Two items relevant to long COVID

One of the tricky issues in studying in long COVID is: how widely do researchers cast their net? Initial reports acknowledged that people who were hospitalized and in intensive care may take a while to get back on their feet. But the number of people who had SARS-CoV-2 infections and were NOT hospitalized, yet experienced lingering symptoms, may be greater. A recent report from the United Kingdom, published in PLOS Medicine, studied more than Read more

All your environmental chemicals belong in the exposome

Emory team wanted to develop a standard low-volume approach that would avoid multiple processing steps, which can lead to loss of material, variable recovery, and the potential for Read more

Signature of success for an HIV vaccine?

Efforts to produce a vaccine against HIV/AIDS have been sustained for more than a decade by a single, modest success: the RV144 clinical trial in Thailand, whose results were reported in 2009. Now Emory, Harvard and Case Western Reserve scientists have identified a gene activity signature that may explain why the vaccine regimen in the RV144 study was protective in some individuals, while other HIV vaccine studies were not successful. The researchers think that this signature, Read more

pediatrics

Playing tetherball with HIV

Raise your hand if you played tetherball in grade school. Paul Spearman and his colleagues have a new paper in the journal Cell Host & Microbe probing a protein called “tetherin” that keeps HIV ensnared within cells it is infecting.

The paper includes electron microscopy images that make it possible to imagine a tiny cord attached to a nascent HIV particle within the cell. In these images, we don’t see the tetherin protein directly. However, we do see gold beads, bound to antibodies against the tetherin protein, which indicate where the protein is. The microscopy was performed at Emory’s Robert P. Apkarian Integrated Electron Microscopy Core.

Tetherin is a so-called “restriction factor,” one of several proteins within the cell that interfere with parts of the viral life

The black dots are antibody-linked gold beads, which indicate where the tetherin is. The larger globules are viral capsids.

cycle. Other restriction factors include enzymes that strip the viral RNA or impede the assembly of the viral capsid. Tetherin also interferes with a variety of other viruses such as Ebola.

Some viral proteins such as HIV’s Vpu or Nef fight back against the action of tetherin. Tracking how this kind of arms race has developed can help scientists follow how HIV evolved from similar retroviruses that infect non-human primates. In addition, knowing how tetherin works could be important in efforts to eradicate potential reservoirs of HIV in infected individuals, and in understanding how the virus is transmitted from person to person.

In their paper, first author Hin Chu and Spearman wanted to determine why infection looks different in two different cell types vulnerable to HIV. In T cells, HIV assembly occurs near the membrane, but in macrophages, HIV assembly occurs in an internal compartment.

“The reason that there is a large, internal collection of HIV particles in macrophages is hotly debated,” Spearman explains. “Some see this as a reservoir of virus that is available to spread to other cells, others would say this is a dead-end compartment. We found that the compartment basically goes away when we deplete tetherin, so tetherin is essential to the existence of the virus-containing compartment.”

Chu and his co-workers examined what happened in macrophages when they used a tool called “RNA interference” to turn off the tetherin gene.

Hin Chu

“We found that cell-cell transmission was enhanced when we depleted tetherin. My interpretation is that when tetherin is upregulated in macrophages, viral particles are rapidly internalized and are not transmitted.”

“Another significant finding is that Vpu doesn’t work well in macrophages. If we can determine why it doesn’t work well in this cell type, it will help us understand how Vpu does work so efficiently in other cells such as T cells. Macrophages are one of the most important cell types infected by HIV, so these questions are likely to be very important in how virus spreads and is maintained in infected individuals.”

Spearman is chief research officer for Children’s Healthcare of Atlanta and director of the Children’s Center for Vaccines and Immunology, within the Emory-Children’s Pediatric Research Center. He is also professor and vice chair of research in pediatrics at Emory. Hin Chu is a graduate student in the Microbiology and Molecular Genetics program.

Posted on by Quinn Eastman in Immunology 1 Comment

Americans cutting sugar – but it’s still not enough

In America’s battle against obesity, there is some good news. According to a study conducted by Emory researchers, Americans consumed nearly a quarter less added sugars in 2008 than they did 10 years earlier.

The study, published in the American Journal of Clinical Nutrition in July 2011, found that the consumption of added sugars, such as those found in sodas, sports drinks, juices and sweetened dairy products, decreased among all age groups over a decade. The largest decrease came in the consumption of sodas, traditionally the largest contributor to added sugar consumption, according to Jean Welsh, MPH, PhD, RN, study author and post-doctoral fellow in pediatric nutrition at Emory University School of Medicine.

“While we were hopeful this would be the case, we were surprised when our research showed such a substantial reduction in the amount of added sugar Americans are consuming,” said Welsh. “We’re hopeful this trend will continue.”

So, why the change? One of Welsh’s partners in the study, Miriam Vos, MD, MSPH, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Children’s Healthcare of Atlanta, attributes much of the shift to public education.

“Over the past decade, there has been a lot of public health awareness about obesity and nutrition, and I think people are starting to get the message about sugar,” says Vos. “We’re not trying to send a message that sugar is inherently bad. It’s more that the large amounts of sugar we consume are having negative effects on our health, including increasing our risk of obesity, diabetes and cardiovascular disease.”

The study interpreted data of 40,000 people’s diets collected by the Centers for Disease Control and Prevention (CDC) over 10 years.  From the surveys, researchers were able to calculate how much added sugar – that is sugar that is not originally part of a food – that Americans are consuming. In 1999-2000, the typical person’s daily diet included approximately 100 grams of added sugar, a number that had dropped to 77 grams by 2007 and 2008.

While the study shows that the amount of added sugar Americans are consuming is lower, it doesn’t mean the amount is low enough.

“The American Heart Association recommends that we get about five percent of our calories from added sugars,” says Vos. “In 1999 to 2000, people were consuming about 18 percent of their calories from added sugars. Over 10 years, that amount decreased to 14.5 percent of our daily calories, which is much better. But, clearly, 14.5 percent is still three times more than what is considered a healthy amount. We’re on the right track, but we still have room for improvement.”

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Emory experts weigh in on obesity at AACC Annual Meeting

The obesity epidemic took center stage at this year’s American Association of Clinical Chemistry (AACC) Annual Meeting. Several Emory experts took the podium to further explore obesity not only as a public health problem, but also as an issue that is changing the way we diagnose diseases and treat health issues in children.

Jeffrey Koplan, MD, MPH

Jeffrey Koplan, MD, MPH, director of the Emory Global Health Institute, led one of the meeting’s plenary sessions, emphasizing that obesity must be fought with changes in both public policy and personal decision-making. Koplan also noted that strategies to address obesity must be localized to fit each community because eating and exercise habits are often culturally specific.

Rising rates of obesity also are changing the way physicians and researchers define and diagnose certain diseases, including metabolic syndrome, a cluster of risk factors including insulin resistance, high blood pressure, cholesterol abnormalities and an increased risk for clotting. The common thread among patients with metabolic syndrome is that they are often overweight or obese.

Ross Molinaro, PhD

Pathologist Ross Molinaro, PhD, medical director of the Core Laboratory at Emory University Hospital Midtown and co-director of the Emory Clinical Translational Research Laboratory, presented insights into the important role of lab testing in the definition and diagnosis of metabolic syndrome.  In addition to new markers, Molinaro addressed the global prevalence of metabolic syndrome and the evolving criteria for diagnosis.

Miriam Vos, MD, MSPH

Responding to their members’ demand for more information on how obesity affects children, the AACC hosted a full-day symposium on pediatric obesity and related health complications such as diabetes and high blood pressure.  Miriam Vos, MD, MSPH, assistant professor of pediatrics in  Emory School of Medicine and a physician at Children’s Healthcare of Atlanta described non-alcoholic fatty liver disease as an increasingly common complication of childhood obesity that can cause inflammation and scarring of the liver.

Stephanie Walsh, MD

Stephanie Walsh, MD, assistant professor of pediatrics in Emory School of Medicine and medical director of child wellness at Children’s Healthcare of Atlanta, leads Children’s efforts in preventing and treating childhood obesity in Georgia, which currently has the second highest rate of childhood obesity in the country. Walsh addressed the effect of Children’s wellness initiative, called Strong4Life, on childhood obesity prevention in Georgia.

“From those in the lab, to those in clinic, to those who strategize and implement public health campaigns, we’re all going to need to work together to protect our children’s future,” says Walsh.

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Emory University Hospital Set to Be Launch Site for EPIC

Can it really be possible to transform a person’s own cells into a weapon against various forms of disease? And what if those very cells could be retrained to attack cancer cells or to prevent autoimmune diseases?

Answers to these questions and many more are about to soon be realized, as Emory University Hospital will serve as the launch site for the very appropriately-named EPIC (Emory Personalized Immunotherapy Center).

The new Center, which is the creation of Dr. Jacques Galipeau, MD, professor of hematology and medical oncology & pediatrics of Emory University, will soon be operational after final touches have been put on construction of the lab. This cell processing facility will foster development of novel personalized cellular therapies for Emory patients facing catastrophic ailments and unmet medical needs.

According to Galipeau, the premise of EPIC and its overlying mission will focus on cellular and biological therapies that use a patient’s own cells as a weapon to seek and destroy cells that actually make a person sick. In partnership with the Winship Cancer Institute of Emory University, Children’s Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center and the Emory School of Medicine, EPIC seeks to improve the health of children and adults afflicted with cancer and immune disease.

“First and foremost, we seek to bring a level of care and discovery that is first in Georgia, first in human and first in child. Blood and marrow derived cells have been used for more than a quarter century to treat life threatening hematological conditions and are now established therapies worldwide. More recently, the use of specific adult somatic cells from marrow, blood and other tissues are being studied in cellular medicine of a wide array of ailments including heart, lung, neurological and immune diseases,” says Galipeau. “The use of blood borne immune cells can also be exploited for treatment of cancer, autoimmune disease, organ transplantation and chronic viral illnesses such as HIV.”

Galipeau said that once operational, EPIC will begin by working with Crohn’s disease in pediatric and adult patients, an inflammatory bowel disease. Symptoms of Crohn’s disease include severe abdominal pain, diarrhea, fever, weight loss, and the inability for a child to properly grow. Resulting bouts of inflammation may also affect the entire digestive tract, including the mouth, esophagus and stomach.  In some cases, a radical surgery involving the removal of part of the lower intestinal tract is required.

“There is no current answer for what specifically causes Crohn’s disease, nor is there a cure. But we hope that through our research and efforts, we will be able to first target the inflammatory mechanisms in these patients through immunotherapy, and in turn reduce the amount of flare-ups and limit  the damage that occurs from this disease,” says Galipeau.

Galipeau says the EPIC program could represent a powerful cornerstone to the launch and the development of an entirely new, Emory-based initiative which bundles the strengths of the School of Medicine, Emory University Hospital, Children’s Healthcare of Atlanta, and many Woodruff Health Sciences Center centers of excellence,” says Galipeau.

“My ultimate goal is to elevate the biomedical scientific and scholarly enterprise to a higher level – making a difference in the lives of people. The EPIC program and multi-levels of support could be a fundamental underpinning to our success.”

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Emory researchers receive grants to further work in pediatric brain tumor research

Dr. Castellino explains his research on medulloblastomas to participants attending the SBTF’s Grant Award Ceremony.

Two Emory researchers are being recognized by the Southeastern Brain Tumor Foundation (SBTF) for their work in pediatric brain tumor research.

Tracey-Ann Read, PhD, assistant professor in the Department of Neurosurgery, Emory University School of Medicine and director of the Pediatric Neuro-Oncology Laboratory at Emory was awarded a $75,000 grant for her work. She is studying the cell of origin that is responsible for the highly malignant pediatric brain tumor known as an Atypical Teratoid Rhabdoid Tumor (AT/RT). She is also developing a mouse model to study this very lethal brain cancer that occurs in early childhood.

Robert Craig Castellino, MD, assistant professor of pediatrics at Emory and pediatric hematologist/oncologist at Children’s Healthcare of Atlanta at Egleston received $50,000 to support his research efforts. He is studying how the childhood brain cancer, known as medulloblastoma, can metastasize from the brain to other sites in the body, specifically the spine. Medulloblastoma is the most common pediatric malignant brain tumor.

SBTF board members and researchers who were awarded grants pose following the April ceremony.

Read and Castellino received the awards at the SBTF’s Grant Awards Ceremony in April at Emory University Hospital Midtown. Two other researchers from Duke University were also presented with grant money for their contributions in brain tumor research in adults.

Emory neurosurgeon Costas Hadjipanayis, MD, PhD, is the president of the Southeastern Brain Tumor Foundation. He says research, from young investigators such as these, is crucial in the race to find a cure for brain tumors. As federal research funding becomes even more difficult to obtain with cuts in funding, private foundation grants, such as from the SBTF, can permit researchers to start important research projects that can provide preliminary data for bigger grant proposals.

The SBTF awards $200,000-300,000 each year to major medical centers throughout the Southeast in support of cutting-edge brain and spinal tumor research.

 

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Kidney donation kicks off life-saving chain reaction


In this video, players in this extraordinary transplant exchange tell their story.
You can also watch “The Mother of All Swaps,” a news report from 11 Alive Atlanta

When Jon Pomenville of Anderson, SC, decided to donate a kidney altruistically to someone – anyone in need, anywhere in the country – little did he know his selfless sacrifice would in turn change the lives of not one, but numerous individuals and their families, including one little boy from Atlanta.

And little did he know that the selfless, anonymous act would quickly become not so anonymous. During a recent post-surgical clinic visit to Emory University Hospital, Pomenville met by accident – right in the transplant clinic waiting room – many of the individuals whose lives were changed. Soon the patients – recipients and donors – two father and son combinations and Pomenville, the man who would give to anyone – were hugging, shaking hands, and recounting their backgrounds and experiences.

Pomenville and the others, who were all part of what is called a paired kidney exchange, were unwittingly scheduled for appointments within a short period of one another. As one person began recounting the experience, eyes and ears began to focus on the tale being told from across a crowded room.

People involved in the six-person kidney exchange

A chance meeting in a doctors’ waiting room led to a meeting between most of the people involved in the paired kidney exchange.

The Emory Transplant Center created and opened its innovative Paired Donor Kidney Exchange Program in 2009, providing greater hope for patients in need of kidney transplants. According to Kenneth Newell, MD, director of Emory’s living donor program, a paired exchange donation allows healthy individuals to donate a kidney to either a friend, loved one, or even altruistically to a stranger, despite incompatible blood matches. In paired donation, a donor and recipient are matched with another incompatible donor and recipient and the kidneys are exchanged between the pairs.

The procedure is another form of living donor transplantation. Donated kidneys also come from recently deceased donors. While most kidneys from deceased donors function well, studies have shown that a kidney from a living donor, either a blood relative or an unrelated person, provides the greatest chance for long-term success.

“Paired donor exchanges allow us to cast a much wider net to find compatible donors and recipients,” says Newell. “With a paired kidney transplant, one incompatible donor-pair is able to give a healthy kidney to a compatible recipient. In exchange, the second donor-recipient pair will give a compatible kidney to the first donor-recipient pair, making two compatible living donor transplants possible and increasing the potential number of available donor kidneys. This option can help those patients waiting for kidney transplants who have family members or friends willing to be donors and who are medically suitable, but who have an ABO blood type that is incompatible with the recipient’s blood type.”

Because of Pomenville’s donation, a 7-year-old boy named Zion was able to receive a lifesaving kidney from an unrelated donor because his dad, Mike, was able to donate. His surgery took place at Children’s Healthcare of Atlanta at Egleston.

And Gerald Smith of Five Points, Ala., would receive his life-saving kidney because his son, Matt, a recent University of Alabama graduate, would donate his to Zion. And finally, 20 year-old Edward Hill of Macon, a young man with a history of health challenges, would also receive his transplant at Children’s Healthcare of Atlanta – completing the six-person cycle, although the donor of Edward’s kidney is still unknown.

And Zion and Matt Smith will not only share a common bond and connection throughout life in the form of a kidney, but something even sweeter that that … blue Powerade.

“I’ve always really enjoyed drinking Powerade, particularly the blue flavor,” says Smith. Shortly after Zion awoke from his surgery, he inexplicably began requesting the blue-tinted soft drink too.

Other powerful kidney transplant stories out of Emory:

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Children with Food Allergies Offered Better Diagnosis and Treatment with New Guidelines

Twenty years ago, food allergies had barely been heard of. Now, they are a $500 million health problem that affects more than 12 million Americans, including three million children. New federal guidelines issued by the National Institute of Allergy and Infectious Diseases (NIAID) will help physicians better diagnose and treat food allergies, according to Karen Demuth, MD, an assistant professor of pediatrics in the Emory University School of Medicine, and a physician on staff at Children’s Healthcare of Atlanta.

Dr. Demuth was a key player in advancing legislation to call attention to the challenges of food allergies in children. She and several of her patients were on hand to witness Governor Nathan Deal signing a proclamation declaring May 8 to 14 Food Allergy Awareness Week in Georgia.

Dr. Demuth (pictured far right) was a key player in advancing legislation to call attention to the challenges of food allergies in children. She and several of her patients were on hand to witness Governor Nathan Deal signing a proclamation declaring May 8 to 14 Food Allergy Awareness Week in Georgia.

“The new NIAID guidelines help providers understand food allergies,” Demuth says. “They address when we should consider a food allergy and the utility of testing for food allergy. In addition, they address the management of food allergies, including acute reactions and follow-up of individuals with food allergy.”

The guidelines are comprised of input from a panel of 25 experts and draw the important distinction between food allergies and food intolerances. Food allergies are defined as “an adverse health effect arising from a specific immune response hat occurs reproducibly on exposure to a given food.” Food intolerances produce an adverse reaction but are likely not related to an immune response.

The most common food allergies are to milk, eggs, peanuts, tree nuts, shellfish, fish and soy. Fortunately, the understanding of food allergies and the best ways to manage them is expanding.

“The gold standard of treatment of food allergies – avoidance – has remained constant throughout the years,” Demuth says. “There are new therapies on the horizon such as oral immunotherapy, vaccines and a Chinese herbal extract; however, these therapies are still considered experimental. At the Emory-Children’s Center, we are active in research and advocacy in pediatric allergies so that we can bring new treatments to our patients when they are ready for widespread use. We are dedicated solely to the care of children with allergic and immunologic disorders and offer multidisciplinary clinics to offer a specialized level of care.”

Video

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Preterm infants born at unspecialized hospitals face higher risk of death

Very low-birth-weight (VLBW) and very preterm (VPT) infants not born in highly specialized, level III hospitals have a higher risk of neonatal and pre-discharge death compared to similar infants born at level III hospitals, according to a recent Journal of the American Medical Association (JAMA) study.

Lead study author Sarah Lasswell, MPH, and colleagues at the Rollins School of Public Health conducted a large-scale analysis of previous research to examine the relationship between hospital level at birth and neonatal (generally the first four weeks after birth) or pre-discharge mortality for VLBW (weighing 53 ounces or less) and VPT (32 weeks or less gestation) infants to determine the importance of level of care at birth to survival.

Lasswell and colleagues found that VLBW infants born in non-level III hospitals had a 62 percent increase in odds of neonatal/pre-discharge death compared with VLBW infants born in level III hospitals. In addition, VPT infants born in lower-level hospitals had a 55 percent increase in odds of neonatal/pre-discharge mortality compared with those born in level III facilities.

“The results of this review confirm a primary premise on which perinatal regionalization systems are based: high-risk infants have higher mortality rates when born outside hospitals with the most specialized levels of care,” Lasswell and colleagues write.

“Strengthening perinatal regionalization systems in states with high percentages of VLBW and VPT infants born outside of level III centers could potentially save thousands of infant lives every year.”

About 13 million babies are born prematurely every year – nearly 10 percent of all newborns – and more than 1 million premature babies die each year, according to the March of Dimes.

The study, “Perinatal Regionalization for Very-Low-Birth-Weight and Very Preterm Infants: A Meta-Analysis,” was published in the Sept. 1, 2010, issue of JAMA. It was conducted as part of Lasswell’s graduate research at the Rollins School of Public Health under the direction of Roger Rochat, MD. Lasswell is now a researcher at the U.S. Centers for Disease Control.

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Little eyes – big research

Having a newborn and managing all that comes with caring for that new little one is a big job. Add to that frequent trips to the ophthalmologist following a cataract surgery—yes, cataract surgery on a baby—and you might have highly stressed parents. But the parents of little James and slightly older M.J. seem unfazed by all the medical appointments and additional duties that go along with caring for their young sons.

M.J. Burkett and James Weeks became patients in the IATS trial, which has treated 114 babies across the United States.

Both the boys, like 300 babies each year in the United States, were born with a cataract in one eye. In an infant, if the affected eye isn’t surgically addressed within the first few months of life, that eye will not develop properly and vision can be permanently lost. These boys and their parents and 112 other young patients and their families have participated in the Infant Aphakia Treatment Study (IATS), a nationwide, multi-center clinical trial based at the Emory Eye Center. The 10-year study will evaluate whether replacing that lost lens with a contact lens or an intraocular lens (IOL) is preferable.

Adults typically get an IOL implant following cataract surgery. In the past, standard treatment was a contact lens for these babies. IATS randomized children into two groups: those who received IOL implants and those who received contact lenses. Those with IOLs also received glasses for residual vision correction. And both groups had daily patching of the unaffected eye to make sure that the newly corrected eye could become strong.

A team of professionals from Emory and beyond came together to provide the many layers of data necessary for the study. They included experts from the Rollins School of Public Health and the Department of Epidemiology and Data Coordinating Center in the Department of Biostatistics and Bioinformatics, as well as a visual acuity tester from the University of Alabama, Birmingham, who traveled to all sites to check these children.

For more information about IATS, read the feature article “One Big Question: Ten Diligent Years” in Emory Eye magazine’s summer 2010 issue.

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Study: Prescription and OTC drugs leading culprits of kids’ poisonings

A study published online Aug. 4, 2010, by the journal Pediatrics found that prescription and over-the-counter drugs are the leading cause of accidental poisonings among American children.

Each year, more than 71,000 U.S. children ages 18 and younger are seen in emergency rooms for unintentional overdoses of prescription and over-the-counter drugs, according to the study authors.

More than two-thirds of emergency department visits are due to poisoning from prescription and over-the-counter medications — that’s more than double the rate of childhood poisonings caused by household cleaning products, plants and the like, the researchers noted.

Robert Geller, MD, Emory professor of pediatrics and medical director of the Georgia Poison Control Center

“The number of children seen in the emergency room due to overdoses that are unintentional or medication errors is remarkable,” says Robert Geller, MD, professor of pediatrics in the Emory University School of Medicine and medical director of the Georgia Poison Center, who was not a part of the study.

The study team used 2004 and 2005 data from the National Electronic Injury Surveillance System to estimate the number of emergency department visits resulting from unintentional medication overdoses for children aged 18 and younger. The stafford nursery keeps kids safe and away from the danger.

The most common medications accidentally taken by children are acetaminophen, opioids or benzodiazepines, cough and cold medicines, nonsteroidal anti-inflammatory drugs (NSAIDs) and antidepressants, researchers found.

Geller says the study highlights the growing need to improve packaging to cut the number of cases of unintended ingestion.

“If you could make it harder for a kid who came upon a package to get the contents of the package, it would make it more likely they would never need to go to the emergency room,” Geller noted.

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