That’s why they’ve developed a technique to test for cardiac problems in endangered manatees, both in the wild and in captivity. The new technique will enhance knowledge of how the manatee heart functions.

The UF researchers are using the technique to gather data they hope to share with wildlife and zoo veterinarians to ultimately save more manatee lives. Collaborating with scientists from Tampa’s Lowry Park Zoo and the Florida Fish and Wildlife Conservation Commission’s marine mammal pathology laboratory in St. Petersburg, they are using echocardiography on the large creatures, making use of a specially designed table built to hold animals weighing up to 2,000 pounds.

“There are a lot of gaps in our knowledge base on basic anatomy and physiology of manatees due to the obvious limitations of working with a 1,000- to 1,500-pound animal that spends its entire life in the water,” said Trevor Gerlach, an intern in UF’s aquatic animal health program and lead author on a paper that documents the first phase of the researchers’ study in the June issue of the Journal of Zoo and Wildlife Medicine. “Due to their current endangered status, it is important that we understand the animal in its entirety so that we can better tailor conservation efforts for the species.”

The researchers’ long-term goal is to provide practitioners at rehabilitation facilities and those working in the field with data from clinically healthy animals. Such animals could be compared to animals of concern to determine if cardiac disease is present.

To allow for effective testing, the researchers first developed a table built to hold the weight of 2,000-pound animals that were part of a large-scale manatee health assessment conducted by the U.S. Geological Survey in Crystal River. Fourteen healthy, wild and captive Florida manatees underwent echocardiography, administered using the table technique, between fall 2011 and winter 2012. The group included eight females and six males of various ages.

“We were able to clearly visualize all valves and chambers,” Gerlach said, adding that other key indicators of heart function also were successfully obtained. Some abnormalities in the study animals also were documented.

“Our results indicate that echocardiography in the Florida manatee is possible, which has both clinical and research implications in larger epidemiologic studies evaluating diseases of the cardiopulmonary and cardiovascular systems,” Gerlach said.

Although extensive research has been conducted on comparative anatomy, physiology and ecology of sea cows, very few studies have evaluated the manatee heart. Basic cardiac morphology and a test called an electrocardiogram have been examined, but the diagnostic value is limited to electrical imbalances in the heart, the researchers said.

“Echocardiography is the gold standard for diagnosing valve diseases and structural abnormalities, and provides other information as well,” Gerlach said.

Researchers are finishing up the second phase of the study, which entails collecting more data from echocardiographs to establish normal testing parameters for manatees of various ages.

“Once we establish the parameters, we can begin larger epidemiological studies on the prevalence of heart disease in the wild population, which is one of our long-term goals,” Gerlach said.

Bob Bonde, a manatee researcher with the USGS, praised the new technique.

“Out-of-water, real-time assessment of these large aquatic mammals will benefit our evaluation of manatee health-related indices in the wild population,” “Knowledge of manatee reproductive fitness and nutritional condition is paramount to our fully understanding their recovery.”

Utilizing the diffusion tensor imaging technique, as it is known, could allow clinicians to assess people earlier, leading to improved treatment interventions and therapies for patients.

The three-year study looked at 72 patients, each with a clinically defined movement disorder diagnosis. Using a technique called diffusion tensor imaging, the researchers successfully separated the patients into disorder groups with a high degree of accuracy.

The study is being published in the journal Movement Disorders.

“The purpose of this study is to identify markers in the brain that differentiate movement disorders which have clinical symptoms that overlap, making [the disorders] difficult to distinguish,” said David Vaillancourt, associate professor in the department of applied physiology and kinesiology and the study’s principal investigator.

“No other imaging, cerebrospinal fluid or blood marker has been this successful at differentiating these disorders,” he said. “The results are very promising.”

Movement disorders such as Parkinson’s disease, essential tremor, multiple system atrophy and progressive supranuclear palsy exhibit similar symptoms in the early stages, which can make it challenging to assign a specific diagnosis. Often, the original diagnosis changes as the disease progresses, Vaillancourt said.

Diffusion tensor imaging, known as DTI, is a non-invasive method that examines the diffusion of water molecules within the brain and can identify key areas that have been affected as a result of damage to gray matter and white matter in the brain. Vaillancourt and his team measured areas of the basal ganglia and cerebellum in individuals, and used a statistical approach to predict group classification. By asking different questions within the data and comparing different groups to one another, they were able to show distinct separation among disorders.

“Our goal was to use these measures to accurately predict the original disease classification,” Vaillancourt said. “The idea being that if a new patient came in with an unknown diagnosis, you might be able to apply this algorithm to that individual.

He compared the process to a cholesterol test.

“If you have high cholesterol, it raises your chances of developing heart disease in the future,” he said. “There are tests like those that give a probability or likelihood scenario of a particular disease group. We’re going a step further and trying to utilize information to predict the classification of specific tremor and Parkinsonian diseases.”

Vaillancourt and his team are part of the National Institute of Neurological Disorders and Stroke Parkinson’s Disease Biomarkers Program, an effort that was launched in 2012 and awarded nine grants to scientists across the U.S., totaling more than $5 million in the first year. The program gives researchers access to a much broader community of individuals and patients as part of a biomarker initiative for Parkinson’s disease.

Vaillancourt’s team is engaged in a longitudinal study at UF that will assess between 150 and 180 people over the next few years. His team will be using DTI as well as other MRI-based techniques to classify subjects and track their progression, he said.

Adam Barry, an assistant professor of health education and behavior at UF, and his team interviewed and breath-tested more than 1,000 bar patrons in the downtown restaurant and bar district of a major university town in the Southeast. Of the designated drivers who had consumed alcohol, half recorded a blood-alcohol level higher than .05 percent — a recently recommended new threshold for drunken driving.

“If you look at how people choose their designated drivers, oftentimes they’re chosen by who is least drunk or who has successfully driven intoxicated in the past — successful meaning got home in one piece … that’s disconcerting,” Barry said.

The results are published in the July issue of the Journal of Studies on Alcohol and Drugs.

The researchers recruited patrons as they left bars between 10 p.m. and 2:30 a.m. across six Friday nights before home football games in fall 2011. The mean age of the 1,071 people who agreed to be tested was 28. Most were white male college students, while 10 percent were Hispanic, 6 percent were Asian and 4 percent were African-American.

After completing a 3-5 minute interview about demographic data and alcohol-related behaviors, participants then had their blood-alcohol content tested with a hand-held breath-testing instrument.

The non-driving participants had significantly higher levels than the designated drivers, but 35 percent of the 165 self-identified designated drivers had been drinking. Seventeen percent of all those drivers tested had blood-alcohol levels between .02 and .049 percent, while 18 percent were at .05 percent or higher.

The National Transportation Safety Board last month recommended all 50 states adopt a blood-alcohol content cutoff of 0.05 compared with the 0.08 standard used today to prosecute drunken driving. The American Medical Association made the same recommendation in the 1980s, Barry said.

Barry said he doesn’t know why a designated driver would consume alcohol, but factors could include group dynamics or the driver’s belief that one or two drinks won’t impair his skills if he is an experienced drinker.

Some field-based research suggests designated drivers might drink because the group did not consider who would drive before drinking commenced. Barry also suggested that it’s tricky for anyone to accurately evaluate their own sobriety.

“That’s the insidious nature of alcohol — when you feel buzzed, you’re drunk,” he said.

There is no universally accepted definition of a designated driver, according to the research. Although most U.S. researchers say drivers should completely abstain, international researchers believe they can drink as long as his or her blood-alcohol level remains below the legal limit. However, the U.S. limit is much higher than in most other countries.

At .08 percent, the U.S. has one of the highest allowable legal limits of any developed country. Countries such as Denmark, Finland and Greece use the .05 level; Russia and Sweden are at .02; and Japan has a zero percent tolerance.

Co-researchers were Beth H. Chaney and Michael L. Stellefson, also assistant professors in health education and behavior, College of Health and Human Performance.

These findings, published June 4 EDT in The Lancet, are the latest results from ongoing collaborative work by 42 researchers from 17 institutions in the International Warfarin Pharmacogenetics Consortium led by University of Florida Health researcher Julie A. Johnson, a distinguished professor of pharmacy and medicine and director of the UF Center for Pharmacogenomics.

A highly effective blood thinner taken by patients at risk for strokes caused by clotting, warfarin also contributes to nearly one-third of all hospital admissions for adverse drug events.

“Warfarin dose requirements vary substantially among all patients and the perfect dose is critical,” said Johnson, the V. Ravi Chandran professor of pharmaceutical sciences at the UF College of Pharmacy. “A little high might mean bleeding risk, a little low raises a danger of a clot that can cause pulmonary embolism or stroke.”

Also known as Coumadin, warfarin is a low-cost drug option that may be prescribed for short- or long-term blood-thinning therapy. Last month, the IMS Institute for Healthcare Informatics reported that more than 33 million U.S. prescriptions for warfarin were filled in 2012.

Among all patients, warfarin daily doses range anywhere from 1 milligram to 20 milligram, and even a small miscalculation can lead to complications. It may take a couple of weeks to several months to determine the right dose without the use of genetics, leaving patients vulnerable in the process. By compiling genetic data along with other factors that affect dosing, such as patients’ weight, age and other drugs being taken, doctors can prescribe a more accurate dosage for any patient from the start. For African-Americans, however, that wasn’t enough to predict the widely variable dose of warfarin, so the researchers began looking for additional factors. They discovered a difference in one part of the genome that strongly influences how people of African-American descent metabolize these drugs.

After adding this genetic marker to dosing algorithms, co-author Minoli Perera, an assistant professor of medicine at the University of Chicago, showed a 21 percent improved predictability of warfarin dosing for the at-risk population, who often require a higher dosage.

“This finding demonstrates the potential for genetic studies, especially those applied to minority groups, to make a substantial impact on both the population and the personal level,” Perera said. “Physicians will appreciate its impact on the management of this common and difficult-to-dose drug. Patients who carry this mutation will appreciate that their doctors can start them at a lower dose that is closer to what they really require.”

Studies conducted at the University of Illinois at Chicago and the University of Chicago identified novel genetic associations with warfarin dose requirements in African-Americans. Study co-author Larisa H. Cavallari, an associate professor in the UIC department of pharmacy practice, has been a member of the consortium since its early efforts to identify a dosing algorithm for warfarin.

Existing pharmacogenetic algorithms have not accurately predicted the best warfarin dose in African-Americans, said Brian F. Gage, an internist and a professor of medicine at Washington University in St. Louis whose work is independent of the consortium.

Gage developed a website, www.warfarindosing.org, that offers a calculator for his widely used warfarin dosing algorithm for clinicians evaluating new patients or seeking scientific resources, including patient education. Johnson and her colleagues, who also have contributed a dosing algorithm to the site, believe that doctors and their patients will benefit with the addition of the consortium’s newest findings.

The consortium obtained genetic samples African-American participants with an average age of 59. To compare the results of the new dosing predictions, researchers collected genetic samples from several clinical study sites. They analyzed 533 samples from the discovery group and compared them to a 432-validation group of African-American adult volunteers — all taking maintenance dose of warfarin.

“Incorporating this gene variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population and help more patients arrive at their optimal dose more quickly,” said Nita Limdi, an associate professor in the department of neurology at the University of Alabama at Birmingham School of Medicine, and a co-author of the study.

The UAB, with a large demographic population at risk for health care disparities, enrolled the largest number of patients in the study.

“This newly discovered polymorphism will improve prediction substantially,” Gage said. “Furthermore, because it affects warfarin metabolism, accounting for it should significantly decrease the risk of overdosing African-Americans who are initiating warfarin.”

The consortium researchers all hope to improve patients’ outcomes worldwide by taking the next steps to apply what they have learned.

“We are currently genotyping all patients newly starting warfarin at the University of Illinois Hospital & Health Sciences System. We plan to add the new variant, described in the Lancet paper, to our genotyping platform,” Cavallari said.

David Borchelt, a professor of neuroscience affiliated with the Evelyn F. and William L. McKnight Brain Institute of UF, emphasized the importance of verifying promising research results before investing in clinical studies or testing potential therapies in people. Bexarotene has known side effects that include effects on the liver, blood and other metabolic systems.

“We wanted to repeat the study to see if we could build on it, and we couldn’t,” he said. “We thought it was important that something like this, which got a lot of publicity and patients were immediately looking to try to get access to this drug, that it was important to publish the fact that we couldn’t reproduce the most exciting part of the study. Maybe there should be some caution going forward in regard to patients.”

Borchelt and Kevin Felsenstein, an associate professor of neuroscience, said a drug called bexarotene that their team orally administered to mice did not reduce amyloid plaques, waxy buildups on the brain that are a key culprit in Alzheimer’s disease. Their findings will be published in the May 24, 2013, issue of the journal Science magazine, with two additional articles detailing similar results from other researchers.

The research follows up on a 2012 Science article that claimed bexarotene had reversed Alzheimer’s-like symptoms in mice afflicted with the plaques. Authors of that study also administered the drug orally.

The paper “indicated that with as little as three days of treatment, they basically cleared the amyloid deposits from these animals, as well as restored cognitive abilities,” Felsenstein said of the 2012 paper.

He said the results of the original study were surprising, given decades of research that had failed to find a therapy successful in dismantling amyloid plaques.

“We can shut down the production of amyloid in these animal models and the deposits in these animal models don’t disappear,” Felsenstein said. “These deposits have been described by some as cement, and it will take a lot to get rid of them. The fact that something could actually make them disappear in literally a couple of days is — again — very remarkable.”

Interested to see how bexarotene might work to break down amyloid plaques, Felsenstein and Borchelt selected mice approximately the same age as those used in the 2012 study and orally administered the drug to the mice. Tests confirmed the drug had reached its target genes in the mice, and that it elevated levels of a protein called apolipoprotein E. Some scientists believe one of the forms of this protein may prevent the buildup of amyloid brain plaques in people who don’t have Alzheimer’s disease.

But elevated levels of the protein in the mice studied by UF researchers seemed to have no effect on the animals’ amyloid plaques. Samples taken after seven days of treatment with bexarotene showed no significant difference in the number or size of plaques in the animals’ brains. Two teams of researchers from other institutions also were unable to replicate the breakdown of amyloid plaques.

Felsenstein emphasized that his team does not claim the previous study indicating bexarotene’s effectiveness is “totally wrong.”

“We’re just saying right now it’s extremely difficult to replicate and there may be little nuances, that there’s something that we don’t quite understand,” he added. Felsenstein and Borchelt both work at UF’s Center for Translational Research in Neurodegenerative Disease.

The other two research groups who published papers in this week’s journal Science were led by Dr. Bart De Strooper, director of the VIB Center for the Biology of Disease in Belgium, and Sangram S. Sisodia, director of the Center for Molecular Neurobiology at the University of Chicago.

The insecticide would work by interfering with an enzyme found in the nervous systems of mosquitoes and many other organisms, called acetylcholinesterase. Existing insecticides target the enzyme but affect a broad range of species, said entomologist Jeff Bloomquist, a professor in UF’s Emerging Pathogens Institute and its Institute of Food and Agricultural Sciences.

Acetylcholinesterase helps regulate nervous system activity by stopping electrical signaling in nerve cells. If the enzyme can’t do its job, the mosquito begins convulsing and dies. The research team’s goal is to develop compounds perfectly matched to the acetylcholinesterase molecules in malaria-transmitting mosquitoes, he said.

“A simple analogy would be that we’re trying to make a key that fits perfectly into a lock,” Bloomquist said. “We want to shut down the enzyme, but only in target species.”

Malaria is spread by mosquitoes in the Anopheles genus, notably Anopheles gambiae, native to Africa. The disease is common in poor communities where homes may not have adequate screens to keep flying insects out.

Malaria is caused by microscopic organisms called protists, which are present in the saliva of infected female mosquitoes and transmitted when the mosquitoes bite.

Initial symptoms of the disease can include fever, chills, convulsions, headaches and nausea. In severe cases, malaria can cause kidney failure, coma and death. Worldwide, malaria infected about 219 million people in 2010 and killed about 660,000, according to the Centers for Disease Control and Prevention. About 90 percent of those infected lived in Africa.

Bloomquist and colleagues at Virginia Tech, where the project is based, are trying to perfect mosquito-specific compounds that can be manufactured on a large scale and applied to mosquito netting and surfaces where the pests might land.

It will take at least four to five years before the team has developed and tested a compound enough that it’s ready to be submitted for federal approval, Bloomquist said.

The team recently published a study in the journal Pesticide Biochemistry and Physiology comparing eight experimental compounds with commercially available insecticides that target the enzyme.

Though they were less toxic to mosquitoes than commercial products, the experimental compounds were far more selective, indicating researchers are on the right track, he said.

“The compounds we’re using are not very toxic to honeybees, fish and mammals, but we need to refine them further, make them more toxic to mosquitoes and safer for nontarget organisms,” he said.

In the project, Bloomquist tests experimental compounds on Anopheles gambiae mosquitoes, held in a quarantine facility on the UF campus. He worked at Virginia Tech for 20 years and came to UF in 2009. Bloomquist joined the project at the behest of lead investigator Paul Carlier, a professor of organic and medicinal chemistry in Virginia Tech’s College of Science.

Funding for the project came from a five-year, $3.6 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

In Florida, malaria was a significant problem in the early 20th century, transmitted by native Anopheles mosquitoes. The disease has been greatly curtailed via mosquito-control practices but even today, cases are occasionally reported in the Sunshine State.

Approximately 50 million people in the United States pop a daily aspirin pill to treat or prevent heart disease. Of these, at least half take more than 100 milligrams of the drug — more than one baby aspirin — a day. Although aspirin has been widely used in cardiovascular medicine over the past 20 to 30 years, a review of research papers suggests that the widely used over-the-counter medicine does not benefit everyone to the same degree, report Dr. Ki Park and Dr. Anthony A. Bavry in the May issue of Cleveland Clinic Journal of Medicine.

“Not all patients with coronary disease are the same,” said Park, a physician in the department of medicine’s division of cardiovascular medicine.

Park and Bavry’s algorithm leads physicians through a series of questions that consider the patient’s age, sex and current health status. The answers help them determine whether the course of care should include aspirin.

“It’s an evolving assessment that should be repeated every few years as conditions change,” Park said.

Most studies on the effects of aspirin therapy in patients who had previous heart attacks have focused on men. While examining the literature, Park and Bavry found that less is known about the effects of aspirin on women, people with diabetes, the elderly and even patients who are at risk of a heart attack but have never had one.

“In this paper we highlight gaps in knowledge where we don’t fully know if aspirin should be used or not,” said Bavry, an assistant professor of cardiovascular medicine. “There’s still room to study its optimal use.”

While people may see aspirin as a harmless drug, taking a daily aspirin does carry some risk of side effects such as gastrointestinal bleeding. Park and Bavry’s review contains an analysis to help physicians determine whether the risks outweigh the benefits.

Their review showed that while aspirin therapy remains a good way to prevent further heart attacks, more is not better. A low-dose aspirin, such as an 81-milligram pill, gives the same amount of protection as a standard dose of 325 milligrams and lowers the risk of bleeding.

But even at a lower dose, the current literature suggests certain patients may not benefit from aspirin therapy. In women, for instance, evidence shows aspirin can help prevent certain types of stroke, but does not appear to prevent heart attacks as effectively as it does in men. On the other hand, women appear to have a lower risk of gastrointestinal bleeding than men do.

Risk factors also change with age and the estimated 10-year risk for heart disease. The rise in use of cholesterol-lowering drugs called statins also can affect whether a patient should take aspirin. And aspirin therapy for patients with diabetes, who are automatically considered to be at high risk for cardiovascular disease, remains controversial.

“A lot goes in to estimating a patient’s risk,” Bavry said.

Yes, according to a new book written by University of Florida addiction medicine specialists Dr. Scott Teitelbaum and Michael Nias. The book, titled “Weed: Family Guide to Marijuana Myths and Facts,” is geared toward helping families wade through conflicting information about the drug, which is now legal for medicinal purposes in 18 states.

One of the main issues people do not understand is that marijuana is a much stronger drug than it was in decades past, due to crop engineering, Teitelbaum said. In fact, the concentration of tetrahydrocannabinol, or THC — the chemical in marijuana that causes users to feel high — is five to seven times higher in the drug today than it was in the 1970s, he added.

“This isn’t your father’s marijuana,” said Teitelbaum, medical director of the UF&Shands Florida Recovery Center and an associate professor of psychiatry in the UF College of Medicine. “The higher THC concentration is associated with more psychiatric problems and more dependence.”

Because of the legalization of medical marijuana in certain states and the decriminalization of the drug in others, many people now see the drug as safe, and this perception directly affects use, Teitelbaum said.

“We know when you look at adolescents, initiation of a drug is inversely proportional to its perceived danger,” he said. “Throughout history if a drug has been perceived as safe and benign, it’s more likely to be tried by young people. But marijuana is not a benign drug. It is associated with addiction and learning problems.”

Marijuana use can be particularly risky for adolescents, whose brains are still developing, Teitelbaum added. Typically, women’s brains reach full development in their early 20s, while men’s brains reach maturity in their mid-20s. Teens who have genetic predispositions for developing certain mental disorders, such as schizophrenia, are particularly at risk.

“Introducing drugs with neurotoxic effects during this time, while the brain is still developing, can be very damaging. It’s similar to a pregnant woman drinking alcohol,” he said.

In addition, teens who try marijuana before age 15 face a four times greater chance of developing an addiction later in life than their peers who don’t smoke pot, according to the book. Unfortunately, Teitelbaum says studies show that about 15 percent of eighth-grade students have already been exposed to the drug.

In addition to busting myths about marijuana, the book also aims to help parents navigate common conflicts in talking to their children about drug use and arm children with the information they need to make the best choices. A particularly tricky area for many parents is how to talk to their children about drugs they may have used themselves at some point. According to the Pew Research Center, 48 percent of Americans say they have tried marijuana.

“The more you can do to stop initiation of drugs and have honest and open communication, the better chance you have of not having your child develop a drug addiction,” Teitelbaum said.

“Weed: Family Guide to Marijuana Myths and Facts” is available for purchase on the University Press of Florida website as well as on amazon.com in both paperback and e-book.

DNA nanotechnology holds great promise as a new way to deliver chemotherapy directly to cancer cells, but until now, scientists have not been able to direct nanotherapies to consistently differentiate cancer cells from healthy ones. Other limiting factors include high costs, too-small amounts of drugs delivered and potential toxic side effects.

“Most nanotechnology relies on a nanoparticle approach, and the particles are made of inorganic materials; after they’ve been used as a carrier for the drug, they’ll be left inside the body,” said the study’s lead investigator, Weihong Tan, a UF distinguished professor of chemistry, professor of physiology and functional genomics, and a member of the UF Shands Cancer Center and the UF Genetics Institute. “Compared to existing nanostructures, our nanotrain is easier and cheaper to make, is highly specific to cancer cells, has a lot of drug-loading power and is very much biocompatible.”

Described in today’s issue of the Proceedings of the National Academy of Sciences, Tan’s DNA nanotrain is a three-dimensional structure composed of short strands of DNA tethered together into one long train. On the end of the nanotrain is an aptamer, a tiny piece of nucleic acid serving as the train’s “locomotive” on biochemical autopilot to home in on and bind to specific cancer cells. Trailing behind are tethered DNA structures that serve as side-by-side, high-capacity “box cars,” transporting bioimaging agents or drug cargos to their targets.

“The beauty of the nanotrain is that by using different disease biomarkers you can hitch different types of DNA probes as the train’s ‘locomotive’ to recognize and target different types of cancers,” Tan said. “We’ve precisely targeted leukemia, lung and liver cancer cells, and because the DNA probes are
so precise in targeting only specific types of cancer cells we’ve seen dramatic reduction in drug toxicity in comparison to standard chemotherapies, which don’t discriminate well between cancerous and healthy cells.”

Tan and his colleagues report that the DNA nanotrains can be cost-effectively made by mixing bits of DNA in a liquid medium. The mixture is then exposed to a compound that stimulates the pieces of DNA to seek each other out and self-assemble into the DNA nanotrains. The type of cancer cell the DNA nanotrain will seek out and destroy is determined by the specific compound added to the mixture as the trigger.

The study demonstrated in vitro and in mice that the DNA nanotrains exclusively target the cancer cells for which their probes were programmed. The DNA probes go straight to the cancer cells, leading the nanotrains to dock on the cell membranes and gain entry into the cells. Once inside, the drug payloads disperse, killing the cancer cells, a process Tan and his team monitored in real time by measuring the amount of fluorescent light emitted. The biodegradable components of the DNA nanotrains decay with the dead cancer cells and are removed by the body’s normal housekeeping mechanisms.

“Our study found that when loaded with anticancer drugs, these nanotrains inhibited tumor growth in mice more than in those that received drugs injected freely into the bloodstream. What’s more exciting is that the mice treated with these nanotrains suffered dramatically fewer side effects than those treated with free drugs,” said Guizhi Zhu, a UF doctoral student who was instrumental in the study. “This is what we aim to achieve for future clinical health care of cancer patients.”

In addition to longer survival and inhibited tumor growth, the mice that were treated with nanotrain drug delivery experienced less weight loss and are in better condition physically than both the mice that received injected therapy and the mouse control group that received no treatment. Tan and his team attribute these improved outcomes to greatly reduced toxicity achieved by the targeted nanotrain drug delivery.

“We think we have demonstrated that these DNA nanotrains are a promising targeted drug transport platform for delivery of cancer chemotherapeutics with very low toxicity to healthy tissues, and that the platform has wide application for many different cancer types,” Tan said. “Moving forward, we are working to identify optimum dosage using mouse models for T-cell leukemia, lung and liver cancers and triple negative breast cancer.

“It’s very exciting, but we still have a long way to go before human trials,” he said.

GAINESVILLE, Fla. — Hepatitis C patients may soon have effective new drugs that can clear the liver of the viral infection.

That’s good news for the population believed to be most affected by hepatitis C: the nation’s more than 70 million baby boomers — those born between 1945 and 1965.

University of Florida professor of medicine David R. Nelson, M.D., and his colleagues report the findings from two studies in the current issue of the New England Journal of Medicine.

“This is the opening of the floodgates to change the treatment paradigms for this disease,” Nelson said. “It’s the beginning of the end for hepatitis C.”

Hepatitis C, a viral liver disease transmitted through contact with an infected person’s blood, can lead to liver problems including liver damage, cirrhosis, liver failure or liver cancer. Because a person with chronic hepatitis C can live symptom-free for years, many people do not know they are infected.

Globally, the World Health Organization estimates about 150 million people are chronically infected with hepatitis C, and more than 350,000 people die each year from related liver diseases. In the United States, estimates put the number of infected people between 3 million and 5 million.

The Centers for Disease Control and Prevention estimates that baby boomers account for about 2 million of those in the U.S. who are chronically infected with the disease. In August, the CDC released new guidelines that urged all baby boomers to get tested for hepatitis C, citing the disease’s prevalence, boomers’ lack of awareness of the disease and recent advances in treatment.

“This is a huge disease in terms of morbidity and mortality and health care costs,” Nelson said.

Until now, treatment for hepatitis C consisted of injections of interferon, a general immune stimulant that turns on the body’s defense mechanisms. However, at the high doses required to treat, interferon often creates toxic side effects, and more than two-thirds of hepatitis C patients cannot use the treatment regimen.

Nelson and colleagues conducted two randomized phase 3 trials, the final testing studies before a drug can be considered for approval. The studies, sponsored by Gilead, the maker of the drug sofosbuvir, were conducted with patients who had one of two types of chronic hepatitis C infection. In a trial called POSITRON, a group of 278 patients who could not take interferon took a combination of oral sofosbuvir and ribavirin or a placebo for 12 weeks. In a trial called FUSION, a group of 201 patients who had no response to prior interferon therapy took the drugs for 12 weeks or 16 weeks.

Sofosbuvir and ribivarin attack the virus itself, preventing the virus from replicating. Because the hepatitis C virus only lives and reproduces in the liver, the combination of antiviral compounds enables the body to eventually clear itself of the virus.

Viral reproduction was successfully suppressed during treatment for patients in both trials. The trials resulted in complete elimination of the virus in 78 percent of patients for whom interferon was not an option and for 50 percent to 73 percent of patients with prior treatment failure.

“A significantly greater number of patients could be cured as these new all oral regimens gain FDA approval,” Nelson said.

If the FDA approves this combination of drugs, they will be the first of their kind for the treatment of this disease.

Nelson reports receiving grant support from Genentech, Kadmon, Merck, Vertex Pharmaceuticals, Gilead, Boehringer Ingelheim and Abbott/Abbvie; and payment for the development of educational presentations from Clinical Care Options, Rush University Medical Center, Practice Point Communications and Chronic Liver Disease Foundation.

GAINESVILLE, Fla. — Two antiviral drugs used to treat hepatitis C appear to work as well in the real world as they did during clinical trials, an international research consortium has observed. The consortium also released data that may help inform how doctors and patients manage treatment-related adverse events.

The international effort, known as HCV-TARGET, follows how newly approved therapies for hepatitis C are used and managed in routine practice. It is led jointly by the University of Florida and the University of North Carolina at Chapel Hill.

The ongoing research suggests that the safety and efficacy of the antiviral drugs telaprevir and boceprevir are similar for North American patients taking the treatments in real-world settings to what was observed in clinical trials.

The evaluation of data available from November 2011 through April 2013, presented at the 48th Annual Meeting of the European Association for the Study of the Liver in Amsterdam, found that anemia was the most relevant adverse event affecting clinical care. Approximately two-thirds of anemic patients were managed with drug dose reductions, which minimized the need for expensive growth factors and blood transfusions. The analysis also reveals that patients with cirrhosis were at increased risk for treatment-related complications, including severe anemia and significant deterioration of the liver, which often resulted in stopping therapy early.

“This is a long-term study, and we plan to release similar interim analyses each spring and fall to provide clinicians with up-to-date knowledge that can inform how we manage therapy for patients with hepatitis C,” said Dr. David R. Nelson, co-principal investigator, director of the UF Clinical and Translational Science Institute and professor of medicine at UF, which serves as the clinical coordinating center for HCV-TARGET.

One of the consortium’s priorities for future analyses will be to investigate indicators that may predict adverse outcomes in cirrhotic patients and guide safer use of these drug regimens.

Hepatitis C is a viral liver disease transmitted through contact with infected blood. Chronic hepatitis C can lead to serious liver problems including liver damage, cirrhosis, liver failure or liver cancer. Because a person with chronic hepatitis C can live symptom-free for many years, many people do not know they are infected.

Globally, the World Health Organization estimates about 150 million individuals are chronically infected with hepatitis C, and more than 350,000 people die each year from hepatitis C-related liver diseases. In the U.S., the Centers for Disease Control and Prevention estimates 3.2 million people are chronically infected with hepatitis
C, although a 2011 review article in Liver International suggests the estimate is likely higher — at least 5.2 million people — if U.S. populations not surveyed by the CDC are included, such as the homeless and incarcerated.

HCV-TARGET was created to inform the ongoing transformation of hepatitis C treatment and research. The HCV-TARGET model is rooted in the infrastructure and collaborative network developed through the National Institutes of Health’s Clinical and Translational Science Award (CTSA) program, which is led by the National Center for Advancing Translational Sciences. In addition to UNC and UF, HCV-TARGET includes 23 other CTSA-supported institutions among its 103 academic and community sites in 31 states, Puerto Rico, Canada and Europe. HCV-TARGET also partners with multiple industry sponsors, regulatory agencies and the patient advocacy community.

In 2011, HCV-TARGET established a nationwide registry to observe patients in the United States undergoing hepatitis C treatment over time and to coordinate real-world monitoring on a national scale for new therapies as they enter the market. For patients who agree to be in the study, the project is capturing demographic, clinical, adverse event and virological data. To date approximately 1,900 patients have agreed to participate, including patients with cirrhosis and other populations underrepresented in clinical trials.

“The data coming out of the HCV-TARGET consortium will help inform physicians and patients as they weigh important decisions regarding therapy, decisions that can greatly impact quality of life,” said Dr. Donald M. Jensen, a professor of medicine at the University of Chicago and a member of the HCV-TARGET Steering Committee.

The network’s initial study has followed a broad population of adult patients in North America treated with telaprevir or boceprevir, which were newly approved by the U.S. Food and Drug Administration when HCV-TARGET launched. In 2013, HCV-TARGET is expanding its study to include European sites and patients treated with any direct-acting antiviral agent approved by the FDA.

“We plan to track up to 5,000 patients internationally over five years to continue to assess the benefits and risks of new treatments in real-world settings,” said Dr. Michael W. Fried, co-principal investigator and professor of medicine at UNC, which serves as the HCV-TARGET data coordinating center. “HCV-TARGET serves as a model for cross-cutting collaborative studies that can rapidly advance knowledge in an important illness of public health concern.”

HCV-TARGET (www.hcvtarget.org) receives ongoing industry support from Merck, Genentech, Kadmon, and Vertex. Dr. Fried receives research grant support from and serves as ad hoc consultant to Genentech, Vertex, Merck, Gilead, Bristol Myers Squibb and Abbott. Dr. Nelson receives grant support from Genentech, Kadmon, Merck, Vertex Pharmaceuticals, Gilead, Boehringer Ingelheim and Abbott/Abbvie; and payment for the development of educational presentations from Clinical Care Options, Rush University Medical Center, Practice Point Communications and Chronic Liver Disease Foundation.

For more than 15 years, scientists have known that two types of brain lesions form in patients with Alzheimer’s disease, one type of lesion forming only after the other. David R. Borchelt, a professor of neuroscience, and Guilian Xu, an assistant research scientist at the UF College of Medicine, have used a mouse model to find a potential explanation for how the first type of brain lesion may trigger the second. They report their findings in the current issue of the journal Human Molecular Genetics.

“Understanding how this sequence of events works is thought to be critical and could lead to new therapeutic approaches,” said Borchelt, director of the SantaFe HealthCare Alzheimer’s Disease Research Center at UF and the McKnight Brain Institute.

The lesion that appears first is an amyloid plaque, an incorrectly folded protein structure that forms when a small peptide called the amyloid-beta peptide clumps together. However, scientists have known that amyloid alone does not produce Alzheimer’s disease, and all patients with symptoms have a second type of brain lesion called a neurofibrillary tangle. This second lesion appears later in the disease, and as more of these lesions develop, patient symptoms get worse.

Finding an explanation for the sequential appearance of these lesions has challenged scientists, but understanding how the amyloid plaques trigger the tangles could help scientists devise ways to slow disease progression.

The explanation lies at the heart of how cells function. All cells produce proteins, the molecular workhorses of the cell. Proteins have specific, three-dimensional shapes critical to proper function. This is so important that large amounts of cell energy go into making correctly folded proteins and eliminating incorrectly folded ones. The study by the Borchelt laboratory provides evidence that the abnormal accumulation of the amyloid peptide in the brain that produces the plaque lesions also interferes with brain cells’ ability to keep proteins correctly folded.

“This deficiency in cell function could set the stage for allowing the formation of the neurofibrillary tangles that seem to be the key pathology to symptoms,” Borchelt said.

These tangles form when a protein called tau loses its normal shape and folds into a shape that allows it to bind to other tau proteins. This becomes a runaway process that fills the cell with abnormally shaped tau clumps that produce the tangles.

In recent years, pharmaceutical and biotech companies have begun to look for drugs that could stimulate better protein folding in brain cells. The study by Xu suggests that these companies may be on the right track. Borchelt cautions that more work is needed to fully understand how amyloid pathology is linked to the tangle pathology, but this recent study offers a new avenue of investigation that could lead to a clearer picture.

Funding sources for this work include the National Institutes of Health and the SantaFe HealthCare Alzheimer’s Disease Research Center

Now, University of Florida researchers and their colleagues are using a new technique that allows them to examine how parts of the brain battle for dominance when a person tries to concentrate on a task. Addressing these fluctuations in attention may help scientists better understand many neurological disorders such as autism, depression and mild cognitive impairment.

Mingzhou Ding, a professor of biomedical engineering, and Xiaotong Wen, an assistant research scientist of biomedical engineering, both of the University of Florida; Yijun Liu of the McKnight Brain Institute of the University of Florida and Peking University, Beijing; and Li Yao of Beijing Normal University, report their findings in the current issue of The Journal of Neuroscience.

Scientists know different networks within the brain have distinct functions. Ding, Wen and their colleagues used a brain imaging technique called functional magnetic resonance imaging and biostatistical methods to examine interactions between a set of areas they call the task control network and another set of areas known as the default mode network.

The task control network regulates attention to surroundings, controlling concentration on a task such as doing homework, or listening for emotional cues during a conversation. The default mode network is thought to regulate self-reflection and emotion, and often becomes active when a person seems to be doing nothing else.

“We knew that the default mode network decreases in activity when a task is being performed, but we didn’t know why or how,” said Ding, a professor of biomedical engineering in the J. Crayton Pruitt department of biomedical engineering. “We also wanted to know what is driving that activity decrease.

“For a long time, the questions we are asking could not be answered.”

In the past, researchers could not distinguish between directions of interactions between regions of the brain, and could come up with only one number to represent an average of the back-and-forth interactions. Ding and his colleagues used a new technique to untangle the interactions in each direction to show how the different brain regions interact with one another.

In their study, the researchers used fMRI to examine the brains of people performing a task that required concentration. The scientists can see the activity in certain areas of the brain at the same time a person is performing a given task. They can see which parts of the brain are active and which are not and correlate this to how successful a person is at a given task. They then applied the Granger causality technique to look at the data they saw in the fMRI. Named for Nobel Prize-winning economist Clive Granger, this technique allows scientists to examine how one variable affects another variable; in this case, how one region of the brain influences another.

“People have hypothesized different functions for signals going in different directions,” Ding said. “We show that when the task control network suppresses the default mode network, the person can do the task better and faster. The better the default mode network is shut down, the better a person performs.”

However, when the default mode network is not sufficiently suppressed, it sends signals to the task control network that effectively distract the person, causing his or her performance to drop. So while the task control network suppresses the default mode network, the default mode network also interferes with the task control network.

“Your brain is a constant seesaw back and forth,” even when trying to concentrate on a task, Ding said.

The Granger causality technique may help researchers learn more about how neurological disorders work. Researchers have found that the default mode network remains unchanged in people with autism whether they are performing a task or interacting with the environment, which could explain symptoms such as difficulty reading social cues or being easily overwhelmed by sensory stimulation. Scientists have made similar findings with depression and mild cognitive impairment. However, until now no one has been able to address what areas of the brain might be regulating the default mode network and which might be interfering with that regulation.

“Now we are able to address these questions,” Ding said.

“For years, African-Americans have been underrepresented in research,” said lead investigator Linda Cottler, chair of the department of epidemiology at the University of Florida College of Public Health and Health Professions and the College of Medicine. “Reasons have included mistrust of the medical community and actually not ever being asked to participate in research. Our study shows that while the participation rate among African-Americans has been very low, their level of interest in research is high. This is exciting news and may reflect the influence of the community engagement programs of the National Institutes of Health’s Clinical and Translational Science Awards.”

More than 80,000 clinical trials are conducted each year in the United States, yet less than 2 percent of the population participates in them. Women, the elderly, racial and ethnic minorities and rural residents are often underrepresented.

“If we’re not getting the participation of diverse groups when we’re studying medications or interventions, then we don’t know how those treatments will work in real life in different populations,” said Cottler, associate dean for research and planning at the College of Public Health and Health Professions and co-director of community engagement for UF’s Clinical and Translational Science Institute. “It’s very important for people to have a voice and be represented.”

The new study was designed to learn the health concerns and research perceptions among underrepresented groups with the goal of improving inclusiveness and relevance of health research. The study was conducted by five universities that are recipients of Clinical and Translational Science Awards: Washington University in St. Louis; the University of California, Davis in Davis, Calif.; the
University of Michigan in Ann Arbor, Mich.; Albert Einstein College of Medicine of Yeshiva University in New York City; and the University of Rochester in Rochester, N.Y. Community health workers in those cities interviewed adults at local gathering spots, such as barbershops, parks, bus stops, churches, grocery stores, laundromats and health fairs.

Among the 5,979 people interviewed, the top five health concerns were high blood pressure, diabetes, cancer, weight and heart problems. Safety and crime were two of the highest-ranked neighborhood concerns.

When asked about their overall interest in medical research, 91 percent of African-Americans expressed an interest in participating compared with 85.5 percent of whites, 84.5 percent of Hispanics and 79 percent of Asians. African-Americans were more likely than other racial groups to express a willingness to participate in research even when it may involve providing blood or genetic samples, granting access to medical records or staying overnight in the hospital.

“This is a groundbreaking study that demonstrates that members of minority communities are interested in research, especially around the diseases and risk factors that are most common in their families and communities,” said Dr. Lloyd Michener, chair of the department of community and family medicine at the Duke University School of Medicine, which was not involved in the study. “As many traditional studies struggle with recruitment, this study suggests that the problem may lie with the lack of awareness of researchers with the methods of community engagement, rather than lack of interest or willingness to engage in research among members of these communities.”

The five universities involved in the current study, along with the University of Florida, are now focused on a new study that aims to better understand outcomes of community engagement programs.

There are many barriers to participating in medical research, and not just for minorities, Cottler said, such as the time of day of required study visits and navigating university campuses. HealthStreet, a community engagement program Cottler founded in St. Louis and Gainesville, Fla., seeks to reduce disparities in health care and improve access to research studies among people who are medically underserved by meeting people out in the community and linking them to services and research opportunities.

“We’re trying to do studies in the community so that it’s much easier for people to participate,” Cottler said. “We are bringing the research to the community instead of bringing the community to the research.”

“We wanted to take a step back and do within-group comparisons of black men with prostate cancer who are native-born African-American, African immigrants and Caribbean immigrants,” said Folakemi Odedina, a UF professor of pharmacy and associate director of health disparities for the UF Shands Cancer Center. “These groups are all genetically predisposed to get prostate cancer, but when you look at their experiences in terms of how the disease affects their lives and how they cope with it, there are a lot of differences among them.”

Odedina’s three-year study, funded by a $1.02 million Department of Defense grant, is the first to compare differences in morbidity, quality of life and survival among diverse groups of black men, who experience a 60 percent greater risk of developing prostate cancer than whites, according to the National Cancer Institute. That risk more than doubles for men with a father or brother who has had prostate cancer. Black men also are more likely to be diagnosed when their cancers are at an advanced stage, and they are more than twice as likely as white men to die of the disease.

“Our study will use ‘grounded theory’ to look at the broad continuum of prostate cancer care for these men in an effort to understand how to successfully deal with the disease through every phase, including prevention, detection, diagnosis, treatment, survivorship and advocacy,” Odedina said.

Grounded theory is a form of ethnographical analysis wherein investigators don’t begin with a hypothesis as the theoretical framework for the study. Instead, investigators begin by collecting data — in this case, interviews with black men and their wives or caregivers about their experiences, beliefs and feelings about the detection, treatment and survival of prostate cancer. During the grounded theory process of social-science super sleuthing, hypotheses are then reverse-engineered from the data.

To capture this data, 2,000 black men will be randomly selected from the Florida Cancer Data System database. In 2010, the most recent year for which data are available, that database represented about 38,000 black men in Florida.

Investigators will contact each man via telephone or postcard in an effort to identify which group he may fall into, whether native-born African-American, African immigrant or Caribbean immigrant. Sixty of these men will be asked to participate in in-depth interviews, some of which will use a method called “photo voice.” In this method, each participant is given a disposable camera and asked to take photos over the course of a week of people, places and objects that define his prostate cancer experience. At the end of the week, the photos are printed and each man is asked to tell the stories behind the photos and their impact on his prostate cancer experience.

As part of the prostate cancer care and survivorship model for black men, the study also will produce a video documentary of 30 of the men and their caregivers talking about the full range of their prostate cancer experiences. The team also will explore the process of how men move from being prostate cancer patients to becoming prostate cancer advocates in their communities. Workshops throughout the state will take place during the final phase of the effort, to report findings back to African-American, African and Caribbean communities and to cultivate prostate cancer advocates in those communities.

“I think the whole thing we have to look at, in reality, is that for many people, the word cancer conjures up such fear that the fear often times overrides the individual’s need to get the facts that will enable them to fight the disease,” said Virgil H. Simons, a prostate cancer survivor and founder of The Prostate Net, an international, not-for-profit prostate cancer patient advocacy organization. “This study is important because it will help people understand some of those things can be controlled and dealt with on an individual basis, and identify those things that can be addressed on a community basis.