Good afternoon all, Now that our second exam is completed, we will spend a bit of time discussing the nervous and endocrine systems as we start into the 3rd unit of our course. These are the two primary regulatory systems in the body, which makes their place in our homeostatic control very important. Accordingly then, when these systems are dysregulated or hijacked, the problems that arise can be very severe. We do not have a chapter assigned for tomorrow (Friday 18 Oct), so I would like to give you some supplemental reading, instead. You can review this material on your own, so we will not have to meet in person on Friday (tomorrow). In lecture yesterday, we outlined the cellular basis of the nervous system, and the method by which neurons communicate with each other and their targets at synapses. Synapses are points of communication between cells, but are not actual points of physical contact between cells. The communication is achieved not by direct cell-to-cell transfer of materials, but rather through neurotransmitters, chemical signals that are released from the 'signaling' cell, drift across the synapse space, and bind to receptors on the 'receiving' cell. If you think back to early in the term about our discussions of how cells can communicate with each other, you will picture that these neurotransmitters can have effects on their target cells by binding to receptors on the cells, and causing some change: perhaps ion channels open or close, ions move in or out of the cell (or stop flowing), or some enzyme is activated that changes the metabolism of the target cell. These changes might have the effect of stimulating the target cell (causing it to perform more of its cellular function), or inhibiting it. As I pointed out in lecture yesterday, synapses also are the place where most of our drugs (both legal and illegal) influence nervous system function. Our drugs may change the amount of neurotransmitter that is released, or cause it to stay in the synapse for a longer or shorter time. Some drugs block neurotransmitters from binding to their receptors, or artificially activate the receptors even when no neurotransmitter is present. These all are potentially very powerful effects on synaptic function, and thus brain function. If the effects of medications are targeted to specific neural systems (sensory, motor, motivation, reward, or other), they can drastically alter our behavior and our capabilities. When we quickly reviewed some some common drugs and their effects at the end of lecture yesterday, I noted that heroin is among our most dangerous drugs, for its ability to cause very high levels of dependence (users can't bear to be without the drug) and tolerance (users need successively larger doses to feel the same effect). Heroin is one of the opioid drugs, a class of drugs long known for their ability to relieve pain and provide pleasure/euphoria. This class of drugs includes morphine, long used clinically for pain relief. Historically, heroin was derived from natural (plant) sources, and humans have been cultivating and using opioids for thousands of years. Poppy plants have long been grown for their opium sap, which can be consumed as-is, or refined into more-potent forms. With the advent of global travel, poppies grown in Afghanistan can produce opium sap, which can be refined into heroin and trafficked for thousands of miles. This wave of heroin across the planet initiated the opioid crisis, decades ago. More recently, pharmaceutical advances have led to the development of many other opioids: hydrocodone, oxycodone, fentanyl, and others. They are so effective at providing pain relief that they have been heavily marketed, and heavily prescribed. Black-market sourcing and illegal use of synthetic opioids now far outstrips that of heroin, as the pharmaceuticals are typically cheaper, easier to obtain, and preferred by users because they are, in many cases, more potent. Fentanyl, for example, is estimated to be 20x as potent as heroin. Other synthetic opioids may be as much as 500x as potent. Prescription and illegal use of opioids now has reached a crisis point in our country. One cannot listen to the news without hearing of opioid uses and deaths (even here at IUP). Opioids do target the pleasure and pain centers of the brain, but they also serve as a general depressant of respiratory function. As users become dependent upon and more tolerant of these drugs, they acquire and use them in higher amounts. This puts them more and more at risk of respiratory failure: their brains simply stop signaling enough breathing. This is especially problematic when users consume illegal drugs, for their contents may not be well-regulated. Far too often, users overdose on drugs which are more concentrated, or in higher doses, than expected. And so, for your reading on this topic, I'm offering here below a link not to a recent news story, but rather to a more comprehensive news report that was issued last Fall. It describes some of the biology and the neuroscience of opioid addiction, but also presents a variety of personal perspectives from addicted individuals. In many ways, addiction can be considered to be a disease, and the viewpoints and anecdotes describing addiction are both powerful and scary. https://www.nytimes.com/interactive/2018/us/addiction-heroin-opioids.html This article also includes links to a few other resources on the topic of opioid addiction. But let us add to this discussion some good news: Because the action of opioids is relatively well-understood, pharmaceutical advances have made available a very effective antidote to opioid overdose. Commonly referred to by its product name (Narcan), naloxone is a substance that binds to opioid receptors, in place of the opioids themselves. But, naloxone does not activate the receptor in the same way as do the opioids; rather, it blocks the receptor from being activated by the opioids. Naloxone is remarkably effective, and many first responders and emergency personnel now carry it. They find themselves using more frequently than they would like, but there is no doubt that it has saved thousands of lives. Naloxone is so important in the fight against opioid abuse that the Pennsylvania Department of Health has issued a standing order that allows public citizens to obtain it, if they believe that having Narcan might help them prevent an opioid overdose. If you think that having it would benefit you or those around you, I'd encourage you to consider obtaining it. You can start at the PA Department of Health web site, especially the text pertaining to ACT 139, which described how private citizens might obtain naloxone, through a standing prescription order: https://www.health.pa.gov/topics/disease/Opioids/Pages/Naloxone.aspx There also are opioid resources available here at IUP, through IUP's Center for Health and Well-Being: https://www.iup.edu/chwb/ I can help you navigate these resources, if you like. I hope that these materials help to put our discussions of brain structure/function and synapses into some context. I'd be happy to provide more material on these topics, if anyone is interested. Have a great weekend - see you on Monday. Sincerely, Dr. Nealen
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Good morning all, In recent weeks we have considered the role of the circulatory and respiratory systems in collecting and delivering oxygen to our tissues, and just last week I sent you a long article about altitude-induced hypoxia and the physiological challenges that it stimulates. We've also discussed the kidney hormone EPO, and its role in stimulating the production of RBCs. Fresh on the heels of those discussions and reading, this week's science news included the awarding of this year's Nobel Prize in Medicine, to a group of three researchers who study this very phenomenon, the physiological responses to oxygen. Their work is crucial to an understanding of how cells adapt to changing oxygen levels. https://www.cnn.com/2019/10/07/health/nobel-prize-for-medicine-2019-intl/index.html Nobel Prizes in science fields are awarded to researchers who have long, established careers and who have made discoveries that defined their fields. This year's winners are no exception - these scientists are well-established and highly respected. And, not surprisingly, they are still active. They also are likely to follow another tradition in that they most likely will use the award not to enrich themselves personally, but to support the work of their research groups. It's a great example of the selflessness that drives much of science: exploration and discovery for the greater good. There are plenty of other news stories on these awards, including https://www.sciencemag.org/news/2019/10/medicine-nobel-honors-work-cellular-system-sense-oxygen-levels?utm_campaign=news_weekly_2019-10-11&et_rid=17390186&et_cid=3026386 https://www.the-scientist.com/news-opinion/cells-oxygen-sensing-discovery-earns-nobel-prize-66538 Breakthroughs in science normally come after long, hard work, built from many small steps of progress - and informed by many failed experiments, a lot of trial-and-error, and requiring much patience. One prize winner (of years past) said that 'if I have seen further than others, it is only because I have stood on the shoulders of those who came before me'. They say that 'no man is an island', and in science that is certainly true - modern science is a highly collaborative venture, and today's advances are built upon the progress of earlier investigators. When you contribute to a project, no matter how small or insignificant your part may seem, it's important to remember that it adds to our collective knowledge and capability. Who knows? Future Nobel Prizes may depend on you! Have a great weekend - Dr. Nealen Good morning all, In recent weeks, our lab exercises have considered EEGs, sensory function, as well as muscle control. In the news this week is a report that links all of these, in a way that may prove to be revolutionary for those with spinal injuries. Recall that from an EEG, one can evaluate the activity in underlying neural tissue. You also will remember our diverse tests of sensory systems, which were good reminders of how broad and how important our sensory capabilities are. Most recently, we discussed how action potentials in motor neurons can be used to activate skeletal muscle. Researchers have managed to marry all of these elements in new technology that is a real-life version of something from science fiction: a robotic suit. They have used sensory receivers and brain implants to allow a paralyzed man to control this suit, enabling him to walk for the first time in years. The subject received bran implants into his motor cortex, which recorded his motor signals. Because of his spinal injury, these signals could not be relayed to his muscles through the spine. Here, the signals were routed to electronic equipment, and then to prosthetic limbs. It look a lot of practice learning how to associate his own thoughts into the motions of his prosthetics, and there is much about the device yet to be improved, but the result remains extraordinary. https://www.bbc.com/news/health-49907356 We live in a world in which advances in neuroscience and advances in technology occur at a rapid pace, and their intersections are often astonishing, and fruitful. Have a great weekend - Dr. Nealen Good evening all, As we remain caught-up on our lecture schedule, we do not need to meet in person on Friday (04 Oct) for lecture. Instead, I'd like to you to consider a recent science news article that bears on our lecture material. In recent weeks, we have considered the properties of our blood, its red blood cells and hemoglobin, as well as the ways in which the circulatory and respiratory systems interact to deliver oxygen to our tissues. We've also described how erythropoietin (EPO, a hormone released from the kidneys in response to low blood oxygen levels) can stimulate the production of more RBCs. The article I am sending you considers these same phenomena in a human population that lives (but not thrives) in perhaps the highest-elevation city in the world, La Rinconada, Peru. La Rinconada sits at an elevation of 5,100 m (more than 16,500 ft) above sea level, and has a regular population of >50,000 at this very high altitude, there to work in gold mines. The air at this elevation contains only half as much oxygen as the air at sea level. Persons not accustomed to living at high altitude can become very ill (sometimes fatally) at elevations above 9,000 ft. To give you an idea of how high in the Andes this city is, consider that 'mountain climbing' here is the US is typically considered to be very technical above 12,000 ft in elevation, and not for amateurs. At La Rinconada, people may spend their entire lives above 16,000 ft in elevation. The physiological challenges of life at this altitude are many and severe. The low oxygen levels stimulate extremely high levels of RBCs and hemoglobin, as much as 3x those considered to be normal. This, in turn, causes blood viscosity to rise dramatically, which causes abnormally high blood pressures. These elevated blood pressures place extra strain on the heart, causing it to enlarge, often dramatically. Despite these adjustments, many suffer from chronic hypoxia, termed 'chronic mountain sickness', or CMS. Blue-ish skin, fatigue, and low endurance all are common symptoms of CMS, and all stem from low levels of blood oxygen. Curiously, populations long adapted to life at high altitudes (including some populations in these South American Andes mountains, and others in the Himalayas of Southern Asia) seem to have evolved at least some protections against chronic hypoxia and the challenges it poses. This suggests that there may be genetic tools that can be put to use in helping others who suffer from hypoxia not because of altitude, but because of diseases related to cardiac or respiratory function. This article describes one team of physiologists and their efforts to assess human physiology and health at this altitude. Their initial focus was on CMS and body responses to it, but they quickly became caught-up in the socio-economic plight of the people there - life is brutal for the residents of this city, and the researchers felt, in many ways, helpless to help them. They certainly could not improve the economic status of the town's residents, nor could they offer a cure for CMS. There, as in many parts of the world (including our own country), the working class are too easily exploited, too easily marginalized. Lack of access to basic health care is often one of the first signs of a population that is short of options and resources. When that combines with dangerous forms of employment for the un- or under-educated, health issues rise and life expectancy falls. https://vis.sciencemag.org/hypoxia-city/ There is a companion podcast for this article as well: http://traffic.libsyn.com/sciencemag/SciencePodcast_190913.mp3 As you review these materials, I'd like you to think about the basic physiological mechanisms at play: how low blood oxygen levels can stimulate RBC responses, and, in turn, how these can contribute to blood pressure, which itself can trigger responses (remember ANF, when blood pressure rises?). Keeping ourselves in homeostatic conditions is complex even under typical environmental conditions; life under extreme conditions only amplifies the challenge. I hope that you enjoy this article, and I hope that you enjoy the Homecoming weekend. Please be safe, and I will see you on Monday. Sincerely, Dr. Nealen Good morning all, The results of our vaping survey are in! We had 93 responses in total. Almost exactly 2/3 (61/93) respondents said that they do not vape. Almost exactly 1/3 (32/93) respondents reported that they did vape at least one per week. Those respondents who did not vape rated its danger as 8.1 out of 10. Those who do vape rated its pleasurability as 6/10, and its danger as 7.3/10. (interesting that users ranked the pleasurability lower than the danger, isn't it?) Those who vape do so an average of 12x per week (range:1-100 times per week). 17/31 (42%) of those who vape do check the source/ingredients, while the majority (17/31, 55%) do not. The vaping materials used (and the number of people who reported using them) are don't know 1 Juul 2 mint 3 nicotine 3 blueberry 1 tobacco 12 other 12 These findings reflect much of what is reported in the recent news: - vaping is very popular among college-age students - additives or alternatives to tobacco are prominently used - users pay relatively little attention to the ingredients or sourcing of vaping products. These are dangerous trends! That one can directly and intentionally infuse nicotine is especially worrisome, as is the fact that users do not know with great confidence the source or identify of the other compounds that are inhaling. Our lungs are designed for exposure to atmospheric gases only - introducing any other compounds is potentially quite risky. We will continue to discuss this topic, and I will continue to pass along more information. Education and effort are the keys to behavioral change - with any luck, we can increase awareness of the dangers of vaping and reduce its prevalence. The numbers of vaping-associated cases of severe respiratory distress and mortality continue to climb - please be aware of the dangers, and use that knowledge to make good choices about your health. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html Sincerely, Dr. Nealen Good morning all, We recently described human blood in lecture, noting that it is red in color (of course!), and that its color comes from the hemoglobin pigment inside of our red blood cells. How about a person whose whole blood is blue? In the news this week is a report about a woman who used excessive amounts of a common over-the-counter analgesic (benzocaine) which rendered her hemoglobin blue in color: https://www.cnn.com/2019/09/19/health/blue-blood-trnd/index.html Persons of low blood oxygen levels are considered to be 'cyanotic', and often have a pale or bluish cast to their skin. If their hemoglobin has been poisoned, it can impair oxygen transport/delivery, at worst, to a fatal degree. In this case, the blue color was not physiologically problematic. This woman's blood was still relatively high in oxygen content, but contained more cyanomethemoglobin (which causes the blue color) than is normal (few percent). Luckily for this woman, her problem was cosmetic only, and the antidote (ironically, doses of methylene blue) was both simple and effective. Interestingly, blue blood is perfectly normal in crustaceans (such as crabs and lobsters), because they employ hemocyanin (rather than hemoglobin) for oxygen transport. Their blood is of such great medical utility for testing of toxins and contamination that a large (and controversial) industry is devoted to its collection: https://www.theatlantic.com/science/archive/2018/05/blood-in-the-water/559229/ And, there is a known genetic disorder than causes cyanosis to run in (a small number of) families, including the famous 'blue Fugates of Kentucky': https://www.iflscience.com/health-and-medicine/the-science-behind-the-mysterious-blue-people-of-kentucky/all/ So, the next time you hear the term "blue bloods", you might wonder if it is genetic, pharmaceutical, or crustacean in its basis... Have a great weekend - Dr. Nealen Your Environment Is Cleaner. Your Immune System Has Never Been So Unprepared. - The New York Times9/19/2019 Good evening everyone, At the end of this week we find ourselves in the midst of a discussion of immune function, first with our lecture yesterday on the immune system (Chapter 7), to be followed by our next lecture on infectious disease (Chapter 8), scheduled for next Monday. Recall that for tomorrow's class (Friday 20 Sept), we will not meet in person. Instead, I'd like you to read/digest a news article on a current and very relevant immune topic, that of environmental exposure to antigens. For much of the history of our species, human life and society was based around agriculture, including exposure to domesticated animals. In the last hundred years, of course, that has changed for many, as populations became more urban. During this same period, the use of cleansing and sanitizing products in the household has increased dramatically, culminating recently in the explosion of "anti-bacterial" products, such as soaps, wipes, and tissues. Most immunologists believe that we have taken cleanliness a bit too far. According to the "hygiene hypothesis", natural exposure to antigens keeps the immune system primed for action, and enables it to make robust responses to actual disease agents. In our ultra-clean worlds, however, many (especially the young children of cleaning-obsessed parents) are coming into contact with fewer and fewer natural antigens, and increasingly their immune systems are ill-equipped to respond to them when they do, leading to a rash (no pun intended) of allergies, sensitivities, or, at worst, autoimmune disorders. This article explores the "hygiene hypothesis" and some of its implications. As you go through it, I'd like you to consider a few key questions: - what happens to our immune system when we are exposed to naturally-occurring antigens? - why should exposure to non disease-causing antigens enable us to better respond to more serious antigens? - do you personally use anti-bacterial products in your household? - does this article make you want to reconsider their use, in any way? https://www.nytimes.com/2019/03/12/health/immune-system-allergies.html?searchResultPosition=19 Our immune system is wonderfully complicated and powerful, but some think that our social behaviors have evolved faster than is good for it. Perhaps a nice walk outdoors, a swim in a lake, or a picnic in the grass is just what we need... #ReturnToNature Have a great weekend - see you on Monday. Dr. Nealen Good morning all, As a follow-up to the news article I last sent, here are a couple of updates on this developing story: Severe illness and unexplained deaths associated with vaping have continued to occur, and, while no definitive cause has been identified, the majority of cases seem to be linked to the inhalation of vaping substances that are coating or irritating the lining of the lungs, preventing proper gas exchange. Vaping materials often have additives, such as flavorings or oils, that are the prime target. A number of persons suffering respiratory distress after vaping seem to have oils lining their lung surface. As one researcher put it, 'The lungs are designed to encounter gases only. Inhalation of other substances is inherently risky'. https://www.nytimes.com/2019/09/07/health/vaping-lung-illness.html https://www.washingtonpost.com/health/2019/09/07/what-we-know-about-mysterious-vaping-linked-illnesses-deaths/?tid=pm_national_pop I understand that vaping is quite popular, and I worry (a lot) about how dangerous it is. It is trendy and new, but not well regulated, and too recent to have been well studied. I suspect there will be much more news on this topic, and likely soon many more regulations about what can or cannot be included in vaping materials. I hope that you do not vape - but if you choose to do so, please be informed, for your own safety. Sincerely, Dr. Nealen First Death in a Spate of Vaping Sicknesses Reported by Health Officials - The New York Times8/29/2019 Good evening all, As I mentioned in lecture on Wednesday, we are still on track schedule-wise, and do not have a chapter planned for Friday of this week. Thus, let's not meet in person for class tomorrow. Instead, I'm passing along (below) a link to a recent news article that I would like you to read, about some of the dangers associated with vaping, a topic that is certainly of the latest health issues of concern. As a former smoker, I know first-hand the 'rush' associated with nicotine; as a physiologist, I know too well the dangers associated with inhaled substances. To me, vaping seems to present dangerous levels of both. I will occasionally pass along science and health news articles of this type during the semester. My purpose in doing so is to help you to become more aware of topics at the interface of biology and society, and also to help you assess how you obtain your science and health news. Those of us working in science obtain our scientific news, quite often, directly from the original sources: the people conducting the studies and reporting the results. They publish their findings in science journals, or present them at conferences. Most people do not obtain science news directly, but hear news via secondary sources, such as news releases from scientific organizations, or news stories from the major news outlets. These secondary reports often are then carried by tertiary outlets (smaller/other reporting sources, including news aggregators and media feeds). Along the way from source to audience, science news is normally distilled (a lot) - much of the detail is excluded or simplified, and the reports often are boiled-down to singular take-home messages, which may (or may not) be good representations of the original work. When you browse the links that I will forward, or when you access science and health news on your own, I'd encourage you to delve a little bit deeper into them, to read more than just the summaries, and to follow links back to original sources when possible. I'd also encourage you to think a little about the translation of news from source to consumer, and the reputability of the news outlets that you use. You will not be formally tested on any of the material in the news stories that I will send you, but I do hope that the material in them makes its way into our conversations. This first link is from the New York Times, which provides one of the best (e.g., best funded and most reliable) secondary sources of science and health news. They do limit access to only a handful of free articles each month, so I will use them sparingly. https://www.nytimes.com/2019/08/23/health/vaping-death-cdc.html Here's wishing you all a safe and enjoyable Labor Day weekend - see you next week. Sincerely, Dr. Nealen Good morning all, As our term comes to a close, I'll use my last news message to send along the latest news from on ongoing story in exercise physiology that raises interesting, and difficult, questions about sex differences in physiology and the regulation of sporting events. As we have described in class, both males and females have circulating testosterone, with males generally having much higher levels than females, on average. But, like all aspects of physiology, there is a wide range of what constitutes "normal" values, and there is overlap between the ranges of naturally-occurring male and female levels. The science of testosterone is fairly well-understood in terms of its anabolic effects. Testosterone enables muscle fiber development to a larger size, and facilitates its maintenance at that size. Testosterone supplements have been used (both knowingly and unknowingly) for decades to help athletes build muscle, and its use was the primary factor which led to the formation of the World Anti-Doping Agency (WADA) and the associated regulations restricting the use of chemicals to enhance the physiology and performance of athletes, especially those competing in sanctioned (e.g., large, high-profile, big money) events. Over the last few years in particular, however, we have gained an understanding that much of what makes us male or female is not always so perfectly discrete, so categorical. For some aspects of our genetics, anatomy, physiology, and performance, male and female traits are most often clearly binary (e.g., one way or the other). But other of our traits, especially some of our physiology, is not so dimorphic or discrete, and circulating testosterone levels fit into this category. Males and females generally compete only within same-sex sporting events because, for most events, males hold a competitive advantage. This is certainly true for track-and field race events, which place emphases on speed and endurance. This is not to say that female athletes are in any way unimpressive or not elite - they certainly are, and many would leave male competitors 'in the dust'. But, in general, males outperform females in foot races, and testosterone seems to provide at least some of that advantage, through enhanced muscle size and performance. Recent analyses have shown that the top female athletes in female track events have testosterone levels higher than the average woman. This is perhaps not a surprise, as these elite female athletes carry more muscle than the average woman as well. We must ask - which came first? Did higher testosterone promote more muscle, which led to racing success? Or does intense training lead to muscle development and an altered hormonal profile? Probably some of both. This situation has reached a peak in recent years over the case of Caster Semenya, an Olympic medalist who hails from South Africa. By all published accounts, Caster is genetically and physically female, but exhibits hyperandrogenism, a state of producing greater than the normal amount of androgens (male hormones). She is the most-accomplished middle-distance female athlete of the last decade, to the point at which protests against her have been raised, and regulations put in place to prevent her from racing unless she takes medications to reduce her androgen levels. She has appealed those decisions, to no avail. This issue raises many difficult considerations, from the personal (is this athlete being singled-out? Has her privacy been unfairly invaded?), to the social and political (is this another, familiar case of racism in sport?), to the athletic (is Caster really benefiting from her androgen levels?). As such, it seems unlikely to be settled easily, or soon. Nonetheless, it serves as a useful reminder that natural variability is, well, natural - it is an essential part of what allows us to exist as 7 billion different individuals. There are those among us who are short or tall, thick or thin, slow, - or very fast. Can we really regulate or legislate ourselves into categories, for competition, or for other reasons? Most of our physical and physiological traits vary broadly over a continuum, which means that drawing categorical boundaries may be somewhat artificial. In this case, we seem to have a single physical trait, with a well-understood connection to physical performance, that has become exposed in the very high-profile (and big-money) world of competitive sporting. https://www.nytimes.com/2019/05/01/health/caster-semenya-testosterone.html As we learn more about physiology, we are likely to revisit this issue many times again, and in new ways. How long will it be before we hear "Is it fair for me to compete against someone who has a better genetic profile than I do?". I suspect that, in the coming decades, we will be discussing less the physiological and hormonal aspects of physical and mental performance, but rather the genetic bases for them instead. I'm signing off for the term now. I hope that these weekly news messages have been useful to you. This is the first semester that I have used them to this extent, and it has been a learning experience for me. In particular,
In the end, though, I remain very optimistic. Science is "mankind's organized quest for knowledge" (Floyd Bloom), and we already know that "knowledge is power" (Francis Bacon). It is science that offers us the best hope to deeper understanding, new therapies and treatments, new cures, and new adventures. We will encounter many speed-bumps along the way, to be sure. I hope that our course has inspired you to be a part of this quest, and to make the best use of the knowledge that you gain while on it. Have a great weekend, and best of luck with all of your exams next week. Dr. Nealen |
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