in Boston. I knew of who had a virus Papilloma grow in the middle of his forehead just below his surgical cap. Oh He did a lot of these kinds of surgeries so I Never was too thrilled with This is just shows some of the artifact of Doing video Laryngoscopy in the office But here's a better picture This shows Beautiful a beautifully normal larynx. That's the epiglottis. This is the front. That's the enter commissure the posterior commissure True cord.  You do not have much aspiration and survive So when all that happens the larynx gets pulled up this piriform sinus here widens and the trichopharyngeus muscle in the back loosens and Stuff the bolus runs through it goes through about 21 feet a second Oh Pretty quick lick of the split This is a vocal nodule. I was trying to remember. It's like Kenny Rogers had these singer Julie andrews. I think had him as well Singer's notes are called and as opposed to Pallipoid chords, which is like a blues singer might have like Janice Joplin or James Brown Singer's nodules really cause terrible dysphonia You don't really want to hear a singing with that And it would make it make it worse Now if a baby is born through a birth canal that has papilloma virus in it and they aspirate some of the particles Viral particles or the virons They can end up with it growing in their throat Especially on their larynx and their trachea That's called juvenile laryngeal papillomatosis and it there are cases where it's taken over the trachea in the lungs and the Had never had it clear up.  That's been reported It's uh, there's some success in treating that with interferon um No, it's better to avoid this virus. Uh, that's More laryngeal papilloma there and there That's epiglottis there again In this case, that's epiglottis and the anterior cord is uh there in the front Let's see This is a papilloma on the uh, attached to uvula and the arch Above the palatine tonsil and that that's after it was excised and I appreciate, uh, dr. Kavanaugh Sharing this slide with me I have a whole lot of slides, but they're buried in boxes My house has been turned upside down Here's a microscopic of that kind of uvular papilloma and there's all these fronds and such And you can see it's Similar in its appearance eosinophilic meaning it's kind of pinkish with these blue areas Where you probably have basal cells Uh Similar to slides. I showed of the skin. Here's another nasopharyngeal papilloma And that was excised those can be tough to get to Often if it's purely oropharyngeal, I would do an office procedure to remove it and again, I don't like using laser For a lot of people lasers their favorite hammer and People will go to somebody because they are here they use laser and they've got no clue about The amount of problem that can cause They have a totally unschooled view of it and you can't tell them they just think oh, that's that's cutting the edge or something in someway people this Could be just a papilloma It turns out it's a cancer. This guy also had uh smoking and alcohol history which is so Not um everyone who has uh hbv just has uh bad as their Only risk factor. He also had a lung cancer from his smoking This is the oral tongue it's coated These are the brise of the upper lip Any ideas what this thing is Anyone Euler Ferris Bueller That's a tongue cancer That's a malignancy That's the kind of thing that uh I've dealt with a lot. You can actually take Remove half the tongue and a person will still have adequate amount of tongue muscle for Declutition and articulation And they'll be alive Able to taste Something as big as that he would probably need radiation as well. Uh, this is a Pathological slide of it. It's comes it's sort of lobulated and The thing is with these palatine tonsil cancers This is not that one I just showed you but it's Just an example of cancer and their throat from hpv and Azeloid is is one variation that actually I've been Seeing surprisingly more of in the past 10 years It varies itself in all that lymphoid tissue. It doesn't grow Exithetically or outward like a fungus like what I showed you on the tongue And People often don't have too much in the way of symptoms. They might get ear pain because some of the same nerves particularly glossopharyngeal cranial nerve has branches to the middle ear and They'll get ear pain I had people that would come in with ear pain and I find they have a lump in their neck because these will have early metastases to lymph nodes in the neck Sometimes they come in with just a neck mass and you can't find the tumor You no matter how hard you try The positron emission tomography or PET scans have helped quite a lot In determining it. This is a close-up of it So I got over time. I want to keep going here real I'll let you look at that in the handout if you want to see it more Cells have some innate immunity You have also your specific immunity once you've had exposure But before that happens you have naive cells Particularly your basal cells in your skin can elaborate Cytokines and things that promote inflammatory cells moving in To protect you But so it's a two-edged sword in a way undifferentiated basal keratinocytes are the primary target skin infections of HPV and mucosal infections, I think Are similar in this regard, but they also have some resistance to the infection And sometimes that's not enough There are dendritic cells, which I wanted to point out which move around and they are throughout all layers of skin and they end up getting sloughed, but if they find Antigens that they don't like they will process them and try to hand them off to immune cells and Activate your immune system protect you Takes a week or two this is from my non-alcoholic fatty liver disease talk and it doesn't show but you have I just brought it back because you have Dentate cells throughout the liver as well And They're they're throughout the body. They're not just in the skin There was a medical student Paul Langerhans In 1868 who thought he was seeing nerve cells in the skin But he was actually seeing these dendritic cells Which are antigen presenting immune cells Um They're from a couple there is a couple of sources for them bone marrow and lymphoid And uh, I just wanted you to be aware of them immunoproxidized Immunoproxidase stain helps to show these And If you look uh, I thought that this was pretty good. They sort of they're sort of like an octopus They have all little all kinds of little strands coming out Fingers reaching out So These have what are called beerbeck bodies or beerbeck granules They were first described in 1961 and they're seen on electron microscopy, especially in the spiny layer of skin Something happened here Here we go and this is just a source for my next four slides I just wanted to quickly show you I love electron microscopy uh nucleolus Nucleus the nucleus is bound in a membrane in a eukaryotic cell mitochondria have a membrane and they have chrystae That's where cellular respiration takes place. You have Golgi complex trans Golgi network which produces endosomes and you get lysosomes which can be off smooth endosomatic particular Process that tend to have enzymes that will kill stuff Uh I'll just run through these so I want to show you some beerbeck bodies There's a second one so you can look at more detail from the handout in the shareable link There's a beerbeck body. Here's a beerbeck body. There's a beerbeck body Get I don't think you could really see that with the microscope I've never seen one with a microscope and uh a light microscope there's one and there's one sometimes they're a little bit like club shaped and uh So Continuing on I'm almost done You get pattern recognition receptor cells like the dentate cells uh that can recognize things like the an example of uh one of the types of uh Things that those cells can recognize are lipopolysaccharides of gram negative bacteria That is like the stuff that the dysbiosis or bad unfavorable bacteria in the in a disease microbiome Uh Is producing all the time that gets absorbed into your portal circulation and percolates through the liver And and damages your liver progressively until you get fatty change possibly uh inflammation and fibrosis And then cirrhosis Liver cancer um So this is a major point I wanted to make these undifferentiated basal cells keratinocytes or just basal cells of the mucosa as well um Our primary target and you have these dangerous sensing immune cells which helps clearance and most of these types of viruses get cleared in a couple years But when they don't You got a real problem um Okay, I'm going to try to wrap it up here So this is a busy slide, but it talks about growth factors chemokines and cytokines molecules um that um Are secreted by the basal cells uh to as part of the in innate immune system before you have when you have a naive immune system before it gets sensitized to a specific agent in addition some of these will suppress the growth of uh of HPV transformed keratinocytes So um another big point E5 E6 E7 are oncogenic meaning they can immortalize a cell or transform it lead to its transformation to a malignant cell malignancy means it can kill you Benign means it's not going to kill you that's that simple uh E6 and E7 uh also nefariously inactivate suppressor proteins like p53 and p retinoblastoma suppressor proteins And this is an example is Iquitin ligase ligase to ligate means to bind together it helps to bring together this viral protein E6 to join up with this friendly um host produced Sorry, I bumped my microphone uh p53 tumor suppressor molecule that helps you to not get cancers it binds them and when it does that this assembly mark is marked for destruction This is how E6 which is being produced in abundance by the virus um subverting your um uh cells uh uh governs um like a coup um Takes out the uh justice system so that it can survive and become dictator Here's a nice reference you might want to look at and I want to point out once again that uh national libraries of medicine and the national institutes of health are a wonderful source of information and I came across and I told this morning, uh, this is a Quote that was shared with me by a concert pianist in brooklyn who's a recording artist Uh, it's a friend of mine. I thought was wonderful love this quote and it uh Related to it And what occurred to me and I wrote this out. I just read it very quickly is something moving through a trajectory A trajectory of points over time can follow an infinite straight line Just one of those points is not collinear even by an infinitesimal mount then the trajectory lies in the plane If at least two other points such points and the continuous locus of points are not coplanar space curve in the case the complex deal once destiny greater with small excursions from a predictable path In a sense any pursuit of free will that may be possible must entail Seeking those small degrees of freedom from which divergence can arise Opening up the unknown Outcomes take note of anything does not make sense for it may be Person who can show way to all the others I really liked that and I wrote that out to read to you My response to this quote One last point I would make and I was very blunt about this this morning I think anyone who is a child and doesn't get the vaccinated against hbv by age of 11 um Is stupidly negligent? um I Also pointed out your chance and you put your child on a bus in the morning to go to school They're probably at greater risk for not being never ever able to come home From that than they would ever be at taking this vaccine uh I'm emphasizing this because I wish That if you were prepared for it if you could see the things i've seen the suffering i've seen the deaths The things people go through And some of it's because of new lifestyle things of that aren't necessarily that new but um Like anal sex and oral sex and those things And that's ubiquitous where sexual creatures and everybody's active at some point um Your children are going to be active They're going to be exposed um To get a rectal cancer and have it excised by an anterior posterior resection and have a colostomy end up with liver disease about full of metastases sometimes anyway and dying from it or nodules in the lungs or cervical cancer involves the colon and rectum our radiation for it cleans the rectum and its function and its quality of life and I go to tumor board on a weekly basis and the urologists are Very frequently presenting cases of penile cancer which are treated by partial amputation And aside from that these head neck procedures partial glasectomy laryngeal for injectomy Sometimes requiring free flaps Pectoralis major myocutaneous flaps just to bring up enough tissue to reconstruct so they have a conduit for which they can swallow uh losing voice and Much of the tissue in one side of the neck or both sides of the neck if they end up with bilateral radical neck dissections or the diffuse fibrosis of the neck from radiation therapy and the zero stomia no saliva Miserable swallowing problems that are usually permanent. They might improve a bit over years and years but All those along with the toxicity of chemotherapy Who would you wish that upon? Certainly not your children not other people's children.  I have no investments in any in Gardasil or any of these pharmaceutical companies I'm not invested in pharmaceutical companies. I'm not um In any way Benefiting from uh promoting any particular uh treatment or process Other than I'd like to see people do well and I like to see people being informed. I love science and I love teaching and Share some of what I knew You and hope maybe you can share it with some others That's the end of my talk Thank you Any any questions? Thank you Shantung Yeah a day vaccinate Oh, I don't have anything planned Thank you dolly But I have some ideas It's unfair to the children in my thinking That's what I'll put Vic ideas of the seed of plans The seeds of plans Was it a better sound production with my headset? I bought a headset about a week ago terrific Was it not loud enough? Syarchy Synergy Okay Is that a question for me Vic? Or for the crowd I like most anything that is presented here. I always get something from everything I hear and um I was thinking of maybe another talk I might talk about us five or six common substances that are medically toxic that are fairly ubiquitous in society That might be interesting. I think as it would have applicability to A lot of people's lives I think one learns a lot by teaching and having to organize your thoughts to present Thank you Vic. Thank you Tata Yes, I like to hear music when I'm working and in fact when I was in medical school I always played classical music As I was studying and it struck me It may be just my brain. There's a lot of people wanted absolute silence but And I would get up at four in the morning and put on headphones and listen to Brandon Barrett concertos and things like this Mozart's good Really almost anything. I love Brahms Brahms Forth symphony actually Sibelius is wonderful but It seemed to me my A different part of my brain Processed the music. I could listen to the music independently while I studied and still And also when I would get up at four in the morning and study and Be really intense and That was my own pattern I may have been a bit unusual to wake in that early But I would study really intensely and it would seem like a couple hours had passed and I would look and it was like 15 minutes 20 minutes had gone by and I thought wow I've got tons of time left and My retention seemed to be really good when I studied that way so I guess after uh Whatever many hours of sleep. I cleared the toxins from my brain And it was functioning better It is an interesting question Vic about math mathematics music um And There is such a pattern base to music uh I when I do sadoku Puzzles I can go really fast if I see a pattern Oftentimes a patterner just it solves itself and then some seem like it was Random and it's like a chess board if you have a chess master and you put The pieces on the board at random. They won't do any better than the average person who might be a chess player Because there's no recognizable pattern there But the brain seems to pick up on patterns Some people's brains are more pattern oriented than others. Maybe that's it I would say that in terms of socializing um I always got along better with mathematicians and uh physicists And chemists as well, uh, although I had a few chemists that I came across who I couldn't relate to Uh, but I got along better with them than with the physicians And no chemistry with some chemists. Yes I Had a volatile reaction but with A lot of physicians I had, um They are I don't know saying this is yeah, I shouldn't talk to me They uh They had a different kind of background from what I had grown up in and Didn't see the world At all the same as I so I just kept my mouth shut. That's cool. Vic Biochemistry is an immense subject. It's so cool And so many gaps are being filled in Thank you cb My pleasure. I appreciate, uh, the attendance and attention that everyone gave And the good questions I guess I'll turn my microphone off now Thank you everyone


I'll be presenting three cases today and then do a brief overview of the disease process. This is a mystery diagnosis and we'll do a brief review of the literature. So the first case is a 17-year-old Hispanic man that came in with blurry vision in one eye, mild discomfort, he had a non-contributory past medical and ocular history. Vision in the affected eye was slightly decreased at 2025, he had normal pupils and pressures. And the affected eye had a mild anterior chamber reaction with 2-plus vitreous cell, a little bit of haze. And we can see the photo of the left eye, a little bit of hazy view, just overlying the lesion which is some retinal whitening along the inferior arcade associated with hemorrhage. And you can see at the lower part of the arcade maybe an area that looks a little more pigmented or atrophic, which we can see in this photo, so a pigmented scar. This is an OCT through the area, normal, temporally, and then on the nasal side there's a hyperreflective infiltrate of the retina. Fluorescent angiography early shows some blockage in the area of retinal hemorrhage. And then later some hyperfluorescence or leakage in the area of retinitis and a little bit of retinal vascular leakage. Of note, also in the peripheral retina, distant to the area of activity, there's also some retinal vascular leakage. So this patient has anterior chamber reaction, vitreous inflammation, and a coriorentinal lesion, so that fits the diagnosis of a pan-uveitis. And a unilateral pan-uveitis, top of the differential, is infection, infection, infection. So ocular toxoplasmosis, a viral retinitis, could be syphilis or TB, and then lower on the list would be an inflammatory pan-uveitis. So this patient walked into the clinic, he was young, he had good vision, you don't know what his immune status is. So he received an AC tap, checking for a viral PCR, and they injected intravitral clindamycin to cover toxo, as well as phosphocarnate to cover viral etiologies. These are the labs that were checked, and they were started on valtrex and Bactrum. Seeing a couple days later, the serum, toxo-IGG was positive, but had a negative IgM, and the PCR was negative for all things checked. However, the sensitivity of PCR for toxoplasmosis of an aqueous sample is under 50%. So with retinal whitening adjacent to a pigmented scar, those are the buzzwords for ocular toxoplasmosis, so he was treated as such for presumed ocular toxoplasmosis. He received Bactrum, six to eight weeks BID, he also had azithromycin for a portion of that period, and oral steroids was added a couple days after antibiotics. Final visual acuity was 2020, and this is the resolved lesion, just a hyperpigmented scar. This is a similar case, 21-year-old woman from Venezuela, so also a Hispanic woman. She notes she had some kind of eye infection when she was younger, wasn't sure which eye. Vision's mildly affected. Pressure's high. Also has a mild anterior chamber reaction and some vitritis, a similar photo, so nasal to the nerve, there's a hyperpigmented corioretinal scar with adjacent retinal whitening, and we can see some periflebitis as well. Interestingly in the other eye, she has 2020 vision asymptomatic, and she also has a hyperpigmented scar nasal to the nerve with some fibrosis on the nerve. These are the buzzwords, focal area of retinal whitening adjacent to a hyperpigmented scar, so all the residents are going to nail this case on the moth world boards. Ocular toxoplasmosis. She was uninsured, self-pay, so we were trying to really limit the cost of this workup. It looked really classic. We just did a very limited lab workup, which was normal, ruling out HIV and syphilis, and she was treated as ocular toxo with a great result, and that's the atrophic scar. So a different case with a different outcome. This may seem familiar. I presented this last month at the Grand Rounds for Morbidity and Blindness, a 39-year-old woman that had come to us a year after her symptoms had started, decreased vision in the left eye, non-contributory medical history, but she was from Mexico. We looked at outside records, and a year before, she had presented to an outside provider with floaters and blurred vision, also what someone else called pink eyes, so you can assume some anterior chamber reaction, redness and pain. The vision was 2,400 at the time. They noticed a diffuse vitritis, and then diffuse retinal thickening on the OCT, which they were saying was consistent with macular edema. So their plan was to do a workup for pan-uvidus and see her back a few days later. Vision was unchanged. This was the workup they did for the pan-uvidus, so they ruled out syphilis. She said they had a normal chest X-ray and PPD, and then they checked VZV and HSV antibodies, which were positive in the serum. We typically don't check them, because a lot of us are exposed, and it's not positive for the retinitis. So at this point, they felt it was non-infectious and injected intravitural triampsin alone.  She went from 2,400 to 2,200 for a few weeks, and then a couple months later, she comes back with worsening vision again, now has mutton fat KP, a diffuse vitritis, and so they re-inject triampsin alone into the eye. So she came to us several months after that. Unfortunately, her vision had declined to light perception only, 2 plus APD. She's had some mild anterior chamber inflammation, now a diffuse PSC cataract from the intravitural steroids, diffuse vitritis. And this is a photo, very hazy view, but you can see multiple areas of retinal whitening confluent. Here's another island of retinal whitening. And this is an op-dose photo. It gives us a little bit of a different perspective, and you can see in the infrotemporal quadrant, there's a vessel that looks elevated, so there's a sub-retinal fluid and retinal detachment on ultrasound. So we'll talk a little bit about ocular toxoplasmosis and management, and then we'll come back to that last case. So toxoplasma is an intracellular protozoa, infects over a third of the human population worldwide. That number's a lot higher in Latin American and South American countries, over 80%. Most people are exposed either through undercooked meat or more commonly contaminated water or soil. Infection in the retina can be reactivation of a congenital infection, or there's evidence now that most cases are acquired postnatally. And congenital infections typically are bilateral, 75% of the cases, and they're more likely to involve the macula, so congenital at 60% involvement of the macula in acquired cases less than 40%. Retinal whitening adjacent to a scar. The diagnosis is clinical. Serologies can help, especially to rule it out. And then it's the number one cause of infectious posterior uveitis worldwide. So exam findings, like we mentioned, I put an asterisk near marked vitritus because sometimes it's not a diffuse vitritus, but just a clump of vitrious cells overlying the areas of activity. Or if they're immunocompromised, there can be a lack of vitritus. So vascular sheathing, as we saw in the flourishing angiography, can be separate from the area of activity. Anterior uveitis can be fine KP or mutton fat KP. High IOP, so that I think second case I showed had an intraocular pressure of 25, and that can be classic. And then these periartereal plaques, which is a term I don't know how to pronounce. So is treatment necessary? In immunocompetent patients, the lesions become inactive with well-defined borders within six to eight weeks, even without treatment. So there's little firm evidence that shows that antimicrobial therapy alters the natural course or the visual outcome and disease in immunocompetent patients. So if we think back to that other patient, and as doctors first do no harm, if this patient had never even gone to an eye doctor, she may have fared better in the long run. In 2016, a Cochrane Reviews published looking at antibiotics versus no treatment for toxoplasmosis, and it summarized in this vague statement, treatment with antibiotics probably reduces the risk of recurrence, but there's no good evidence showing that it leads to better visual outcomes. However, absence of evidence of effect is not the same as evidence of no effect. So there's definitely cases, everyone's in agreement for treating if it's near the fovea or macula, or sorry, fovea or optic nerve. They're symptomatic, significant vitritis, a large size of a lesion, persistence after time, multiple lesions, and then we always treat pregnant patients, immunocompromised patients, and congenital infections. So there are some providers that will just monitor a peripheral small lesion that's asymptomatic. I think in our department we treat every active lesion we see. In classic treatments, triple therapy, so sulfidizing, pyrimethamine, and fulinic acid. The pyrimethamine causes decreased platelets in white blood cells. That's why we use the fulinic acid. And then there's many alternative treatments described in the literature that are better tolerated. And then briefly touch on oral steroids in the use of ocular toxo. So typically if there's a significant inflammatory vitreous response, I'll add oral steroids 48 hours after starting antibiotic therapy. So steroids themselves aren't contraindicated in ocular toxoplasmosis, but unchecked steroids, meaning the use of steroids, especially periocular steroids, in the absence of antibiotic therapy is a contraindication. So that's stated here. So absolute contraindication. We think it can cause uninhibited retinal necrosis. So inappropriate use. There's many cases of literature showing disastrous outcomes when we inject intracular steroids in an eye with toxo. And there's some wise words in the middle there from ophthalmologists in a Latin American country reminding us to consider toxoplasmosis for any pan-uvietus in an exposed patient population rather than assuming it's an autoimmune process. And then there is some appropriate way to use intravitural steroids. There's reports of using dexamethasone intraviturally, which is much shorter acting, concurrently with clindamycin, intraviturally with good outcomes. For prophylaxis, you can imagine if you have a patient that was recently treated or they have an inactive scar, but that's close to the fovea or the optic nerve, you want to be able to prevent recurrences in the future. So using Bactrum one tab three days a week, so Monday, Wednesday, Friday, has been shown to reduce the risk of recurrence. But typically we thought it was just when they're on that medication. Once they stop it, the recurrence rate goes back to normal. There's some new evidence from a group out of Brazil that shows that Bactrum one tab every other day treating for about a year can have some long lasting effects. This was a randomized double mass trial with 141 patients. They all had active lesions initially treated with six weeks of Bactrum. Those lesions healed and then they were randomized one to one to receive either Bactrum every other day or placebo for 311 days. So just under a year and they showed the recurrence rate for the treated group was zero for three years compared to an increasing rate of recurrence in the group that received placebo. For pearls, this is a clinical diagnosis. Serology can help rule it out and then an AC tap, remember the sensitivity is about 50% or less. If you have a patient in your office and you're not sure what it is, they have significant vitritis. You can inject things to cover for multiple etiologies, antivirals, clindamycin, just don't inject steroids alone if you don't know what it is. And dilate every patient with aviitis.


Oh Now you got me nervous I'm not saying the color black makes me nervous I'm saying the black screen makes me nervous because that means something's epic is about to happen.   Oh My god, bro This show has its ways with its intros take away this guy's voice and that scene would not have hit as hard as it did It's the voice actor that really completed that emotional connection right there the delivery of those words This show is gonna make me like League of Legends. I know it.  Aren't I on? stream Nicholas light TV twitch I Don't think it's them They would not have waited an episode if it's gonna be the cops. I knew it. I knew it. I knew I know how these shows work You've got a good heart Don't ever lose it. Oh, don't talk don't talk like don't talk like this. He's talking like he's about to say goodbye I know how these shows work.  Okay, protect the family. Oh my god This is the last time they're gonna see you This is beautiful. He's gonna sacrifice himself to save his daughter You're gonna let us make the arrest or not.  Oh Shit The voice actors for this show is God's here Chum But he runs a time ship bro, don't they hear that Don't they hear that that this girl's banging on the wall or is that only for us to hear?   I thought this was the city of the poor people. Why is this?  So in the beginning In the beginning before the intro when Silco's talking when he's drowning talking about an old friend Was that body that was hovering over him above the water him or was it Vander? Because the way he just said that it's like they know each other. You never did know when to walk away Like he knows they know each other Why did I close there?  Is it the guy they injected with the rat serum?  Yeah, I thought these characters were here to stay Kill him. Well, why'd you leave him alive?  We don't who cares. Oh I know what's gonna happen. Oh My god, this is a this is incredible man I'm guessing the guy that made Silco the way he is is Vander and now Silco Killing everybody else but Vander.  I bet I bet the people like Zorka here by but I feel like they're gonna take Vander and Do whatever they did to this guy this animal they created and do that to him They're gonna use him like like a machine now.  He's gonna get his revenge. Oh my god. That's a powerful scene, bro. Hell, yeah, I Already know why y'all wanted me to react to this episode We could test it if we had access to my equipment which is being destroyed tomorrow man now I understand legal legends They make so much money. It's like one of the most popular games in the world They definitely used that budget on voice actors for this show any animation because this is like they're putting their all Into this show story-telling the animation the voice acting everything and you could feel it is everything my I feel a little connection here. Maybe if we show is it only me and I'm a thing there's lab No, no, no, they're gonna break in the hymen diggers lab He feels that potential That's why they're working together bro.   No, I feel it, bro I feel that tension. I don't know about y'all, but I feel it.   I'm trying to cry trying to praise the Lord It's a little crew the base vise not gonna let this happen, bro They're gonna get that group back together and try to save him. I could feel it with your monsters You won't win a war again under that again You'll get these guys just look like villains for war. They're not even trying to hide it You had my respect the lanes respect, but the whole of the underground United is one. Oh Shit, so he became a lunatic, but they were like brothers.  Oh my god. It was Vander Oh that flashback the way it connects what I did to you.    Oh Shit, I was right.    I know who you are. I Wouldn't hire him.  I would hire him because I'd be afraid if I don't oh Shit, what's that the girl from the bar? She wants to make a change. She hates these these rich pricks in the city. Here they go Stealing from Hyman digger I'd make that line up, too. We figured out.  That's awesome.   I just but my heart smiles man. She's a little baby Who took Vander? I don't know what I need to help him.   He's our father, too, man I may find it that kid, but that was a strong delivery right there. Oh No, no, let's stay back. I don't want to get in trouble.  Don't tell me you're gonna say stay here This is vise mistake right here This is her mistake. This is good to cause a rip in their relationship Mm-hmm. You don't tell her to stay home.    Oh The sound engineering in this show is just crack Yeah, I'm convinced this whole city is deaf man Are they just gonna stare at it like it's a firework show Wait a minute, she's mentally unstable. She's like bipolar.  Oh my god. I never even looked at it like that. I don't like what is going Like I said bro, it's Sunday. I don't want to crowd today. I Love how all of these plots are going together like I don't want to just see one One set of people like I don't want to just see Vi like I want to see these guys working on what they're working on I want to see what's happening in the Vander like there's so many plots going on.  Here we go. I'm not how I thought about that bro.   What are you doing? What are you doing? That was too easy There's guards everywhere an open window and you have to get out Now they wanted you to come they knew you would come Whenever a guy walks in like that. Oh, it's over I've got a boy.  I thought it was me a 3v3, bro. What are these other side characters come from?  I love her.  Y'all know what you were doing the way she Oh Hurry up Milo Milo. This is your moment bro.   I don't know if this guy is 15 or 50 Like that ass, bro. He's one of those people, you know when you look at them You're like, I don't know if he's 20 or 200. That's how I get that feeling, bro I don't know what they With their lifespan is in the arcane worlds Yo, she's a tank This is how she plays in the game.   Oh You could have came here alone by here we go. This is her matchup right here Dude I get the side characters out of my way.  Just go for them skinny dudes girls.   She's returning the avatar. He is flying The Willy Wonka the chocolate factory scene where they're flying are they gonna start singing too?  They're like look at what we just did They're not like huh.  This better go down in flames. Some things should not be invented. Oh, this is powder's time That was deeper than any connection.    This is gonna bring my heart man.   This is crazy to show Is this show? This is like a finale.    Look at that shot, man. Can we please you?    Yeah, he's dead, but the kids Milo and the and the 50 year old kid laid them dying Herbie and the cause of that not knowing that that would happen I can't even put in the words how amazing that was you already know like I don't even got to explain How good that was and I say a lot on this channel that that was the best thing I've seen but You can see in my eyes during that part probably how Impactful that was how incredible that scene was and now I understand What y'all meant by this show is split up between acts like this was act one This was the end of act one.  Let me know down below How that ending impacted you like the last 20 minutes how you felt during that That was like a knife through the heart this episode.  I promise. All right. That's it.  Goodbye


Hello everyone, my name is Sarkar. So, I will say the problem statement first and then I will tell you how my application idea came up. So, there are a lot of enterprise applications out there that are basically for example, there are banking applications and there are other sort of applications that do different things. But the main purpose of these applications is security and when it comes to saving files on the device, hopefully these applications need to implement encryption for these files because an android other applications can also access these files. So, the job of these applications is not basically to implement encryption, their job is to do other things. So, what I intend to do at the end of this hack night is to create a library that would encrypt these files for the applications. Now, this library would do it on a background service on a synchronous thread in the same application process or on the main thread. Now, these would be the configuration provided to the application and the application should be able to just call a simple method from our library and be able to encrypt a file onto the device. Also, I intend to create a demo application that should be using this library and the demo application would be a sort of file manager that you can browse through different files on the device and encrypt a particular file and save it where you want to. So, that is my application idea and well, I am looking for teammates or anybody who wants to join, maximum of one or two sources would be needed. Thank you.


Welcome to the World Summit on the Information Society 2017. I am delighted to be joined by Tish Berard, President-elect at the International Trademark Association. Inter is a not-for-profit organization of trademark owners and professionals. Its mission is to make commerce fairer and protect consumers. So why is an institution like yours at WISIs? We're looking for opportunities where we can partner with other organizations in order to achieve our common goals. And the one thing I've learned attending WISIs, this is my first time being here, is that we do have a lot of goals that are similar. For instance, accessibility, informing and educating consumers and business owners. So there's a lot of things we could do together to accomplish our goals and not have to separate our resources but actually pool our resources together so that we're more effective at doing so. So how can ICT help trademark owners and professionals and give them a more level playing field in business? As ICT's expand, more and more people are going to have access to the Internet. And that means that more and more people are going to be selling their wares, their products, their ideas on the Internet. Oftentimes, they're so concerned about the business aspect of that, reaching consumers, collecting money, that they're not really thinking about the ownership aspects. So at the International Trademark Association, we want to educate people to be at the forefront and to be thinking about those issues at the beginning so that when they're putting their products out there on the Internet, they're not then having unscrupulous business people come in, take their products and their ideas and try to pass them off as their own. We want business owners who come up with these wonderful ideas and products to receive the benefits of those ideas. So it's a double whammy, isn't it? So ICT gives them more protection, but it also gives them access to greater market opportunities. Absolutely. So earlier you spoke on a panel dedicated to gender mainstreaming. Can you tell us what gender mainstreaming is, what you discussed and the key insights? Gender mainstreaming is just trying to make opportunities more available for women, not only in relation to ICTs, but I think in business in general. Even in developed countries, such as the United States, where I'm from, women play a larger role in business, but we're still not paid equally. We still don't have the high level opportunities that others, that men have. And so it's important to bring together groups of people who are thinking about this, and not just women by the way, men and women who are thinking about this issue, it really is incumbent upon all of us to try to make business places equal for everyone, because there's so many women with great opportunities, with great ideas that can contribute, and they're being silenced or not heard just by virtue of simply being a woman. And so some of the key points that were take away from the panel was just that, that we need to work with men, it's not a women's issue, it's an everyone issue. And so partnering with men, with everyone, is a key factor in moving forward these ideas and these goals. Desbris-Range, thank you very much. Thank you.