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How the Flu Vaccine Fails

On April 22, 2019

In Biology, Global Health, Immunology, Lecture, Medicine

Influenza is ubiquitous. Every fall, we line up to get our flu shots with the hope that we will be protected from the virus that infects 10 to 20 percent of people worldwide each year. But some years, the vaccine is less effective than others.

Every year, CDC scientists engineer a new flu virus. By examining phylogenetic relationships, which are based on shared common ancestry and relatedness, researchers identify virus strains to target with a vaccine for the following flu season.

Sometimes, they do a good job predicting which strains will flourish in the upcoming flu season; other times, they pick wrong.

Pekosz’s work has identified why certain flu seasons saw less effective vaccines.

Andrew Pekosz, PhD, is a researcher at Johns Hopkins who examines why we fail to predict strains to target with vaccines. In particular, he examines years when the vaccine was ineffective and the viruses that were most prevalent to identify properties of these strains.

A virus consists of RNA enclosed in a membrane. Vaccines function by targeting membrane proteins that facilitate movement of the viral genome into host cells that it is infecting. For the flu virus, this protein is hemagglutinin (HA). An additional membrane protein called neuraminidase (NA) allows the virus to release itself from a cell it has infected and prevents it from returning to infected cells.

The flu vaccine targets proteins on the membrane of the RNA virus. Image courtesy of scienceanimations.com.

Studying the viruses that flourished in the 2014-2015 and 2016-2017 flu seasons, Pekosz and his team have identified mutations to these surface proteins that allowed certain strains to evade the vaccine.

In the 2014-2015 season, a mutation in the HA receptor conferred an advantage to the virus, but only in the presence of the antibodies present in the vaccine. In the absence of these antibodies, this mutation was actually detrimental to the virus’s fitness. The strain was present in low numbers in the beginning of the flu season, but the selective pressure of the vaccine pushed it to become the dominant strain by the end.

The 2016-2017 flu season saw a similar pattern of mutation, but in the NA protein. The part of the virus membrane where the antibody binds, or the epitope, was covered in the mutated viral strain. Since the antibodies produced in response to the vaccine could not effectively identify the virus, the vaccine was ineffective for these mutated strains.

With the speed at which the flu virus evolves, and the fact that numerous strains can be active in any given flu season, engineering an effective vaccine is daunting. Pekosz’s findings on how these vaccines have previously failed will likely prove invaluable at combating such a persistent and common public health concern.

Post by undergraduate blogger Sarah Haurin

Meet the Researcher Who Changed How We Care for Rape Survivors

By Anne Littlewood

On February 26, 2019

In Behavior/Psychology, Field Research, Global Health, Medicine, Policy

One of the first things I was told during freshman orientation was that two out of every five young women at Duke experience some form of sexual assault during their four years as an undergraduate. Shortly after that, I was informed that as a Duke student, I was not allowed to protect myself with pepper spray, because it is banned by university policy.

At the 2019 Harriet Cook Carter Lecture, Ann Burgess, a professor of psychiatric mental health nursing at Boston College, reported that 25 to 30 percent of women and 10 percent of men will be sexually assaulted in their lifetimes, statistics that make our campus standard of 40 percent seem strikingly high in comparison. Burgess has devoted her life to the support of sexual assault survivors, and pioneered treatments for victims of such abuse. For the past fifty years, she has studied the traumatic effects of rape and violence on patients of all ages, and worked closely with the FBI Academy to research the underlying causes of such crimes. Her work at the FBI was so impactful, Netflix decided to write a TV series about her, a crime drama called “Mindhunter.” Talk about a powerful woman.

Ann Wolbert Burgess, DSNc, APRN, BC, FAAN (Photo from Duke University School of Nursing)

When she began her work with rape survivors in the 1970s, the world was a very different place. Public attitudes towards sexual assault were unsupportive and disapproving of victims. Rape thrived on prudery, silence, and misunderstanding. There were very few reported cases, low conviction rates of criminals, and plenty of victim blaming. “We just didn’t talk about these kinds of things,” Burgess recalled. “There was no public recognition.”

So have we advanced? Yes, absolutely. Throughout the years, Burgess says she has seen a crucial shift towards more support for survivors. She has helped the FBI develop better systems for criminal profiling, and testified countless times in court to ensure justice for survivors of all ages. Burgess has witnessed these court cases changing policies, and affecting the genesis of laws that will better protect citizens against rape and other violent crimes. She has studied lasting trauma in survivors, and used this research to implement new culturally and developmentally appropriate services for victims. She believes that, as a society, we are doing a much better job today to reduce stigma and support survivors, but that the work is not even close to finished.

Sexual assault is still an intensely pervasive issue in society. Rape can happen anywhere, to anyone, and Burgess thinks it all boils down to the cultural emphasis on aggression. “We’ve all become complacent to the violence in the world that we live in,” as panelist Lynden Harris put it. As a society, we perpetuate aggressive masculinity, often without even realizing it. And especially in communities like the military, where women and men alike are highly regulated and taught to avoid showing weakness at all costs, the stigma surrounding sexual assault is intense. Commander Alana Burden-Huber, director of public health services at the Cherry Point Naval Health Clinic, shared her perspective that it can be very difficult to come forward in such a world of conformity. She also mentioned that female jurors in sexual assault cases tend to be much harsher on female survivors than male jurors, and attributes this to the fact that female members of the military are constantly trying to be harder and more stoic, so as to parallel military men.

Mindy Oshrain and Ann Burgess listen intently to the contributions of other panelists

Panelist Mindy Oshrain, a consulting associate in the Duke Department of Psychiatry, quieted the crowd by sharing a moving quote from Maya Angelou: “There is no greater agony than bearing an untold story inside of you.” She reminded us that it is so important to listen to patients, and slow down enough to ask someone multiple times if they are doing okay. It is easy to forget this at a place like Duke, where we are all constantly moving 100 miles a minute, checking boxes as we rush from one activity to the next, but it can make all the difference to stop, and take the time to ask again- How are you really doing? What can I do to support you? Empathy has the power to change the world.

As a sophomore, I now live in a building full of young women on the edge of Central Campus, on a street that is only serviced by Duke transportation in one direction. Just a few months ago, I woke up to a Duke Alert message on my phone, which informed me that a violent rape crime had occurred in the night, just fifty yards from my apartment. While we may have come a long way since the 1970s, the unavoidable fact remains that as young women living in this world, we are not safe. Let’s change that.

HIV Can Be Treated, But Stigma Kills

By Anne Littlewood

On December 6, 2018

In Faculty, Global Health, Immunology, Medicine

Three decades ago, receiving an HIV diagnosis was comparable to being handed a death sentence. But today, this is no longer the case.

Advances in HIV research have led to treatments that can make the virus undetectable and untransmittable in less than six months, a fact that goes overlooked by many. Treatments today can make HIV entirely manageable for individuals.

However, thousands of Americans are still dying of HIV-related causes each year, regardless of the fact that HIV treatments are accessible and effective. So where is the disconnect coming from?

On the 30th anniversary of World AIDS Day, The Center for Sexual and Gender Diversity at Duke University hosted a series of events surrounding around this year’s international theme: “Know Your Status.”

One of these events was a panel discussion featuring three prominent HIV/AIDS treatment advocates on campus, Dr. Mehri McKellar, Dr. Carolyn McAllaster, and Dr. Kent Weinhold, who answered questions regarding local policy and current research at Duke.

From left to right: Kent Weinhold, Carolyn McAllaster, Mehri McKellar and moderator Jesse Mangold in Duke’s Center for Sexual and Gender Diversity

The reason HIV continues to spread and kill, Dr. McKellar explained, is less about accessibility, and more about stigma. Research has shown that stigma shame leads to poor health outcomes in HIV patients, and unfortunately, stigma shame is a huge problem in communities across the US.

Especially in the South, she said, there is very little funding for initiatives to reduce stigma surrounding HIV/AIDS, and people are suffering as a result.

In 2016, the CDC reported that the South was responsible for 52 percent of all new HIV diagnoses and 47 percent of all HIV-related deaths in the US.

If people living with HIV don’t feel supported by their community and comfortable in their environment, it makes it very difficult for them to obtain proper treatment. Dr. McKellar’s patients have told her that they don’t feel comfortable getting their medications locally because they know the local pharmacist, and they’re ashamed to be picking up HIV medications from a familiar face.

HIV/AIDS Diagnoses and Deaths in the US 1981-2007 (photo from the CDC)

In North Carolina, the law previously required HIV-positive individuals to disclose their status and use a condom with sexual partners, even if they had received treatment and could no longer transmit the virus. Violating this law resulted in prosecution and a prison sentence for many individuals, which only enforced the negative stigma surrounding HIV. Earlier this year, Dr. McAllaster helped efforts to create and pass a new version of the law, which will make life a lot easier for people living with HIV in North Carolina.

So what is Duke doing to help the cause? Well, In 2005, Duke opened the Center for AIDS Research (also known as CFAR), which is now directed by Dr. Kent Weinhold. In the last decade, they have focused their efforts mainly on improving the efficacy of the HIV vaccine. The search for a successful vaccine has been long and frustrating for CFAR and the Duke Human Vaccine Institute, but Dr. Weinhold is optimistic that they will be able to reach the realistic goal of 60 percent effectiveness in the future, although he shied away from predicting any sort of timeline for this outcome.

Pre-exposure prophylaxis or PrEP (photo from NIAID)

Duke also opened a PrEP Clinic in 2016 to provide preventative treatment for individuals who might be at risk of getting HIV. PrEP stands for pre-exposure prophylaxis, and it is a medication that is taken before exposure to HIV to prevent transmission of the virus. Put into widespread use, this treatment is another way to reduce negative HIV stigma.

The problem persists, however, that the people who most need PrEP aren’t getting it. The group that has the highest incidence of HIV is males who are young, black and gay. But the group most commonly receiving PrEP is older, white, gay men. Primary care doctors, especially in the South, often won’t prescribe PrEP either. Not because they can’t, but because they don’t support it, or don’t know enough about it.

And herein lies the problem, the panelists said: Discrimination and bias are often the results of inadequate education. The more educated people are about the truth of living with HIV, and the effectiveness of current treatments, the more empathetic they will be towards HIV-positive individuals.

There’s no reason for the toxic shame that exists nationwide, and attitudes need to change. It’s important for us to realize that in today’s world, HIV can be treated, but stigma kills.

Post by Anne Littlewood

Considerations about AIDS from Brazilian literature

By Victoria Priester

On October 24, 2018

In Biology, Global Health, Medicine, Science Communication & Education

To know what illness is, you have to be ill first.

This was one of the points that post-doctoral student and essayist Milena Mulatti Magri emphasized in her talk on Oct. 15. She was discussing Brazilian writer Caio Fernando Abreu’s writings about AIDS and its effect on groups who already faced societal prejudice before the breakout of AIDS in the 1980’s and 90’s, when patients were identified mainly as homosexual.

By studying research done by Professor Vladimir Safatle and physician and philosopher Georges Canguilhem, Magri has pieced together that health is seen as a form of normativity and disease as a deviation. Thus, ostracizing and excluding those who contract disease is seen as justifiable because they have deviated from what is seen as normal, even when the disease is not the fault of the patient.

Magri has also analyzed essays about the relationship between disease, metaphor and patient stigma, such as cancer patients who, in addition to combating the illness growing unwelcome inside their own bodies, also have to deal with social stigmas that come with disease, such as cancer as a representation for evil.

Brazilian author and columnist Caio Fernando Abreu. (Image from KD Frases.)

However, while Magri emphasized that social metaphors of different diseases should be deconstructed, she has also found that literature and personal writing can be a way to discuss and otherwise “incommunicable experience.”

During a time when it was seen as shameful to have AIDS, Caio Fernando Abreu began a biweekly publication of his health chronicles in the newspaper O Estado de São Paulo, which was one of the first instances of someone publicly discussing their experience with AIDS from the perspective of the ill person, as opposed to from the perspective of doctors or health experts.

Abreu’s columns confronted the difficulty of living with disease and living in proximity to death, and discuss the increased social prejudice as a result of the disease. Abreu also wrote a play called “O homem e amancha” (in English, “The Man and the Stain”), which is an intertextual reading of the famous Spanish novel Don Quijote de la Mancha. In her talk, Magri explained that “Mancha,” which in English means “stain,” can refer to both the home of Don Quijote before he sets off of on his adventures and the rare skin cancer that often accompanies AIDS called Kaposi Sarcoma, which forms lesions on the skin that resemble stains.

Abreu intended to use his own experiences to question the social prejudice against AIDS, and there Magri highlighted a marked change, even between his own writings at the beginning of his diagnosis compared to those at the end of his life, when he spoke openly and without metaphor about suffering that is amplified by social exclusion.

Magri believes that Abreu’s writings were pioneering acts of courage, and that from his writing we learn to empathize rather than to judge and stigmatize.

Post by Victoria Priester

Victoria Priester

Creating a Gender Inclusive Campus: Reflecting on “Becoming Johanna”

By Anne Littlewood

On October 17, 2018

In Global Health, Guest Post, Students

Following Duke’s Oct. 4 screening of the 2016 documentary, “Becoming Johanna,” students, faculty, staff and community members in the audience were eager to ask questions of the panel, which included the film’s director/producer, Jonathan Skurnik, and even the film’s transgender subject, Johanna Clearwater herself.

Johanna Clearwater pictured with the film’s director/producer Jonathan Skurnik

The film showcases the heart-wrenching and empowering story of a latina transgender teenager growing up in Los Angeles. After beginning her transition at age 16, Johanna faced the rejection of her mother and intense opposition from school authorities. Soon after, she was abandoned by her family and entered the foster care system, where she was lucky to find a much more supportive family environment. After changing schools, she connected on a personal level with her school principal, Deb, who helped Johanna find a community where she felt understood and supported. This success story of self-advocacy and resilience in the face of abandonment and exclusion highlights the daily struggles of many transgender teenagers. For these individuals, becoming comfortable in their own skin is the end of a long and demanding journey, often made even more difficult by the ignorance and cruelty of society. Finding and following the path to authentic expression takes a huge amount of courage, as this route is often layered with adversity.

Before the screening, Duke clinical social worker Kristin Russel put the film in context for the audience, inviting our reflection with her words: “A well told story… is really what can help us bridge the unfortunate distance that can remain uncrossed and misunderstood if such stories are silenced.” Chief Diversity Officer for the School of Medicine Judy Seidenstein then introduced the film and facilitated the panel discussion.

After the film, the audience was invited to join the conversation. Questions came from every demographic of the crowd, and provided a nice sampling of opinions. Many audience members pointed out how important these conversations are, especially in a conservative state like North Carolina that has so recently struggled with the protection of LGBTQ rights with last year’s ‘Bathroom Bill.’ Specifically, the questions and comments from hospital staff and faculty from the School of Medicine gave a nice insight into the direction of support on campus for sexual and gender diversity.

Audience members reflect on the film with those nearby

Cheryl Brewer, the Associate Vice President of Nursing, told the room about the inclusion work that she is leading in the School of Nursing. They have developed a new core curriculum to promote acceptance and support of gender and sexual diversity through situational trainings. She noted that there have been some people that struggle with implicit biases more than others, but that the program has been a success overall.

Russell spoke briefly about her work with transgender and gender diverse youth in the clinical setting and emphasized the importance of having family support. Legally and psychologically, maintaining family involvement and support of patients is essential for treatment.

Events like this one reflect ongoing efforts to support sexual and gender diversity within and beyond Duke, by promoting conversation and increasing empathy through storytelling. Duke is well on the way to becoming a much more inclusive community, where everyone can feel a sense of belonging.

Guest post by Anne Littlewood

Combatting the Opioid Epidemic

By Sarah Haurin

On September 17, 2018

In Faculty, Global Health, Lecture, Medicine

The opioid epidemic needs to be combatted in and out of the clinic.

In the U.S. 115 people die from opioids every day. The number of opioid overdoses increased fivefold from 1999 to 2016. While increased funding for resources like Narcan has helped — the opioid overdose-reversing drug now carried by emergency responders in cities throughout the country — changes to standard healthcare practices are still sorely needed.

Ashwin A Patkar, MD, medical director of the Duke Addictions Program, spoke to the Duke Center on Addiction and Behavior Change about how opioid addiction is treated.

The weaknesses of the current treatment standards first appear in diagnosis. Heroin and cocaine are currently being contaminated by distributors with fentanyl, an opioid that is 25 to 50 times more potent than heroin and cheaper than either of these drugs. Despite fentanyl’s prevalence in these street drugs, the standard form and interview for addiction patients does not include asking about or testing for the substance.

Patkar has found that 30 percent of opioid addiction patients have fentanyl in their urine and do not disclose it to the doctor. Rather than resulting from the patients’ dishonesty, Patkar believes, in most cases, patients are taking fentanyl without knowing that the drugs they are taking are contaminated.

Because of its potency, fentanyl causes overdoses that may require more Narcan than a standard heroin overdose. Understanding the prevalence of Narcan in patients is vital both for public health and educating patients so they can be adequately prepared.

Patkar also pointed out that, despite a lot of research supporting medication-assisted therapy, only 21 percent of addiction treatment facilities in the U.S. offer this type of treatment. Instead, most facilities rely on detoxification, which has high rates of relapse (greater than 85 percent within a year after detox) and comes with its own drawbacks. Detox lowers the patient’s tolerance to the drug, but care providers often neglect to tell the patients this, resulting in a rate of overdose that is three times higher than before detox.

Another common treatment for opioid addiction involves using methadone, a controlled substance that helps alleviate symptoms from opioid withdrawal. Because retention rate is high and cost of production is low, methadone poses a strong financial incentive. However, methadone itself is addictive, and overdose is possible.

Patkar points to a resource developed by Julie Bruneau as a reference for the Canadian standard of care for opioid abuse disorder. Rather than recommending detox or methadone as a first line of treatment, Bruneau and her team recommend buprenorphine , and naltrexone as a medication to support abstinence after treatment with buprenorphine.

Buprenorphine is a drug with a similar function as methadone, but with better and safer clinical outcomes. Buprenorphine does not create the same euphoric effect as methadone, and rates of overdose are six times less than in those prescribed methadone.

In addition to prescribing the right medicine, clinicians need to encourage patients to stick with treatment longer. Despite buprenorphine having good outcomes, patients who stop taking it after only 4 to 12 weeks, even with tapering directed by a doctor, exhibit only an 18 percent rate of successful abstinence.

Patkar closed his talk by reminding the audience that opioid addiction is a brain disease. In order to see a real change in the number of people dying from opioids, we need to focus on treating addiction as a disease; no one would question extended medication-based treatment of diseases like diabetes or heart disease, and the same should be said about addiction. Healthcare providers have a responsibility to treat addiction based on available research and best practices, and patients with opioid addiction deserve a standard of care the same as anyone else.

Post by undergraduate blogger Sarah Haurin

Medicine, Research and HIV

By Sarah Haurin

On September 12, 2018

In Animals, Biology, Global Health, Medicine, Students

Duke senior Jesse Mangold has had an interest in the intersection of medicine and research since high school. While he took electives in a program called “Science, Medicine, and Research,” it wasn’t until the summer after his first year at Duke that he got to participate in research.

As a member of the inaugural class of Huang fellows, Mangold worked in the lab of Duke assistant professor Christina Meade on the compounding effect of HIV and marijuana use on cognitive abilities like memory and learning.

The following summer, Mangold traveled to Honduras with a group of students to help with collecting data and also meeting the overwhelming need for eye care. Mangold and the other students traveled to schools, administered visual exams, and provided free glasses to the children who needed them. Additionally, the students contributed to a growing research project, and for their part, put together an award-winning poster.

Mangold’s (top right) work in Honduras helped provide countless children with the eye care they so sorely needed.

Returning to school as a junior, Mangold wanted to focus on his greatest research interest: the molecular mechanisms of human immunodeficiency virus (HIV). Mangold found a home in the Permar lab, which investigates mechanisms of mother-to-child transmission of viruses including HIV, Zika, and Cytomegalovirus (CMV).

From co-authoring a book chapter to learning laboratory techniques, he was given “the opportunity to fail, but that was important, because I would learn and come back the next week and fail a little bit less,” Mangold said.

In the absence of any treatment, mothers who are HIV positive transmit the virus to their infants only 30 to 40 percent of the time, suggesting a component of the maternal immune system that provides at least partial protection against transmission.

The immune system functions through the activity of antibodies, or proteins that bind to specific receptors on a microbe and neutralize the threat they pose. The key to an effective HIV vaccine is identifying the most common receptors on the envelope of the virus and engineering a vaccine that can interact with any one of these receptors.

This human T cell (blue) is under attack by HIV (yellow), the virus that causes AIDS. Credit: Seth Pincus, Elizabeth Fischer and Austin Athman, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Mangold is working with Duke postdoctoral associate Ashley Nelson, Ph.D., to understand the immune response conferred on the infants of HIV positive mothers. To do this, they are using a rhesus macaque model. In order to most closely resemble the disease path as it would progress in humans, they are using a virus called SHIV, which is engineered to have the internal structure of simian immunodeficiency virus (SIV) and the viral envelope of HIV; SHIV can thus serve to naturally infect the macaques but provide insight into antibody response that can be generalized to humans.

The study involves infecting 12 female monkeys with the virus, waiting 12 weeks for the infection to proceed, and treating the monkeys with antiretroviral therapy (ART), which is currently the most effective treatment for HIV. Following the treatment, the level of virus in the blood, or viral load, will drop to undetectable levels. After an additional 12 weeks of treatment and three doses of either a candidate HIV vaccine or a placebo, treatment will be stopped. This design is meant to mirror the gold-standard of treatment for women who are HIV-positive and pregnant.

At this point, because the treatment and vaccine are imperfect, some virus will have survived and will “rebound,” or replicate fast and repopulate the blood. The key to this research is to sequence the virus at this stage, to identify the characteristics of the surviving virus that withstood the best available treatment. This surviving virus is also what is passed from mothers on antiretroviral therapy to their infants, so understanding its properties is vital for preventing mother-to-child transmission.

As a Huang fellow, Mangold had the opportunity to present his research on the compounding effect of HIV and marijuana on cognitive function.

Mangold’s role is looking into the difference in viral diversity before treatment commences and after rebound. This research will prove fundamental in engineering better and more effective treatments.

In addition to working with HIV, Mangold will be working on a project looking into a virus that doesn’t receive the same level of attention as HIV: Cytomegalovirus. CMV is the leading congenital cause of hearing loss, and mother-to-child transmission plays an important role in the transmission of this devastating virus.

Mangold and his mentor, pediatric resident Tiziana Coppola, M.D., are authoring a paper that reviews existing literature on CMV to look for a link between the prevalence of CMV in women of child-bearing age and whether this prevalence is predictive of the number of children suffer CMV-related hearing loss. With this study, Mangold and Coppola are hoping to identify if there is a component of the maternal immune system that confers some immunity to the child, which can then be targeted for vaccine development.

After graduation, Mangold will continue his research in the Permar lab during a gap year while applying to MD/PhD programs. He hopes to continue studying at the intersection of medicine and research in the HIV vaccine field.

Post by undergraduate blogger Sarah Haurin

First Population Health Conference Shares Energy, Examples

By Karl Bates

On April 6, 2018

In Behavior/Psychology, Business/Economics, Global Health, Medicine

Logo: Population Health at Duke ‘Population Health’ is the basis of a new department in the School of Medicine, a byword for a lot of new activity across campus , and on Tuesday the subject of a half-day symposium that attempted to bring all this energy together.

For now, population health means a lot of different things to a lot of different people.

The half-day symposium drew an overflow crowd of faculty and staff. (photo – Colin Huth)

“We’re still struggling with a good definition of what population health is,” said keynote speaker Clay Johnston, MD, PhD, dean of the new Dell School of Medicine in Austin, Texas. Smoking cessation programs are something most everyone would agree is taking care of the population outside of the clinic. But improved water quality? Where does that fit?

“We have an intense focus on doctors and their tools,” Johnston said. Our healthcare system is optimized for maximum efficiency in fee-for-service care, that is, getting the most revenue out of the most transactions. “But most of health is outside the clinic,” Johnston said.

Perhaps as a result, the United States pays much more for health care, but lives less well, he said. “We are noticeably off the curve,” when compared to health care costs and outcomes in other countries.

This graphic from a handout shared at the conference shows how population health spans the entire university.

As an example of what might be achieved in population health with some re-thinking and a shift in resources, the Dell School went after the issue of joint pain with input from their engineering and business schools. Rather than diagnosing people toward an orthopedic surgery – for which there was a waitlist of about 14 months – their system worked with patients on alternatives, such as weight loss, physical therapy and behavioral changes before surgery. The 14-month backlog was gone in just three months. Surgeries still happen, of course, but not if they can be comfortably delayed or avoided.

“Payment for prevention needs serious work,” Johnston said. “You need to get people to buy into it,” but in diabetes or depression for example, employers should stand to gain a lot from having healthier employees who miss fewer days, he said.

Health Affairs Chancellor Eugene Washington commented several times, calling the discussion “very interesting and very valuable.” (photo -Colin Huth)

Other examples flowed freely the rest of the afternoon. Duke is testing virtual ‘telemedicine’ appointments versus office visits. Evidence-based prenatal care is being applied to try to avoid expensive neonatal ICU care. Primary care and Emergency Department physicians are being equipped with an app that helps them steer sickle cell patients to appropriate care resources so that they might avoid expensive ED visits.

Family practitioner Eugenie Komives, MD, is part of a team using artificial intelligence and machine learning to try to predict which patients are most likely to be hospitalized in the next six months. That prediction, in turn, can guide primary care physicians and care managers to pay special attention to these patients to help them avoid the hospital. The system is constantly being evaluated, she added. “We don’t want to be doing this if it doesn’t work.”

Community health measures like walkability and grocery stores are being mapped for Durham County on a site called Durham Neighborhood Compass, said Michelle Lyn, MBA, chief of the division of community health. The aim is not only to see where improvements can be made, but to democratize population health information and put it in peoples’ hands. “(Community members) will have ideas we never could have thought of,” Lyn said. “We will be able to see change across our neighborhoods and community.”

Patient input is key to population health, agreed several speakers. “I don’t think we’ve heard them enough,” said Paula Tanabe, PhD, an associate professor of nursing and medicine who studies pain and sickle cell disease. “We need a bigger patient voice.”

Health Affairs Chancellor and Duke Health CEO Eugene Washington, MD, has made population health one of the themes of his leadership. “We really take seriously this notion of shaping the future of population health,” he said in his introductory remarks. “When I think of the future, I think about how well-positioned we are to have impact on the lives of the community we serve.”

Lesley Curtis, PhD, chair of the newly formed Department of Population Health Sciences in the School of Medicine, said Duke is creating an environment where this kind of work can happen.

“I, as an organizer of this, didn’t know about half of these projects today!” Curtis said. “There’s so much going on at an organic level that the challenge to us is to identify what’s going on and figure out how to go forward at scale.”

Post by Karl Leif Bates

Obesity: Do Your Cells Have a Sweet Tooth?

By Lydia Goff

On March 26, 2018

In Biology, Genetics/Genomics, Global Health, Lecture, Medicine

Obesity is a global public health crisis that has doubled since 1980. That is why Damaris N. Lorenzo, a professor of Cell Biology and Physiology at UNC-Chapel Hill, has devoted her research to this topic.

Specifically, she examines the role of ankyrin-B variants in metabolism. Ankyrins play a role in the movement of substances such as ions into and out of the cell. One of the ways that ankyrins affect this movement is through the glucose transporter protein GLUT4 which is present in the heart, skeletal muscles, and insulin-responsive tissues. GLUT4 plays a large role in glucose levels throughout the entire body.

Through her research, Lorenzo discovered that with modern life spans and high calorie diets, ankyrin-B variants can be a risk factor for metabolic disease. She presented her work for the Duke Developmental & Stem Cell Biology department on March 7th.

Prevalence of Self-Reported Obesity Among U.S. Adults by State, 2016

GLUT4 helps remove glucose from the body’s circulation by moving it into cells. The more GLUT4, the more sugar cells absorb.

Ankyrin-B’s role in regulating GLUT4 therefore proves really important for overall health. Through experiments on mice, Lorenzo discovered that mice manipulated to have ankyrin-B mutations also had high levels of cell surface GLUT4. This led to increased uptake of glucose into cells. Ankyrin-B therefore regulates how quickly glucose enters adipocytes, cells that store fat. These ankyrin-B deficient mice end up with adipocytes that have larger lipid droplets, which are fatty acids.

Lorenzo was able to conclude that ankyrin-B deficiency leads to age-dependent obesity in mutant mice. Age-dependent because young ankyrin-B mutant mice with high fat diets are actually more likely to be affected by this change.

Obese mouse versus a regular mouse

Ankyrin-B has only recently been recognized as part of GLUT4 movement into the cell. As cell sizes grow through increased glucose uptake, not only does the risk of obesity rise but also inflammation is triggered and metabolism becomes impaired, leading to overall poor health.

With obesity becoming a greater problem due to increased calorie consumption, poor dietary habits, physical inactivity, environmental and life stressors, medical conditions, and drug treatments, understanding factors inside of the body can help. Lorenzo seeks to discover how ankyrin-B protein might play a role in the amount of sugar our cells internalize.

Post by Lydia Goff

Growing “Mini Brains” To Understand Zika’s Effects

By Thabit Pulak

On February 14, 2018

In Biology, Biomedical Engineering, Global Health, Medicine

You probably remember what the Zika virus is because of the outbreak in 2015 that made global headlines.

An infant with microcephaly (left) with a reduced head circumference, as compared to an infant born with a regular head circumference (right) Picture credit: https://commons.wikimedia.org/w/index.php?curid=63278345

The serious nature of the virus was apparent when hundreds of infants across South America were born with microcephaly – a condition characterized by a very small head circumference as a result of abnormally slow brain growth.

The sudden outbreak of Zika in South America led to a panic of the possibility of spread into the United States as well as beyond – and thus, research into learning more about the disease mechanisms of Zika expanded. However, one of the problems in studying a disease like Zika is the difficulty of modeling a complex organ like the developing brain.

Until now, the current way to model the brain was with a brain organoid – a brain grown in a lab. Organoid structures attempt to mimic whole developing organs – however, current brain organoid technology required the use of a large spinning bioreactor to facilitate nutrient and oxygen absorption to mimic the function of the vascular system in our brains. Large spinning bioreactors are expensive to run and bulky—they require large volumes of expensive media that mimic brain fluid. The size and cost has meant that only a few organoids can be grown and studied at once.

Guo-li Ming, University of Pennsylvania

Dr. Guo-li Ming, a professor of neuroscience from the Perelman School of Medicine at the University of Pennsylvania, set out to work on finding a way to solve this problem. She came down to Duke University last week to give a talk on her findings. As she spoke, I could feel the minds of the audience firmly captivated by her words. It was truly fascinating stuff – Ming was actually growing brains in the lab!

The work began by finding a way to take the large spinning reactor that the existing brain organoid required and make it smaller. Three clever high school students working in her lab used a 3D printer and a small motor that involved spinning 12 tiny interconnected paddles within 12 small cell culture wells. Each of the wells contain a paddle that is spun by one gear. All of the individual gears connect to a continually rotating central gear driven by a motor.

The Spin bioreactor. Source: http://www.cell.com/cell/abstract/S0092-8674(16)30467-6

After many optimizations, the final design was called SpinW, which ultimately required a mere 2 ml of media per well, resulting in a net 50-fold reduction in media consumption, as well as dramatically reduced incubator space. The large number of wells, combined with dramatically reduced cost of the apparatus and media consumption, allowed for optimal conditions to run multiple test scenarios with ease – essentially meaning that 12 “mini brains” could be tested at the same time.

The design of SpinW costed a mere $400, while the commercial design costs over $2,000, with the added burden of consuming 50 times more media. The success of the design only serves to prove that age doesn’t matter when it comes to great ideas!

A brain organoid infected with Zika virus. ZIKV envelope protein is shown in green; neural progenitor cells marked by SOX2 are shown in red; neurons marked by CTIP2 are shown in blue.
CREDIT: Xuyu Qian/Johns Hopkins University

Dr. Ming and her team used the apparatus to model the Zika virus’s impact on the brain.

The findings indicate that Zika works by killing off neural stem cells, as well as causing a thinning of key brain structures. One of the observations was that, by day 18 of Zika infection of a brain organoid, there was an overall decrease in size, which points to the link of Zika causing microcephaly. The Zika infection of early-stage organoids corresponded to the first trimester of human fetal development.

The brain is the most complex organ in the body, and one of the least understood. The work Dr. Ming and her team has done goes a long way towards helping us understand the way the human brain develops and works, as well modeling its reaction to things like viruses. It was a pleasure and honor to hear Dr. Ming talk to us about her work –I am eager to hear about further developments in this field!

Post by Thabit Pulak

Duke Research Blog

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

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