Duke Research Blog

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

Category: Medicine Page 1 of 15

How the Flu Vaccine Fails

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.

‘Death is a Social Construct’

Of the few universal human experiences, death remains the least understood. Whether we avoid its mention or can’t stop thinking about it, whether we are terrified or mystified by it, none of us know what death is really like. Turns out, neither do the experts who spend every day around it.

Nobody who sees this guy reports back, so we can only guess.

This was the overarching lesson of Dr. Robert Truog’s McGovern Lecture at Trent Semans Center for Health Education, titled “Defining Death: Persistent Problems and Possible Solutions.”

Dr. Truog is this year’s recipient of the McGovern Prize, an award honoring individuals who have made outstanding contributions to the art and  science of medicine. Truog is a professor of medical ethics, anesthesiology and pediatrics and director of the center for bioethics at Harvard Medical School. He is intimately familiar with death, not only through his research and writings, but through his work as a pediatric intensive care doctor at Boston Children’s Hospital. Truog is also the author of the current national guidelines for end-of-life care in the intensive care unit.

In short, Truog knows a lot about death. Yet certain questions about the end of life remain elusive even to him. In his talk, he spoke about the biological, sociological, and ethical challenges involved in drawing the boundary between life and death. While some of these challenges have been around for as long as humans have, certain ones are novel, brought on by technological advancements in medicine that allow us to prolong the functioning of vital organs, mainly the brain and the heart.

The “irreversible cessation of function” of these organs results in brain and cardiac death, respectively. When both occur together, the patient is declared biologically dead. When they don’t, such as when all brain function except for those that support the patient’s digestive system is lost, for instance, the patient can be legally alive without any hope of recovery of consciousness.

Robert Truog teaching (Harvard photo)

According to Truog, it is in these moments of life after the loss of almost every brain function that we realize “death is a social construct.” This claim likely sounds counterintuitive, if not entirely nonsensical, as dying is the moment we have the least control over our biology. What Dr. Truog means, however, is that as technology continues to mend failures of biology that would have once been fatal, our social and philosophical understanding of dying, what he calls “person death” will increasingly separate from the end of the body’s biological function.  

Biologically, death is the moment when homeostasis, the body’s internal state of equilibrium including body temperature, pH levels and fluid balance, fails and entropy prevails.

Personhood, however, is not mere homeostasis. Dr. Truog cited Robert Veatch, ethicist at Georgetown University, in defining person death as the “irreversible loss of that which is essentially significant to the nature of man.” For those patients who are kept alive by ventilators and who have no hope of regaining consciousness, that essentially significant nature appears to have been lost.

Nonetheless, for loved ones, signs like spontaneous breathing, which can occur in patients in persistent vegetative state, intuitively feel like signs of life. This intuitive sign of life is what made Jahi McMath’s parents refuse an Oakland California hospital’s declaration that their daughter was dead. A ventilator kept the 13-year-old breathing, even though she had been declared brain-dead. After much conflict, McMath’s parents moved her to a hospital in New Jersey, one of just two states where families can reject brain death if it does not align with their religious beliefs. In the end, McMath had two death certificates that were five years apart.


Muslim cemetery at sunset in Marrakech Morocco.
(Mohamed Boualam via Wikimedia commons)

The emotional toll of such an ordeal is immense, as the media outcry around McMath made more than clear. There are more concrete, quantifiable costs to extending biological function beyond the end of personhood: the U.S. is facing an organ shortage. As people are kept on life support for longer periods, it is going to become increasingly difficult for patients who desperately need organs to find donors.

In closing, Dr. Truog reminded us that “in the spectrum between alive and dead, we set the threshold… Death is not a binary state, but a complex social choice.” People will likely continue to disagree about where we should set the threshold, especially as technology develops.

However, if we want to have a thoughtful discussion that respects the rights, wishes, and values of patients, loved ones, and everybody else who will one day face death, we need to first agree that there is a choice to be made.

Guest Post by Deniz Ariturk, Science & Society graduate student

Zapping Your Brain Is Dope

Emerging technology has created a new doping technique for athletic performance that is, as of now, perfectly legal.

Coined “neuro-doping,” this method sends electric current through one’s brain to facilitate quicker learning, enhanced muscular strength, and improved coordination. Use of this electronic stimulus has taken off in the sports world as a replacement for other doping methods banned by the World Anti-Doping Agency (WADA). Because it’s relatively new, WADA has yet to establish rules around neuro-doping. Plus, it’s virtually undetectable. Naturally, a lot of athletes are taking advantage of it.

Image result for doping

One specific method of neuro-doping is known as Transcranial Direct-Current Stimulation (tDCS). It works by sending a non-invasive and painless electrical current through the brain for around three to 20 minutes, in order to excite the brain’s cortex, ultimately increasing neuroplasticity (Park). This can be done commercially via a headset like device for $200.

Image result for transcranial direct current stimulation headset
The Halo Sport

Weight lifters, sprinters, pitchers, and skiers are just some of many types of athletes who can benefit from tCDS. By practicing with these headphones on, new neural pathways are constructed to help their bodies achieve peak performance. Dr. Greg Appelbaum, director of Opti Lab and the Brain Stimulation Research Center, says it’s especially useful for athletes where technique and motor skills triumph — such as a sprinter getting out of the blocks or an Olympic ski jumper hanging in the air. Top-tier athletes are pushing that fine limit of what the human body can accomplish, but neuro-doping allows them to take it one step further.

Neuro-doping has other applications, too. Imagine insanely skilled Air Force pilots, surgeons with exceptionally nimble hands, or soldiers with perfect aim. tCDS is being used to make progress in things like Alzheimer’s and memory function because of its impact on cognitive functioning in the forms of increased attention span and memory. You could even learn the guitar faster.

In this sort of context, it’s a no brainer that neuro-doping should be taken advantage of. But how ethical is it in sports?

The precedent for WADA to ban a substance or technique has been based on meeting two of the following three criteria: (1) drugs or tools that likely enhance performance to secure a winning edge; (2) drugs or tools that place athletes’ health at risk; (3) any substances or techniques that ruin the “spirit-of-sport” (Park). Lots of research has shown tCDS is pretty legit. As for health risks, tCDS is still in the experimental stage, so not much can be said about its side effects. Ethically, it causes a lot of controversy.

Many issues come into play when thinking about allowing athletes to neuro-dope. Given its similarities with other popular drugs, tCDS could introduce unfair advantages. Furthermore, not everyone may have access to the technology, and not everyone may want to use it. However, it’s important to note that sports already have unfair advantages. Access to things like proper coaching and nutrition may not be a reality for everyone. Sports are just inherently competitive.

Back when baseball players doped, it was awesome to watch them crush balls out of the park. Reintroducing performance enhancement through tCDS could mean we start seeing mountain bikers launching insane air and world records being smattered. The human body could achieve newfound heights.

Are the benefits worth it? Does neuro-doping ruin the “spirit of the sport?” Regardless of these important questions, tCDS is a fascinating scientific discovery that could make a difference in this world. So, what do you think?

Will Sheehan
Post by Will Sheehan

Park, Cogent Social Sciences (2017), 3: 1360462
https://doi.org/10.1080/23311886.2017.1360462

Meet the Researcher Who Changed How We Care for Rape Survivors

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.

Post by Anne Littlewood, Trinity ’21

Using Genetic Clues to Reform Cardiac Care

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

Nature vs. Nurture and Addiction

Epigenetics involves modifications to DNA that do not change its sequence but only affect which genes are active, or expressed. Photo courtesy of whatisepigenetics.com

The progressive understanding of addiction as a disease rather than a choice has opened the door to better treatment and research, but there are aspects of addiction that make it uniquely difficult to treat.

One exceptional characteristic of addiction is its persistence even in the absence of drug use: during periods of abstinence, symptoms get worse over time, and response to the drug increases.

Researcher Elizabeth Heller, PhD, of the University of Pennsylvania Epigenetics Institute, is interested in understanding why we observe this persistence in symptoms even after drug use, the initial cause of the addiction, is stopped. Heller, who spoke at a Jan. 18 biochemistry seminar, believes the answer lies in epigenetic regulation.

Elizabeth Heller is interested in how changes in gene expression can explain the chronic nature of addiction.

Epigenetic regulation represents the nurture part of “nature vs. nurture.” Without changing the actual sequence of DNA, we have mechanisms in our body to control how and when cells express certain genes. These mechanisms are influenced by changes in our environment, and the process of influencing gene expression without altering the basic genetic code is called epigenetics.

Heller believes that we can understand the persistent nature of the symptoms of drugs of abuse even during abstinence by considering epigenetic changes caused by the drugs themselves.

To investigate the role of epigenetics in addiction, specifically cocaine addiction, Heller and her team have developed a series of tools to bind to DNA and influence expression of the molecules that play a role in epigenetic regulation, which are called transcription factors. They identified the FosB gene, which has been previously implicated as a regulator of drug addiction, as a site for these changes.

Increased expression of the FosB gene has been shown to increase sensitivity to cocaine, meaning individuals expressing this gene respond more than those not expressing it. Heller found that cocaine users show decreased levels of the protein responsible for inhibiting expression of FosB. This suggests cocaine use itself is depleting the protein that could help regulate and attenuate response to cocaine, making it more addictive.

Another gene, Nr4a1, is important in dopamine signaling, the reward pathway that is “hijacked” by drugs of abuse.  This gene has been shown to attenuate reward response to cocaine in mice. Mice who underwent epigenetic changes to suppress Nr4a1 showed increased reward response to cocaine. A drug that is currently used in cancer treatment has been shown to suppress Nr4a1 and, consequently, Heller has shown it can reduce cocaine reward behavior in mice.

The identification of genes like FosB and Nr4a1 and evidence that changes in gene expression are even greater in periods of abstinence than during drug use. These may be exciting leaps in our understanding of addiction, and ultimately finding treatments best-suited to such a unique and devastating disease.   

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

HIV Can Be Treated, But Stigma Kills

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

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

Drug Homing Method Helps Rethink Parkinson’s

The brain is the body’s most complex organ, and consequently the least understood. In fact, researchers like Michael Tadross, MD, PhD, wonder if the current research methods employed by neuroscientists are telling us as much as we think.

Michael Tadross is using novel approaches to tease out the causes of neuropsychiatric diseases at a cellular level.

Current methods such as gene editing and pharmacology can reveal how certain genes and drugs affect the cells in a given area of the brain, but they’re limited in that they don’t account for differences among different cell types. With his research, Tadross has tried to target specific cell types to better understand mechanisms that cause neuropsychiatric disorders.

To do this, Tadross developed a method to ensure a drug injected into a region of the brain will only affect specific cell types. Tadross genetically engineered the cell type of interest so that a special receptor protein, called HaloTag, is expressed at the cell membrane. Additionally, the drug of interest is altered so that it is tethered to the molecule that binds with the HaloTag receptor. By connecting the drug to the Halo-Tag ligand, and engineering only the cell type of interest to express the specific Halo-Tag receptor, Tadross effectively limited the cells affected by the drug to just one type. He calls this method “Drugs Acutely Restricted by Tethering,” or DART.

Tadross has been using the DART method to better understand the mechanisms underlying Parkinson’s disease. Parkinson’s is a neurological disease that affects a region of the brain called the striatum, causing tremors, slow movement, and rigid muscles, among other motor deficits.

Only cells expressing the HaloTag receptor can bind to the AMPA-repressing drug, ensuring virtually perfect cell-type specificity.

Patients with Parkinson’s show decreased levels of the neurotransmitter dopamine in the striatum. Consequently, treatments that involve restoring dopamine levels improve symptoms. For these reasons, Parkinson’s has long been regarded as a disease caused by a deficit in dopamine.

With his technique, Tadross is challenging this assumption. In addition to death of dopaminergic neurons, Parkinson’s is associated with an increase of the strength of synapses, or connections, between neurons that express AMPA receptors, which are the most common excitatory receptors in the brain.

In order to simulate the effects of Parkinson’s, Tadross and his team induced the death of dopaminergic neurons in the striatum of mice. As expected, the mice displayed significant motor impairments consistent with Parkinson’s. However, in addition to inducing the death of these neurons, Tadross engineered the AMPA-expressing cells to produce the Halo-Tag protein.

Tadross then treated the mice striatum with a common AMPA receptor blocker tethered to the Halo-Tag ligand. Amazingly, blocking the activity of these AMPA-expressing neurons, even in the absence of the dopaminergic neurons, reversed the effects of Parkinson’s so that the previously affected mice moved normally.

Tadross’s findings with the Parkinson’s mice exemplifies how little we know about cause and effect in the brain. The key to designing effective treatments for neuropsychiatric diseases, and possibly other diseases outside the nervous system, may be in teasing out the relationship of specific types of cells to symptoms and targeting the disease that way.

The ingenious work of researchers like Tadross will undoubtedly help bring us closer to understanding how the brain truly works.

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

 

Smart Phones Are the New Windows to the Soul

It’s one of those things that seems so simple and elegant that you’re left asking yourself, “Geez, why didn’t I think of that?”

Say you were trying to help people lose weight, prep for a surgery or take their meds every day. They’re probably holding a smartphone in at least one of their hands — all you need to do is enlist that ever-present device they’re staring at to bug them!

So, for example, have the health app send a robo-text twice a day to check in: “Did you weigh yourself?” Set up a group chat where their friends all know what they’re trying to accomplish: “We’re running today at 5, right?”

This is a screenshot of a Pattern Health app for pre-operative patients.

It’s even possible to make them pinky-swear a promise to their phone that they will do something positive toward the goal, like walking or skipping desert that day. And if they don’t? The app has their permission to lock them out of all their apps for a period of time.

Seriously, people agree to this and it works.

Two app developers on this frontier of personalized, portable “mHealth” told a lunchtime session  sponsored by the Duke Mobile App Gateway on Thursday that patients not only willingly play along with these behavioral modification apps, their behaviors change for the better.

The idea of using phones for health behavior came to pediatric hematologist Nirmish Shah MD one day while he attempted to talk to a 16-year-old sickle cell disease patient as she snapped selfies of herself with the doctor. Her mom and toddler sister nearby both had their noses to screens as well. “I need to change how I do this,” Shah thought to himself.

Pediatric hematologist Nirmish Shah MD

Pediatric hematologist Nirmish Shah MD is director of Duke’s sickle cell transition program.

Twenty health apps later, he’s running phase II clinical trials of phone-based interventions for young sickle cell patients that encourage them to stay on their medication schedule and ask them often about their pain levels.

One tactic that seems to work pretty well is to ask his patients to send in selfie videos as they take their meds each day. The catch? The female patients send a minute or so of chatty footage a day. The teenage boys average 13 seconds, and they’re grumpy about it.

Clearly, different activities may be needed for different patient populations, Shah said.

While it’s still early days for these approaches, we do have a lot of behavioral science on what could help, said Aline Holzwarth, a principal of the Center for Advanced Hindsight and head of behavioral science for a Durham health app startup called Pattern Health.

Aline Gruneisen Holzwarth

Aline Holzwarth is a principal in the Center for Advanced Hindsight.

“It’s not enough to simply inform people to eat better,” Holzwarth said. The app has to secure a commitment from the user, make them set small goals and then ask how they did, enlist the help of social pressures, and then dole out rewards and punishments as needed.

Pattern Health’s app says “You need to do this, please pick a time when you will.” Followed by a reward or a consequence.

Thursday’s session, “Using Behavioral Science to Drive Digital Health Engagement and Outcomes, was the penultimate session of the annual Duke Digital Health Week. Except for the Hurricane Florence washout on Monday, the week  has been a tremendous success this year, said Katie McMillan, the associate director of the App Gateway.

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