Research Roundup |
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September 29, 2015, Volume 62, No. 07 |
Penn/Baylor Med Study Describes Underlying Cause of Diabetes in Dogs
Penn Nursing Study May Lead to More Effective Treatment of Chemotherapy Side Effects
Which PSAs Make Parents More Likely to Cut Kids’ Soda Intake?
Simplified Recycling of Rare-earth Magnets
Effects of Incarceration Spill Over into Health Care System, Penn Study Finds
Penn Scientists Identify Key Genetic Factor That Keeps Moles From Turning Into Melanoma
Penn/Baylor Med Study Describes Underlying Cause of Diabetes in Dogs
Researchers from the University of Pennsylvania and Baylor College of Medicine have used advanced imaging technology to fill in details about the underlying cause of canine diabetes, which until now has been little understood. For the first time, they’ve precisely quantified the dramatic loss of insulin-producing beta cells in dogs with the disease and compared it to the loss observed in people with type 1 diabetes.
“The architecture of the canine pancreas has never been studied in the detail that we have done in this paper,” said Rebecka Hess, professor of internal medicine at Penn’s School of Veterinary Medicine and an author on the study.
Despite important differences between the disease in dogs and humans, the study also identified key similarities that suggest investigating diabetes in dogs may yield valuable insights into treating humans.
The research was led by Emily Shields, currently a graduate student in Penn’s Perelman School of Medicine, who completed much of the work as a high school and then college student in labs at Penn and Baylor. Jake A. Kushner, formerly of Penn and now a McNair Medical Institute Scholar and chief of pediatric diabetes & endocrinology at Baylor College of Medicine, was the senior author. Together with Dr. Hess, they collaborated with Thomas J. Van Winkle of Penn Vet, Matthew M. Rankin of Penn Medicine and Children’s Hospital of Philadelphia and Carol J. Lam and Aaron R. Cox of Baylor. Their study was published on June 9 in PLOS ONE.
Canine diabetes can be managed with insulin, similar to type 1 diabetes in humans. But unlike the human version of the disease, dogs typically develop diabetes in middle or old age, while people with type 1 diabetes are typically diagnosed during childhood. In addition, while type 1 diabetes is known to be an autoimmune condition, researchers haven’t found conclusive evidence that the same is true in dogs.
To learn more about the factors that contribute to canine diabetes, the researchers made use of a repository of donated tissue samples from dogs —23 with diabetes and 17 without—who had been treated at Penn Vet’s Ryan Hospital. The team used robotic microscopes that rapidly moved around a slide taking images of pancreas tissue samples, which were then analyzed by a computer to determine their contents.
“In a larger view we could look at the entire cross-section of the pancreas to determine how many islets there were and how big they were,” Ms. Shields said. “Then we could zoom in to differentiate beta cells, which produce insulin, from alpha cells, which produce glucagon.”
They found that beta cells dropped off in dramatic fashion in diabetic dogs, reduced 13-fold compared to non-diabetic animals. They also found that non-diabetic canine islets contained a large percentage of beta cells, comprising about 80 percent of endocrine cells. In contrast, beta cells comprise slightly more than 50 percent of endocrine cells in non-diabetic human islets. The researchers noted that this may mean that dogs need to lose more beta cells than humans do before experiencing symptoms of diabetes. The observation could explain why dogs develop a form of diabetes that is similar to type 1 diabetes, but do so later in life, compared to humans.
They also identified features of the islets and pancreatic structures that were different in dogs than in humans.
“In sharp contrast to human diabetes, in which there are a lot of islets still present but none contains insulin, we found in dogs that only a few beta cells were present and the islets were incredibly small,” Dr. Kushner said.
While the researchers had hoped to be able to visualize immune cells infiltrating the pancreas and attacking beta cells, they failed to do so. While other signs point to canine diabetes being an autoimmune condition, this study did not find a “smoking gun.”
Though the work highlights differences between canine and human diabetes, it also points to a number of similarities that distinguish the two from diabetes in rodents, which are often used as models to study the disease. For example, the scientists observed that dogs’ beta cells were distributed throughout the islets, as beta cells in humans are. In rodents, beta cells are concentrated in the center of the islet.
“Now that we know more about the disease in dogs and in particular how they are similar to humans in ways that rodents are not, it makes them more appealing as a model,” Dr. Kushner said.
At Penn, Dr. Hess is currently working to look for genetic markers in dogs that heighten a dog’s risk of developing diabetes. “My hope is that with genetic screening we can eventually identify pre-clinical diabetic dogs, potentially making breeding recommendations that could decrease the incidence and prevalence of the disease in dogs,” she said.
The research was supported by the NIH, Robert and Janice McNair Foundation, Pathology and Histology Core at Baylor College of Medicine and Diabetes Research Center of the Baylor College of Medicine.
Penn Nursing Study May Lead to More Effective Treatment of Chemotherapy Side Effects
Annually, hundreds of thousands of patients battling cancer undergo chemotherapy, which often results in poorly-tolerated side effects such as nausea, vomiting and loss of the desire to eat.
Bart C. De Jonghe, assistant professor of nursing and senior author of a new study published on August 5 in the Journal of Neuroscience, has advanced our understanding of how chemotherapy causes side effects related to nausea, vomiting and anorexia using pre-clinical rodent models of chemotherapy-induced illness.
“This publication shows that blocking specific receptors for the neurotransmitter glutamate within the amygdala, an area of the brain associated with feeding, sickness and emotion, results in a robust alleviation of sickness and anorexia produced by cisplatin chemotherapy treatment in the animals. This work has also helped us construct a clearer picture of how the anatomy of the brain is organized and connected to facilitate these observations. It is our hope that this knowledge can be used to inform future research with the goal of further limiting, or even altogether preventing, common chemotherapy side effects in cancer patients,” Dr. De Jonghe explains.
In his role as senior author and director of the project, Dr. De Jonghe coordinated with lead author Amber Alhadeff as part of an ongoing research collaboration between the De Jonghe laboratory and the laboratory of Harvey Grill in the department of psychology. This work also highlights Penn undergraduates as partners in Dr. De Jonghe’s transdisciplinary research, with laboratory members Ruby A. Holland (SAS ’16) and recent BSN graduate Alexandra Nelson (SON ’14) earning co-authorship on the paper as a result of their significant contributions.
Dr. De Jonghe is currently funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by the American Cancer Society.
Which PSAs Make Parents More Likely to Cut Kids’ Soda Intake?
Getting children to cut back on sugar-sweetened beverages like soda and energy drinks has been the goal of anti-obesity public service advertisements (PSAs) in cities across the United States. But to achieve that, the PSAs use very different strategies – some aim for humor, some use scare tactics and some appeal to parents’ nurturing instincts.
A new study takes an experimental approach to identify the effectiveness of specific persuasive techniques used in PSAs. Researchers found that the PSAs that were perceived as making a stronger argument for reducing sugary beverages and produced greater feelings of hope and empowerment made parents more likely to say they intended to cut back on their children’s intake of sugary drinks.
The study, “Sugar-Sweetened Beverage-Related Public Service Advertisements and Their Influence on Parents,” was conducted by researchers at the University of Pennsylvania and published online on July 21 in American Behavioral Scientist. The public service ads targeted sugary beverages including non-diet soda, sweetened tea and sports, energy and fruit drinks.
The study, involving a national sample of 807 parents with children ages 3 to 17, found that persuasive techniques that used fear or nurturance were more significantly related to an ad’s perceived argument strength. Those emotional appeals may be more promising strategies for health-related messages directed at parents, the researchers said.
“Study after study shows that sugar-sweetened beverage consumption is associated with weight gain in children,” said Amy Jordan, lead author of the research and adjunct full professor at the Annenberg School for Communication. She is also a distinguished research fellow of the Annenberg Public Policy Center (APPC) and president of the International Communication Association. “There are now a plethora of campaigns encouraging healthier beverage consumption, and research like this helps to identify which strategies have the greatest likelihood of resonating with parents.”
Amy Bleakley, a senior research scientist at APPC and a co-author of the study, said, “It’s important to have research-based, evidence-driven ads. You want to know before you create the ads which strategies are effective for your audience.”
This study followed one published earlier this year in which teens were shown the same PSAs. It found that PSAs based on fear—which warned about the health consequences of too much sugar, including obesity, diabetes and amputations —had the greatest effect on the teens’ intention to cut back on sugary drinks. It was published in the Journal of Health Communication.
In addition to Dr. Jordan and Dr. Bleakley, the study’s authors were Michael Hennessy (formerly of APPC); Karen Glanz (Penn’s School of Nursing) and Andrew A. Strasser (Penn’s Perelman School of Medicine), both also APPC distinguished research fellows; and Sarah Vaala (Vanderbilt University School of Nursing).
Simplified Recycling of Rare-earth Magnets
Despite their ubiquity in consumer electronics, rare-earth metals are, as their name suggests, hard to come by. Mining and purifying them is an expensive, labor-intensive and ecologically devastating process.
Researchers at the University of Pennsylvania have now pioneered a process that could enable the efficient recycling of two of these metals, neodymium and dysprosium. These elements comprise the small, powerful magnets that are found in many high-tech electronic devices.
In contrast to the massive and energy-intensive industrial process currently used to separate rare earths, the Penn team’s method works nearly instantaneously at room temperature and uses standard laboratory equipment.
Sourcing neodymium and dysprosium from used electronics, rather than the ground, would increase their supply at a fraction of the financial, human and environmental cost.
The research was lead by Eric J. Schelter, assistant professor in the department of chemistry in Penn’s School of Arts & Sciences, and graduate student Justin Bogart. Connor A. Lippincott, an undergraduate student in the Vagelos Integrated Program in Energy Research, and Patrick J. Carroll, director of the University of Pennsylvania X-Ray Crystallography Facility, also contributed to the study.
The study was published in Angewandte Chemie, International Edition.
“Neodymium magnets can’t be beat in terms of their properties,” Dr. Schelter said. “They give you the strongest amount of magnetism for the smallest amount of stuff and can perform at a range of temperatures.” These thermal qualities are achieved by mixing neodymium with other elements, including the rare-earth metal dysprosium, in different ratios. Because those ratios differ based on the application the magnet is being used for, the two metals need to be separated and remixed before they can be reused.
“It’s, in principle, easier to get the neodymium and dysprosium out of technology than it is to go back and mine more of the minerals they are originally found in,” Dr. Schelter said. “Those minerals have five elements to separate, whereas the neodymium magnet in a wind turbine generator only has two.”
Currently, whether purifying the neodymium and dysprosium out of minerals or out of an old power tool motor, the same costly and energy-intensive process is used. The technique, known as liquid-liquid extraction, involves dissolving the composite material and chemically filtering the elements apart. The process is repeated thousands of times to get useful purities of the rare-earth metals, and so it must be conducted on an industrial scale.
Rather than this liquid-liquid method, Dr. Schelter’s team has devised a way to separate the two metals.
“When we started,” Mr. Bogart said, “our goal was to make rare earth separations simpler and more efficient and we have made strides towards just that. We have designed a way to separate the two metals by selectively dissolving the neodymium in a solution and leaving behind the dysprosium as a solid. This quick and easy method has allowed us to separate equal mixtures of the metals into samples that are 95 percent pure.”
Starting with the two elements as a mixed powder, a metal-binding molecule known as a ligand is applied. The type of ligand the research team designed has three branches, which converge on the metal atoms and hold them in the aperture between their tips. Because of neodymium’s slightly larger size, the tips don’t get as close together as they do around dysprosium atoms.
“The difference in size between the two ions is not that significant, which is why this separation problem is difficult,” Dr. Schelter said, “But it’s enough to cause that aperture to open up more for neodymium. And, because it is more open, one ligand-neodymium complex can combine with another, and that really changes its solubility.”
The combination of the two neodymium complexes, known as a dimer, encapsulates the neodymium ions, enabling them to dissolve in solvents like benzene or toluene. The dysprosium complexes do not dissolve, enabling the two metals to be easily separated. Once apart, an acid bath can strip the ligand off both metals, enabling it to be recycled as well.
“If you have the right ligand, you can do this separation in five minutes, whereas the liquid-liquid extraction method takes weeks,” Dr. Schelter said. “A potential magnet recycler probably doesn’t have the capital to invest in an entire liquid-liquid separations plant, so having a chemical technology that can instantaneously separate these elements enables smaller scale recyclers to get value out of their materials.”
Future work will involve improving the stability of the ligand so it is less likely to fall off before the metals are separated.
“These results are encouraging,” Mr. Bogart said. “We feel that through slight adjustments to the system, the purity level could be increased even further.”
Further modification of the ligand could enable other rare earths in technology products, such as compact fluorescent light bulbs, to be recycled this way.
The research was supported by the Early Career Research Program of the US Department of Energy’s Office of Science and the Research Corporation for Science Advancement.
Effects of Incarceration Spill Over into Health Care System, Penn Study Finds
The consequences of incarceration on former inmates and their families are well known. But how does imprisonment affect the health care system as a whole? A new study, led by Jason Schnittker of the University of Pennsylvania and published in the September issue of The Milbank Quarterly, finds that states with the highest incarceration rates experience significant declines in overall access to and quality of care.
Through this research, Dr. Schnittker, a professor in the department of sociology in Penn’s School of Arts & Sciences, and colleagues from the University of Minnesota and the University of Georgia address the ties between the prison system and other social systems—and bring to light the broader social costs of incarceration. It is what’s often called a spillover effect.
Spillover occurs when the behavior of one group in the community changes the situation of others. In the case of incarceration, the issue stems from relatively poor health among former inmates, higher levels of uninsurance and a greater risk of uncompensated care.
“There’s an emerging consensus that we incarcerate too many people and that incarceration has a huge negative impact on the lives of former inmates,” Dr. Schnittker said. “There were reasons to expect that incarceration could, through a series of steps, affect health care systems. Our job was to show how that could happen.”
To reach these conclusions, Dr. Schnittker and colleagues evaluated health care behavior at the individual level as a function of state-level incarceration rates, as well as a variety of control variables. They learned that in US states that incarcerate a greater number of people, populations experience less overall access to care and reduced access to specialists. They also feel less trust toward physicians and less satisfaction with their care.
Though former inmates and their families suffer the most, their situation also “affects the care of those removed from them,” the researchers noted, including the uninsured, those older than 50, non-Hispanic whites, women and those with incomes that far exceed the federal poverty level. Despite the widespread potential impact, these consequences often remain “hidden from mainstream society…but they are nonetheless quite powerful.”
The solution? “Addressing the health care needs of former inmates,” Dr. Schnittker said, adding that this could be an “important step toward preventing further damage to the health care system.”
Study authors include the University of Minnesota’s Christopher Uggen and Suzy Maves McElrath, as well as Sarah K.S. Shannon from the University of Georgia. This research was funded in part by a Robert Wood Johnson Foundation Health Investigator Award to Dr. Schnittker and Dr. Uggen.
Penn Scientists Identify Key Genetic Factor That Keeps Moles From Turning Into Melanoma
Moles are benign tumors found on the skin of almost every adult. Scientists have known for years that a mutation in the BRAF gene makes them start growing, but until now haven’t understood why they stop. Now, researchers from the Perelman School of Medicine at the University of Pennsylvania have identified a major genetic factor that keeps moles in their usual non-cancerous, no-growth state. The study was published online first this summer in the journal Cancer Discovery.
“The BRAF mutation that stimulates the initial growth of moles also stimulates the production of a tumor suppressor protein, p15, which ultimately acts as a powerful brake on further cell division,” said senior author Todd W. Ridky, an assistant professor of dermatology at Penn. “It’s this cell division that ultimately allows the transition from a normal mole into melanoma. When mole cells lose the p15 brake, cells can start dividing again and can progress into cancer.”
For their study, Dr. Ridky and his colleagues developed a new model of human melanoma, using tissue engineering to make skin grafts containing human mole cells in which p15 was removed. When combined with other mutations known to be important for the development of melanoma and transplanted into mice, the p15 depleted cells progressed into melanoma.
“The model tissues are medically relevant because they used the naturally occurring human mole cells in the three-dimensional environment of living skin, which allows detailed functional studies – the field hasn’t had an experimental system like this before,” said lead author Andrew McNeal, a research specialist in Dr. Ridky’s lab. |