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Stopping teen dating violence a priority for Jane Fonda

Jane Fonda, founder/chair of the Georgia Campaign for Adolescent Pregnancy Prevention (GCAPP), along with local teenagers and Atlanta community groups have launched the Start Strong: Building Healthy Teen Relationships Program. Its goal is to stop teen dating violence and abuse before it starts.

The Jane Fonda Center at Emory was chosen as one of 11 community organizations nationwide to receive $1 million in funding through the Robert Wood Johnson Foundation’s national Start Strong initiative. This is the largest national public health initiative ever funded, targeting 11-to-14-year-olds, to stop teen dating violence.

Jane Fonda speaks at the event

Jane Fonda speaks at the event

Fonda says the initiative, both locally and nationally, promises to educate and empower teens and their surrounding communities that dating violence and abuse among teenagers must be stopped before it ever starts.

With teen dating abuse a significant public health issue in this country, Fonda wants to focus on teaching young people to develop healthier and more positive relationships at an early age.

As part of this four-year initiative, Start Strong Atlanta will rally the entire community, including teenagers, parents, caregivers, educators, coaches and community leaders to build environments that support healthy relationships and ensure violence and abuse are never tolerated.

Students perform at the Start Strong event

Students perform at the Start Strong event

Melissa Kottke, MD, MPH, assistant professor in the Department of Gynecology and Obstetrics, Emory School of Medicine, is the director of the Jane Fonda Center. She notes that October is Domestic Violence Awareness Month and the campaign’s launch was the perfect tie-in. Kottke is also the principal investigator of the national initiative at Emory.

The Jane Fonda Center along with its partners, Atlanta Public Schools and Grady Memorial Hospital Teen Services Program, have together developed a comprehensive community plan for this initiative. This plan will focus on four core strategies involving education, policy change, community outreach and social marketing campaigns to empower local teens to develop healthier relationships.

Learn more about Start Strong Atlanta and other related events going on during Domestic Violence Awareness Month. Find out what Fonda said about the event on her blog.

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Evolution doesn’t run backwards: Insights from protein structure

“The past is difficult to recover because it was built on the foundation of its own history, one irrevocably different from that of the present and its many possible futures.”

Whoa. This quote comes from a recent Nature paper. How did studying the protein that helps cells respond to the stress hormone cortisol inspire such philosophical language?

Biochemist Eric Ortlund at Emory and collaborator Joe Thornton at the University of Oregon specialize in “resurrecting”and characterizing ancient proteins. They do this by deducing how similar proteins from different organisms evolved from a common root, mutation by mutation. Sort of like a word ladder puzzle.

Ortlund and Thornton have been studying the glucocorticoid receptor, a protein that binds the hormone cortisol and turns on genes in response to stress. The glucocorticoid receptor is related to the mineralocorticoid receptor, which binds hormones such as aldosterone, a regulator of blood pressure and kidney function.

If these receptors have a common ancestor, you can model each step in the transformation that led from the ancestor to each descendant. But Ortlund says that protein evolution isn’t like a word ladder puzzle, which can be turned upside-down: “You can’t rewind the tape of life and have it take the same path.”

The reason: Mutations arise amidst a background of selective pressure, and mutations in one part of a protein set the stage for whether other ones will be viable. The researchers describe this as an “epistatic rachet”.

Mutations that occurred during the transformation between the ancestral protein (green) and its descendant (orange) would clash if put back to their original position.

Mutations that occurred during the transformation between the ancestral protein (green) and its descendant (orange) would clash if put back to their original position.

This work highlights the increasing number of structural biologists like Ortlund, Christine Dunham, Graeme Conn and Xiaodong Cheng at Emory. Structural biologists use techniques such as X-ray crystallography to figure out how the parts of biology’s machines fit together. Recently Emory has been investing in the specialized equipment necessary to conduct X-ray crystallography.

As part of his future plans, Ortlund says he wants to go even further back in evolution, to examine the paths surrounding the estrogen receptor, which is also related to the glucocorticoid receptor.

Besides giving insight into the mechanisms of evolution, Ortlund says his research could also help identify drugs that activate members of this family of receptors more selectively. This could address side effects of drugs now used to treat cancer such as tamoxifen, for example, as well as others that treat high blood pressure and inflammation.

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Raising awareness for sickle cell disease

September is National Sickle Cell Awareness Month, and when it comes to assessing and treating sickle cell disease, there is no other place in the world like the Georgia Comprehensive Sickle Cell Center at Grady Memorial Hospital.

James R. Eckman, MD

James R. Eckman, MD, with a patient

Led by James R. Eckman, MD, pioneering medical director and professor of medicine at Emory School of Medicine, the Center is the world’s first 24-hour comprehensive primary care clinic for patients with sickle cell syndromes. It is comprised of a multidisciplinary team with the a mission to educate and provide preventative and comprehensive primary care, while responding to sickle cell emergencies quickly and efficiently.

Millions of people worldwide suffer from the affects of sickle cell anemia – especially those of African, Mediterranean and Indian descent. According to CDC, more than 70,000 people in the United States have sickle cell disease, mostly African Americans. Each year more than 1,000 babies are born with sickle cell disease.

The inherited disorder affects the blood’s hemoglobin, which produces stiff, misshapen red blood cells that deliver less oxygen and can disrupt blood flow, resulting in joint and organ damage and potential clots and strokes. The sickling of red blood cells is aggravated by infections, extreme hot or cold temperatures, poor oxygen intake, not drinking enough fluids and stress.

Read more

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Reality check for HIV vaccine design

HIV doesn’t have a brain and it doesn’t strategize.

But the way that the virus mutates and evades the immune system in the early part of an infection, you might think it did.

Emory Vaccine Center researcher Cynthia Derdeyn and her colleagues have a new paper in PLOS Pathogens that is a reality check for researchers designing possible HIV vaccines. The results come from a collaboration with the Rwanda Zambia HIV Research Group. (Although the patients in this paper are from Zambia only.)

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems. The rest of the envelope protein is blue.

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems.

Recently there has been some excitement over the discovery of robust neutralizing antibodies in patients.

The bottom line, according to Derdeyn’s team: even if a vaccine succeeds in stimulating antibodies that can neutralize HIV, the virus is still going to mutate furiously and may escape those antibodies. To resist HIV, someone’s immune system may need to have several types of antibodies ready to go, their results suggest.

A companion paper in the same issue of PLOS Pathogens from South African scientists has similarly bracing results.

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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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Pancreatic cancer: Front and center

With the sad news today of the death of actor Patrick Swayze, the public is again focused on pancreatic cancer and searching for more information on this aggressive cancer.

Recently, David Kooby, MD, Emory Winship Cancer Institute, and an assistant professor, Department of Surgical Oncology, authored a blog for the Atlanta Journal-Constitution’s “Doctor Is In” on this topic.

Emory Winship Cancer Institute

Emory Winship Cancer Institute

The following is an excerpt from the blog:

Pancreatic cancer is an aggressive malignancy that begins in the cells of the duct (or tube) running along the length of the pancreas. Each year about 42,000 new cases of pancreatic cancer are diagnosed and more than 35,000 people die from this cancer. A diagnosis of pancreatic cancer is usually made after discovery of a mass or a dilated duct in the pancreas.

Pancreatic cancer can be difficult to diagnose. Patients often come in for a doctor’s visit with non-specific symptoms such as abdominal or back pain or weight loss. Some patients will develop jaundice (yellowing of the skin) as a result of the tumor blocking the duct draining bile from the liver

No one knows the exact causes of pancreatic cancer, although some risk factors are known through research that has been done.

According to the National Cancer Institute, the following are risk factors for development of pancreatic cancer:

  • Age — The likelihood of developing pancreatic cancer increases with age. Most pancreatic cancers occur in people over the age of 60.
  • Smoking — Cigarette smokers are two or three times more likely than nonsmokers to develop pancreatic cancer.
  • Diabetes mellitus — Pancreatic cancer occurs more often in people who have diabetes than in people who do not.
  • Being male — More men than women are diagnosed with pancreatic cancer.
  • Being African-American — African-Americans are more likely than Asians, Hispanics or whites to get pancreatic cancer.
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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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Manage stress to your advantage

Recently Charles Raison, MD, assistant professor, Emory Department of Psychiatry and Behavioral Sciences, wrote a blog for the Atlanta Journal-Constitution on stress. As clinical director of the Emory Mind-Body Program and director of the Behavioral Immunology Program, he has been studying stress.

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Raison says stress is everywhere today, both in our private and public lives, but also relentlessly in print, with discussion after discussion regarding what it is and what can be done to ease it.

He notes that you should think of stress like a sandwich. One trick for dealing with stress is to try to stay in the middle of the stress sandwich in the meat of life – the optimal challenge. The basic idea, he comments, is that you see what’s in front of you as a challenge, neither boring nor threatening, difficult enough to keep you fully engaged, easy enough for you to accomplish your goals.

You can read more by Raison by visiting the Atlanta Journal-Constitution Doctor Is In blog online.

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