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Python how to use capstone do my capstone salt lake city utah la mafia corse reportage [MUSIC] Based upon my earlier conversations, I think this is a very friendly group so I'm going to just start with, I guess the drinks flowed freely, I'm gonna give a short bio and then tell you about one of the projects in the lab and how kinda was sponsored by my participation in the Center for Sensory Biology. So I'm Paul Fuchs, I'm a professor of otolaryngology and director of research in that department. I am the second of 11 children in a German Catholic family. Grew up outside of St. Louis in what was then a small farming community. Now it's a suburb. And being a goal directed, ambitious, young kid in a Catholic family, I figured well, the best thing to do is to go into the seminary and planned to become a priest, which I did. So I then spent my high school years and a year of college in a seminary in the order of the Society of the Precious Blood. And about midway through my freshman year in college I took a sharp left turn and transferred to Reed College in Portland Oregon and if you know that place that may raise some questions in your mind about what that involved but we'll leave that for later discussion. >> [LAUGH] >> And then at Reed, but Reed was great for me. It really was a fantastic place. I eventually majored in biology and then went on from there to get a doctorate in neurobiology at Stanford University. Throughout all that training period, I was very focused on the topic I still study which is synaptic physiology. I'm really interested in how neurons communicate with one another, the details of those molecular mechanisms and have been what I call an electro jockey throughout my entire life. I'm a electrophysiologist who likes to look at electrical recordings. I did a second post stock in Cambridge England with a man named Robert Fettiplace who had at that time decided to use the turtle as an interesting model system to study how the periphery of the auditory system operates. There's lots of reasons for doing that, but I joined him there and learned from him a lot, and that really turned me in the direction of studying hearing. Initially as a model system to look at synaptic signaling cuz it's very intriguing, but it turns out there's some really nice other things that impact our own health, of course. So my laboratory now continues to be in centered on synaptic physiology. We look at how signals in the ear are transmitted to the brain. We also look at how signals in the brain are transmitted back to the ear through some efferent neurons, which actually turn our ears off in interesting ways. Tonight I want to just tell you about one project which springs out of my participation in the Center for Sensory Biology. So two other colleagues there, Xinzhong Dong and Michael Catarina, are outstanding sensory physiologists and molecular biologists, and they study pain, and noxious stimulation of somatosensory receptors, pain, and itch, and temperature sensation. And in our conversations, our chalk talks, our coffee klatches, whatever you wanna call it, we were inspired to ask the question, well, maybe there's something that mediates ear pain, and can we learn something from Katerina and Jim Jong Dong about how to study that? So you might be asking yourself if you're not old enough, what is ear pain? There's no such thing. Well, there is. And some of you that may, like me, have reached the stage of age related hearing loss where you now know that there are some paradoxical gain of function pathologies that go along with hearing loss. One of them is tinnitus, that's pretty famous. Lot's of people have ringing in their ears, for some people it's extremely irritating. But there's also something called hyperacusis which, again, is paradoxical because you may be less sensitive to quiet sounds, but you become much less tolerant of loud sounds. So that things that didn't bother you at all as a young person, now you find irritating, or in fact, frankly painful. People with really severe hyperacusis are really devastated. They become recluses. They don't go out in society any longer. They become highly depressed. You might imagine there's a lot of very severe morbidities that go along with the situation where you can no longer function in society because too much sound is painful. And when they describe the pain, they describe pain in their ear. Which is burning, long-lasting, it sounds like neuropathic pain. The sort of thing that go comes along with diabetic neuropathy, for example. So we thought, maybe there's something there that can serve as the substrate for hyperacusis and neuropathic type of pain from the ear. And in fact, there's a hint, and people have talked about this for a long time. So if you look at the afferent neurons that carry information from the ear to the brain, most of them are large diameter myelinated neurons, and they carry acoustic information. They tell us how we hear the world. 5% are very different. They are small diameter, unmyelinated, they have very strange peripheral arbors which are very different looking. And the very few in vivo recordings that have been made in animal models said that they didn't seem to respond to sound. The loudest sounds that could be produced in the experimental situation didn't really cause these neurons to fire action potentials, the signal. So we thought, let's dive into this. We have some suggestions from our colleagues, maybe we can learn something from our technologies. And so, Catherine Weiss, a graduate student in the department, began to learn how to record from type two afferents and excised pieces of the cochlea of a rat or a mouse. And she learned from her work that indeed these are very unusual neurons if they're cochlea afferents because they're very poorly activated by transmitter release from hair cells. They do get it, and they do get a little signal but it's weak, it goes along with the idea they may not respond to sound very well at all. What Catherine or Cat also found was that, they were sensitive to ATP. And so, then Chong Lu, another student who took over after Cat left, established that not only are these neurons sensitive to ATP. But if you record from one of these Type II neurons in this X sized piece of tissue, and damaged tissue, causing the release of ATP which comes out of cells when they're damaged, these Type II afferents fire like crazy. They respond very strongly to ATP which is a common mediator of trauma in skin, and causes activity of somatic nociceptors. And so, at this point, we are pretty happy with the idea that Type II afferents may be cochlear pain fibers. They may be the substrate by which hyperacusis and tinnitus gets started. And so, because we are cellular electrophysiologists and we study ion channels and things, we know now what some of the channels are that are operating there. We know that some of the neurotransmitters receptors are that mediate these responses. We know some small molecules that interrupt the activity of Type II afferents. And so, I think we're well on our way to beginning to work out a rational basis for thinking about therapeutic strategies to treat conditions like hyperacusis and tinnitus. Because now we know what the cells are we think, and then we're beginning to know what the molecular mechanisms are and that knowledge springs directly out of my interactions and participation in the center for sensory biology. I'm quite confident we wouldn't be studying this project today if I hadn't had Michael Katerina and Jin Jan Dong sitting down with me for chalk talks ones a month and telling me about their research and me telling about theirs. So I'll stop there, and thank you very much for your attention. bsn nursing capstone project topics Icahn School of Medicine at Mount Sinai.