Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

Research

World Alzheimer’s Day – brain health tips from Emory

Today is World Alzheimer’s Day 2009 and Emory’s Alzheimer’s Disease Research Center is part of an effort nationwide to address this disease through research and state-of-the-art care for patients.

Allan Levey, MD, PhD, chair of Emory’s Department of Neurology and an Alzheimer’s researcher and clinician, says millions of baby boomers are entering late adulthood and experts expect the number of patients with Alzheimer’s disease to increase drastically over the next several decades. Prevention and early detection are extremely important, he says.

Emory’s Center is a National Institute on Aging funded center focused on clinical trials and research for Alzheimer’s disease. It is the only comprehensive program in Georgia and one of only 32 nationwide.

Levey, who directs the Center, offers the tips for good brain health:

Stay socially active
Remaining socially engaged in activities that stimulate the mind and body can reduce stress levels and help maintain healthy connections among brain cells.

Stay active, say experts

Stay active, say experts

Be physically active
Exercising your body regularly is vital for maintaining good blood flow to the brain and encouraging the growth of new brain cells.

Stay mentally active
Your brain needs mental stimulation to allow it to function at its peak. Research shows that keeping the brain active helps increase its vigor and may strengthen brain cells and the connections between them, and may even generate new ones.

Protect your head
Injury to the head can increase your risk of dementia as you get older. Make sure you wear a helmet when you ride a bike, skate, ski or engage in any activity where you may injure yourself.

Eat brain healthy foods
The brain, like the heart, needs the proper balance of nutrients, including protein and sugar, to optimally function. According to current research, certain foods appear to protect brain cells so increase your intake of these protective foods.

Levey says scientists are finding more clues that high blood pressure, high cholesterol and diabetes may increase a person’s risk of getting Alzheimer’s disease. He says to keep your weight in a healthy range, lower your cholesterol if it is high and maintain control of your blood glucose and blood pressure.

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Delivering nutrition to critical care patients

Emory clinical nutrition expert Thomas Ziegler, MD, has a case report article in the Sept. 10 issue of the New England Journal of Medicine.

The case report describes a woman with diabetes who needed surgery because of loss of blood flow to abdominal organs. While she is in intensive care after surgery, it becomes clear that a feeding tube leading from her nose to her stomach is not working. That makes her a good candidate for parenteral nutrition, or bypassing the digestive system and delivering nutrients directly into her blood.

Malnutrition is common in patients who are critically ill and often worsens with prolonged hospitalization. Some patients can’t eat normal food or benefit from a feeding tube into the stomach.

Thomas Ziegler, MD, Director, Center for Clinical and Molecular Nutrition, Department of Medicine

Thomas Ziegler, MD, Director, Center for Clinical and Molecular Nutrition, Department of Medicine

Yet few well-designed clinical trials studying parenteral nutrition have been conducted, Ziegler writes. He also notes that there is considerable debate over when parenteral nutrition is appropriate during critical care and how to administer it.

Ziegler’s own research has shown the beneficial effects of the amino acid glutamine, which must be added fresh to feeding formulas, for some critical care patients.

Several of the questions Ziegler outlines in his article will be issues investigators at Emory’s new Center for Critical Care will tackle. Recently, Timothy Buchman, MD, PhD, joined Emory to lead the critical care team.

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Voles and the neurochemistry of social behavior

A new study has shown that prairie voles may be a useful model in understanding the neurochemistry of social behavior. By influencing early social experience in prairie voles, researchers hope to gain greater insight into what aspects of early social experience drive diversity in adult social behavior.

VolesPrairie voles are small, highly social rodents that often form stable, life-long bonds between mates. In the wild, there is striking diversity in how offspring are reared. Some pups are reared by single-mothers, some by both parents (with the father providing much of the same care as the mother) and some in communal family groups.

Researchers Todd Ahern, a graduate student in the Emory Neuroscience Program, and Larry Young, PhD, professor of psychiatry and behavioral sciences at the Yerkes National Primate Research Center and Emory School of Medicine, compared pups raised by single mothers (SM) to pups raised by both parents (BP) to determine the effects of these types of early social environments on adult social behavior.

The study showed SM- and BP-reared animals experienced different levels of care during the neonatal period and that these differences significantly influenced bonding social behaviors in adulthood. Pups raised by single mothers were slower to make life-long partnerships, and they showed less interest in nurturing pups in their communal families.

Researchers also found differences in the oxytocin system. Oxytocin is best known for its roles in maternal labor and suckling, but, more recently, it has been tied to prosocial behavior, such as bonding, trust and social awareness. Very simply, altering their early social experience influenced adult bonding.

Further studies will look at the altered oxytocin levels in the brain to determine how these hormonal changes affect relationships.

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Healthy aging on the Emory front

Emory’s Center for Health and Aging is addressing health care issues affecting the rapidly growing senior population in the United States through research, clinical care, community outreach and education.

One of the greatest challenges now facing the health care system in the United States is the rapid growth of the numbers of aging adults. It will have an unprecedented impact on the delivery of medical care, including supply of and demand for health care workers.

It is expected that the supply of health care providers may decrease at a time huge numbers of workers retire or reduce their working hours. And older adults consume a disproportionate share of American health care services, resulting in greater demand for services.

There are compelling demographic reasons to study aging. According to U.S. census records, a wave of 2.7 million Americans will turn 65 by 2011, and each succeeding year the swell gets higher until it peaks in 2025 with 4.2 million new 65-year-olds. By 2030, when the youngest boomers have become seniors, the number of Americans 65 and older is expected to be more than 70 million – nearly twice as many as in 2005, according to a report by the National Academies’ Institute of Medicine

Ted Johnson, MD

Ted Johnson, MD, MPH

Led by Theodore (Ted) Johnson II, MD, MPH, the Center benefits from well-established and successful programs in clinical care, aging research and education at Emory’s Wesley Woods Center, one of the nation’s few campuses devoted to the health and well being of older adults.

Wesley Woods is one of the nation’s most comprehensive centers for aging-related research, care and quality of life, serving more than 30,000 elderly and chronically ill patients each year through outpatient clinics, a hospital, skilled nursing care facility and residential retirement facility. In addition, Emory is affiliated with the Atlanta Veterans Affairs Medical Center, which has an extensive array of geriatric clinical, research and training programs.

The health care implications for seniors in Georgia and the U.S. are tremendous, according to Johnson. He says that the sheer numbers of older adults will place strains on our healthcare system and the family and professional caregivers who help them.

Johnson,who heads Emory’s Division of Geriatric Medicine and Gerontology, notes that it’s the cumulative effect of that surge – plus the fact that people are living far longer than ever before – that poses a looming crisis for the health care system.

For a glimpse of aging care and research at Emory: dementia research, Alzheimer’s DETECT device, diagnosing memory loss, preventing heart failure, disease prevention through nutrition, aging and fitness, and more about health initiatives at Emory Healthcare.

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Helping stem cells find their new homes

The idea that doctors could use stem cells to treat diseases ranging from amyotrophic lateral sclerosis (ALS) to stroke, spinal cord injury and heart disease has stimulated excitement and research funding over the last decade.

One critical obstacle is getting the stem cells to survive in the harsh environment of injured tissue and turn into the right kind of cell where they are needed. In both laboratory experiments and clinical trials, most of the stem cells usually die a few days after transplantation.

Exposing stem cells to reduced levels of oxygen may actually help protect them from the stressful process of being transplanted into the heart, according to recent research.

Shan Ping Yu and Ling Wei, who moved their laboratories about a year ago to Emory’s Department of Anesthesiology, were the first to show the effects of “hypoxic preconditioning.” Wei says the low oxygen strategy is a continuation of previous collaboration with Comprehensive Neurosciences Center director Dennis Choi. There, they had used the tactic of overexpressing BCl2, a gene that counteracts cell death, but the new approach avoids permanently altering the genes in stem cells, which may have long-term adverse effects.

Effects on mesenchymal stem cells' ability to implant into heart tissue. In D, the stem cells were exposed to low oxygen but in C they were not. Blue shows all cell nuclei, while green shows implanted stem cells. Yellow indicates the activation of an enzyme that leads to cell death.

Effects on mesenchymal stem cells' ability to implant into heart tissue in rats. In D, the stem cells were exposed to low oxygen but in C they were not. Blue shows all cell nuclei, while green shows implanted stem cells. The greater presence of yellow in C, a couple days after transplantation, displays the activation of an enzyme that leads to cell death. From the Journal of Thoracic and Cardiovascular Surgery.

In a way, this is consistent with the work of former Emory investigator Marie Csete, who showed that stem cells are happier and healthier in oxygen concentrations that reflect the levels they experience in the body: between 2 and 5%.

To achieve their protective effects, Yu and Wei are using oxygen concentrations of 0.5%. For comparison, room air has about 20% oxygen.

In an editorial, Yu, Wei and graduate student Molly Ogle discuss how they have been exploring whether inhibitors of enzymes that sense levels of oxygen in cells could have the same protective effects as exposure to low oxygen. Yu also reports that his group is studying how low oxygen helps stem cells home to target tissues better. Their hypothesis is that low oxygen stimulates cells’ motility — their ability to migrate into the right place. Wei’s research has shown that lower oxygen helps more stem cells to turn into neuronal cells.

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Study looks at teenage brain and risk-taking

A new study using brain imaging to study teen behavior indicates that adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

The brain goes through a course of maturation during adolescence and does not reach its adult form until the mid-twenties. A long-standing theory of adolescent behavior has assumed that this delayed brain maturation is the cause of impulsive and dangerous decisions in adolescence. The new study, using a new form of brain imaging, calls into question this theory.

In order to better understand the relationship between high risk-taking and the brain’s development, Emory University and Emory School of Medicine neuroscientists used a form of magnetic resonance imaging (MRI) called diffusion tensor imaging (DTI) to measure structural changes in white matter in the brain. The study’s findings are published in the Aug. 26, 2009 PLoS ONE.

“In the past, studies have focused on the pattern of gray matter density from childhood to early adulthood, says Gregory Berns, MD, PhD, principal investigator and professor of Psychiatry and Neuroeconomics at Emory University and director of the Center for Neuropolicy. “With new technology, we were able to develop the first study looking at how development of white matter relates to activities in the real world.”

Gray matter is the part of the brain made up of neurons, while white matter connects neurons to each other. As the brain matures, white matter becomes denser and more organized. Gray matter and white matter follow different trajectories. Both are important for understanding brain function.

Berns suggests that doing adult-like activities requires sophisticated skills.

“Society is a lot different now than it was 100 years ago when teens were expected to go to work and raise a family,” says Berns. “Now, adolescents aren’t expected to act like adults until they are in their twenties, when they have finished their education and found a career. Listen to Berns discuss the changing definition of adulthood.

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A shift in how geneticists study complex diseases

An Emory project studying schizophrenia genetics is a good example of how geneticists are shifting from examining small, common mutations to “rare variants” when studying complex diseases.

From studies of twins, doctors have known for a long time that heredity plays a big role in causing schizophrenia. But dissecting out which genes are the most important has been a challenge.

Three landmark studies on schizophrenia genetics published this summer illustrate the limitations of “genome wide association” studies. New York Times science reporter Nicholas Wade summarized the results in this way:

“The principal news from the three studies is that schizophrenia is caused by a very large number of errant genes, not a manageable and meaningful handful.”

The limitations from this type of study comes from the type of markers geneticists are looking at, says Steve Warren, chair of the human genetics department at Emory.

Genome wide association studies usually follow SNPs — single nucleotide polymorphisms. This is a one-letter change somewhere in the genetic code that is found in a fraction of the population. It’s not a big change in the genome, and in many cases, it will have a small effect on disease risk.

Researchers looking for the genes behind complex diseases such as schizophrenia and autism are starting to shift their efforts away from genome wide association studies, Warren says.

Think of a SNP like a misspelling of a word in a certain place in a book, he says. In contrast, the “rare variants” geneticists are starting to study more intensively are more like printers’ errors or missing pages. The rapid sequencing technology that allows scientists to investigate these changes easily is just now coming on line, he says.

One example of these rare variants is DiGeorge syndrome, a deletion that gets rid of dozens of genes on one copy of chromosome 22. Children who have this chromosomal alteration often have anatomical changes to their heart and palate. But it also substantially increases the risk of schizophrenia – to about 25% lifetime risk. That’s a lot more than any of the SNPs identified this summer.

Working with several Emory colleagues, researcher Brad Pearce is planning to examine the genes missing in DiGeorge syndrome in several groups of patients: people with DiGeorge, patients with “typical” schizophrenia and people at high risk of developing schizophrenia.

An article in this spring’s Emory Health describes genetic research on autism. Several of the researchers mentioned there, such as geneticist Joe Cubells and psychiatrist Opal Ousley, are involved in this schizophrenia project as well, because deletions on chromosome 22 also lead to an increased risk of autism.

Pearce’s project is funded through American Recovery and Reinvestment Act money from the NIH.

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Gaining better medicine in translation

 

David Stephens, MD

David Stephens, MD

Translational research has traditionally been thought of as the process of moving a discovery in one direction – from the laboratory to the patient. More recently, though, researchers have recognized the importance of community engagement in the biomedical discovery process. That’s because involving the community makes for better medical care for patients.

The Atlanta Clinical and Translational Science Institute (ACTSI) is a partnership of educational, research, and health care institutions that involves the community in clinical research that translates laboratory discoveries into advanced treatments for patients. The ACTSI is part of the Clinical and Translational Science Awards (CTSA) of the National Center for Research Resources (NCRR) of the National Institutes of Health.

The ACTSI’s goal of supporting more effective clinical and translational research has led to a broader definition of translation: discovering what new healthcare tools, diagnostic tests and therapies a community needs and then taking that information back to the laboratory or conducting clinical research to find ways to meet those needs.

David Stephens, MD, is principal investigator of the ACTSI. Stephens says community engagement brings together leaders who discuss the health care needs of their respective communities. Researchers can then periodically meet with leaders, and let them know what progress is being made in the laboratory.

The ACTSI also brings together laboratory scientists with clinical investigators, community clinicians, professional societies and industry collaborators in a wide variety of research projects.

The ACTSI is led by Emory University, along with Morehouse School of Medicine, the Georgia Institute of Technology, Children’s Healthcare of Atlanta, and Kaiser Permanente Georgia. Other partners include the Centers for Disease Control and Prevention, Grady Health System, the Georgia Research Alliance, Georgia Bio, the Atlanta Veterans Affairs Medical Center, and the American Cancer Society.

To hear Stephens’ own words about translational research and the ACTSI, listen to Emory University’s Sound Science podcast.

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H1N1 pediatric flu vaccine clinical trials underway

Emory doctors discuss H1N1 flu vaccine testing

Emory doctors discuss H1N1 flu vaccine testing

Clinical trials are underway at Emory and Children’s Healthcare of Atlanta testing an investigational H1N1 flu vaccine along with the seasonal flu vaccine. Emory will enroll about 100 children, ages six months to 18 years, and up to 650 children nationally will participate in the study.

The study will look at the safety of and measure the body’s immune response to the H1N1 flu vaccine. In addition, it will help determine how and when the vaccine should be given with the seasonal flu vaccine to make it most effective.

Another important factor is learning if there are any potential problems by giving the vaccines together, such as whether one vaccine will undermine the protective power of the other.

The answer is important because experts are predicting that both strains of flu will circulate this fall and winter.

The clinical trial is part of the Vaccine and Treatment Evaluation Units (VTEUs), supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). At Emory, this team is led by Mark Mulligan, MD, executive director of the Hope Clinic of the Emory Vaccine Center.

The Emory pediatric clinical trial is taking place at the Emory-Children’s Center. It is led by Emory VTEU co-directors Harry Keyserling, MD, professor of pediatric infectious diseases at Emory School of Medicine and Paul Spearman, MD, chief research officer for Children’s Healthcare of Atlanta and vice chair of research for Emory’s Department of Pediatrics, along with Allison Ross, MD, Emory assistant professor of pediatric infectious diseases.

Keyserling says that because children and young adults are considered among the most vulnerable populations for new and emerging strains of influenza, such as the current H1N1 pandemic, it is critically important that testing for a vaccine is quick and efficient.

The pediatric trial follows the launch of a VTEU-led adult clinical trial of the H1N1 and seasonal flu vaccines, which began at Emory’s Hope Clinic on Aug. 10 and will continue with followup visits for the next six weeks by a group of more than 170 volunteers.

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Jeff Koplan discusses H1N1 on panel

Experts on H1N1 influenza are collaborating all across the country to learn more about the virus and how to prevent its transmission. In a race against time, Emory studies are taking place in the lab and in human clinical trials to help find a vaccine that can be used in the near weeks to come.

Recently, Emory’s Jeff Koplan, MD, vice president for global health and past CDC director, participated in a Breakthroughs panel sponsored by Big Think, Pfizer and Discover to discuss the latest issues in pandemic and genomic science, fields that have not only made big headlines recently but also promise to be two of the most pressing topics in global science and medicine in coming years.

Jeffrey P. Koplan, MD, MPH

Jeffrey P. Koplan, MD, MPH

The panel focused on the real-time, round-the-clock scientific mission to understand the history, significance, and future of the new strain of flu that emerged suddenly this spring. Panelists included Koplan; Barry Bloom, Joan L. and Julius H. Jacobson Professor of Public Health at Harvard; Peter Palese, chairman of the microbiology department at Mt. Sinai Medical Center; and Michael Worobey, ecologist and evolutionary biologist at the University of Arizona.

View: Superbug – Are We Prepared for The Next Great Plague?


Emory began signing up several hundred interested volunteers several weeks ago for a clinical trial of the H1N1 vaccine along with the seasonal flu vaccine. About 170 adults have now been vaccinated in the trial, which will last about nine weeks and involve several vaccinations and blood tests. A clinical trial testing the H1N1 vaccine in children will begin at Emory and Children’s Healthcare of Atlanta in the next few days, followed by another adult clinical trial adding an adjuvant to the H1N1 vaccine.

In addition, a multi-pronged attack against the H1N1 virus by Emory researchers is using a new method of rapidly producing highly targeted monoclonal antibodies to develop a diagnostic test as well as a temporary therapy to stave off the H1N1 virus. The antibodies, which can be isolated from a small amount of the blood of humans infected with the virus, could be targeted against H1N1 and rapidly reproduced to detect or attack the virus.

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