Aug 15th, 2014
Two APK faculty members are being recognized for performing with distinction. Read more here […]
Aug 15th, 2014
Dr. Ashley Smuder, a NIH post-doctoral fellow in the Department of Applied Physiology and Kinesiology, has been promoted to Research Assistant Professor. She will continue her work in Dr. Scott […]
Nov 3rd, 2014
We are excited to announce that Dr. Beth Barton, currently in the Department of Anatomy and Cell Biology at the University of Pennsylvania, has been hired by APK as part […]
July 13, 2017
Trillions of microorganisms live inside your gut. Anatomy Insider/Shutterstock.com Jasenka Zubcevic, University of Florida and Christopher Martyniuk, University of Florida A universe of organisms living inside you may affect every part of your body, from your brain to your bones, and even your thoughts, feelings and your attempts to lose weight. This is a universe of trillions of microorganisms – or what we biologists call microbiota – that live in your gut, the part of your body responsible for digestion of the food you eat and the liquids you drink. As researchers, we have been looking increasingly into the effect these bacteria have on their host’s body, from obesity to mental illness and heart disease. With obesity, for example, these tiny organisms may play a big role by influencing what foods we crave and how our bodies hold onto fat. In a recent study of the gut microbiome, we set out to determine whether the microbiota in the gut can be affected not only by our nervous system but also by an unsuspected source – our bone marrow. Our hope is that, by understanding the interactions of the microbiome with other parts of the body, one day treatments could be developed for a range of illnesses. The gut-brain-bone marrow connection The gut, which includes your esophagus, stomach, small and large intestines, colon and other parts of your digestive system, is the first line of defense and the largest interface between the host – in this case, a person – and the outside world. After birth, the gut is the first point of entry for environmental and dietary influences on human life. Thus, the microbiota in the gut play a crucial role during human growth, as they contribute to development and maintenance of our immune system throughout our lifetime. While we initially thought of the microbiota as relatively simple organisms, the fact is that they may not be so simple after all. Gut microbiota can be as personal and complex as a fingerprint. There are more bacteria in your gut alone than cells in your entire body. This vast bacterial universe contains species that combined can have up to 150 times more genes than exist in humans. Research suggests that the bacteria in our gut predates the appearance of humans and that they may have played an important role in evolutionary separation between our ape ancestors and us. Healthy bacteria actively interact with the host immune system in the gut. They contribute to the barrier between disease-causing microorganisms or infections introduced via ingestion. They also help prepare the host immune system to defend the body. The wrong mix of microbes, on the other hand, can contribute to many digestive, immune and mental health disorders and even obesity. These tiny organisms work very hard in digestion. They help digest our food and can release nutrients and vitamins essential for our well being, all in exchange for the privilege of existing in a nutritious environment. Researchers are actively exploring the many facets of this symbiotic relationship. Recent data show a link between gut microbiota diversity and richness and the way we store fat, how we regulate digestion hormones and blood glucose levels, and even what types of food we prefer. The gut micro biome can influence our cravings for food, including chocolate. beats1/Shutterstock.com This may also be a reason our eating habits are so difficult to change. Some research suggests that microbiota may generate cravings for foods they specialize in – even chocolate – or those that will allow them to better compete for resources against other bacteria. A three-way call? There’s growing evidence of a link between the brain and our microbiota as well. The brain is the equivalent of a computer’s main processor, regulating all physiological variables, including the immune system, the body’s defense against infection and illness. All immune cells are “born” in the bone marrow. From our previous research, we knew that increased bone marrow inflammation, one of many consequences of high blood pressure, was driven by a direct message from the brain. The gut, too, plays an important role in preparing the immune system for battle. From deep within our bones, our bone marrow may be communicating with other parts of our bodies. sciencepics/Shutterstock.com So we wondered: Could the bone marrow immune cells be playing a role in signaling between the brain and the gut? We wanted to find out. Using a novel experimental mouse model, we replaced the bone marrow that occurs naturally within a mouse with bone marrow cells from a different, genetically modified mouse. This replacement marrow was deficient in a specific molecule called adrenergic receptor beta, which made the bone marrow less responsive to the neural messages from the brain. In this way we could investigate how the host brain-immune communication will modify gut microbiota. Indeed, by studying this new mouse model, we determined that our nervous system – directed by our brain – can modify the composition of gut microbiota by communicating directly with the bone marrow immune cells. The brain, therefore, can change our gut microbiota indirectly by talking to the bone. Fewer inflammatory cells in bone marrow resulted in fewer in the gut Based on our experiments, we observed that fewer inflammatory cells were present in the circulation of mice that received the special bone marrow replacement than in those that didn’t. This means there are fewer immune cells able to infiltrate the gut and influence the bacterial environment. Thus, by suppressing the communication between the brain and the bone marrow, we observed a muted inflammatory response in the gut and a consequent shift toward a “healthier,” more diverse microbiome. This appears to be mediated via specific changes in inflammatory genes in the gut. However, this interaction between the host and the gut microbiota is very complex, and much more research is needed to pinpoint the exact mechanisms of their close communication. This may also be protective against weight gain, due to the very important role that both microbiota and the immune system play in obesity. A key to heart health, mental health and weight loss? This finding may also have implications in immune diseases as well as treatments either resulting in or employing immunosuppression. The latter may affect the gut microbiota, which in turn may cause unwanted effects in the body, including those associated with digestive and mental health conditions. In the context of cardiovascular disease, this muted inflammatory response appears to be beneficial, as it leads to beneficial lowering of blood pressure in our experimental mice. Most interestingly, a link between gut microbiota and our mental health has recently become clearer. In particular, some have suggested that gut microbiota influence the stress and anxiety pathways in the brain in a way that can alter mood and behavior both positively and negatively, giving a whole new meaning to the term “gut feeling.” This could soon lead to a new class of drugs, called psychobiotics. Much like the “chicken and the egg” scenario, however, this complex interplay warrants further investigation to fully understand the consequences (or benefits) of perturbing one single component of the gut microbiota. This understanding is essential if we are to fully harness the power of manipulation of gut microbiota in health and disease, without negative side effects. Jasenka Zubcevic, Assistant Professor, University of Florida and Christopher Martyniuk, Associate Professor of Toxicology, University of Florida This article was originally published on The Conversation. Read the original article.
June 16, 2017
Women with breast cancer have long faced complicated choices about the best course of treatment. One particular concern has been the daily radiation therapy many women with breast cancer receive for six weeks after surgery. This form of therapy, also known as conventionally fractionated external beam radiation, has generally been recommended for most women undergoing breast conservation therapy. The goal has been to rid the body of any remaining cancerous cells that the surgeon’s tools could not remove. Radiation, however, can be time-consuming and expensive for the patient and society. It also carries a small risk for late complications, such as heart disease. New therapies have been tested that would shorten the length of radiotherapy from six weeks to three weeks, or deliver a single dose at the time of the lumpectomy procedure in the operating room. A shorter course of radiation means more convenience, perhaps, fewer side effects and fewer out-of-pocket expenses. And a single dose of radiation is much cheaper than whole breast radiation therapy delivered over multiple weeks, but is associated with a slightly higher risk of local recurrence. So which option should patients and physicians choose? In our recently published paper in the Journal of the National Cancer Institute, we came up with what we think is an answer. We showed through computer modeling that there is a better way for women – and one that can save our health care system nearly US$100 million every year. Problem and possible solutions For decades, breast cancer was considered such a formidable foe that doctors who treated it and women who had it wanted to use everything in their arsenal to fight it. That included the radical Halsted mastectomy, which often took out chest muscles along with the breast and left women disfigured. A woman’s chest a year after a double mastectomy. Flaxphotos/From www.shutterstock.com It also included lengthy radiation treatments, sometimes for as long as seven weeks (known as conventionally fractionated radiation), given every day Monday through Friday after surgery. This form of radiation comes at great cost to women and causes hardships for those who live far away from radiation clinics. In recent years, doctors studied new therapies for breast cancer. Halsted radical mastectomy has been replaced with a lumpectomy procedure that is usually performed on an outpatient basis. The radiation course has been shortened and is now delivered using sophisticated equipment, sparing unnecessary dose to the heart and lungs. The better equipment also began to allow researchers to look at ways to shorten treatment. Hypofractionated radiation, in which a portion of the breast is treated for a shorter time, was one result. Alternative therapies to conventional and hypofractionated radiation have also been recently introduced to deliver a single dose of radiation just to the tumor bed at the time of surgery. This is known is intraoperative radiotherapy, or IORT, meaning performed during the course of a surgical operation. Given the availability of choices with overlapping costs and outcomes, clinicians always face a dilemma: Which treatment is best for my patient? Likewise, patients can ask their clinicians, “What’s best for me?” And, if both treatments are equally effective, is there a difference in price that might guide decisions? Multiple randomized trials have shown that a 3- to 4-week course of whole breast radiation therapy is equivalent to a 6- to 8-week course. In fact, the National Comprehensive Cancer Network (NCCN) guidelines endorse the short hypofractionated course as the preferred approach. Despite all this, American doctors have not widely adopted the new strategy. The reasons for this are varied, including dissemination of new findings to private practitioners and financial incentives of treating with a longer course. Our current fee-for-service reimbursement structure pays more for the longer treatment, which may be a factor in the surprisingly slow adoption of the convenient hypofractionated whole breast radiotherapy approach. What might be adding more to this dilemma? Clinical trials have compared these treatment choices with one another. Several large randomized trials have compared a 6-week course to a 3- to 4-week course of whole breast treatment and found that the two treatment approaches are equivalent in terms of cancer control. In fact, one trial found that the shorter course of treatment yielded lower rates of acute toxic effects compared to the longer course. Several randomized trials have compared conventionally fractionated radiation therapy to a single fraction intraoperative treatment just to the tumor bed at the time of surgery. Although extremely convenient, IORT was slightly worse at controlling cancer recurrence. Yet, no single clinical trial has compared all three available options head-to-head. Another dilemma is that clinical trials usually follow patients for a period of five to 10 years, not a lifetime. That left an important question unanswered: How do we know which treatment is most beneficial over patient lifetime, and at what cost? Our study To solve this conundrum, we used computer modeling along with a cost-effectiveness analysis. In our study, our interdisciplinary team tried to identify the most optimal radiation therapy – that is, one that provides maximum value for money – for women diagnosed with early stage breast cancer. We simulated (created in computer) a hypothetical population of women diagnosed with early stage breast cancer. As per standard of care guidelines, women first get surgical treatment (lumpectomy). Now comes the uncertainty! These hypothetical women can get either conventional whole breast radiation, hypofractionated radiation or one-time intraoperative radiation. We obtained data from several clinical trials and databases to define treatment effectiveness and side effects, improvement or deterioration in quality of life, inconvenience (measures in term of travel time, lost wages, travel cost) and future consequences, including a possibility of cancer coming back or spreading to other organs. In our simulation, we then followed these hypothetical women over their lifetime to identify which treatment strategy is most valuable, or cost-effective. After extensive validation, we found that hypofractionated radiation is the most valuable treatment almost under all scenarios. It not only improves quality of life without compromising survival (adds four additional months of life with improved quality of health) but it also saves nearly $3,500 per patient. We also learned that IORT, or radiation treatment at the time of operation, may be appropriate for older women who live far from radiation facilities and would have to endure hardship when traveling for daily whole breast radiation for three to four weeks. Win-win for all! Our society saves health care dollars, and patients benefit most from treatment. Key takeaways Our analysis showed that conventionally fractionated radiation, in which women receive the radiation over six weeks, is not cost-effective under any scenario and should not be considered as a choice by physicians or patients. Our study is the first to evaluate this using the latest available data. A single dose of intraoperative radiation therapy, despite being much more convenient and less expensive, is associated with higher cancer recurrence rates. This difference in the risk of recurrence ends up costing the patient and society more than the hypofractionated treatment over a patient’s lifetime. Intraoperative radiation might be an option for older women who live in regions with poor access to health services. The shorter hypofractionated course is less expensive and improves quality of life substantially! With growing health care costs and an aging population, we are starting to focus more and more on identifying treatments that are less expensive and equally effective. We found that the use of the optimal strategy in this situation has the potential to improve health outcomes and save at least $100 million every year. This article was originally published on The Conversation. Read the original article.
June 16, 2017
Tourette syndrome is a mysterious medical curiosity that has puzzled doctors for more than a century. People who have it suffer from tics and other behavioral problems, such as obsessive compulsive traits and attention deficit disorder. In addition, they are cursed by a stereotype that they swear loudly and inappropriately. In reality, 10 percent actually experience these verbal outbursts, but many are stigmatized and isolated nonetheless. I have studied Tourette syndrome for years, and recently published a book about treatments and the common spectrum of behavioral disorders associated with it. Swearing isn’t even one of the more frequent ones. The fact is that over the last several years, many exciting and life-altering treatments have become available to Tourette patients and their families. We have reached a crossroads in this disease where it will become increasingly critical to reeducate the public and to make new therapies widely available. Twitches and tics French scientist Jean-Martin Charcot, the founder of modern clinical neurology, coined the eponym “Tourette syndrome” after his student, Georges Albert Gilles de la Tourette, who in 1885 described nine patients suffering from the tic “malady.” Jean-Martin Charcot, considered the founder of neurology. From wikimedia.com Researchers soon noticed that Tourette occurred among multiple family members across multiple generations. Over the generations, however, new knowledge came slowly. Critical gaps in our understanding of the syndrome remain, and half of all cases remain undiagnosed. Even the precise number of people affected has been hard to know. For example, the Centers for Disease Control and Prevention (CDC) estimates that one in 362 children, or 0.3 percent, has Tourette. The Tourette Association of America, on the other hand, estimates the disease is twice as common, with one in 166 kids (0.6 percent) affected. Some Tourette syndrome cases are mild, with symptoms such as nonbothersome eye blinking, or mild body twitching. In many cases, the motor tics will resolve in late adolescence or early adulthood. Many patients will even lead relatively normal lives. Lessons from the brain yield advances Knowledge of the syndrome has increased as scientists have learned more in general about the brain. The normal functions of the human brain seem to be dictated by rhythmic oscillations that continuously repeat over and over, much like a popular song on the radio. These oscillations change and modulate, and they act to control various human behaviors. If an oscillation “goes bad,” it can result in a disabling tic or other behavioral symptoms of Tourette syndrome. An important secret to the development of new therapies for Tourette is that we can alter these oscillations with rehabilitative therapies, cognitive behavioral intervention therapy (CBIT), medications such as tetrabenazine or even deep brain stimulation, which involves a small straw-like probe being inserted into the brain. Electricity can be delivered through this probe to disrupt the abnormal oscillations responsible for tics. Continued study also helping The genetics of Tourette remain opaque. Despite the fact that the disease tends to run in families, no one has discovered a single DNA abnormality linking all, or even most, cases. In the meantime, however, technology is offering new means of detection and treatment. Scientists have recorded tic signals from the human brain and even deployed the first smart devices to detect and suppress tics. Some investigators are studying newer generations of medicines that decrease the complications that can occur with old-fashioned drugs, such as Haloperidol, that have traditionally been used to treat Tourette. Scientists are also looking for way to suppress or modulate inappropriate brain signals, spurring development of new drugs with novel brain targets, such as cannabinoid receptors. Using marijuana to treat the symptoms of Tourette syndrome makes some scientific sense. Cannabinoids occur naturally in the body, and cannabinoid receptors are found throughout many brain regions. In fact, CB1 cannabinoid receptors are located in high concentrations in regions of the brain thought to be involved in Tourette syndrome. Living with Tourette syndrome While it may appear to the casual observer that someone with Tourette syndrome outgrows it in adolescence or early adulthood, in fact most do not. While the motor and vocal tics wane in most cases, the obsessive-compulsive and behavioral features may persist and even escalate. These behavioral features in Tourette syndrome, if left undiagnosed and untreated, will make it harder to live a normal life and will affect the person more than the noticeable motor and vocal tics. While new treatments may lie in the future, there are many things that patients and their families can do today. Many changes, often very simple, can be incorporated into patients’ lives. Comprehensive care teams from different disciplines play a key role. For example, a social worker can help to set up an individualized school education plan and connect families to resources that can transform difficult school situations into success stories. A rehabilitative therapist can now in many cases successfully address tics without the use of a single medication. Children and teens celebrate at the end of a week of camp at Twitch and Shout in Winder, Georgia in 2014. Building relationships with others who have Tourette syndrome is believed to be beneficial for young people. David Goldman/AP Our care team has taken care of close to 10,000 movement disorder patients at the University of Florida and tens of thousands more with our colleagues in the Southeast Regional Tourette Association of America Center of Excellence, which also includes neurologists, psychiatrists, rehabilitative specialists, social workers and scientists at the University of South Florida, Emory University, University of Alabama and the University of South Carolina. There are good reasons to try different treatments, even if none seems to work. Patients need to learn how to recognize when a plan or therapy isn’t working and how to speak with their doctors and care team about trying something else. The point is that left unchecked, brain vibrations can, in some Tourette cases, lead to neck-snapping tics which can cause injuries, even paralysis. Today even the most severe cases have a chance for treatment with deep brain stimulation. Though Tourette syndrome remains mysterious in the public eye, it is important that we teach families about the broad palette of options that provide tangible benefits for quality of life. That is definitely something worth shouting about. This article was originally published on The Conversation. Read the original article.