The journey of a marathon sleeper

A marathon sleeper who got away left some clues for Emory and University of Florida scientists to Read more

A push for reproducibility in biomedical research

At Emory, several scientists are making greater efforts to push forward to improve scientific research and combat what is being called “the reproducibility crisis.” Guest post from Erica Read more

Exosomes as potential biomarkers of radiation exposure

Exosomes = potential biomarkers of radiation in the Read more

Heart

Leslee Shaw explains coronary artery calcium scoring

On Thursday, cardiology researcher Leslee Shaw, PhD joined an exclusive club at Emory with her 2015 Dean’s Distinguished Faculty Lecture and Award.* Shaw is the co-director of Emory’s Clinical Cardiovascular Research Institute and research director of Emory Women’s Heart Center. Her lecture focused on the utility of coronary artery calcium (CAC) scoring in predicting cardiovascular disease.

Much cardiovascular risk research has focused on finding imaging or biomarker tests that can provide doctors with cost-effective decision-making power. One prominent question: should the patient take cholesterol-reducing statins? These tests should provide information above and beyond the Framingham Risk Score or its ACC/AHA update, which incorporates information about a patient’s age, sex, cholesterol/HDL, blood pressure and diabetes status.

CAC scoring is a good place to start, Shaw said, since it is a standardized, relatively inexpensive test that measures the buildup of calcium in atherosclerotic plaque, and the radiation dose is low compared with other cardiac imaging techniques. Read more

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ACC 2015: Newer heart risk calculator may better accounts for racial differences

A risk calculator for cardiovascular disease, developed as a companion for the 2013 American College of Cardiology/American Heart Association cholesterol guidelines, may account for racial differences in sub-clinical vascular function better than the Framingham Risk Score, Emory cardiology researchers say.

Their findings are scheduled for presentation Monday at the American College of Cardiology meeting in San Diego.

African Americans, especially men, tend to have a higher prevalence of cardiovascular disease, but this differences are not reflected in the Framingham Risk score. Arterial stiffness is a sign of heart disease risk that tends to appear more prominently among African Americans than whites. Cardiovascular research fellow Jia Shen, MD, MPH, and Emory colleagues analyzed data on arterial stiffness and structure from 1235 people – 777 whites and 458 African-Americans — enrolled in two large studies (Center for Health Discovery and Well Being and META-Health). Read more

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Who regulates the regulators? Drosha

MicroRNAs have emerged as important master regulators in cells, since each one can shut down several target genes. Riding on top of the master regulators is Drosha, the RNA-cutting enzyme that initiates microRNA processing in the nucleus. Drosha and its relative Dicer have been attracting attention in cancer biology, because they are thought to be behind a phenomenon where cancerous cells can “infect” their healthy neighbors via tiny membrane-clothed packets called exosomes.

At Emory, pharmacologist Zixu Mao and colleagues recently published in Molecular Cell their findings that Drosha is regulated by stress (experimentally: heat or peroxide) through p38 MAP kinase.

Although we mention relevance to cancer above, this is one of those basic cell biology findings that may have applicability to several areas of medicine. Alterations in miRNA processing have been linked to neurodegenerative disease (Fragile X-associated tremor/ataxia syndrome, for one example). MicroRNA-packed exosomes are also being studied by biomedical engineers as potential therapeutic tools in regenerative medicine, so knowing what cellular stress does to miRNA production could be useful. Read more

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Extend that New Year’s energy – to what benefit?

Surveys indicate that many of us make New Year’s resolutions to eat more healthily or exercise more frequently, yet do not sustain the enthusiasm of January throughout the year.

What if the burst of energy and good intentions could be maintained over a longer period, perhaps with the help of a coach? What kinds of health benefits would appear?

Researchers from Emory and Georgia Tech recently published an analysis of the changes in the health profiles in 382 Center for Health Discovery & Well Being participants who completed a one-year evaluation.

The senior author is Greg Gibson, PhD, professor of biology and director of the Center for Integrative Genomics at Georgia Tech. Georgia Tech postdoctoral fellow Rubina Tabassum, now at the University of Helsinki, is the first author.

“What do most people in developed countries need to do? Eat better, exercise more regularly and stress less,” Gibson says. “It’s unclear whether most of the impact comes from the interaction with partners, or simply from participation and goal-setting, but the overall effect is quite good.”

The main points:

*These are “essentially healthy” people — healthier than the general population in the United States – but almost half started out with high blood pressure and cholesterol levels. There was no control group, and not everyone pursued the same exact program. The average age was 48 years and 28 percent of the group was considered obese. That’s less than the United States population as a whole.

*On average, the 382 participants lost a moderate amount of weight (it works out to about three pounds) and saw their blood pressure and LDL-cholesterol go down significantly over that first year (121 to 116 mmHG for systolic BP, 112 to 105 mg/dL for LDL-C). They also reported lower scores for depression and anxiety.

Read more

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Stem cell/cardiology researcher Hee Cheol Cho joins Emory

Please welcome stem cell/cardiology researcher Hee Cheol Cho to Emory. Starting in September, Cho joined the Wallace H Counter Department of Biomedical Engineering at Georgia Tech and Emory, and Emory-Children’s Pediatric Research Center. He and his team will focus on developing gene-and cell-based therapies for cardiac arrhythmias. Their research will adding to and complement the research of several groups, such as those led by Chunhui Xu, Young-sup Yoon, Mike Davis and W. Robert Taylor.

Cho comes from Cedars-Sinai Medical Center in Los Angeles, where he specialized in understanding cardiac pacemaker cells, a small group of muscle cells in the sinoatrial node of the heart that initiate cardiac contraction. These cells have specialized electrophysiological properties, and much has been learned in the last few years about the genes that control their development.

Cho and colleagues from Cedars-Sinai recently published a paper in Stem Cell Reports describing how the gene SHOX2 can nudge embryonic stem cells into becoming cardiac pacemaker cells. Read more

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The other “cho-” cardiovascular disease biomarker

Quick, what biomarker whose name starts with “cho-” is connected with cardiovascular disease? Very understandable if your first thought is “cholesterol.” Today I’d like to shift focus to a molecule with a similar name, but a very different structure: choline.

Choline, a common dietary lipid component and an essential nutrient, came to prominence in cardiology research in 2011 when researchers at the Cleveland Clinic found that choline and its relatives can contribute to cardiovascular disease in a way that depends upon intestinal bacteria. In the body, choline is part of two phospholipids that are abundant in cell membranes, and is also a precursor for the neurotransmitter acetylcholine. Some bacteria can turn choline (and also carnitine) into trimethylamine N-oxide (TMAO), high levels of which predict cardiovascular disease in humans. TMAO in turn seems to alter how inflammatory cells take up cholesterol and lipids.

Researchers at Emory arrived at choline metabolites and their connection to atherosclerosis by another route. Hanjoong Jo and his colleagues have been productively probing the mechanisms of atherosclerosis with an animal model. Very briefly: inducing disturbed blood flow in mice, in combination with a high fat diet, can result in atherosclerotic plaque formation within a few weeks. Jo’s team has used this model to examine changes in gene activation, microRNAs, DNA methylation, and now, metabolic markers.

Talking about this study at Emory’s Clinical Cardiovascular seminar on Friday, metabolomics specialist Dean Jones said he was surprised by the results, which were recently published by the American Journal of Physiology (to be precise, their ‘omics journal). The lead author is instructor Young-Mi Go. Read more

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In landmark study of cell therapy for heart attack, more cells make a difference

Patients who receive more cells get significant benefits. That’s a key lesson emerging from a clinical trial that was reported this week at the American Heart Association meeting in Chicago.

In this study, doctors treated heart attack patients with their own bone marrow cells, selected for their healing potential and then reinjected into the heart, in an effort to improve the heart’s recovery. In the PreSERVE-AMI phase II trial, physicians from 60 sites (author list) treated 161 patients, making the study one of the largest to assess cell therapy for heart attacks in the United States. The study was sponsored by NeoStem, Inc.

“This was an enormous undertaking, one that broke new ground in terms of assessing cell therapy rigorously,” says the study’s principal investigator, Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine and co-director of the Emory Clinical Cardiovascular Research Institute. “We made some real progress in determining the cell type and doses that can benefit patients, in a group for whom the risks of progression to heart failure are high.” Read more

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Plaque erosion: heart attacks triggered by a whimper, not a bang

Cardiologist Bob Taylor and colleagues have a new paper in PLOS One this week, looking at the biomechanical forces behind plaque erosion.

Plaque erosion is a mechanism for blood clots formation in coronary arteries that is not as well-understood as its more explosive counterpart, plaque rupture. Plaque erosion disproportionally affects women more than men and is thought to account for most heart attacks in younger women (women younger than 50).

“We believe that this work has implications for our better understanding of the underlying biology of coronary artery disease in women,” Taylor says. The first author of the paper is biomedical engineering graduate student Ian Campbell, who now has his PhD. The team collaborated with cardiovascular pathologist Renu Virmani in Maryland.

Cardiologists have well-developed ideas for how plaque rupture works*; see the concept of “vulnerable plaque.” Cholesterol and inflammatory cells build up in the coronary arteries over several years. At one point in a particular artery, the plaque has a core of dying inflammatory cells, covered by a fibrous cap. If the cap is thin (the patterns of blood flows near the cap influence this), there is a risk that the cap will break and the contents of the core will spill out, triggering a blood clot nearby.

Plaque erosion is more mysterious and can occur more gradually, the researchers have found. Read more

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Bits from HIV + Aging conference

What conferences like the HIV + Aging meeting recently held by Emory in Decatur offer the visiting writer: anecdotes that illustrate issues of clinical care.

To illustrate her point that assumptions about who is likely to develop a new HIV infection may lead doctors to miss possible diagnoses, keynote speaker Amy Justice from Yale described a patient who was seen last year at Yale-New Haven Hospital.

A 60 year old man reported fatigue and had lost 40 pounds over the course of a year. Despite those symptoms, and the discovery of fungal and viral infections commonly linked to HIV/AIDS, it took nine months before a HIV test was performed on the patient, a delay Justice deplored.

Sex and substance abuse do not end at age 50, she said, citing data showing that the risk of HIV transmission can be greater among older adults, and that substance abuse is more likely among adults who are HIV positive compared to those who are HIV negative.

Justice also highlighted the issue of polypharmacy (interactions between prescription drugs at the same time), a concern even in people who are not living with HIV. Common blood pressure medications taken by older adults to prevent heart disease have been suspected of increasing the risk for falls. That’s a problem especially for people living with HIV, because HIV infection has been linked to weakened bone. Read more

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The age of blood

Nature Medicine has a nice feature from Jeanne Erdmann highlighting the debate over how long donated blood can be stored. It sets the stage for two prospective clinical trials (RECESS and ABLE), which recently concluded but are still being analyzed. The trials were looking at how the age of stored blood affects patients undergoing cardiac surgery or in intensive care, respectively. Erdmann also mentions that the NIH’s Clinical Center already has tightened its standards for blood storage time.

Emory Blood Bank director John Roback and cardiologist Arshed Quyyumi have been participants in this debate, both theoretically and experimentally. In 2011, they proposed that depletion of the messenger molecule nitric oxide limits the benefits donated blood can provide to patients. In addition to nitric oxide depletion, the “storage lesion” is likely to include several changes, such as lysis of red blood cells, mechanical alterations in the remaining cells, and other chemical changes.

Since then, Emory research has shown that transfusion of donated blood more than three weeks old results in impaired blood vessel function in hospitalized patients, but in contrast, not in healthy volunteers. This information could allow doctors to prioritize fresher blood for patients with cardiovascular diseases.

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