Category: Cardiology Page 1 of 3

Only Mostly Dead? The Evolving Ethics of Evaluating Death

On March 31, 2023

In Behavior/Psychology, Biology, Biomedical Engineering, Cardiology, Lecture, Medicine, Religion, Responsible Conduct

I recently had the pleasure of attending Professor Janet Malek’s lecture: Only Mostly Dead? The Evolving Ethical Evaluation of Death by Neurologic Criteria, a lecture sponsored by the Trent Center for Bioethics, Humanities & History of Medicine.

Dr. Malek is an associate professor in the Duke Initiative for Science & Society, and at the Baylor College of Medicine Center for Medical Ethics and Health Policy.

We don’t often talk about death. On the surface, it seems like it would be a straight-forward concept. You’re either dead, or you’re not dead. Right? It turns out that clinically defining death is not so simple.

Popular media has some grasp on the ambiguity of the definition of death. Remember this scene from the popular movie, The Princess Bride? Suspecting that the protagonist is dead, his friends bring him to a miracle-worker and have the following conversation.

Miracle Max: “Whoo-hoo-hoo, look who knows so much. It just so happens that your friend here is only MOSTLY dead. There’s a big difference between mostly dead and all dead. Mostly dead is slightly alive. With all dead, well, with all dead there’s usually only one thing you can do.

Inigo Montoya: What’s that?

Miracle Max: Go through his clothes and look for loose change.

In real life, death used to be determined by cardiopulmonary criteria – when the heart and lungs stop working. In recent decades the idea that death can be determined using neurologic criteria – when the brain stops working – has gained acceptance. As neuroscience and technology has evolved, so too have our definitions. Now that we know more about how the brain works, we know that there may be some brain activity even after a person has met the criteria for death by neurologic criteria (DNC). This leads to philosophically rich and practically relevant questions of ethics – for example, when do we stop providing life-sustaining care? In the field of bioethics and beyond, there is high demand for discussion on this topic.

There has been controversy over defining death since the 1650’s — when a woman named Anne Greene woke up after being hanged. It wasn’t until the 1980’s that a consensus definition of death was first identified. Here is a brief history:

1950s

Widespread availability of ventilators led to the identification of a state described as death of the neurological system.

1960s

Advances in organ transplantation foster discussion on the ethics of defining death.
A committee at Harvard Medical School examined the definition of Brain Death. They created a definition of “Irreversible Coma,” which focused on loss of neurological function.

1980s

The 1980 Uniform Determination of Death Act (UDDA) provided a legal basis for clinically determining death as: an individual who has sustained either 1) irreversible cessation of circulatory and respiratory functions OR 2) irreversible cessation of functions of the entire brain.
1981: President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research report. Findings are centered on questions of functioning of the organism as a whole and the brain’s role in coordinating it.

1990s-2000s

Clinicians arrive at general agreement that a patient in a state of coma or unresponsiveness, without brainstem reflexes and who fails an apnea test is dead by neurologic criteria. Largely it is accepted that “brain death is death” but there is not complete consensus.

2010-late

2013: Case of Jahi McMath. A 13-year old girl was declared “brain dead” in California, and a death certificate was issued. However, the family fought to have her maintained on life support. They moved to New Jersey, the only state which recognized objections to brain death, and the “brain dead” declaration was reversed. Jahi lived there for 4 years before passing away. This famous case caused people to reconsider the concept of brain death.

2020s:

Recent innovations in heart transplantation technology will likely challenge the acceptance of the Dead Donor Rule (DDR) which requires that an individual is clinically declared dead before vital organs are removed for transplantation.
2021: Assembly of the Determination of Death Committee, tasked with updating the Uniform Determination of Death Act (UDDA). Duke faculty (and founding director of Science & Society) Nita Farahany, is involved with this process.

What ethical issues and practical questions challenging Death by Neurologic Criteria (DNC) today? Dr. Malek shared the following case.

Following a tragic car accident, Ms. Jones, a 20-year-old college student, was brought to the hospital, having suffered significant anoxic brain injury. The medical team determined that she met criteria for DNC. However, her family refused to allow for further testing. Several days passed. Ms. Jones was maintained on life support, during which she did not show signs of improvement. After several difficult conversations, the family consented for assessment and Ms. Jones was declared dead — using the criteria associated with DNC.

What is the proper amount of time to continue life-sustaining treatment if a physician suspects the patient will never recover?

Although this may sound like an uncommon occurrence, nearly half of neurologists have been asked to continue neurologic support for patients that may meet criteria for DNC.

Obligating life support for patients suspected of meeting DNC, either through the family’s refusal for testing or by direct request, would likely result in ethical harms such as violation of the dignity of decedent, unjustly using scarce resources, or causing moral distress in caregivers.

However, it may be permissible to maintain life support in these situations. Dr. Malek says that we do not yet have a good ethical framework for this. Reasonable accommodations that are in line with professional guidelines probably have minimal impact, and might provide some psychosocial benefits to families.

Is consent required to test for DNC? Should it be?

Legal and professional standards favor the idea that testing for DNC likely falls under the category of implied consent, which assumes that a person would want reasonable medical care in the event of unconsciousness. In fact, 80% of neurologists think that getting consent for these evaluations is unnecessary.

These are extremely difficult questions, and there is continuing controversy over what the correct answers should be. Dr. Malek advises medical experts to work with healthcare administrators to develop clear institutional policies.

Post by Victoria Wilson, 2023 MA student in Bioethics & Science Policy

Kinsie Huggins: the Future Doctor Who Could Shot-Put

By Camila Cordero

On March 29, 2022

In Biology, Cardiology, Data, Field Research, Genetics/Genomics, Global Health, Medicine, Policy, Students

From shot-putting, to helping conduct two research studies, to being selected for a cardiology conference, meet: Kinsie Huggins. She is from Houston, Texas, currently majoring in Biology and minoring in Psychology with a Pre-Med track here at Duke. With such a simple description, one can already see how bright her future is!

“I want to be a pediatrician and work with kids,” Huggins says. “When I was younger, I lived in Kansas, and in my area, there were no black pediatricians. My mother decided to go far to find one and I really bonded with my pediatrician. One day, I made a pact with her in that I would become a pediatrician too so that I can also inspire other little girls like me of my color and other minority groups.”

Having such a passion to let African-American and minority voices be heard, Huggins is also part of the United Black Athletes, using her shot-put platform to make sure these voices are heard in the athletics department.

And while she may be a top-notch sportswoman, she is also just as impressive when it comes to her studies and research. One of her projects focuses on the field of nephrology – the study of kidneys and kidney disease. She and a pediatric nephrologist are currently working on studying rare kidney diseases and the differences in DNA correlating to these diseases.

Kinsie is also a researcher at GRID (Genomics Race Identity Difference), which studies the sickle cell trait in the NCAA. With the sudden deaths of college athletes from periods of over-exhaustion during conditioning, there has been a rise in attention of sickle cell trait and its impact on athletes. At first, the NCAA implemented a policy that made it mandatory for college athletes to get tested for sickle cell in 2010, but some were wary about the lack of scientific validity in such claims. Now, the NCAA has funded GRID to conduct such research.

_{The difference of Normal red blood cell and sickle cell (CDC).}

“We are analyzing the policy (athletes need to be tested for sickle cell), interviewing athletes in check-ups, and looking at data to see if the policy is working out for athletes and their performance/health,” Huggins explains.

With such an impressive profile, it doesn’t go without saying that Huggins didn’t go unnoticed. The American College of Cardiology (ACC) select high school and college students interested in the field of medicine and have them attend a conference in Washington D.C. to hear about research presentations, groundbreaking results of late-breaking clinical trials, and lectures in the field. Having worked hard, Huggins was selected to be part of the Youth Scholars program from the ACC and was invited to the conference on April 2-4.

Let’s wish Kinsie the best of luck at the conference and on her future research!

Post by Camila Cordero, Class of 2025

Duke has 38 of the World’s Most Highly-Cited Scientists

By Karl Bates

On November 16, 2021

In Behavior/Psychology, Biology, Biomedical Engineering, Cardiology, Climate/Global Change, Engineering, Environment/Sustainability, Faculty, Immunology, Medicine, Neuroscience, Physics

Peak achievement in the sciences isn’t measured by stopwatches or goals scored, it goes by citations – the number of times other scientists have referenced your findings in their own academic papers. A high number of citations is an indication that a particular work was influential in moving the field forward.

Nobel laureate Bob Lefkowitz made the list in two categories this year.

And the peak of this peak is the annual “Highly Cited Researchers” list produced each year by the folks at Clarivate, who run the Institute for Scientific Information. The names on this list are drawn from publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index – the most-cited of the cited.

Duke has 38 names on the highly cited list this year — including Bob Lefkowitz twice because he’s just that good — and two colleagues at the Duke NUS Medical School in Singapore. In all, the 2021 list includes 6,602 researchers from more than 70 countries.

The ISI says that US scientists are a little less than 40 percent of the highly cited list this year – and dropping. Chinese researchers are gaining, having nearly doubled their presence on the roster in the last four years.

“The headline story is one of sizeable gains for Mainland China and a decline for the United States, particularly when you look at the trends over the last four years,” said a statement from David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information. “(This reflects) a transformational rebalancing of scientific and scholarly contributions at the top level through the globalization of the research enterprise.”

Without further ado, let’s see who our champions are!

Biology and Biochemistry

Charles A. Gersbach

Robert J. Lefkowitz

Clinical Medicine

Pamela S. Douglas

Christopher Bull Granger

Adrian F. Hernandez

Manesh R.Patel

Eric D. Peterson

Cross-Field

Richard Becker

Antonio Bertoletti (NUS)

Yiran Chen

Stefano Curtarolo

Derek J. Hausenloy (NUS)

Ru-Rong Ji

Jie Liu

Jason W. Locasale

David B. Mitzi

Christopher B. Newgard

Ram Oren

David R. Smith

Heather M. Stapleton

Avner Vengosh

Mark R. Wiesner

Environment and Ecology

Emily S. Bernhardt

Geosciences

Drew T. Shindell

Immunology

Edward A. Miao

Microbiology

Barton F. Haynes

Neuroscience and Behavior

Quinn T. Ostrom

Pharmacology and Toxicology

Robert J. Lefkowitz

Plant and Animal Science

Xinnian Dong

Sheng Yang He

Philip N. Benfey

Psychiatry and Psychology

Avshalom Caspi

E. Jane Costello

Honalee Harrington

Renate M. Houts

Terrie E. Moffitt

Social Sciences

Michael J. Pencina

Bryce B. Reeve

John W. Williams

Post by Karl Bates

New Blogger Vibhav Nandagiri: The Curious Student Blogger

By Vibhav Nandagiri

On September 27, 2021

In Biomedical Engineering, Cardiology, Global Health, Neuroscience, Science Communication & Education, Students

Hey everyone! My name is Vibhav Nandagiri, I use he/him/his pronouns, and I’m currently a first-year student at Duke. Amidst the sea of continuous transition brought upon by college, one area of my identity that has stayed fairly constant is my geography. I’ve lived in North Carolina for sixteen of my eighteen years, and my current home lies just twenty minutes from campus in sunny, suburban Cary, NC.

The two missing years are accounted for through my adventures in my parents’ hometown–Hyderabad, India–as a toddler. Spending some of my earliest years surrounded by a large and loving family impacted my life profoundly, forever cementing a strong connection to my emotional, cultural, and linguistic roots.

The latter had a secondary impact on me, one I wouldn’t discover until my parents enrolled me in preschool after returning to the States. With hubris, I marched into my first day of class, ready to seize the day, until I soon discovered an uncomfortable fact: I couldn’t speak English. I am told through some unfortunate stories that I struggled considerably during my first month in a new, Anglicized environment; however, I soon learned the quirks of this language, and two-year-old me, perhaps realizing that he had some catching up to do, fully immersed himself in the English language.

Nowadays, I read quite a bit. Fiction and journalism, academic and satire, I firmly believe that all styles of literature play a role in educating people on the ebbs and flows of our world. In recent years, I’ve developed a thematic fascination with the future. The genre of far-future science fiction, with its rich exploration of hypothetical advanced societies, has led me to ask pressing questions about the future of the human species. How will society organize itself politically? What are the ethical implications of future medical advancements? Will we achieve a healthy symbiosis with technology? As a Duke Research Blogger, I hope to find answers to these questions while getting a front-row, multidisciplinary seat to what the future has to offer. It’s an invigorating opportunity to grow as a writer and communicator, to have my curiosity piqued on a weekly basis, to understand the futuristic visions of innovators at the top of their field.

Prior to Duke, I had the opportunity to conduct research at the Appalachian State University Pediatric Exercise and Physiology Lab, where I co-authored a published paper about adolescent fat metabolism. Not only was I introduced to the academic research process, but I also learned the importance of communicating my findings clearly through writing and presentations. I intend to bring these valuable lessons and perspectives to the Duke Research Blog.

Beyond exercise science, I am intrigued by a diverse range of research areas, from Public Health to Climate Change to Business to Neuroscience, the latter of which I hope to explore further through the Cognitive Neuroscience and Law FOCUS. I was drawn to the program for the opportunity to build strong relationships with professors and investigators; I intend to approach my work at the Duke Research Blog with a similar keenness to listen and connect with researchers and readers alike. When I’m not reading or typing away furiously at my computer, you can find me hitting on the tennis courts, singing Choral or Indian Classical music, or convincing my friends that my music taste is better than theirs.

Post By Vibhav Nandagiri, Class of 2025

Physician-Scientist Takes the Long View and Sets Her Sights High

By Guest Post

On January 8, 2021

In Cardiology, Guest Post, Medicine

Dr. Bryan Batch, a Duke endocrinologist and researcher, studies treating metabolic disorders (like diabetes) with non-pharmacological approaches. But, she says, her parents’ medical professions, and the hard work that went into them, resulted in her not wanting to pursue science at all as a child.

When she took biology in middle school however, it clicked. It didn’t feel like “the slog of math,” she says, because she enjoyed studying life in its different forms. This infatuation with science combined with a love for other people pushed her to pursue medicine.

Now, Dr. Batch focuses on racial disparities. She says that a huge issue with disparities, whether they involve race, poverty, food insecurity, educational opportunity, or health insurance, is that they are often driven by policy. “We are not trained to know how to affect change in policy in medical school — it’s not something we are taught. But I do think if physicians got more involved in politics and policy we would be able to make significant positive impact.”

What she does try to do is adapt to individual patient needs in the moment. Her work at Duke signifies what she, as a healthcare provider, can do within the time spent with patients to interact in the best way possible. For example, she can understand if someone has a literacy issue and adapt her methods of explanation so that their literacy doesn’t hinder their understanding. While it can be challenging for one person to change systemic issues or share lived experiences with people of different backgrounds, Dr. Batch makes every effort to create a comfortable environment where she is able to leave a positive impact.

These impacts have no doubt been affected by COVID-19, which Dr. Batch describes as one of the most challenging experiences in her twenty years of practicing medicine. Although telephone and video conferencing have been available for years, Dr. Batch explains that only now is there a drive to put them to use. “It was like someone came up behind you and just whacked you on the head,” she says — no warning, no time to get organized.

Dr. Batch feels lucky to be in endocrinology, where there is flexibility for remote visits. Yet, even when patients do have the chance to have an in-person visit, some don’t want to. If they do, the physical separation, masks, and face shields create a feeling of distance. Dr. Batch spends much of her clinical time at the Durham Veteran Affairs Hospital, across the street from Duke Hospital, where many hearing-impaired patients have difficulty understanding her words because her mask takes away the ability to read lips.

Dr. Batch says that even after the pandemic has passed, more than 30% of visits may remain over the telephone, which can give patients increased access to their doctors.

The challenges have infiltrated her research too, where now the only people she can bring in are those who need to visit the VA Medical Center for another reason anyway, like going to the eye doctor. Overall, she says, she has been surrounded by phenomenal people who rolled up their sleeves and said “let’s get it done.” Still, it has been exhausting.

The Durham Veterans Administration Medical Center, where Dr. Batch conducts most of her practice.

To her, family is everything, and she tries her best to stay in touch with the people who matter most as a way to get through it all.

Even before COVID-19, Dr. Batch has been intentional about living her life to the fullest and staying true to her core values. If that means rescheduling things at work to be with her kids, she is unapologetic. She chose endocrinology as a specialty in part because it’s very family-oriented, and she feels lucky to have colleagues who understand the flexibility she values. Her ultimate goal is to leave a mark on the world but she also wants her happiness to come from what matters, so she stays close to her big family and lots of friends.

While sacrifices are inevitable in any career, Dr. Batch tries not to make large ones on the homefront. She takes it day by day, week by week, she says, to make it such that “work” and “life” are in harmony as much as possible. It is easy to get caught up and have the years go by, one day realizing that the important people have pulled away. Dr. Batch is deliberate about making the time for these people, including her two children and husband.

Dr. Batch is a role model for young people, particularly for women of color. She shared an anecdote about her inattentive high school counselor, to whom she went for a signature on her college application list. Seeing Yale, Harvard, and Brown, he told her that she was “reaching too high.” Batch responded, “I’m not here for your opinion on this list. I’m here for you to sign this form..

She ended up at Yale.

She says she had the courage to talk back to the counselor because her parents instilled the idea of working hard and pushing higher. What matters, she says, is believing in yourself and surrounding yourself with people who believe in you.

Unfortunately, Batch said, underestimation by others resonated throughout her college, medical school, residency, and fellowship, because she is a woman or because she is Black.

At the end of the day, Dr. Bryan Batch never let other people define her experience but instead allowed her hard work to prove her value and propel her to always reach higher.

Guest Post by Viha Patel, Class of 2021, NC School of Science and Math

Designing Tomorrow, One Healthcare Innovation at a Time

By Cydney Livingston

On October 28, 2019

In Biomedical Engineering, Business/Economics, Cardiology, Engineering, Medicine

Imagine a live, health-focused version Shark Tank open to the public: presentations from real health professionals, presenting real innovations they developed to address real health care issues. And yes, there are real money awards at stake.

It’s the 2019 Duke Health Innovation Jam.

At ten minutes ‘til show time, people gather in small groups clothed in suits, business attire, and white coats. They chat in low voices. The hum of comfortable conversation buzzes through the room. The sixth floor of the Trent Semans Center is quite the setting. Three sides of the room are encapsulated in glass and you can easily see an expansive view of both Duke’s West and Medical campuses, as well as luscious green trees comprising parts of Duke’s Forest. Naturally, there is a glorious view of the Chapel, basked in sunlight.

This light finds its way into the room to shine on various research posters at the back displayed on a few rows of mobile walls. Though a few strays meander through the stationary arrangements – stopping to look more closely at particular findings – most people make their way into the room and find a seat as the minutes dwindle away. The hum grows and there is a bit of anticipatory energy among those readying themselves to present.

At three minutes after 10, the program director of the Duke Institute for Health Innovation, Suresh Balu, takes position at the front of the room, standing before the small stage at center that is surrounded by lots of TV monitors. No seat in the room is a bad one. Balu indicates that it is time to begin and the hum immediately dissipates. He explains the general format of the event: six pitches total, five minutes to present, eight minutes to answer questions from investors, a show-of-hand interest from investors, and transition to the next pitch, followed by deliberation and presentation of awards.

After a round of thanks, introduction of the emcee – Duke’s Chief of Cardiology, Dr. Manesh Patel – the curtains opened – figuratively – on Duke’s fifth annual Innovation Jam.

Groups presented on the problems they were addressing, their proposed innovations, and how the innovations worked. There was also information about getting products into the market, varying economic analysis, next steps or detailed goals for the projection of the projects, and analysis of the investment they are currently seeking and for what purposes.

The first group pitched an idea about patient-centric blood draw and suggest a device to plug into existing peripheral draws to reduce the frequent poking and prodding that hospital patients often experience during their hospital stay when blood is needed for lab tests. Next up was a group who designed an intelligent microscope for automated pathology that has a programmable system and uses machine learning to automate pathological blood analysis that is currently highly time consuming. Third at bat was a group that made a UV light bag to clean surgical drain bags that frequently become colonized with bacteria and are quite frankly “nasty” – according to the presenter.

Batting cleanup was PILVAS – Peripherally Inserted Left Ventricular Vent Anticoagulation System – which is a device that would be accessory to VA ECMO support to reduce thromboembolism and stroke that are risks of ECMO. Fifth was the ReadyView and ReadyLift, a laparoscopic tool set that is much cheaper than current laparoscopic tools and methods, and because of its ability to be used with any USB compatible laptop, it would increase access to laparoscopic surgery in countries that have a high need for it. Last, but not least, was an innovation that is the first synthetic biometric osteochondral graft for knee cartilage repair that hopes to improve knee osteoarthritis surgical care as the first hydrogel with the same mechanical properties of cartilage.

Following a quick ten-minute break for investors to huddle around and discuss who should win the awards – $15,000 for Best Innovation and $15,000 for Best Presentation – the winners were announced. Drumroll, please.

ReadyView won Best Presentation and the synthetic osteochondral graft won Best Innovation. A pair of representatives from Microsoft were also in attendance – a first for the Innovation Jam – and awarded SalineAI, the group who designed the intelligent microscope with an independent award package.

Patel, the emcee, says we are in the midst of a fourth industrial revolution.

“What is the biggest cinema in the world?” Patel asked. “Netflix,” he says. Industries are reimagining themselves and healthcare is no exception.

What is the best healthcare system of the future going to look like? Of course, we really don’t know, but there are certainly people who are already doing more than just think about it.

Using Genetic Clues to Reform Cardiac Care

By Anne Littlewood

On February 20, 2019

In Biology, Cardiology, Genetics/Genomics, Medicine

Experiencing cardiac arrest can be compared to being in a hot air balloon in a room that is rapidly filling with water. You are trapped, desperately aware of the danger you are in, and running out of time.

Andrew Landstrom, PHD, MD, shared this metaphor with his audience in the Duke Medicine Pavilion last Thursday, and a wave of empathy flooded through his listeners. He works as an Assistant Professor of Pediatrics in Duke University’s School of Medicine, and devotes his time and energy to studying the genetic and molecular causes of sudden cardiac death in the young.

Andrew Landstrom, PHD, MD (Photo from Duke Center for Applied Genomics and Precision Medicine)

For families of children who have died suddenly and unexpectedly, the worst thing of all is hearing their doctors say, “we have no idea why.” A third of sudden death cases in children have negative autopsies, which means these children die with no explanation.

When faced with an inconclusive autopsy, everyone wants answers. Why did these children die? How do we know it’s a problem with the heart? What can be done about it? What does it mean for the siblings of the child who died?

It has since been discovered that many of these unexplained deaths are actually the result of cardiac channelopathies, which are DNA mutations that cause ion channel defects in heart cell proteins. These mutations can mess up the electrical activity of the heart and cause a heart to beat in an irregular rhythm, which can have fatal consequences. Since this is a molecular problem, and not a structural one, it cannot be identified with a conventional autopsy, and requires a deeper level of genetic and molecular analysis.

One type of channelopathy is a condition known as CPVT, which is short for catecholaminergic polymorphic ventricular tachycardia. This potentially life-threatening genetic disorder is the result of a point mutation in the genome, which means that one tiny nucleotide being changed in the DNA can lead to the single most fatal arrhythmia (irregular heart rhythm) known.

Sixty percent of children suffering from CPVT have a mutation in their RYR2 gene. This gene encodes for a protein that is found in cardiac muscle, and is a key player in how calcium is processed in heart cells. The mutated version of this gene results in proteins that let way too much calcium flood the cell, which can cause fatal changes in heart rhythm.

Dr. Landstrom has been using genome research to identify and explain sudden cardiac death in children, but the human genome doesn’t always provide straightforward answers. The problem is, a mutation in the RYR2 gene doesn’t always mean a person will have CPVT, and having an incidental RYR2 gene is much more common than being diagnosed with CPVT. Dr. Landstrom is studying this gene to try to figure out which variants are pathologic, and which are physiological.

“The human genome is a lot more confusing than I think I gave it credit for, and we’re just learning to deal with that confusion now,” he admitted to his audience Feb. 14.

The Components of the Human Genome (photo from NHS National Genetics and Genomics Education Centre)

If a variant is falsely identified as pathologic, a patient will be given incorrect therapies, and suffer through unnecessary procedures. However, if a variant is falsely identified as physiological, and the patient isn’t given the necessary treatment, there will be no mitigation of the patient’s life threatening disease. Neither of these are good outcomes, so it’s very important to get it right. The current models for predicting pathogenicity are poor, and Dr. Landstrom is looking to design new model that will be able to avoid the personal, subjective opinions of human doctors and determine if a variant is pathologic or not.

Could serotonin levels be used to predict an infant’s vulnerability to SIDS? (photo from Elmedir, Wikimedia Commons)

Another area that is of interest to Dr. Landstrom is the problem of Sudden Infant Death Syndrome (SIDS), which affects about six in every 10,000 infants, and cannot be diagnosed before death. He is on the search for a biomarker that would be able to predict an infant’s vulnerability to SIDS, and thinks that these deaths may be related to elevated levels of serotonin. Finding a marker like this would allow doctors to save many healthy infants from unexplained death. Dr. Landstrom knows its not easy research and admitted “we have to fail — we are meant to fail,” on the path to success. He is very aware of both the ethical complexity and the exciting implications of genome research at Duke, and committed to converting his research into patient care.

Post by Anne Littlewood

Researchers Get Superman’s X-ray Vision

By Robin Smith

On February 2, 2018

In Animals, Biology, Cardiology, Computers/Technology, Engineering, Students, Visualization

X-ray vision just got cooler. A technique developed in recent years boosts researchers’ ability to see through the body and capture high-resolution images of animals inside and out.

This special type of 3-D scanning reveals not only bones, teeth and other hard tissues, but also muscles, blood vessels and other soft structures that are difficult to see using conventional X-ray techniques.

Researchers have been using the method, called diceCT, to visualize the internal anatomy of dozens of different species at Duke’s Shared Materials Instrumentation Facility (SMIF).

There, the specimens are stained with an iodine solution that helps soft tissues absorb X-rays, then placed in a micro-CT scanner, which takes thousands of X-ray images from different angles while the specimen spins around. A computer then stitches the scans into digital cross sections and stacks them, like slices of bread, to create a virtual 3-D model that can be rotated, dissected and measured as if by hand.

Here’s a look at some of the images they’ve taken:

See-through shrimp

If you get flushed after a workout, you’re not alone — the Caribbean anemone shrimp does too.

Recent Duke Ph.D. Laura Bagge was scuba diving off the coast of Belize when she noticed the transparent shrimp Ancylomenes pedersoni turn from clear to cloudy after rapidly flipping its tail.

To find out why exercise changes the shrimp’s complexion, Bagge and Duke professor Sönke Johnsen and colleagues compared their internal anatomy before and after physical exertion using diceCT.

In the shrimp cross sections in this video, blood vessels are colored blue-green, and muscle is orange-red. The researchers found that more blood flowed to the tail after exercise, presumably to deliver more oxygen-rich blood to working muscles. The increased blood flow between muscle fibers causes light to scatter or bounce in different directions, which is why the normally see-through shrimp lose their transparency.

Peer inside the leg of a mouse

Duke cardiologist Christopher Kontos, M.D., and MD/PhD student Hasan Abbas have been using the technique to visualize the inside of a mouse’s leg.

The researchers hope the images will shed light on changes in blood vessels in people, particularly those with peripheral artery disease, in which plaque buildup in the arteries reduces blood flow to the extremities such as the legs and feet.

The micro-CT scanner at Duke’s Shared Materials Instrumentation Facility made it possible for Abbas and Kontos to see structures as small as 13 microns, or a fraction of the width of a human hair, including muscle fibers and even small arteries and veins in 3-D.

Take a tour through a tree shrew

DiceCT imaging allows Heather Kristjanson at the Johns Hopkins School of Medicine to digitally dissect the chewing muscles of animals such as this tree shrew, a small mammal from Southeast Asia that looks like a cross between a mouse and a squirrel. By virtually zooming in and measuring muscle volume and the length of muscle fibers, she hopes to see how strong they were. Studying such clues in modern mammals helps Kristjanson and colleagues reconstruct similar features in the earliest primates that lived millions of years ago.

Try it for yourself

Students and instructors who are interested in trying the technique in their research are eligible to apply for vouchers to cover SMIF fees. People at Duke University and elsewhere are encouraged to apply. For more information visit https://smif.pratt.duke.edu/Funding_Opportunities, or contact Dr. Mark Walters, Director of SMIF, via email at mark.walters@duke.edu.

Located on Duke’s West Campus in the Fitzpatrick Building, the SMIF is a shared use facility available to Duke researchers and educators as well as external users from other universities, government laboratories or industry through a partnership called the Research Triangle Nanotechnology Network. For more info visit http://smif.pratt.duke.edu/.

Post by Robin Smith, News and Communications

Fostering a Collaborative Research Environment in Peru

By Lola Sanchez-Carrion

On October 5, 2016

In Biomedical Engineering, Cancer, Cardiology, Field Research, Global Health

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.

Helena Frischtak conducting research with Peruvian children in the field.

Helena Frischtak, a 4^th 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.

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_100hed Post by Lola Sanchez-Carrion

A Link Between Stress and Aging in African-Americans

By Karl Bates

On March 14, 2016

In Cancer, Cardiology, Genetics/Genomics, Guest Post

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)

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.

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.”

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