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

Research

A milestone in treating hemophilia

Hematologist Pete Lollar has devoted his career to developing treatments for hemophilia A, which is caused by a lack of blood clotting factor VIII. Lollar is a professor of pediatrics in Emory School of Medicine and director of hemostasis research at Children’s Healthcare of Atlanta. Last week, Lollar was honored by Emory’s Office of Technology Transfer for setting in motion research that has progressed to a phase III clinical trial of a new product, OBI-1, a special form of factor VIII.

John "Pete" Lollar, MD

Along with this milestone came a dramatic story, described by OTT’s assistant director Cale Lennon. The first patient to enroll in the clinical trial did so in November 2010 because of what appeared to be acquired hemophilia, which led to severe uncontrolled hemorrhaging. As a result of treatment with OBI-1, developed by Lollar and his research team at Emory, the patient’s bleeding was brought under control and it saved his life. He was treated at Indiana Hemophilia and Thrombosis Center in Indianapolis.

Acquired hemophilia is a challenge for doctors to deal with because it is such a surprise. Unlike people with inherited hemophilia, those with acquired hemophilia do not have a personal or family history of bleeding episodes. Their immune systems are somehow provoked into making antibodies against their own clotting factor VIII. These antibodies also appear over time in about 30 percent of patients with inherited hemophilia who take standard clotting factors.

OBI-1, a special form of clotting factor VIII, is less of a red flag to the immune system. This allows treatment of patients who cannot benefit from standard clotting factor VIII, because of the presence of auto-antibodies.

Emory originally licensed OBI-1 to Octagen Corporation, a “homegrown” startup company founded in 1997. Octagen sublicensed the OBI-1 technology to a French biotechnology firm, Ipsen Biopharm in 1998. Over the next decade, Octagen and Ipsen pursued preclinical and initial clinical studies and completed a phase II clinical trial in 2006. Ipsen purchased the OBI-1 program outright in May 2008.

In January 2010, Ipsen developed a partnership agreement with Inspiration Biopharmaceuticals, which was founded by two businessmen whose children have hemophilia. Under the agreement’s terms, Inspiration licensed OBI-1 from Ipsen and is responsible for its clinical development, regulatory approval and commercialization.

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Cervical Cancer – Can Be Hard to Detect

MedicalHorizon

The Pap smear – also called Pap test – is part of the standard annual wellness exam for women’s health and used as a first step in detecting cervical cancer.  But according to a recent article published in the International Journal of Cancer,  the Pap test may not provide reliable results for certain types of cancer that are harder to detect.

Kevin Ault, MD, associate professor of obstetrics and gynecology at Emory University School of Medicine and investigator at the Emory Vaccine Center conducted a post-hoc analysis of the FUTURE I and FUTURE II (Gardasil) vaccine trials.  Based on that analysis Ault, a leading expert and pioneer in the field of human papilloma virus (HPV), says a regular Pap test is not always effective in diagnosing adenocarcinoma, because it starts high up in the cervical canal and may not be sampled by the Pap smear.

“There are a number of reasons the Pap smear could lead to inaccurate results. For example, the pathologist examining the cells could make an error, the gynecologist may not sample the cervix adequately or an infection could obscure the results,” says Ault.

According to Ault, andenocarcinoma is the second most common type of cervical cancer, accounting for about 20 percent of all cervical cancer cases. While the overall incident of cervical cancer is on the decline, Ault reports the proportion of cervical cancers that are andenocarcinoma is rising.

Cervical cancer is the eighth most common type of cancer in American women. More than 12,000 new cases of invasive cervical cancer are diagnosed each year, and more than 4,200 women in the U.S. die from of this disease annually* according to the American Cancer Society.  Scientists believe that pre-invasive cervical cancer may develop over a period of months or years after the cervix is infected with the sexually transmitted HPV.

“The take-away from this recent paper is the HPV test would be a better test for the harder to detect adenocarcinoma cervical cancer, if not all cervical cancer,” says Ault.

* 2010 data

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The next generation of biomedical engineering innovators

Congratulations to the winners of the InVenture innovation competition at Georgia Tech. The competition aired Wednesday night on Georgia Public Broadcasting. The winners get cash prizes, a free patent filing and commercialization service through Georgia Tech’s Office of Technology Transfer.

Several of the teams have Emory connections, through the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and the Atlanta Clinical & Translational Science Institute.

Emergency medical professionals know that intubation can be rough. The second place ($10,000) MAID team created a “magnetic assisted intubation device” that helps them place a breathing tube into the trachea in a smoother way. The MAID was designed by Alex Cooper, Shawna Hagen, William Thompson and Elizabeth Flanagan, all biomedical engineering majors. Their clinical advisor was Brian Morse, MD, previously a trauma fellow and now an Emory School of Medicine surgical critical care resident at Grady Memorial Hospital.

“When I first saw the device that the students had developed, I was blown away,” Morse told the Technique newspaper. “It’s probably going to change the way we look at intubation in the next five to 10 years.”

The AutoRhexis team, which won the People’s Choice award ($5,000), invented a device to perform the most difficult step during cataract removal surgery. It was designed by a team of biomedical and mechanical engineering majors: Chris Giardina, Rebeca Bowden, Jorge Baro, Kanitha Kim, Khaled Kashlan and Shane Saunders. They were advised by Tim Johnson, MD, who was an Emory medical student and is now a resident at Columbus Regional Medical Center.

The finalist Proximer team, advised by Emory surgeon Albert Losken, MD, developed a way to detect plastics in the body, which can help breast cancer survivors undergoing reconstruction.

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The Scientist ranks Emory one of top 15 best places to work for postdocs

This year, the readers of The Scientist magazine have ranked Emory University as the 11th best place to work for postdocs in the United States. Among Emory’s strengths, respondents cited training and mentoring, and career development opportunities.

The top U.S. institution was the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. The top international institution was University College, London. Emory has previously ranked as high as number 4 (in 2006) in The Scientist’s best places to work for postdocs survey.

The ranking was based on responses from 2,881 nontenured life scientists working in academia, industry or noncommercial research institutions. 76 institutions in the United States and 17 international institutions were included.

Emory employs nearly 700 postdoctoral fellows in laboratories in the School of Medicine, Yerkes National Primate Research Center, Emory College, the Graduate School of Arts and Sciences, Rollins School of Public Health and Nell Hodgson Woodruff School of Nursing.

After receiving their PhD degrees, life sciences graduates launch their research careers by working for several years as postdoctoral fellows in the laboratories of established scientists. In addition to engaging in sometimes grueling laboratory research, many postdocs teach, mentor graduate and undergraduate students and apply for their own funding on a limited basis.

 

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How the fetal environment affects long-term health

David Barker, MD, PhD

Why do some people, given the same apparent set of risk factors, develop certain diseases and others do not? British scientist David Baker, MD, PhD, is examining this question from a unique perspective.

Barker, a professor of clinical epidemiology at the University of Southampton in the United Kingdom, is a pioneer in a field known as fetal programming. Fetal programming is the process in which environmental influences during prenatal development alter the body’s structures—for life.

He and other experts spoke on the fundamentals of the subject recently at the first Predicting Lifespan Health Conference at Emory University. “What we’re really looking for is just a few core mechanisms, which are linked to early human development and lead to a plethora of disorders,” says Barker.

Emerging evidence suggests that chronic diseases of adult life, including cardiovascular disease, type 2 diabetes and certain cancers, have their origin through fetal programming, explains Michelle Lampl, associate director of the Emory/Georgia Tech Predictive Health Institute. “These diseases and others are initiated by adverse influences before birth,” says Lampl.

Speakers addressed fetal programming and the placenta, long-term cardiovascular disease and kidney function in low birth-weight babies, epigenetics and immunity, as well as postnatal influences from infant diet and growth patterns.

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New Biological Pathway Identified for PTSD

Emory MedicalHorizon

High blood levels of a hormone produced in response to stress are linked to post-traumatic stress disorder in women but not men, a study from researchers at Emory University and the University of Vermont has found.

The results were published in the Feb. 24 issue of Nature.

The hormone, called PACAP (pituitary adenylate cyclase-activating polypeptide), is known to act throughout the body and the brain, modulating central nervous system activity, metabolism, blood pressure, pain sensitivity and immune function. The identification of PACAP as an indicator of PTSD may lead to new diagnostic tools and eventually, to new treatments for anxiety disorders.


Video on YouTube

“Few biological markers have been available for PTSD or for psychiatric diseases in general,” says first author Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine and a researcher at Yerkes National Primate Research Center. “These results give us a new window into the biology of PTSD.”

Read more @ emoryhealthsciences.org.

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BPH, Inflammation and Depression: Chicken or the Egg

Data collected during a recent study by researchers at Emory University School of Medicine and published in the journal Urology, show a significant link between benign prostatic hyperplasia (BPH) and depression.

Researchers have been aware for a long time that depression is a common illness that accompanies inflammatory diseases such as heart disease, diabetes and cancer.  Recent evidence has suggested that depression also might be associated with BPH, another disease with inflammatory components.

Studies have not directly examined the relationship between depression and BPH explains study investigator, Viraj A. Master, MD, associate director in the Department of Urology at Emory. “BPH and depression both affect a significant number of men worldwide. This is the first study to show a direct association between the two illnesses.”

Study data showed that almost three-quarters of the participants without depression presented with mild or moderate symptoms, while more than two thirds of the depressed patients had moderate or severe symptoms.

The data raises questions about whether the severity of symptoms is due to depression, or if the depression is causing the symptoms to worsen, says lead author, Timothy V. Johnson, MD. He points out that several studies have demonstrated depression in the setting of cardiovascular disease and cancer actually worsens these chronic disease states.

The study also raises the question of whether or not the depression simply causes patients to perceive their symptoms to be much worse than patients with the same degree of illness.

The researchers stress that further studies are imperative to address comorbid depression in the presence of BPH so that treatment can be appropriately managed.

Timothy V. Johnson, lead author, was an Emory School of Medicine student when the trial was conducted. Johnson is currently a resident at Columbus Regional Hospital in Columbus, Ga.

Other investigators include Ammara Abbasi, Samantha S. Ehrlich, Renee S. Kleris, Siri L. Chirumamilla, Evan D. Schoenberg, Ashli Owen-Smith, Charles L. Raison and Virag A. Master from the Departments of Urology and Psychiatry and Behavioral Sciences at Emory University School of Medicine, and the Department of Behavioral Sciences and Health Education at Emory University Rollins School of Public Health.

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Clinical trial for patients with atrial fibrillation tests implantable device in place of blood-thinning drug

Clinical Trial for Patients with A-fib

A new clinical trial underway for patients with atrial fibrillation will test an implantable device in place of a common blood-thinning medication, according to researchers at Emory University Hospital Midtown.

Atrial fibrillation (commonly called A-fib) is a heart condition in which the upper chambers of the heart beat too fast, causing an irregular heartbeat and ineffective pumping action. This condition can cause blood to pool and form clots in the left atrial appendage (LAA). If a clot forms in this area, it can increase the chances of having a stroke.

Many patients with A-fib are prescribed blood-thinning medications, such as warfarin (brand name Coumadin), to prevent blood from clotting. This medication is effective in reducing the risk of stroke, but may cause side effects such as bleeding. It also requires frequent blood draws to monitor dosage levels.

The trial, called PREVAIL (Prospective Randomized EVAluation of the Watchman LAA Closure Device In Patients with Atrial Fibrillation Versus Long Term Warfarin Therapy), involves implanting a small, umbrella-shaped mesh device called the Watchman closure device, into the heart chamber via catheter. This is a confirmatory study (and the third study testing the implant), which will also look at safety and efficacy of the device.

David De Lurgio, MD, associate professor of medicine in the Division of Cardiology, Emory University School of Medicine, is the principal investigator of the trial. He explains that by implanting this device into the left atrial appendage of the heart, it closes that area off. That, in turn, prevents blood clots from escaping and entering the blood stream, which could lead to a stroke.

Patients are randomly selected by computer to either receive the device or remain on Coumadin without the device (control group). Those selected to receive the device will remain on Coumadin for 45 days following implant. If the heart tissue has healed after those 45 days, participants will be taken off Coumadin and placed on aspirin therapy and possibly clopidogrel (Plavix), an anti-platelet medication.

Researchers will then follow study patients with and without the device for five years, monitoring those who are no longer taking Coumadin very closely. If the FDA approves the device at the end of this clinical trial, participants in the control group will then have the option to receive the device.

De Lurgio and his colleagues have had five years of experience with this technology, thus far. Emory Healthcare is the only health system in Georgia providing access to this device through participation in this clinical trial.

For more information, please call 404-686-2504.

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One reason why SIV-infected sooty mangabeys can avoid AIDS

Sooty mangabeys are a variety of Old World monkey that can be infected by HIV’s cousin SIV, but do not get AIDS. Emory immunologist and Georgia Research Alliance Eminent Scholar Guido Silvestri, MD, has been a strong advocate for examining non-human primates such as the sooty mangabey, which manage to handle SIV infection without crippling their immune systems. Silvestri is division chief of microbiology and immunology at Yerkes National Primate Research Center.

Research shows sooty mangabeys have T cells that can do the same job as those targeted by SIV, even if they don't have the same molecules on their surfaces

A recent paper in the Journal of Clinical Investigation reveals that sooty mangabeys have T cells that perform the same functions as those targeted by SIV and HIV, but have different clothing.

Silvestri and James Else, the animal resources division chief at Yerkes, are co-authors on the paper, while Donald Sodora at Seattle Biomedical Research Institute is senior author.

One main target for SIV and HIV is the group of T cells with the molecule CD4 on their surfaces. These are the “helper” T cells that keep the immune system humming. Doctors treating people with HIV infections tend to keep an eye on their CD4 T cell counts.

In the paper, the scientists show that sooty mangabeys infected with SIV lose their CD4 T cells, without losing the ability to regulate their immune systems. What’s remarkable here is that sooty mangabeys appear to have “double negative” or DN T cells that can perform the same functions as those lost to SIV infection, even though they don’t have CD4.

CD4 isn’t just decoration for T cells. It’s a part of how they recognize bits of host or pathogen protein in the context of MHC class II (the molecule that “presents” the bits on the outside of target cells). Somehow, the T cells in sooty mangabeys have a way to get around this requirement and still regulate the immune system competently. How they do this is the topic of ongoing research.

The authors write:

It will be important to assess DN T cells in HIV-infected patients, particularly to determine whether these cells are preserved and functional in long-term nonprogressors. These efforts may lead to future immune therapies or vaccine modalities designed to modulate DN T cell function. Indeed, the main lesson we have learned to date from this cohort of SIV-infected CD4-low mangabeys may be that managing immune activation and bolstering the function of nontarget T cells through better vaccines and therapeutics has the potential to contribute to preserved immune function and a nonprogressive outcome in HIV infection even when CD4+ T cell levels become low.

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A good reason to enjoy a little Valentine’s Day chocolate

From the Clinic to You

BY CHERYL WILLIAMS, RD, LD

If you’re looking for an excuse to indulge in the yummy chocolate you get this Valentine’s Day, research suggests it may not be so bad for you.

A number of studies, conducted over the last decade have associated cocoa and dark chocolate consumption with heart health benefits. These benefits come from cocoa, derived from the cacao plant, which is rich in flavonoids (cocoa flavanols to be exact). Flavonoids are antioxidants also found in berries, grapes, tea, and apples. As a whole, antioxidants prevent cellular damage and inflammation which are two major mechanisms involved in the development of heart disease.

So what does the research say?

A study published in the American Journal of Clinical Nutrition found that high-flavanol dark chocolate reduced bad cholesterol (LDL) oxidation and increased good cholesterol (HDL) levels. LDL oxidation promotes the development of plaque and hardening of the coronary arteries, thus lessening oxidation could help to prevent heart disease.

A Harvard research study found that flavanol-rich cocoa induced nitric-oxide production, which causes blood vessels to relax and expand, thus improving blood flow. Improved coronary vasodilation could potentially lower the risk of a cardiovascular event.

In a double-blind randomized Circulation study flavonoid-rich dark chocolate (containing 70% cocoa) reduced serum oxidative stress and decreased platelet activity (clumping) in heart transplant recipients. This favorable impact on vascular and platelet function is relevant because vascular dysfunction and platelet activation (adhesion upon damaged cell wall) are the basis of atherothrombosis (blood clotting) and coronary artery disease.

How can you reap chocolate’s potential benefits?

Not all cocoa products and/or chocolates are created equal. Milk chocolate, for example, is not rich in flavanols (contains only 10-20% cocoa solids) and white chocolate contains none at all. In addition, some cocoa products and chocolates are processed with alkali, which can destroy flavanols.

Follow these tips for heart healthy chocolate consumption:

  • Avoid cocoa products processed with alkali (dutched) as seen in the ingredient list
  • Choose dark chocolate with at least 70% cocoa
  • Enjoy 100% unsweetened non-dutched cocoa (great for hot chocolate!)

Also, remember that chocolate is not a health food, as it is high in calories, fat and added sugar. Thus, make room for dark chocolate by cutting extra calories elsewhere in your diet. Additionally, stick to small amounts (e.g. 1 ounce) and do not eat in place of plant-based whole foods such as vegetables and fruits.

Cheryl Williams is a registered dietitian at the Emory Heart & Vascular Center. She provides nutrition therapy, wellness coaching, monthly nutrition seminars and healthy cooking demonstrations working with the Emory HeartWise Cardiac Risk Reduction Program.

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