March 22, 2017
Dr. Thomas Maren, a founding father of the University of Florida College of Medicine whose four decades of basic scientific research led to the development of a top-selling drug for glaucoma, has been inducted into the Florida Inventors Hall of Fame Maren arrived on the UF campus in 1955 and continued working as a graduate research professor until months before his death at the age of 81 in 1999. Maren gained international recognition for his pioneering investigation of an enzyme called carbonic anhydrase and its role in fluid production and flow in the eyes, brain, spinal cord and lymph system. In 1995, his years of collaborative research with scientists at Merck and Company resulted in an eye drop for glaucoma called Trusopt which worked without many of the side effects of earlier oral medications, such as fatigue, anorexia and numbness in the extremities. “I began working on developing a drug that could be given as drops rather than by the mouth,” Maren said in an oral history interview. “That was the big advance. That might not sound like a very big deal, but for 25 years it was regarded as an impossibility. That dogma was that a drug of this type had to be given orally. We showed that this was incorrect, hence the success of Trusopt.” UF licensed the drug to Merck and it has brought more than $250 million in royalties to the university for reinvestment in new research. Maren also generously donated much of his own royalties back to the university to support research and education. Dr. Jeffrey R. Martens, the Thomas H. Maren Professor and chair of the UF Department of Pharmacology and Therapeutics, wrote in a letter supporting Maren’s nomination to the Hall of Fame that “the impact of these funds, both in terms of scholarship development and continued research opportunities, cannot be underestimated.” “The University of Florida, the state of Florida and the world have benefitted from the invention and success of Trusopt and each will continue to benefit from the legacy of Dr. Maren’s work and the Maren Foundation far into the future,” Martens wrote. David Day, director of UF’s Office of Technology Licensing, noted in his letter nominating Maren to the Inventors Hall of Fame that Maren valued highly his role as a teacher and research mentor. “His work at UF involved his mentoring of young doctors and researchers within the institution, who then carried their expertise to their patients and research labs in Florida and indeed around the nation,” Day said. Maren will be inducted into the Florida Inventors Hall of Fame at a ceremony in September.
March 21, 2017
Driving down a country highway in the Midwest can seem an endless ribbon flanked by green walls of corn, neatly planted in stately rows. But who would guess that a plant that feeds a planet might hold clues that could help us better understand, or perhaps cure, insidious human diseases? Recent research from Dr. Mark Settles at the University of Florida describes a deep evolutionary link between the processes that govern cell identity in a kernel of corn and those that turn a blood stem cell into a cancerous threat to human life. Over my three decades as an academic researcher, I’ve been constantly amazed at how discoveries about fundamental cellular processes in plants parallel, or sometimes precede, discoveries in animals. While we share remarkably similar genetic blueprints, plants and animals are obviously quite different. Learning how two very different life forms draw from a similar set of instructions to meet threats or stop disease could lead to breakthroughs in both agriculture and medicine. It reminds us of why close examination of life in animals needs coinciding research tracks in plants. The rise of new cell types Early in life, a single fertilized cell multiplies in number. As time goes by, the growing number of cells begin to take on different fates – differentiation into various cell types. The processes that govern these changes must be precise, both for ideal function within their context in the organism and to constrain unbridled growth. The latter contributes to human disease, including various cancers. A corn kernel is a complex structure composed of many tiny cells that have specialized jobs. The nutritional content of the kernel is dictated by the genetics and biochemistry of these different cell types. Settles and colleagues analyzed mutant kernels with defective structures and content to unravel how different cells function and communicate while the grain is growing and filling with nutrients. Errors in cell differentiation can lead to discovery of the genes that guide a kernel’s normal development. The majority of a kernel is a starchy matrix called the endosperm. Settles and colleagues show that specialization of cell types depends on what’s known as an RNA splicing factor. DNA is the blueprint in the cell. RNA is a temporary and mobile copy of the DNA’s information that later directs assembly of proteins to perform important roles in the cell. Because it is an intermediate, RNA is subject to many forces that can affect the information it contains. One of these processes is splicing; the cell has mechanisms that can remove essential bits, changing the information and, ultimately, the end product. Settles’ mutant kernels are defective because they lack this RNA splicing factor. In other words, without the RNA splicing factor, the genetic blueprint information that needs to be precisely processed for normal growth remains untouched. This defect leads to cells that divide excessively, similar to cancer cells. But the link goes deeper. From kernels to cancers Corn kernel cell identity is governed by a gene that is common to a type of blood cancer. Mark Settles, University of Florida, CC BY-SA Blood is composed of different cell types that arise from genetic decisions made in primary “stem” cells. Like the cells in a kernel of corn, blood cells specialize based on precise editing of internal instructions, including RNA splicing. Medical researchers have described a blood defect that leads to a disease known as myelodysplasia, or MDS. This disease can progress into acute myeloid leukemia. The work by the Settles group shows that the defects observed in the corn kernels are the same genetic errors, or mutations, in blood cells that lead to some forms of MDS. Genetic mistakes in both corn cells and blood cells affect a similar suite of genes, even though these are very different organisms. This is a remarkable discovery, because it suggests that animal and plant processes that determine cell identity share more similarities than previously thought. But corn kernel cells and blood cells are remarkably different. Can the differences maybe help identify mechanisms in controlling corn kernel cell proliferation that might lead to discovery of ways to curb blood disorders like MDS? In this work, examination of a corn cob with deformed kernels and poor yield led to potential solutions in improving grain yield. However, the knowledge gained could help illuminate new mechanisms to fighting a form of cancer. From animal to plant; plant to animal Corn plants in a field. From www.shutterstock.com The findings remind us of why it is important to study basic plant biology, the kind of work that does not directly translate to the plate. Plants and animals share many commonalities. More than half of our genes perform similar functions, and we share many core metabolic mechanisms. But plants are confined by their roots and can’t move away from stresses, disease or predators. They have to fight back or adapt in order to survive. A substantial part of their genes are dedicated to these processes. These mechanisms of survival are often not present in animal cells or are not as conspicuous. Plants can often define new rules that expand existing models, and their chromosomes may hold more tricks that ultimately can help the human condition. Here defective corn kernels show similarities to cancer cells. Now scientists can extend from those commonalities to look for the differences that can correct or compensate for the defect in plants. Such discoveries may unveil mechanisms that plants evolved in their specialization that could potentially lead to new solutions for confronting human disease. This article was originally published on The Conversation. Read the original article.
March 20, 2017
Recall that last time you had something “go down the wrong pipe”? You spent the next several minutes coughing, choking and feeling like something bad was in your throat. It may seem strange to say this, but count yourself lucky. Your brain was making you do the right things to keep what you drank or ate out of your lungs. The path for air to enter our lungs, the larynx (or voice box), is very close to the upper esophageal sphincter, the entry point for food and liquids to our esophagus. This close anatomical relationship of these two entry points means the brain must coordinate breathing, eating and drinking to ensure the lungs get only air and the esophagus gets only food or liquids. This coordination happens unconsciously, so we never really think about it until we get food or liquid in our airway. As it turns out, millions of people with brain diseases, including those with Alzheimer’s, Parkinson’s, Lou Gehrig’s disease, stroke, multiple sclerosis and traumatic brain injury, have impaired swallowing. As a result, they are unable to protect their lungs in the way that a healthy person can. The result is that millions of brain disease patients are at risk for inhaling food and saliva into the lungs, leading to death by pneumonia or even choking. Detecting and treating impaired swallowing is important, particularly as the nation’s nearly 70 million baby boomers continue to age. Impaired swallowing is associated with many conditions of the elderly, and it is often severely underreported. Clinicians may not detect it or may see it as a side effect of another condition. As a neuroscientist who has studied brain diseases, I know of no pharmaceutical companies that have drug discovery programs aimed at restoring weakened swallow and cough. And yet, it’s a major problem. Hard to swallow, easy to choke An important part of swallowing is complete closure of the larynx while food is moving through the throat. Disordered swallowing, or dysphagia, limits the ability of the muscles in the mouth and throat to move liquid or food into and through the esophagus and on to the stomach. This inability to protect the airways and lungs increases the risk of pneumonia or choking. In addition, many people with brain disorders experience reduced coughing, or a weakened ability to activate breathing muscles to generate airflows that eject material from the lungs. Weakened cough is caused by problems with nerves in our lungs that detect foreign material or with the brain driving the respiratory muscles. Disordered swallowing can also be caused by problems with nerves in the neck. For example, people who have had cancer of the head or neck often undergo extensive surgery to remove the diseased tissue. This process can inadvertently damage nerves that are important for swallowing. Sometimes, the swallowing impairment, rather than the primary brain disease, actually leads to death. When swallowing is impaired, it is more likely that material will enter the lungs and trachea during eating or drinking. This is known as aspiration. Aspirated food or drink “seeds” the lungs with material that is coated with pathogens from the mouth. These pathogens are not normally present in the lungs and can cause chronic inflammation and serious bouts of pneumonia. When a weak cough is a bad sign In patients with acute stroke, severe swallow and cough impairments occur at the same time. Our research has shown that the risk of aspiration due to swallow impairment can be predicted by weakened cough in patients with stroke or Parkinson’s disease. These findings indicate that brain diseases can lead to multiple impairments in how we protect our airways. Another way of thinking about this problem is that the nervous system has many tools, or reflexes, that it uses to perform certain tasks. Each reflex has a specific function, and the brain coordinates the time of occurrence of each to optimize the result. For example, a cough can eject material out of the airways into the throat and out of the mouth. Swallows frequently occur just after coughs to move material that was deposited into the throat into the esophagus and then the stomach. The result is that lungs were cleared by coughing, and swallowing moved any remaining material out of the throat to prevent aspiration. Nearly half of residents of long-term care facilities vulnerable to pneumonia Patient in a care facility. Via Shutterstock. From www.shutterstock.com Simultaneous impairments of cough and swallow lead to high aspiration risk. This high risk is due to seeding of the lower airways with harmful pathogens that increase the risk of pneumonia. Mortality rates of aspiration pneumonia have been reported of over 60 percent, leading to a US$4.4 billion medical burden from hospitalized patients alone in 1997. Aspiration pneumonia costs as much as $17,000 per hospital admission. Further, this type of pneumonia can occur in as many as half of long-term care residents. When members of our research team talk to their friends about airway protection and its consequences, everyone seems to have a story. Most center around an older relative who had a brain disorder and the difficulties this person had eating. Often their relative choked when eating or had to eat special thick foods. These are signs of impaired swallow, cough and aspiration. Speech pathologists specialize in diagnosing and treating swallowing disorders. They often recommend thick foods that are easier to swallow and less likely to penetrate the airways during swallowing. This clinical approach is the most well-accepted. Some companies market devices that apply a weak electrical current to the neck to improve swallowing. The long-term benefit of these devices is controversial. Further, these therapies have not been shown to enhance a weakened cough reflex. There are no drugs for the treatment of impaired swallow or cough. It appears that the pharmaceutical industry has not yet recognized the importance of prevention of aspiration in patients with neurological disease in disease outcome. A team in Japan has promoted a comprehensive protocol using sensory stimuli such as menthol and capsaicin, the pungent ingredient in red peppers, to help elderly people who have serious impairments in swallowing. Their preliminary results show impressive improvements in reducing aspiration pneumonias in these patients. There is a promising approach based on strengthening breathing muscles that has been shown to improve swallow and cough function in patients with Parkinson’s disease and stroke. This approach is called “expiratory muscle strength training,” and it is easy for health care professionals and most patients to perform. The extent to which this method can prevent pneumonia in at-risk patients is unknown at this time. In short, while there are some promising approaches, there are no widely accepted therapies for restoring weakened swallow and cough in patients at significant risk of aspiration. Continued research on the fundamental neurological mechanisms of coughing and swallowing will provide a foundation for new therapies to reduce the occurrence and severity of aspiration pneumonia. This article was originally published on The Conversation. Read the original article.
March 17, 2017
Health care guidelines are produced in ever-increasing numbers. The National Guideline Clearinghouse, a U.S.-based public website compiling summaries of “clinical practice” (health care) guidelines, has over 1,000 entries and is updated weekly. The National Institute for Health and Care Excellence in the U.K. has over 180 clinical guidelines. Health care guidelines cover all aspects of medicine, from using aspirin to prevent heart attacks and colon cancer to managing earwax and caring for athletes with concussions. Health care guidelines impact policy decisions and care for individuals. Recent research, though, suggests that the public has only a vague understanding of what guidelines are and how they are developed. This is consistent with my own experience as a physician studying best practices for patient engagement in guideline development. Most of my patients and focus group participants are unfamiliar with how guidelines are developed. This can lead to uncertainty for patients and contributes to controversy, such as debates about mammography guidelines. What are guidelines? Before widespread internet access allowed people to search systematically for scientific evidence, “guidelines” often reflected suggestions from groups of experts on how to best manage — or prevent — a medical condition. Current high-quality clinical practice guidelines, though, are anchored in a thorough review of available medical evidence. This has led some organizations to revisit recommendations made in older guidelines less firmly based on medical evidence. Last year the Departments of Agriculture and Health and Human Services dropped recommendations for flossing of teeth from their dietary guidelines, though debate about this remains. In this era of evidence-based medicine, various standards exist for developing clinical practice guidelines. These include standards from the Guidelines International Network and the U.S.-based Institute of Medicine. The Appraisal of Guidelines Research & Evaluation Enterprise (AGREE) publishes a tool to assess the quality and reporting of clinical practice guidelines. While different in some nuances, international standards agree on core elements. Guidelines summarize what is known (and not known) about different tests and treatments for health problems. They then make recommendations for expected best care, with specific descriptions of how confident guideline developers are in the research and recommendations. General guidelines may not work for all, and they may not be practical for all. From wwww.shutterstock.com High quality guidelines are developed by groups of patients and other public representatives, professional subject experts (physicians and other health professionals) and guideline specialists. These individuals decide what questions to ask, examine all the available research, grade the research quality, consider other issues (such as risks, benefits, availability, personal preferences and sometimes cost), and then make recommendations about best medical care. Some guideline developers, such as the U.S. Preventive Services Task Force, seek public comment on plans for upcoming guidelines, draft evidence reviews, and recommendation statements to give the public a voice in the development process. The reliance of guidelines on the best medical evidence means the recommendations are now less likely to be driven by panel members’ opinions and personal experiences. Practicing health professionals and the public can be more confident that recommendations are based largely on unbiased reviews of medical research and transparent weighing of benefits and harms. Limitations The term “clinical practice guideline” is reserved to describe “recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options.” However, some recommendations labeled (by developers or the media) as “guidelines” are actually policy or expert consensus statements provided without a full systematic review of medical research or offered in the absence of helpful studies. For example, recent screen time recommendations from the American Academy of Pediatrics are an American Academy of Pediatrics policy statement rather than a formal clinical practice guideline. Even when guidelines are based on systematic grading of the medical evidence, sometimes different developers make different recommendations. These conflicts are confusing for patients and for health professionals. Inconsistencies may reflect different approaches to panel composition, reviewing and grading medical evidence, interpretation of the evidence and/or weighing of risks and benefits. The inconsistencies may also represent more concerning possibilities such as contributions from conflicts of interest. Putting guidelines to good use A common misunderstanding about clinical practice guidelines is that they tell patients and health professionals what to do. Rather than identifying one “best” answer, clinical practice guidelines summarize what is known about medical options and describe anticipated benefits and risks. This information can then be used by patients and health professionals during shared decision making, which combines patients’ values and preferences alongside the best medical evidence to make an individualized decision. Many clinical practice guidelines are now publicly available on websites. One resource for this is the National Guideline Clearinghouse, which accepts only guidelines meeting certain quality standards and which summarizes key elements of their development. Understanding guideline debates can also inform decision making, helping patients and health professionals know when there is uncertainty in the field. Every medical decision is a personal one, and rarely is there a single “right answer.” Trustworthy clinical practice guidelines are an important tool for improving the delivery of high quality health care to a broad audience. Individual decisions, though, are best made when patients partner with their health professionals to understand the evidence and incorporate their own medical history and values to make the best decision in that unique circumstance. This article was originally published on The Conversation. Read the original article.
March 13, 2017
For a second year, the University of Florida and the surrounding community will celebrate creativity with 352Creates. The two-day event March 24-25 invites everyone in the 352 area code to participate in pop-up art activities to promote healthy communities through creativity. “This is a great way of encouraging everyone to learn about and become involved in the arts, helping to ensure that our university community continues to blossom as a place with rich and diverse educational and cultural opportunities,” said UF President Kent Fuchs. On March 24, participants will “create in place,” making art wherever they are. 352Creates invites cultural groups, artists, community agencies, businesses and individuals to get creative. UF Health will host several free events on the Archer Road campus for faculty, staff, students, patients and visitors, including a mural project at noon in the UF Health Shands Hospital Atrium where participants will help design and color sections of a mural that will be installed later on campus. The following day, March 25, focuses on creating in the community, with a public event at Depot Park that features performances from UF hip hop dancers, improv comedians and a cappella singers, as well as a children’s imagination station presented by art education students. Depot Park is one of five community installations of the Before I Die Wall, a public art project where participants reflect on life, death and their personal aspirations. The project, one of more than 2,000 such walls in 70-plus countries, will also promote awareness of advance directives, which allow people to provide instructions for end-of-life health-care decisions. Individuals or groups are invited to host free creative activities that are open to the public, regardless of creative experience or skill. The activities can include hands-on art-making, performance (such as music, song, dance, theatre, spoken word), culinary arts, gardening and contemplative arts (including mindful meditation, yoga, tai chi and qigong). For information on how to participate, visit the 352Creates website or find 352Creates on Facebook, Twitter and Instagram. All events will be promoted with the hashtag #352Creates. Presenting partners for 352Creates include UF Health, UF Health Shands Arts in Medicine, Arts in Medicine Programs at UF and the City of Gainesville.
WEEKLY NEWS: March 23, 2017