Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Cardiology (Page 1 of 3)

Fostering a Collaborative Research Environment in Peru

We are told time and time again that Duke is a global university, one that transcends borders and takes interdisciplinary education to the next level.

On Monday, I was able to experience this international mindset firsthand at the Peru Health Symposium, a conference that celebrated a decade of culminating research efforts by Duke in Peru.

The symposium was organized by Dr. William Pan, a professor of Global Environmental Health at Duke who has worked on many research projects in Peru ranging from reproductive health to tuberculosis. In his opening remarks, Pan said the trademark interdisciplinary nature of Duke has allowed it to succeed as a research institution in Peru, along with its affiliation to pioneers in Peruvian health/environmental research, like John Terborgh.

“We are standing on the shoulders of giants,” said Pan. During the first panel, several research projects were presented.

Field Work in Peru

Helena Frischtak conducting research with Peruvian children in the field.

Helena Frischtak, a 4th year medical student at UVA and former Doris Duke Fellow spent a year studying the neurological effects of mercury exposure on children. She performed basic neurological exams, along with cognitive tests amongst 5-11 year-old children, and preliminary data suggests potential impacts of mercury exposure on cognitive development.

Marlee Krieger of the Center for Global Women’s Health Technologies presented a cervical cancer treatment that brings colposcopy into the primary care setting. When one is screened for cervical cancer, a pap smear is first conducted and if abnormalities are detected, a colposcopy is performed and tissue is biopsied from the cervix. This multiple-step process is tedious, and the number of patients that return for the colposcopy often declines. By combining the steps into one visit and performing it with a simpler and cheaper device, testing efficiency has increased.

Maria Lazo Porras of Cayetano Heredia University (Lima’s prominent medical university) presented findings on the effects of migration from rural to urban regions on chronic disease. Her findings suggest a correlation between urbanization and obesity, but provided surprising results that indicate higher rates of hypertension and diabetes in rural communities.

Peru amazon

Illegal mining scars the Amazon’s lush forests and flushes mercury runoff into streams.

Students doing research in the Amazon presented posters of their findings to faculty members of the Nicolas School and DGHI.

The main theme resonating throughout the conference was the need for collaboration not only to address public/environmental health concerns, but to organize symposiums like this one. The culmination of efforts by the Center for Latin American and Caribbean Studies (CLACS), DGHI, and the Nicholas School have fueled the Peru project’s palpable success.

Below is the link to the documentary shown at the symposium:

http://www.daughterofthelake.pe/ – “Hija de la Laguna” (Daughter of the Lake), 2015. The documentary tells the story of how a Peruvian woman used her powers to stop illegal mining from destroying the lake in her community; a lake that to her, represents her mother’s spirit.

lola_sanchez_carrion_100hedPost by Lola Sanchez-Carrion

A Link Between Stress and Aging in African-Americans

A recent study finds that lifetime stress in a population of African Americans causes chemical changes to their DNA that may be associated with an increased risk of aging related diseases.

(Image: Rhonda Baer, National Cancer Institute)

(Image: Rhonda Baer, National Cancer Institute)

Using a previously established DNA-based predictor of age known as the “epigenetic clock,” researchers found that a cohort of highly-traumatized African Americans were more likely to show aging-associated biochemical signatures in their DNA’s epigenetic clock regions at an earlier age than what would otherwise be predicted by their chronological age.

These chemical alterations to DNA’s epigenetic clock were found to be a result of hormonal changes that occur during the body’s stress response and corresponded to genetic profiles associated with aging-related diseases.

The study was performed by researchers at the Max Planck Institute of Psychiatry in Germany, including Duke University adjunct faculty and psychiatrist Dr. Anthony S. Zannas. The findings were published in a recent issue of Genome Biology.

“Our genomes have likely not evolved to tolerate the constant pressure that comes with today’s fast-paced society,” says lead author Zannas.

Though it may come as no surprise that chronic stress is detrimental to human health, these findings provide a novel biological mechanism for the negative effects of cumulative lifetime stressors, such as those that can come with being a discriminated minority.

Epigenetics is the study of how environmental factors switch our genes on or off. The epigenetic clock is comprised of over 300 sites in our DNA that are subject to a certain chemical modification known as methylation, which physically prevents those sites from being expressed (i.e., turns them off). Conversely, areas within the epigenetic clock can also be de-methylated to turn genes on. Each methylation event can be thought of as a tick of the epigenetic clock’s metaphorical second-hand, corresponding to the passing of physiological time.

During times of stress, a family of hormones known as glucocorticoids becomes elevated throughout the body. These glucocorticoids cause the chemical addition or removal of methyl groups to areas of DNA that the authors found to be located in the same regions that comprise the epigenetic clock. What’s more, the specific changes in methylation were found to correspond with gene expression profiles associated with coronary artery disease, arteriosclerosis, and leukemias.

This link between stress, glucocorticoids, and the epigenetic clock provides evidence that lifetime stress experienced by highly traumatized African Americans promotes physiological changes that affect their overall health and longevity.

The authors make an important distinction between cumulative lifetime stress and current stress. A small number of instances of acute stress may result in a correspondingly small number of methylation changes in the epigenetic clock, but it is the cumulative methylation events from chronic stress that give rise to lasting physiological detriments.

Though the authors make no direct claims regarding the physiological effects of racial inequities prevalent in today’s society, the findings perhaps shed light on the health disparities observed between disadvantaged African American populations and more privileged demographics, including increased mortality rates for cancer, heart disease, and stroke.

KatyRiccione

Glucocorticoids become elevated during the body’s stress response and lead to changes in DNA methylation that promote the expression of genes associated with aging.
Illustration by Katy Riccione

Interestingly, the epigenetic effects of lifetime stress were blunted in individuals who underwent significant childhood trauma, suggesting that early trauma may trigger mechanisms of physiological resilience to chronic stress later in life. In other words, if racial minorities are more likely to face hardships during their upbringing, perhaps they are also better prepared to cope with the chronic stress that comes with, for instance, losing a job or ending a marriage.

Though the study relies on data from an African American cohort, Dr. Zannas believes that the same conclusions are likely applicable to other highly stressed populations: chronic stress leads to lasting changes in our epigenome that may increase our likelihood of aging-related diseases, while acute stress was not found to have any long-term epigenetic effects.

So a single tough calculus exam won’t shave years off of your life, but consistent 80-hour work weeks just may.

In a world where everyday stress is unavoidable, whether it be from the hardships faced as a minority or the demands of being a full-time student, what lifestyle choices can we make to limit the detriments to our health? Dr. Zannas emphasizes that the “solution is not to avoid all stressors, but to prevent excessive stressors when possible and to learn to live with unavoidable stress constructively.”

The study underscores the importance of stress management on our general well-being. Future research may highlight the direct chemical benefits to our epigenome that are afforded by mindfulness, psychotherapy, diet/exercise, and other modes of stress relief. “Learning to better cope with stress is the best way to reduce our physiological response to it and the resultant harmful effects.”

Katy_Riccione_100Guest Post by Katy Riccione, Ph.D. Candidate in Biomedical Engineering

Measuring the Mechanical Forces of Disease

“All these complicated diseases that we don’t have a good handle on — they all have this mechanical component. Well why is that?”

Brent Hoffman is an assistant professor of biomedical engineering

Brent Hoffman is an assistant professor of biomedical engineering

This is exactly the question Brent Hoffman, Duke biomedical engineering assistant professor, is helping answer. Many of the common diseases that we fear have a mechanical component. In asthma attacks, a chemical or physical stimulus causes the air channels in the lung to shut as the muscles that control the width of the channel contract– the mechanical component.

Another example is atherosclerosis, commonly known as the hardening of the arteries, the leading killer in developed countries. Instead of air flow, blood flow is affected as the walls of the blood vessels get thicker. Factors such as smoking, being overweight, and having high cholesterol increase the chance of getting this disease. However, examining the mechanical portion, the plaques associated with atherosclerosis tend to occur at certain parts of the blood vessels, where they branch or curve. You can think of it like a hose. When you kink a hose or put your thumb over the nozzle, the fluid flows in a different way. Hoffman said there are similar stories concerning mechanical portions of major diseases, such as muscular dystrophy and breast cancer.

Hoffman's lab is building tension sensors to measure forces during collective cell migration.

Hoffman’s lab is building tension sensors to measure forces during collective cell migration.

This all sounds very biological, so why is he in the engineering department? As mechanobiology is a new field, there are few tools available for reporting a protein’s shape or its forces inside living cells. Hoffman makes the tools enabling the study of mechanobiology. During Hoffman’s postdoctoral research, he worked on recording forces across proteins in living cells, their natural environment. Now, he’s expanding that technology and using it to do basic science studies to understand mechanobiology.

Hoffman said he hadn’t planned this. From high school, he knew he wanted to be an engineer. As an undergraduate, Hoffman interned at IBM, where he worked on the production of chip carriers using copper-plating. Hoffman was able to apply knowledge, such as changing pH to get various amounts of copper, and make everything perform at optimal performance, but he wanted to know more about the processes.

So he set out to get his Ph.D in process control, which involves deciding how to set all the numbers and dials on the equipment, how large the tank should be, what pressure and temperature should be used, etc. in chemical plants. Hoffman was set on the path to become a chemical engineer. However, during the first week of graduate school, he attended a biophysics talk, in which he understood very little. Biophysics interested Hoffman, so he went from intending to do research on one of the most applied engineering projects on campus to arguably one of the least applied in a week. This was the beginning of his biophysics journey. However, as his Ph. D was much more heavily interested in the physics aspect, Hoffman chose to do his postdoc in cell biology to balance his training. Mixing everything together, he got biomedical engineering.

Hoffman reflects that his decisions were logical, but he had not planned to take the route he did. Hoffman cautions that it is better to have a plan than not because if you do not plan, you won’t know where you are going. However, he advises that since a person learns more about likes and dislikes as one proceeds on their route, students should not be afraid to incorporate what they learn into their plans.

Hoffman’s journey is characterized by finding and doing what he enjoyed. Trained in both the worlds of physics and biology, but never intending to pursue a future in either, Hoffman is uniquely suited for his current position in the revolutionary emerging field of mechanobiology. He is able to put his biology hat on and his physicist hat on for a bit, while the engineer in him is thinking, “is any of this practical?”
“If you had to pick out the key to my success, it would be doing that,” Hoffman said.

AmandaLi_100Guest Post by Amanda Li, a senior at the North Carolina School of Science and Math

 

E-cigarettes might help smoking cessation

Research has shown that nicotine replacement therapies such as the patch, gum lozenges and nasal spray are only 25 percent effective in smoking cessation within the first year of use.

Jed Rose, Ph.D.

Jed Rose, Ph.D.

Jed Rose, Director of the Duke Center for Smoking Cessation, thinks the use of e-cigarettes, or electronic nicotine delivery systems (ENDS) could be a better way to quit smoking.

Rose spoke Tuesday in a session sponsored by the Center on Addiction and Behavior Change.

He said nicotine replacement is delivered at a slower rate and a lower dose than in actual cigarettes, so it fails to curb craving among smokers. Replacements also don’t replicate one of the main sensory behaviors of smoking: inhalation.

Rose discussed a study in which he and his colleagues anesthetized participants’ airways to see if they could detect the smoke, while keeping the same dose of nicotine to the brain. When participants couldn’t feel the smoke as much, there were more cravings for cigarettes and less satisfaction.

An e-cigarette vaporizes nicotine with battery power, avoiding the combustion byproducts of burning tobacco. (TBEC Review, via Wikimedia Commons

An e-cigarette vaporizes nicotine with battery power, avoiding the combustion byproducts of burning tobacco. (Vaping360, via Wikimedia Commons

They’ve also found that replacement treatments, when given on a temporary basis of just one year, often resulted in relapse.

So what does an e-cigarette actually do? The battery of this electronic cigarette heats an oil that vaporizes the nicotine with a substance called propylene glycol. The gas is released and condenses immediately into a cloud of smoke.

Why is the e-cigarette safer? It’s the combustion products in smoke, rather than the nicotine, that are responsible for most smoking-related disease. Rose cited the 2010 Surgeon General’s Report that backs up this claim that nicotine itself is not responsible for cardiovascular problems or cancers.

GUIDE-Inside-a-eCig

Rose thinks that e-cigarettes could be the best of both worlds, allowing smokers the same sensory effects they enjoy, while possibly avoiding other health hazards of regular cigarette smoking.

Rose also addressed concerns about formaldehyde being present in e-cigarettes. He says this is rare, and only occurs with e-cigarettes that have higher voltages which causes overheating to occur. While there is evidence from two trials that the new devices help smokers to stop smoking long-term compared with placebo, unfortunately, very few studies have looked at this issue. Rose also shares concerns that the new product could be picked up by youth who wouldn’t normally smoke cigarettes, or serve as a gateway between e-cigarettes and real ones.

In the end, however, he thinks this product has the potential to be highly effective in treating addiction, and hopes it will be evaluated further.

“The agency that has to sort through this is the FDA,” he said. “They have to prove that it will help society as a whole. It has to benefit the health of the population.”

 

madeline_halpert_100By Madeline Halpert

Synergizing Partnerships of the Heart

Guest post by Dharshini Subbiah

With diseases like heart disease, high blood pressure and diabetes on the rise in Asia and throughout the world, six Duke University faculty made the trip to Singapore last week to be a part of the symposium, “Synergizing Biomedical Research in Cardiovascular and Metabolic Disorders.”

The symposium featured experts presenting their research related to the clustering of metabolic syndrome, diabetes, hypertension, hyperlipidemia and cardiovascular disease — a global epidemic that is emerging as a major cause of mortality and human suffering in Asia.

A major objective of the meeting was to develop productive partnerships and collaborations to enhance research in the field. The Duke faculty were joined by colleagues from the Duke-National University of Singapore Graduate Medical School (Duke-NUS), SingHealth, A*Star, the National University of Singapore, the National University Health System, and the NTU Lee Kong Chian School of Medicine.

“I dare say it would be difficult to go anywhere in the world and find a scientific program with the breadth and quality of what we’ve heard during this Symposium. After reflecting on the various presentations and what people are doing, I believe there are many potential areas where we can work together productively,” declared Duke-NUS Dean-designate Tom Coffman.

Professor Coffman, who for many years was the Chief of Nephrology at Duke University, was both optimistic and clear about his expectations, “I think it’s on us, to take advantage of the opportunities to bring together Duke and Singapore in order to harness our resources, talents and energy to do some great things. We can have a real impact in this area and improve what happens to our patients.”

The Symposium was held on January 19-20 and was the first in a series of activities marking the tenth year of Duke-NUS.

 

Working in concert for the future of medicine are researchers from Duke-NUS, SingHealth, A*Star, the National University of Singapore, the National University Health System, and the NTU Lee Kong Chian School of Medicine. Shown on the extreme left is Thomas Coffman, M.D., Director of the Cardiovascular Research Center at Duke Medicine.

Working in concert for the future of medicine are researchers from Duke-NUS, SingHealth, A*Star, the National University of Singapore, the National University Health System, and the NTU Lee Kong Chian School of Medicine. Shown on the extreme left is Thomas Coffman, M.D., Director of the Cardiovascular Research Center at Duke Medicine.

Duke Researchers Cited for Their Influence

 

We are the champions, my friend.

We are the champions, my friend.

By Karl Leif Bates

A new compilation of the world’s most-cited scientists just released by Thomson Reuters (our friends from March Madness), shows that 32 Duke researchers are in the top one percent of their fields.

There are 3215 most-cited scientists on the list, so perhaps that makes Duke the one percent of the one percent?

Most-cited means a particular paper has been named frequently in the references by other papers in that field.

And that “is a measure of gross influence that often correlates well with community perceptions of research leaders within a field,” Thomson Reuters says. The database company admits their study methodology does favor senior authors who have had their papers out there longer, but there are quite a few younger Duke researchers in this list too.

From the Medical Center, the tops in citations in clinical medicine are cardiologists  Eric Peterson, Robert Califf, Christopher Granger, and Eric Magnus Ohman. Michael Pencina, a biostatistician at the Duke Clinical Research Institute, is also most-cited in clinical medicine.

Perhaps not surprisingly, Nobel laureate, biochemist, and father of the G-protein coupled receptor Robert Lefkowitz made the list in pharmacology and toxicology.

Barton Haynes and David Montefiori of the Duke Human Vaccine Institute are listed in the microbiology category.

Medical School basic scientist Bryan Cullen of Molecular Genetics and Microbiology was cited in microbiology.

In psychiatry/psychology, A. John Rush, the vice dean for clinical research at Duke-NUS School of Medicine in Singapore, made the list, as did Richard Keefe, Joseph McEvoy of psychiatry and Avshalom Caspi, and Terrie Moffitt of Psychology & Neuroscience in Arts & Sciences.

Also from Trinity College of Arts and Sciences, Ahmad Hariri and HonaLee Harrington of Psychology & Neuroscience also made the list in psychiatry/psychology. Benjamin Wiley was oft-cited in Chemistry, James Berger and Ingrid Daubechies in mathematics, and plant biologists Philip Benfey, Xinnian Dong and Tai-Ping Sun in the category of plant and animal science.

Sanford School of Public Policy Dean Kelly Brownell is on the list in general social sciences, along with Arts & Sciences sociologist James Moody and nutrition researcher Mary Story of community and family medicine and the Duke Global Health Institute.

Nicholas School of the Environment researchers Robert Jackson and Heather Stapleton were cited the environment/ecology category.

From the Pratt School of Engineering, David R. Smith was cited in the physics category and Jennifer West in materials science.

The economics and business category includes Dan Ariely along with his Fuqua School of Business colleagues Campbell Harvey and Arts & Sciences economist Tim Bollerslev.

The Thomson Reuters analysis is based on their Web of Science database. This is the first time it has been done since 2001, when there were 45 Duke names on the list (including five that appeared again this time), but the methodology has changed somewhat.

UPDATE – There’s now a full PDF report  from Thomson Reuters for download – http://sciencewatch.com/sites/sw/files/sw-article/media/worlds-most-influential-scientific-minds-2014.pdf

 

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