Newswise — Among the most well-known disease carrying bugs in Texas are mosquitos, spiders, cockroaches and ticks. But the Kissing Bug is a serious, lesser known threat to Texans. While it has a cute name, many folks don’t know there’s a not-so-cute, deadly parasite the bug can transmit. Texas State Assistant Professor Dr. Paula Stigler Granados has spent several years researching Chagas disease, a “silent killer” carried through many Kissing Bugs. Dr. Stigler Granados recently shared what the disease means, especially for migrants, as well as those who may contract the disease locally without realizing it. What is Chagas Disease? “The disease itself is interesting and complex,” explained Dr. Stigler Granados. Caused by a parasite called T. Cruzi, Chagas disease manifests itself in two stages: acute and chronic. During the acute phase of eight to 12 weeks, people may experience mild flu-like symptoms, itchiness at the site of the bite, or no symptoms at all. Once the acute phase is over, the person enters into the chronic stage, which can either be with or without symptoms. The beginning chronic stage of Chagas can last for years or even decades with no symptoms at all, hence the name “silent killer”. Many people will never know they have encountered a kissing bug or even know they have the disease. However, if the disease isn’t found and treated before the person develops symptoms, they may go on to develop symptoms and the disease will often be untreatable and fatal. Symptoms include irreversible cardiac complications (including heart failure) and sometimes intestinal issues such as megaesophagus and megacolon. Only 30-40% of infected individuals will go on to ever develop symptoms, while 60% can live out their lives with no complications. Who is most at risk? The insects and the disease are more prevalent in Latin American countries partly due to climate and poorer living conditions. However, the insects are common in the southern U.S. and Chagas disease has been documented in the U.S. as early as the 1930’s. Because Texas is an entry point for many migrants from areas where Chagas is more prevalent means consideration should be given on how to treat persons coming from higher risk areas. When people coming from Latin American countries are able to be seen by local physicians, the doctors aren’t often familiar with the disease and treatment options that are available. When time is of the essence, treatment cannot wait. Chagas disease is a relatively slow moving disease and is not contagious. It cannot be transmitted from animal to human or human to human, except it can be passed from mother to fetus. Pregnant women coming from endemic areas are encouraged to know their status to prevent passing on the disease to their children. Additionally, Texas residents are still at risk, regardless of where they come from. More than 60% of Kissing Bugs in the state have been found to carry the parasite. Although not commonly found in urban areas, they are attracted to any areas where they can easily access a blood meal. Rats nests, animal kennels, wooded areas and debris piles are all good living conditions for kissing bugs. How is research changing the conversation? As Dr. Stigler Granados shared, “not everyone is talking about this disease- one of the biggest barriers is lack of awareness amongst the health communities in the United States.” Research, such as Dr. Stigler Granados’ recent study on healthcare gaps for patients, help connect the dots. Because Chagas is a zoonotic disease, animals can contract the disease as well. Veterinarians who are seeing the disease more often than physicians and are more familiar with the disease can actually help communities better understand their risks. With such a huge lack of awareness in the U.S. about the disease, one of Dr. Stigler Granados’ biggest concerns is congenital transmission. If most pregnant women are seeking health care, it’s a great opportunity to implement a screening program to catch the disease early. Right now, she’s advocating for more physicians to screen pregnant mothers in an effort to better understand prevalence. There are newly available effective and inexpensive treatment options for both the infants and the moms, making it a win-win situation when it is caught early. “Once we start raising awareness with one audience of health professionals and mothers, we can work on providing greater education to others,” added Dr. Stigler Granados. She’s hoping to get approval on a grant to implement screening newborns, which would be a big milestone to help with understanding prevalence and leading to better diagnosis and treatment.
Newswise — The neuropeptide oxytocin blocks enhanced drinking in alcohol-dependent rats, according to a study published April 16 in the open-access journal PLOS Biology led by Drs. Tunstall, Koob and Vendruscolo of the National Institutes of Health, and Drs. Kirson and Roberto of The Scripps Research Institute. Targeting the oxytocin system, the authors note, may provide novel pharmaceutical interventions for the treatment of alcohol-use disorder. Administering oxytocin can decrease consumption, withdrawal symptoms, and drug-seeking behavior associated with several drugs of abuse, and shows promise as a pharmacological approach to treat drug addiction. But first, researchers need to understand how oxytocin mediates these effects in animal models. To address this question, Tunstall and colleagues tested the hypothesis that oxytocin administration could normalize the maladaptive brain changes that occur in alcohol dependence and thereby reduce alcohol drinking in an established rat model of alcohol dependence. The authors investigated oxytocin’s effects on dependence-induced alcohol consumption and altered signaling of the inhibitory neurotransmitter GABA in the central nucleus of the amygdala (CeA) -- a key brain region in the network affected by alcohol dependence. The experiments demonstrated that oxytocin administered systemically, intranasally or into the brain blocked excess drinking in alcohol-dependent but not in normal rats. Moreover, oxytocin blocked GABA signaling in the CeA. Taken together, these results provide evidence that oxytocin likely blocks enhanced drinking by altering CeA GABA transmission. These results provide evidence that aberrations in the oxytocin system may underlie alcohol use disorder and that targeting this system, possibly by intranasal administration, could prove a promising therapy in people who misuse alcohol.
Novel strategy could be useful component of comprehensive smoking cessation plan, study says WASHINGTON -- Smokers who are trying to quit may not always have to reach for a piece of nicotine gum to stave off a craving. Deliberately inhaling a pleasant aroma may be enough to reduce the urge to light up, at least temporarily, and could be used as part of an effective smoking cessation strategy, according to research published by the American Psychological Association. “Despite disappointing relapse rates, there have been few new approaches to smoking cessation in general and to craving relief in particular,” said lead author Michael Sayette, PhD, of the University of Pittsburgh. “Using pleasant odors to disrupt smoking routines would offer a distinct and novel method for reducing cravings, and our results to this end are promising.” The research was published in the. While smoking rates have fallen over the past 50 years, approximately 40 million Americans still smoke, according the U.S. Centers for Disease Control and Prevention. Most adult smokers want to quit and at least half report trying in the past year, yet half of those who try relapse within two weeks. “Even with nicotine replacement, relapse is common. New interventions are urgently needed to help the millions who wish to quit but are unable,” said Sayette. The researchers recruited 232 smokers, ages 18 to 55, who were not trying to quit at the time and were not using any other nicotine delivery system, such as gum or vaping. They were asked not to smoke for eight hours prior to the experiment and were required to bring a pack of their preferred cigarettes and a lighter with them. Upon arrival, the people first smelled and rated a number of different odors generally considered to be pleasant (e.g., chocolate, apple, peppermint, lemon or vanilla) as well as one unpleasant chemical odor, tobacco from the participant’s preferred brand of cigarettes and one blank (no odor). They were then asked to light a cigarette and hold it in their hands, but not smoke it. After 10 seconds, the participants verbally rated their urge to smoke on a scale of 1 to 100 before extinguishing the cigarette and putting it in an ashtray. The participants then opened a container that held either the scent they had rated most pleasurable, the scent of tobacco or no scent and sniffed it once before again rating their urge to smoke. They continued to sniff the container they were given for the next five minutes, rating their urge to smoke every 60 seconds. The average craving score just after lighting the cigarette was 82.13. Regardless of what odor they smelled, all participants experienced a decreased urge to smoke after sniffing the container, but the average craving scores for those who smelled pleasant odors dropped significantly more (19.3 points) than those who smelled tobacco (11.7 points) or received the blank (11.2 points). The researchers were not surprised by the findings, as they confirmed and extended results from a much smaller, exploratory study they had previously conducted, according to Sayette. “These days, replicating prior findings is not something I take for granted, and extending the research by showing that we can maintain the effect for as long as five minutes suggests it might offer enough time for a smoker to decide to avoid or leave their high-risk situation,” he said. Sayette believes that part of the reduction seen in all three conditions may be due to smokers extinguishing the cigarette and removing temptation. As for why pleasant aromas achieved a greater reduction in cravings, he thinks they may work by distracting smokers from thoughts of their craving to memories linked to these olfactory cues (e.g., peppermint reminded some of the smokers of childhood Christmas holidays spent at a grandparent’s home), but more research would need to be done to confirm his hypothesis. “Our research suggests that the use of pleasant odors shows promise for controlling nicotine cravings in individuals who are trying to quit smoking,” said Sayette, who noted that additional research needs to be done to see if this strategy could prove useful alone or in combination with other approaches to smoking cessation. Article: “Pleasant Olfactory Cues Can Reduce Cigarette Cravings,” by Michael Sayette, PhD, Mary Marchetti, BS, Lea Martin, PhD, and Molly Bowdring, MS, University of Pittsburgh, and Rachel Herz, PhD, Brown University. Journal of Abnormal Psychology. Published online April 15, 2019. Full text of the article is available from the APA Public Affairs Office and at www.apa.org/pubs/journals/releases/abn-abn0000431.pdf. Contact: Michael Sayette can be reached via email at email@example.com or by phone at (412) 624-8799.
Newswise — ANN ARBOR, Michigan — A prototype wearable device, tested in animal models, can continuously collect live cancer cells directly from a patient’s blood. Developed by a team of engineers and doctors at the University of Michigan, it could help doctors diagnose and treat cancer more effectively. “Nobody wants to have a biopsy. If we could get enough cancer cells from the blood, we could use them to learn about the tumor biology and direct care for the patients. That’s the excitement of why we’re doing this,” says Daniel F. Hayes, M.D., the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center and senior author on the paper in Nature Communications. Tumors can release more than 1,000 cancer cells into the bloodstream in a single minute. Current methods of capturing cancer cells from blood rely on samples from the patient—usually no more than a tablespoon taken in a single draw. Some blood draws come back with no cancer cells, even in patients with advanced cancer, and a typical sample contains no more than 10 cancer cells. Over a couple of hours in the hospital, the new device could continuously capture cancer cells directly from the vein, screening much larger volumes of a patient’s blood. In animal tests, the cell-grabbing chip in the wearable device trapped 3.5 times as many cancer cells per milliliter of blood as it did running samples collected by blood draw. “It’s the difference between having a security camera that takes a snapshot of a door every five minutes or takes a video. If an intruder enters between the snapshots, you wouldn’t know about it,” says Sunitha Nagrath, Ph.D., associate professor of chemical engineering at U-M, who led the development of the device. Research shows that most cancer cells can’t survive in the bloodstream, but those that do are more likely to start a new tumor. Typically, it is these satellite tumors, called metastases, that are deadly, rather than the original tumor. This means, cancer cells captured from blood could provide better information for planning treatments than those from a conventional biopsy. The team tested the device in dogs at the Colorado State University’s Flint Animal Cancer Center in collaboration with Douglas Thamm, VMD, a professor of veterinary oncology and director of clinical research there. They injected healthy adult animals with human cancer cells, which are eliminated by the dogs’ immune systems over the course of a few hours with no lasting effects. For the first two hours post-injection, the dogs were given a mild sedative and connected to the device, which screened between 1-2 percent of their blood. At the same time, the dogs had blood drawn every 20 minutes, and the cancer cells in these samples were collected by a chip of the same design. The device shrinks a machine that is typically the size of an oven down to something that could be worn on the wrist and connected to a vein in the arm. For help with the design, the engineering team turned to Laura Cooling, M.D., a professor of clinical pathology at U-M and associate director of the blood bank, where she manages the full-size systems. “The most challenging parts were integrating all of the components into a single device and then ensuring that the blood would not clot, that the cells would not clog up the chip, and that the entire device is completely sterile,” says Tae Hyun Kim, Ph.D., who earned his doctorate in electrical engineering in the Nagrath Lab and is now a postdoctoral scholar at the California Institute of Technology. They developed protocols for mixing the blood with heparin, a drug that prevents clotting, and sterilization methods that killed bacteria without harming the cell-targeting immune markers, or antibodies, on the chip. Kim also packaged some of the smallest medical-grade pumps in a 3D-printed box with the electronics and the cancer-cell-capturing chip. The chip itself is a new twist on one of the highest-capture-rate devices from Nagrath’s lab. It uses the nanomaterial graphene oxide to create dense forests of antibody-tipped molecular chains, enabling it to trap more than 80 percent of the cancer cells in whole blood that flows across it. The chip can also be used to grow the captured cancer cells, producing larger samples for further analysis. In the next steps for the device, the team hopes to increase the blood processing rate. Then, led by Thamm, they will use the optimized system to capture cancer cells from pet dogs that come to the cancer center as patients. Chips targeting proteins on the surfaces of canine breast cancer cells are under development in the Nagrath lab now. Hayes estimates the device could begin human trials in three to five years. It would be used to help to optimize treatments for human cancers by enabling doctors to see if the cancer cells are making the molecules that serve as targets for many newer cancer drugs. “This is the epitome of precision medicine, which is so exciting in the field of oncology right now,” says Hayes. Note: Patients with questions about cancer treatment options can call the U-M Cancer AnswerLine at 800-865-1125. Funding: Susan G. Komen Foundation, the Fashion Footwear Charitable Foundation of New York/QVC Present Shoes on Sale, National Institutes of Health Citation: Nature Communications, “A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells,” doi: 10.1038/s41467-019-09439-9, published April 1, 2019
Newswise — ORLANDO, Fla., April 1, 2019 — Major depression, obesity and chronic pain are all linked to the effects of one protein, called “FK506-binding protein 51,” or FKBP51. Until now, efforts to inhibit this target have been hampered by the difficulty of finding something specific enough to do the job and not affect similar proteins. Now a research group has developed a highly selective compound that can effectively block FKBP51 in mice, relieving chronic pain and having positive effects on diet-induced obesity and mood. The new compound also could have applications in alcoholism and brain cancer. The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition. ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features nearly 13,000 presentations on a wide range of science topics. “The FKBP51 protein plays an important role in depression, obesity, diabetes and chronic pain states,” says Felix Hausch, Ph.D., the project’s principal investigator. “We developed the first highly potent, highly selective FKBP51 inhibitor, called SAFit2, which is now being tested in mice. Inhibition of FKBP51 could thus be a new therapeutic option to treat all of these conditions.” Hausch, who is at the Technical University of Darmstadt, started the project when studies were published linking the protein to depression. “I was intrigued by the peculiar regulatory role it seemed to play in cells,” he says. “And there was a known natural product that could serve as a starting point. Collectively, this looked like an interesting protein to work on.” FKBP51 is expressed in multiple places throughout the body, such as the brain, skeletal muscle tissue and fat. It also has multiple effects. For example, the protein can restrict the uptake of glucose and the browning of fat, so that the body stores fat instead of burning it. It also affects stress responses. So, Hausch and his colleagues figured that blocking this protein could be the key to developing drugs to treat a variety of conditions. But FKBP51 looks a lot like its closest protein cousin, FKBP52. “These two proteins are very similar in structure, but they are doing opposing things in cells,” Hausch says. “We have this yin-yang situation. Selectivity between these two proteins is thought to be crucial, but this is hard to achieve since the two proteins are so similar. We discovered that FKBP51 can change its shape in a way that FKBP52 can’t, and this allowed the development of highly selective inhibitors.” The researchers have now used nuclear magnetic resonance techniques to detect a previously hidden binding site in FKBP51. The approach could help other researchers identify similar “cryptic” binding sites in challenging drug targets in the future, Hausch says. His team is now testing SAFit2, the lead FKBP51 inhibitor they developed from these studies, in animals. “It indeed helps mice cope better in stressful situations,” Hausch says. In mice, SAFit2 reduced stress hormone levels, promoted more active stress coping, was synergistic with antidepressants, protected against weight gain, helped normalize glucose levels and reduced pain in three animal models. According to Hausch, much more needs to be done to get FKBP1 inhibitors to the point where they could be used as a drug molecule in human testing. In the meantime, the team is also exploring FKBP51 inhibitors in other applications. So far, the group has conducted a number of mouse studies on the involvement of FKBP51 in alcoholism, but results are still preliminary. In addition, Hausch points out that certain types of glioblastoma tumors overexpress FKBP51. He hopes that this result indicates FKBP51 inhibitors could be used in cancer treatment, when patients’ tumors mutate beyond current drugs’ capacity to treat them. “We may be able to resensitize them to different types of chemotherapy using these specific inhibitors,” he says. The researchers acknowledge support and funding from European Research Area Industrial Biotechnology, the Federal Ministry of Education and Research and the Pioneer Fund of the Technical University of Darmstadt. The American Chemical Society, the world’s largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio. This research will be presented at a meeting of the American Chemical Society.
They are seizures, but they aren’t epilepsy. They’re called by many names: psychogenic non-epileptic seizures, non-epileptic attack disorder, dissociative seizures, stress-induced seizures, pseudoseizures. They’re not epilepsy, but they do cause upheaval in education, employment, relationships and independence. They’re ranked in the top three neuropsychiatric problems worldwide. Nina Pye was a college student in the United Kingdom when she began collapsing. After months of tests and frustration, she learned she had psychogenic non-epileptic seizures. That wasn't the end of the story; it was only the beginning. Here's Nina. Nina Pye: They started sometime in January 2015; I was at college doing performing arts. I can remember the first one. I was in a dance class and all of a sudden my heart started racing for no reason. You know how you get when you’re anticipating something and you’re kind of a bit nervous about it — you get a heart-racing feeling and it doesn’t feel good? I got that, and it was weird because there was nothing making me anxious; I love dance. There was no reason for me to feel like this. It felt like all the energy drained from my body. I felt like I was going to faint, but I didn’t feel faint, and I fell to the floor. I stayed there unable to move for a few seconds, and then I got back up again. It was so weird because I didn’t actually faint, and I’ve never fainted or had anything like that so I was like what happened? Did I lose my balance? It felt like I should have had control over it. I just got back up again, no big deal was made and I carried on. Something like a week or two later I fell down again, and this time I stayed down. I remember lying there unable to get up. I could hear everything going on around me but it felt very distant. I felt like I was slightly outside of my body — it was a really weird feeling. And I’m thinking “What’s going on?” I don’t feel like anything is seriously wrong with me, it’s just that my body wants to get on the floor for a while. It’s like spontaneous lying down, except I fall. This happened a few times and each time it got longer and longer and eventually it got long enough that my college called an ambulance. My dad had died in 2013 and it was all quite fresh and new for me. I was schooled at home until college, and I didn’t have a good relationship with my father. He was abusive. Despite that, I was close to my parents, so when he died it was surreal and I didn’t find a way of dealing with it. And my mum was ill as well, she had terminal cancer, so there was a lot of stress in my life at that point. When these attacks happened, I assumed they were some kind of stress reaction. I didn’t necessarily deal with things emotionally, so it would come out in a lot of physical issues, like stomach cramps, eating issues, anxiety, depression. So when this started happening I jumped to the conclusion that it was stress and probably nothing. When I went to the hospital, they started running tests. At first they thought it was my heart; they did the 24-hour monitor and all of that. They didn’t jump to seizures or epilepsy because it was just a faint, a collapse, there was no seizure-like activity. After the first couple of hospital visits, my experience with hospitals completely changed. The more often it happened, they just… paramedics assumed I was faking and was doing this as a cry for attention. I didn’t know what to feel. I wondered, “Is there something wrong? Am I putting this on and not knowing it?” They found nothing physically wrong. I was a bit malnourished but that was it. It went on for a couple of months before I told anyone else; I didn’t even tell my mum until they started getting more frequent and other people started seeing it happen. I was passed around from cardiologist to neurologist, went for all of these tests. It was a strange time because I’d never had anything like this. I’d had back surgery for scoliosis but this felt different and weird and concerning. They were talking about did I have a brain tumor, heart issues, all that. I started to shake when I went down and have spasms, and so they thought maybe I had epilepsy. This carried on for a few more months and I kept ending up in the emergency room, and some medical staff treated it seriously and others said oh she’s faking, it’s just an attention thing. I had paramedic after paramedic saying “This is what some people do — they find a thrill in having ambulances called for them.” I had paramedics ask me, “Don’t you realize we have actual lives to save?” Yeah, I do know that, I’ve lost a parent, I know what ambulances do. Do you think I want ambulances called for me? I know it’s not life threatening but I can’t help it. I can’t tell people that I don’t need an ambulance because I don’t know when these are going to happen. I went to stay with my family three or four months after these started. I had a seizure while I was there and ended up going to a hospital in London. Because my family saw it, they pushed to get a diagnosis and were doing research to try to figure out what it was. We discovered cataplexy and narcolepsy, and the symptoms fit. So I went to a private neurologist who referred me to a sleep center. Everything came back inconclusive; they said I had mild sleep apnea and that was it. But, I had a seizure there and they had a visiting neurologist and he saw it, and he said “Yeah, you have dissociative seizures. It happens to a lot of people who’ve had something psychologically traumatic in their life, or PTSD.” I suffer from PTSD. So when I found this out, I felt relieved but ashamed as well. I thought, “Oh, it really is all in my head then.” I judged myself. It didn’t help that they are called psychogenic seizures. I felt very misunderstood. I ended up homeless for a time, not because of the seizures but because of the breakdown in the relationship with my mum. I was kicked out of college because they couldn’t deal with the seizures, which I didn’t think was possible, that you could be kicked out for something you had no control over. It was a pretty dark time in my life. A few other things happened, and it was one thing after the other. Around mid-2015 it got so bad that I made attempts to end my life three times in one month. Then my family started to take me seriously and realized I was really unwell, both mentally and physically. They took me back to London to live with them. It was a relief because I didn’t have to live in a homeless unit, which was horrible. I had no money, couldn’t work, couldn’t go to college and I thought this was my life sentence, this strange condition that had just happened and had no cure. I couldn’t get on with any antidepressants, they caused me so many side effects that I couldn’t take them. There was no support, there was no counseling. Everything that I was referred to never happened. I got 6 weeks of cognitive behavioral therapy (CBT) and that was the only proactive treatment I had for my seizures. At my worst point I had 20 seizures a day. I was banging my head on doorframes or floors, I was collapsing in the middle of roads, grazing my legs and my elbows. How I escaped without broken bones I don’t know. Everywhere I went, there was such a lack of understanding. Later in 2015, the seizures began to ease up. I’d had my CBT by then and was beginning to deal with issues that had arisen from my father dying, and my PTSD was beginning to get a little better. I was able to have unbroken nights of sleep without awful dreams, and have a normal day, and go out and get some independence. It started to feel like “Okay, this is something I can work through and get over.” I qualified as a level 1 cricket coach; my uncle was involved in cricket coaching and I was looking for something to do, just anything, and I love sports and working with kids. That was amazing and because I was really into dance, I managed to teach the kids to dance. I had roomfuls of these 8, 9, 10-year-old boys who wanted to just play cricket and football — I had them dancing. I started making progress, and once I started it accelerated really fast. Looking back, now that the seizures have come and gone and come back again, I don’t think it was necessarily good that they went away so quickly, because I don’t think I found a way of dealing with them — I just found a way to suppress them. So while I made a huge amount of progress and I was able to dance again and have some independence, there was a lot I hadn’t dealt with. I joined a dance troupe that my cousin was running. It’s not really something that most people would consider doing for seizures but I did that for about four years. I just recently left. I think the dancing helped me deal with some of the stuff I’ve been through – it worked as therapy for me. And the traveling we got to do and all of it, it pushed me out of my comfort zone and gave me mental strength. I made close friendships with the other people in the band and became very close with my cousin, and things were going quite well. And then in May 2016 my mother passed away from her fight with cancer. 2017 I think was probably my best year, despite everything; I was moving house and traveling and dancing. There was a lot of stress as well, though, and I wasn’t really dealing with the fact that my mother had died. I was just engrossed in the practical matters and not dealing with the emotional side of things. So by the end of 2017, the seizures were creeping back into my life again. In 2018 there was a lot of stress, things going wrong, breakdowns in relationships. But it kind of prompted me to go okay, this time I really want to do it right – I want to find the root of what makes me have a seizure and deal with it so that they don’t come back at all. It didn’t really happen like that. Other things got in the way. In September 2018 I returned to education. As well as dance, my other passion is medicine; I’ve always been interested in medicine and wanted a career in it. I enrolled in an access to university course, which is quite intense – it fits two A-level years into one year. At the enrollment day I told the school that look, I have seizures and they’re reasonably under control, but they will happen from time to time. They said okay, that’s fine, and set up a treatment plan with me. It’s not just the seizures, it’s the anxiety and brain fog and the general feeling of exhaustion when you’re fighting against your own body. Unfortunately my grandfather passed away at the beginning of this year; he was like a second father to me, although recently we weren’t as close. I kind of pushed him away because I couldn’t deal with any more family issues. But it has still been a great loss for me, and the repeated pattern of not really dealing with it and pretending everything is fine has not really worked for me. Now, seizures happen about once a week. Sometimes I can go a few weeks without having one. I’m hoping to build up to the point where I can go many months without one, but I think that will take some time. I want to not repress anything and deal with everything properly. The past few months I’ve reached out to other people online who are going through similar things. I thought I was alone and this was such a rare condition and little understood, but I found groups of people going through the exact same thing. They had the same experiences with the medical profession and the lack of understanding. Some people who were trying to have jobs and support themselves, some trying to get through university and support themselves. They experienced the issues in relationships, and just how hard it is generally to cope with. However hard it is for anyone else to cope with, it’s harder for us; we can’t get away from it. I wish there was more knowledge and understanding about the difference between epileptic and non-epileptic seizures. I wish medical professionals especially knew the difference and the right ways to treat people. They kind of have two extremes: Treat it like epilepsy, which can be dangerous if you’re given medication for epileptic seizures, or the other extreme of there’s actually nothing wrong with you, which is unfair. It’s in interesting journey I’ve been on and the seizures are just a small part of it, but I feel very strongly about raising awareness about them and finding ways to get people to be more supportive and more help to be available and more understanding, more knowledge for people who suffer with these seizures and their families, friends and carers. Doctors and paramedics should know about this and should have training. I feel like it’s so inadequate, considering how many people suffer with these seizures and how many are initially diagnosed with epilepsy and then find out they’re non-epileptic seizures. In truth, it helps to have doctors who are “people people” – they like people, they get on with people. You have to face people all the time, and you have to face people on their worst day. They’re having the worst day of their live when you see them, especially in hospitals and emergency departments. It doesn’t take too much to just show a little bit of understanding. I know there are people who abuse the system. I know there are fakers, I know there are drug abusers, but at the end of the day, they’re ill too. It’s a different kind of ill. Everyone is ill, but if someone is going to all the trouble of faking something or going to all this trouble to get drugs, there’s something there that needs to be treated too.
Newswise — White blood cells known as B cells have been shown to be effective for predicting which cancer patients will respond to immune checkpoint blockade (ICB) therapy, according to a study at The University of Texas MD Anderson Cancer Center. Study results will be presented April 2 at the AACR Annual Meeting 2019in Atlanta. The study, led by Jennifer Wargo, M.D., professor in the Surgical Oncology and Genomic Medicine, found that some B cells with unique characteristics predicted response and may be contributing mechanistically to the immune system’s response. The B cells had activated effector phenotypes and were located within lymphoid formations found at the tumor site, known as tertiary lymphoid structures (TLS). The researchers looked at samples from metastatic melanoma and kidney cancer patients who had received ICB as their initial treatment. The B cells may be impacting the immune system’s response through secretion of antibodies and/or by processing and delivering antigens to white blood cell subtypes called T lymphocytes. “This is an exciting and emerging area of study that appears to hold promise for more accurately understanding which patients are most likely to be treated effectively with ICB therapy, and it also could help us identify new therapeutic targets.” said Wargo. “We are able to demonstrate through single-cell RNA sequencing that switched memory B cells and plasma cells were significantly associated with ICB response in a cohort of metastatic melanoma.” While cytotoxic T-cell markers, PD-L1, and mutational burden have been previously identified as biomarkers of response to ICB, there is a growing appreciation of B cells as biomarkers mediators of response, although B cells have also been linked to negative cancer outcomes. “Whole transcriptomic analysis of the cohort of melanoma patients receiving ICB initially revealed that most differentially expressed genes by response were related to B cells,” said Wargo. “In further investigation of specific characteristics of B cells located within the tumor, we identified naive, class-switched and unswitched memory B cells, and plasma cell-like populations.” Class-switch references a B cell’s ability to change production of an antibody from one class to another. The team found higher frequencies of class-switched memory B and plasma-like cells in patients who responded to ICB. Patients who did not respond to ICB had higher levels of naïve B cells which have not yet been activated for a designated purpose. “We don’t have a complete understanding of how these B cells contribute to therapeutic response, but we and others are working on this, and we hope this research will stimulate additional study in this area,” said Wargo. “There is still much to learn and the strongest gains are made through collaboration. It is something we owe to our patients.” MD Anderson study team participants included Sangeetha Reddy, M.D.; Beth Helmink, M.D., Ph.D.; Vancheswaran Gopalakrishnan, M.D.; Elizabeth Burton; and Jeffrey Gershenwald, M.D.; all of Surgical Oncology; Jianjun Gao, M.D., Ph.D.; and Padmanee Sharma, M.D., Ph.D., of Genitourinary Medical Oncology; Shoaojun Zhang, Ph.D.; Guangchun Han, Ph.D.; and Linghua Wang, Ph.D.; of Genomic Medicine; Jorge Blando, D.V.M.; Wenbin Liu; Hao Zhao, D.Phil.; and James Allison, Ph.D.; of Immunology; Hussein Tawbi, M.D., Ph.D.; Rodaba Amaria, M.D.; and Michael Davies, M.D., Ph.D., of Melanoma Medical Oncology; Michael Tetzlaff, M.D., Ph.D., of Pathology; and Rafet Basar, M.D.; and Katy Rezvani, M.D., Ph.D., of Stem Cell Transplantation and Cellular Therapy. The Broad Institute of the Massachusetts Institute of Technology also participated in the study. The study was funded by the Parker Institute for Cancer Immunotherapy, and was also supported with funding from the Melanoma Moon Shot™, part of MD Anderson’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives. A complete list of disclosures can be found in the AACR abstract.
Newswise — People under age 50 with hearing loss misuse prescription opioids at twice the rate of their hearing peers, and are also more likely to misuse alcohol and other drugs, a new national study finds. This means that health care providers may need to take special care when treating pain and mental health conditions in deaf and hard-of-hearing young adults, the researchers say. Writing in the April issue of the American Journal of Preventive Medicine, a team from the University of Michigan and VA Ann Arbor Healthcare System describe their findings from data on 86,186 adults who took part in the National Survey on Drug Use and Health. In all, adults under 50 with hearing loss were more likely than others in their age group to have a substance use disorder of any kind, while those over 50 with hearing loss did not differ from their peers in rates of substance issues. Even after the researchers adjusted for differences in social, economic and mental health between the hearing and hard-of-hearing populations, the differences remained. Adults under age 35 with a hearing loss were two and a half times more likely to have a prescription opioid use disorder. Those between age 35 and 49 who had hearing loss were nearly twice as likely as their hearing peers to have disorders related to both prescription opioids and alcohol. Michael McKee, M.D., M.P.H., led the research effort after noticing that that a disproportionate share of his younger patients with hearing loss were struggling with substance use disorders. McKee runs the Deaf Health Clinic that provides primary care and mental health care to d/Deaf and hard-of-hearing patients of Michigan Medicine, U-M’s academic medical center. “Hearing loss is connected with a variety of health problems, including mental and physical health, that may place these individuals at risk for pain disorders,” says McKee. “Also, the marginalizing effects of hearing loss, such as social isolation, may be creating higher rates of substance use disorders too.” For those whose health care providers know of their hearing loss, McKee suspects that the higher rate of prescription opioid use disorder may stem from a higher rate of being placed on controlled substances to quickly address pain issues, perhaps because of communication barriers. “It may be easier to write a prescription rather than engage in complex patient-provider communication between a hearing provider and non-hearing patient,” he says. But the research suggests that part of the issue may be lack of awareness by health care providers of their younger patients’ degree of hearing loss. In all, five percent of adults of all ages taking part in the survey said they had serious hearing loss or were deaf. The proportion ranged from 1.5 percent of those under age 35, to 2.2 percent of those between 35 and 49, to 9.4 percent of those over 50. McKee, a U-M Department of Family Medicine physician who uses a cochlear implant to offset his own hearing loss, says health care providers may be more attuned to potential communication and prescription concerns with older patients. This would mean they would be more likely to avoid many of the prescription use disorders seen in the other two age categories. “We need to first inquire and ensure effective and accessible communication with our patients. We need to be willing to engage in a dialogue to explore the root of their pain/mental health issues rather than just dispensing a prescription that may lead to dependency or addiction,” he says. This means providers should use “universal communication precautions” – approaching each patient without assumptions about their communication abilities, assessing for hearing loss and other communication-related issues, and determining how to accommodate each patient. McKee also notes that lack of access to addiction-related care for deaf and hard-of-hearing patients may play a role. McKee and several co-authors are faculty in the U-M Medical School and members of the U-M Institute for Healthcare Policy and Innovation. They include disability researcher Michelle Meade, Ph.D. of the Department of Physical Medicine and Rehabilitation, chair of Family Medicine Philip Zazove, M.D. and Mark Ilgen, Ph.D., director of the U-M Addiction Treatment Service. The research team also included Haylie Stewart and Mary Jannausch from the U-M Department of Psychiatry and VA Center for Clinical Management and Research, of which Ilgen is also a member.
CDC data confirm: Progress in HIV prevention has stalled Need for immediate action —‘Ending the Epidemic: A Plan for America’ The dramatic decline in annual HIV infections has stopped and new infections have stabilized in recent years, according to a CDC report published today. The report provides the most recent data on HIV trends in America from 2010 to 2016. It shows that after about five years of substantial declines, the number of HIV infections began to level off in 2013 at about 39,000 infections per year. “Now is the time for our Nation to take bold action. We strongly support President Trump’s plan to end the HIV epidemic in America,” said CDC Director Robert R. Redfield, M.D. “We must move beyond the status quo to end the HIV epidemic in America.” The ‘Ending the HIV Epidemic’ Initiative During his State of the Union address to the nation on Feb. 5, President Trump called for support of a national planExternal to end the HIV epidemic in America that is built upon four key strategies, including: Diagnosing HIV as early as possible after infection. Treating HIV rapidly and effectively to achieve sustained viral suppression. Protecting people at risk for HIV using proven prevention approaches like pre-exposure prophylaxis (PrEP), a daily pill to prevent HIV. Responding rapidly to growing HIV clusters to stop new infections. The proposed initiative is designed to rapidly increase use of these strategies in the 48 counties with the highest HIV burden, as well as in Washington, D.C.; San Juan, Puerto Rico; and seven states with a disproportionate rural HIV burden. The goal is to reduce new HIV infections by 90 percent over 10 years. (For more details: HIV.govExternal.) “We have an historic opportunity to improve the precision of prevention,” said Jonathan Mermin, M.D., M.P.H., director, CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. “This infusion of resources will finally relegate America’s HIV epidemic to the pages of history. New HIV Infections in America In addition to the overall trend, the new report examines HIV infections among multiple subgroups. Data indicate that annual HIV infections declined in some populations, but increased in others. CDC estimates that from 2010 to 2016, annual HIV infections: Remained stable among gay and bisexual men, who continue to account for the largest portion (about 70 percent) of new infections. However, trends varied by race/ethnicity and age: By race/ethnicity, infections remained stable among black gay and bisexual men; increased 30 percent among Latino gay and bisexual men; and decreased 16 percent among white gay and bisexual men. By race/ethnicity and age, infections decreased more than 30 percent among black gay and bisexual males ages 13 to 24; remained stable among Latino gay and bisexual males ages 13 to 24; and increased about 65 percent among both black and Latino gay and bisexual males ages 25 to 34. Decreased about 17 percent among heterosexual men and women combined, including a 15 percent decrease among heterosexual African American women. Decreased 30 percent among people who inject drugs, but appear to have stabilized in more recent years. CDC estimates that the decline in HIV infections has plateaued because effective HIV prevention and treatment are not adequately reaching those who could most benefit from them. These gaps remain particularly troublesome in rural areas and in the South and among disproportionately affected populations like African-Americans and Latinos. “After a decades-long struggle, the path to eliminate America’s HIV epidemic is clear,” says Eugene McCray, M.D., director of CDC’s Division of HIV/AIDS Prevention. “Expanding efforts across the country will close gaps, overcome threats, and turn around troublesome trends.” HIV Prevention that Works Some intensified local efforts to prevent HIV have already proven effective. For example, urban areas like New York and Washington, D.C., have developed and enacted plans to eliminate their local HIV epidemics — and they are seeing the results of those commitments. New HIV infections decreased about 23 percent in New York and about 40 percent in Washington, D.C., from 2010 to 2016. CDC provides funds to state health departments and some large local health departments and community-based organizations to deliver interventions proven to reduce HIV infections. Click here for more information about CDC’s approach to HIV prevention. The new initiative would supplement and accelerate these efforts over the next 10 years.
Newswise — By sequencing the entire genomes of tumor cells from six people with a rare cancer of the nose and sinus cavity, Johns Hopkins researchers report they unexpectedly found the same genetic change¾one in a gene involved in muscle formation¾in five of the tumors. “In terms of research linking genetic alterations to cancers, this is a true mountain and not a molehill,” says Gary Gallia, M.D., Ph.D., associate professor of neurosurgery at the Johns Hopkins University School of Medicine. “It’s fairly rare that a single gene is tied so tightly to the same cancers in unrelated people.” In a report on their findings, published Dec. 21, 2018, in Nature Communications, the researchers say the deletions they identified in a gene that codes for dystrophin, a rod-shaped protein that helps anchor muscle fibers in place, were found in olfactory neuroblastoma cells. Olfactory neuroblastomas make up just 6 percent of all sinus and nasal cancers, with a prevalence rate of one person out of every 2.5 million. Nationwide, that translates to about 100 to 200 diagnosed cases each year. Johns Hopkins Medicine’s neurosurgery skull base center is among the most experienced in treating patients with olfactory neuroblastoma. The center also has a robust supply of tissue samples from these tumors. The researchers say their findings contribute not only to a better understanding of the cause of these cancers, but also to the potential for creating animal and cell models for further study and development of treatments that target the tumor’s genetic roots. “Now that we believe we know the genetic cause of olfactory neuroblastoma, we can devise ways to disrupt the cancer, learn how it forms and explore new ways to treat it,” says Chetan Bettegowda, M.D., Ph.D.,associate professor of neurosurgery at the Johns Hopkins University School of Medicine and director of the Johns Hopkins meningioma center. “This was really an unexpected but fruitful finding.” Bettegowda says their finding was unexpected because perceptions of nasal and sinus tissue don’t immediately bring to mind a dominant role for muscle tissues. But, among geneticists, he says, it’s well known that many developmental genes that help form the tissues of the human body are multipurpose. For their study, the researchers first sequenced the tumor and matched normal DNA of nine men and two women with olfactory neuroblastoma taken from patients treated at Johns Hopkins over seven years. The patients ranged in age from 33 to 69. The researchers sequenced the parts of the genomes that make up the genes and not the spaces between the genes. Although they found two tumor samples had mutations in a large gene that makes the protein Titan, the researchers were unsure if these mutations may have contributed to formation of the cancer, as they didn’t see much else in common among the samples. Next, they chose six of these samples at random and did whole genome sequencing that looks at the DNA that makes up the genes and the DNA between the genes. This time they found that five of the six samples had deletions on the X chromosome, and in every case, the deleted portion of DNA spanned the gene DMD, which codes for the protein dystrophin, one of the genes implicated in muscular dystrophy. They then reexamined the original tumor samples, as well as a few others, with other techniques to look for deletions in dystrophin. In total, they found 12 out of 14 tumors had deletions in the DMD gene. In one tumor that didn’t have a DMD deletion, they found a deletion in another muscular dystrophy gene: LAMA2. Dystrophin is one of the longest genes in the human genome, and has 79 pieces of DNA interspersed with bits that don’t code for the gene. Because of the gene’s large size, if part of a chromosome in which it resides is deleted or rearranged, it’s statistically more likely to interrupt a large gene like dystrophin. The researchers aren’t sure if the dystrophin protein is made in the olfactory neuroblastoma or if a shortened mutated form messes up the inner workings of the cells that form the tumor. These are experiments for future studies, they say. The researchers still also don’t know what kind of cells the cancer originates from, although they are thought to arise from the neuroepithelium—the lining—of the sinuses at the point where the smell nerves poke through. As for whether their findings point to potential new therapies for this cancer, Bettegowda says, “Some low-hanging fruit could be to test certain therapies in the lab that have been tried in people with muscular dystrophy. Although those therapies have failed in treating muscles dystrophies, these conditions affect every cell in the body. But this cancer is found in one specific location, so the treatments might have a better chance of finding a target.” Typical signs of olfactory neuroblastoma are congestion, sinusitis, loss of sense of smell and nosebleeds. Other authors include Ming Zhang, Christine Hann, Alison Klein, Qing Wang, Bert Vogelstein, Kenneth Kinzler and Nickolas Papadopoulos of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Yi Ning, Michael Haffner, Denise Batista, Ralph Hruban, Masaru Ishii, Douglas Reh, Lisa Rooper, Rafael Tamargo, Tara Williamson, Tianna Zhao and Alan Meeker of Johns Hopkins; Zev Binder of the University of Pennsylvania; Justin Bishop of the University of Texas Southwestern Medical Center; Vafi Salmasi of Stanford University; Ying Zou of the University of Maryland and Nishant Agrawal of University of Chicago. The research was supported by the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Sequencing Facility at Johns Hopkins, the Johns Hopkins Clinician Scientist Career Development Award, the Burroughs Wellcome Fund Career Awards for Medical Scientists, the Doris Duke Charitable Foundation (2014107), the Department of Neurosurgery at Johns Hopkins and the National Cancer Institute (P50- CA062924). COI: Papadopoulos, Kinzler and Vogelstein are founders of Personal Genome Diagnostics and PapGene. Kinzler and Vogelstein are members of the scientific advisory board of Sysmex Inostics. Vogelstein is a member of the scientific advisory boards of Morphotek and Exelixis. These companies and others have licensed technologies from Johns Hopkins, and Papadopoulos, Kinzler and Vogelstein receive equity or royalties from these licenses.