October 21, 2016
University of Florida Health neuroscience researchers have published findings revealing new insights into the abnormal firing of neurons in the brain associated with dopamine release after intake of the drug methamphetamine. The findings appear in The Journal of Neuroscience. The study identifies a novel mechanism for how methamphetamine adversely affects the firing pattern of dopamine neurons, providing new understanding of how to potentially treat methamphetamine addiction and its neurotoxic effects following long-term exposure to the drug. Dopamine is a chemical messenger released during pleasurable activities such as eating and sex. In the article, “Methamphetamine Regulation of Firing Activity of Dopamine Neurons,” lead author Min Lin, M.D., Ph.D., and Danielle Sambo, a neuroscience graduate student, confirm a long-held hypothesis that methamphetamine extensively releases dopamine in the brain via a carrier called dopamine transporter in what is called a “reverse transport” of dopamine. “When people abuse methamphetamine, the level of dopamine and the duration of this high level of dopamine is much, much longer than, for example, cocaine,” said Lin, an assistant professor in the department of neuroscience. “Cocaine-induced increase in dopamine is about 30 minutes to a maximum of 45 minutes. Methamphetamine is 10 hours.” The research team sought to understand the way in which methamphetamine increases dopamine release from neurons about a thousand-fold above normal. In a mouse model, the study found a unique mechanism in which methamphetamine prompts a “reverse transport” of dopamine via the dopamine transporter from inside a neuron to the outside. Using electrophysiology, high-resolution microscopy and biochemistry, the researchers showed that because long-term exposure to methamphetamine decreases firing activity of dopamine neurons, the “reverse transport” process is the central mechanism for methamphetamine stimulation of dopamine release in the brain, said co-author Habibeh Khoshbouei, Pharm.D., Ph.D., an associate professor of neuroscience at the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. “When you add methamphetamine, for the first one to two minutes, dopamine neurons fire much, much faster,” Khoshbouei said. “But the prolonged effect of methamphetamine actually decreases the firing activity of dopamine neurons. This is the first time this mechanism is understood.” The new findings will help to guide development of novel therapeutic approaches, Khoshbouei said. “Because methamphetamine is neurotoxic, people who have been exposed to methamphetamine for a long time show Parkinson’s-like symptoms,” she said. “If you can treat that, you potentially can alleviate the untoward long-term effects of methamphetamine.”
October 4, 2016
It can be hard enough to shed unwanted pounds. For Spanish speakers seeking weight loss information online, it could be even harder, thanks to the prevalence of inaccurate and incomplete information on popular Spanish-language weight loss sites, report researchers at UF Health and the Texas Tech University Health Sciences Center. The information on the sites was compared with recommendations made by the 2015 Dietary Guidelines for Americans and the American College of Sports Medicine, and quality scores ranged from four points for “excellent” to no points for “nothing” in three key domains: nutrition, physical activity and weight-loss-related behavior change. Only 12 percent of the 66 websites the team analyzed scored more than six out of 12 points on the accuracy and completeness of their weight loss content. The researchers published their findings recently online in the journal Obesity. In addition, the quality of the sites in Spanish is substantially lower than comparable sites in English, with 23 percent of websites in English scoring more than six out of 12 points on these same domains, according to findings from an earlier study conducted by one member of the UF Health research team, François Modave, Ph.D., an associate professor of health outcomes and policy, and colleagues at Texas Tech University HSC at El Paso. “The bottom line is that the weight loss information that Spanish speakers in the U.S. are most likely to see is poor,” said Michelle Cardel, Ph.D., R.D., an assistant professor in the department of health outcomes and policy in the UF College of Medicine. “This is a particularly serious issue given that 42.6 percent of Hispanic adults in the U.S. have obesity and they are the nation’s fastest-growing demographic. Our study reveals one possible contributing factor to these obesity rates: misinformation online.” About 38 percent of Hispanics in the U.S. report mainly speaking, writing and reading in Spanish, indicating the importance of evaluating Spanish-language websites for the quality and comprehensiveness of their content. To conduct the study, a set of 30 weight-loss queries were generated by native Spanish speakers, based on questions in the previous study done in English. Since 90 percent of all clicks on search engines have been shown to be on one of the first five nonsponsored links, the research team identified the first five nonsponsored entries for the 30 different weight loss queries in Spanish, ultimately garnering a bank of 66 websites for analysis. Specifically, the team examined the nutrition-related content for information on healthy eating patterns, balancing energy input and output, and limiting saturated and trans fat, sugar, refined grains and sodium. Regarding physical activity, the team checked for specific recommendations regarding moderate and vigorous activity and muscle strengthening. Lastly, they analyzed the content for suggested behavior changes, such as setting weight loss goals, improving diet, increasing physical activity, addressing barriers to change, self-monitoring, and strategizing how to maintain a healthy lifestyle. Blogs had the lowest average content score at 2.2 out of 12, and they often pointed to sites that were commercial in nature and provided very low-quality information. In addition, 94 percent of the websites included unsubstantiated claims, which the research team defined as any weight loss recommendations that did not align with current evidence-based recommendations. Only 45 percent included reputable references. The team noted that no websites from the medical, government or university communities ranked within the first five entries of the Spanish-language searches. Websites of this nature provided some of the highest-quality information in the earlier study conducted on weight loss websites in English and comprised 13.5 percent of the websites the earlier team analyzed. “It is important to note that high-quality information in Spanish is available on the internet — just not within the top-ranked sites, which is where the vast majority of people go for their information,” said Modave, who added that commercial sites may be investing more in search engine optimization since high-quality sites in Spanish start to appear on page three or further in the search engine results. “To fix this,’’ Modave said, “we recommend that organizations with high-quality information pay attention to search engine optimization. It is not enough to have evidence-based content on your site if most people who need it will never scroll down far enough to see it.”
September 30, 2016
If a workout feels like more pain than gain, here’s some motivation: Exercise releases a hormone that helps the body shed fat and keeps it from forming. A group led by a University of Florida Health researcher has learned more about how the hormone irisin helps convert calorie-storing white fat cells into brown fat cells that burn energy. Irisin, which surges when the heart and other muscles are exerted, also inhibits the formation of fatty tissue, according to the researchers. The findings, published recently in the American Journal of Physiology — Endocrinology and Metabolism, show that irisin may be an attractive target for fighting obesity and diabetes, said Li-Jun Yang, M.D., a professor of hematopathology in the UF College of Medicine’s department of pathology, immunology and laboratory medicine. The study is believed to be the first of its kind to examine the mechanisms of irisin’s effect on human fat tissue and fat cells, researchers said. Irisin appears to work by boosting the activity of genes and a protein that are crucial to turning white fat cells into brown cells, the researchers found. It also significantly increases the amount of energy used by those cells, indicating it has a role in burning fat. Researchers collected fat cells donated by 28 patients who had breast reduction surgery. After exposing the samples to irisin, they found a nearly fivefold increase in cells that contain a protein known as UCP1 that is crucial to fat “burning.” “We used human fat tissue cultures to prove that irisin has a positive effect by turning white fat into brown fat and that it increases the body’s fat-burning ability,” Yang said. Likewise, Yang and her collaborators found that irisin suppresses fat-cell formation. Among the tested fat-tissue samples, irisin reduced the number of mature fat cells by 20 to 60 percent compared with those of a control group. That suggests irisin reduces fat storage in the body by hindering the process that turns undifferentiated stem cells into fat cells while also promoting the stem cells’ differentiation into bone-forming cells, the researchers said. Knowing that the body produces small quantities of fat-fighting irisin underscores the importance of regular exercise, Yang said. More than two-thirds of U.S. adults are overweight or obese, according to the National Institutes of Health. While it’s possible that the beneficial effects of irisin could be developed into a prescription medication, Yang said that is uncertain and remains a long time away. “Instead of waiting for a miracle drug, you can help yourself by changing your lifestyle. Exercise produces more irisin, which has many beneficial effects including fat reduction, stronger bones and better cardiovascular health,” Yang said. The present study builds on other findings about irisin’s beneficial effects. In 2015, Yang’s group found that the hormone helps improve heart function in several ways, including boosting calcium levels that are critical for heart contractions. In June, Yang and a group of scientists in China showed that irisin reduced arterial plaque buildup in mouse models by preventing inflammatory cells from accumulating, resulting in reducing reduction of atherosclerosis. Those findings were published in the journal PLOS One. The findings about irisin’s role in regulating fat cells sheds more light on how working out helps people stay slender, Yang said. “Irisin can do a lot of things. This is another piece of evidence about the mechanisms that prevent fat buildup and promote the development of strong bones when you exercise,” she said.
September 28, 2016
September 26, 2016
It is estimated that about 80 percent of Zika infections are asymptomatic or have symptoms so mild that the disease is not detected. This means the number of cases reported by disease surveillance systems in the U.S. and across the world might be only a small fraction of the actual number of infections. In fact, it’s likely we are are underestimating imported cases in the U.S. and even likely some locally spread cases. In this situation, mathematical and computational models that account for mosquito populations, human mobility, infrastructure and other factors that influence the spread of Zika are valuable because they can generate estimates of the full extent of the epidemic. This is what our research group, made up of physicists, biostatisticians and computer scientists, has done for Zika. The Global Epidemic and Mobility Model (GLEAM) can model the spread of Zika through countries and geographical regions. Our model suggests that while more cases of Zika can be expected in the continental U.S., outbreaks will probably be small and are not projected to spread. By contrast, some countries, like Brazil, have already seen widespread outbreaks. How does the model work? Zika is primarily transmitted by Aedes mosquitoes. For a mosquito to transmit Zika to a human, it must first have bitten a human infected with the virus. If enough people infected with Zika travel to a new area with these mosquitoes, the virus could spread in a new geographic region. That means models for Zika transmission need to take factors like mosquito population, human mobility and temperature, among others, into account. So we begin by dividing the population of the Americas into geographical cells of similar size, and grouping these cells into subpopulations centered around major transportation hubs. 7 Our model also incorporates data on the density of the mosquitoes that transmit Zika, Aedes aegypti and Aedes albopictus, within those subpopulations. Mosquitoes need warm weather to thrive, so we include a daily estimated temperature for each subpopulation. That allows us to factor seasonal temperature changes into our simulations. To breed, mosquitoes need standing water, and to spread Zika, they need people to feed on. Areas with standing water, fewer window screens and less air conditioning, which are often lower-income areas, are at greater risk. The model uses detailed data about socioeconomics for each subpopulation, as well as data on the relationship between socioeconomic status and risk of exposure to mosquito-borne disease. Once all of these factors are incorporated into the model, we simulate a Zika outbreak. These simulations are meant to project what will happen next with Zika, so they need to include information about what has already happened. The simulations were calibrated to match data from countries that experienced the epidemic first, like Brazil and Colombia. We started by “introducing” Zika into one of 12 major transportation hubs in Brazil. Each calibration starts with a different time and place where Zika was first introduced into the country, and simulates about 500,000 possible epidemics. From those we select a few thousand that match surveillance data to project the epidemic forward. Randomness is also incorporated into the simulations so that the resulting “epidemics” can reflect the natural variability in how diseases spread. Zika’s spread in the U.S. will be limited Based on current data, our model projects only small outbreaks from mosquito transmission in the continental U.S. that are likely to die out before spreading to new areas. Alabama, Arkansas, Georgia, Louisiana, Mississippi, Oklahoma, South Carolina and Texas are at risk of these small outbreaks. This is because it is warm enough in these states through the summer and fall to sustain mosquito transmission. But the median number of daily cases from local mosquito transmission in these states is projected to be zero. This means that in general we do not expect an outbreak to happen, though small outbreaks are possible. Any outbreaks in these states are expected to end by November or December 2016, consistent with declining temperatures and the end of mosquito season. Florida, on the other hand, may observe sustained transmission between September and November 2016. After calibrating the model with available surveillance data through mid-August, on average, less than 100 symptomatic Zika cases are projected by the second half of September. As many as eight pregnant women could be locally infected in the first trimester, though these women would not give birth until October 2017. In comparison, over 671 pregnant women infected during travel have already been identified in the U.S. as of September 1, 2016. And, as in other states, when mosquito season ends in December, so will Zika transmission from local mosquitoes. Keep in mind, we are just talking about people getting infected with Zika from local mosquitoes. In the U.S. the number of local cases is expected to be small relative to the number of travel-related infections and to affect comparatively few pregnant women. The number of travel-related and local cases that are detected by the Zika surveillance system in the continental U.S. is likely much smaller than the total number of infections. Our model estimates that only 2 percent to 5 percent of travel-related infections are detected by surveillance. And local infections may not be detected for individuals without symptoms. But even taking frequent travel-related infections and low detection rates into account, our models project few local cases in the continental U.S. It’s a different picture for other parts of the Americas. Our models suggest that larger outbreaks occurred or will occur in Brazil, Colombia, Venezuela and Puerto Rico. All have tropical or subtropical climates, have higher densities of the mosquito vectors, and may be at greater risk due to socioeconomic factors. This is a projection, not a prediction Remember, these are projections for what might happen, not predictions of what will happen. No model can perfectly replicate reality. For instance, this model doesn’t account for sexual transmission. We still don’t know how common it is for a person infected with Zika to transmit it during sex. Sexual transmission may proportionally have a larger effect in domestic outbreaks than we realize. This type of detailed modeling is complex, and that makes it difficult to examine what is happening within states, or even within single counties. It will take more time and data to analyze simulations at such local levels. Finally, the model does not include any interventions, such as increased mosquito control. Unless other modes of transmission, such as sexual transmission, turn out to be significant factors, our projection might be considered a worst-case scenario. Model projections like this should be always scrutinized using information about what is happening on the ground. And they need to be recalibrated and refined as new information becomes available. This article originally appeared in The Conversation on Sept. 12, 2016.
WEEKLY NEWS: October 20, 2016