Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this Read more

Mother's milk is OK, even for the in-between babies

“Stop feeding him milk right away – just to be safe” was not what a new mother wanted to hear. The call came several days after Tamara Caspary gave birth to fraternal twins, a boy and a girl. She and husband David Katz were in the period of wonder and panic, both recovering and figuring out how to care for them. “A nurse called to ask how my son was doing,” says Caspary, a developmental Read more

Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

Department of Medicine

FMT microbial transplant for C diff gaining acceptance

In February, the Infectious Diseases Society of America issued new guidelines for fighting Clostridium difficile, the hardy bacterium that can cause life-threatening diarrhea and whose dominance is sometimes a consequence of antibiotic treatment. The guidelines recommend for the first time that FMT (fecal microbiota transplant) be considered for individuals who have repeatedly failed standard antibiotics.

In a nice coincidence, Emory FMT specialists Colleen Kraft and Tanvi Dhere recently published a look at their clinical outcomes with C diff going back to 2012, in Clinical Infectious Diseases. They report 95 percent of patients (122/128) indicated they would undergo FMT again and 70 percent of the 122 said they would prefer FMT to antibiotics as initial treatment if they were to have a recurrence. Read more

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Nox-ious link to cancer Warburg effect

At Emory, Kathy Griendling’s group is well known for studying NADPH oxidases (also known as Nox), enzymes which generate reactive oxygen species. In 2009, they published a paper on a regulator of Nox enzymes called Poldip2. Griendling’s former postdoc, now assistant professor, Alejandra San Martin has taken up Poldip2.

Griendling first came to Nox enzymes from a cardiology/vascular biology perspective, but they have links to cancer. Nox enzymes are multifarious and it appears that Poldip2 is too. As its full name suggests, Poldip2 (polymerase delta interacting protein 2) was first identified as interacting with DNA replication enzymes.  Poldip2 also appears in mitochondria, indirectly regulating the process of lipoylation — attachment of a fatty acid to proteins anchoring them in membranes. That’s where a recent PNAS paper from San Martin, Griendling and colleagues comes in. It identifies Poldip2 as playing a role in hypoxia and cancer cell metabolic adaptation.

Part of the PNAS paper focuses on Poldip2 in triple-negative breast cancer, more difficult to treat. In TNBC cells, Poldip2’s absence appears to be part of the warped cancer cell metabolism known as the Warburg effect. Lab Land has explored the Warburg effect with Winship’s Jing Chen.

Posted on by Quinn Eastman in Cancer, Heart Leave a comment

Calming an electrical storm in the heart

AT = anterior tubercle of C6, C = carotid artery, LC = longus colli muscle, T = thyroid gland, IJ = internal jugular vein, compressed

The most recent issue of Emory Medicine features a story that first came to Lab Land’s attention when it was presented as an abstract at the 2017 American College of Cardiology Scientific Sessions meeting.

Emory doctors were challenged by a patient who repeatedly developed cardiac arrhythmias, called “refractory electrical storm.” They used a local anesthesia procedure called stellate ganglion block — normally used for complex pain — to calm the storm. Cardiac electrophysiologist Michael Lloyd, who likes solving puzzles, was the one who decided to try it.

Emory anesthesiologist Boris Spektor provided this ultrasound picture of the procedure. Stellate ganglion block is also being tested for conditions such as PTSD. Please read the whole story!

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Long-lasting blood vessel repair in animals via stem cells

Stem cell researchers at Emory University School of Medicine have made an advance toward having a long-lasting “repair caulk” for blood vessels. The research could form the basis of a treatment for peripheral artery disease, derived from a patient’s own cells. Their results were recently published in the journal Circulation.

A team led by Young-sup Yoon, MD, PhD developed a new method for generating endothelial cells, which make up the lining of blood vessels, from human induced pluripotent stem cells.. When endothelial cells are surrounded by a supportive gel and implanted into mice with damaged blood vessels, they become part of the animals’ blood vessels, surviving for more than 10 months.

“We tried several different gels before finding the best one,” Yoon says. “This is the part that is my dream come true: the endothelial cells are really contributing to endogenous vessels. When I’ve shown these results to people in the field, they say ‘Wow.'”

Previous attempts to achieve the same effect elsewhere had implanted cells lasting only a few days to weeks, although those studies mostly used adult stem cells, such as mesenchymal stem cells or endothelial progenitor cells, he says.

“When cells are implanted on their own, many of them die quickly, and the main therapeutic benefits are from growth factors they secrete,” he adds. “When these endothelial cells are delivered in a gel, they are protected. It takes several weeks for most of them to migrate to vessels and incorporate into them.” Read more

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EHR data superior for studying sepsis

Are there more cases of a given disease because something is causing more, or because doctors have become more aware of that disease? A recent paper in JAMA tackles this question for sepsis, the often deadly response to infection that is the most expensive condition treated in US hospitals.

Researchers from several academic medical centers, including Emory, teamed up to analyze sepsis cases using two methods. The first is based on the ICD (International Classification of Diseases) codes recorded for the patient’s stay in the hospital, which the authors refer to as “claims-based.” The second mines electronic medical record (EHR) data, monitoring the procedures and tests physicians used when treating a patient. The first approach is easier, but might be affected by changing diagnosis and coding practices, while the second is not possible at every hospital.

“This project was undertaken by several large, high quality institutions that have the ability to well characterize their sepsis patients and connect their EHR data,” says Greg Martin, MD, who is a co-author of the JAMA paper along with David Murphy, MD, PhD. The lead author, Chanu Rhee, MD, MPH, is from Brigham and Women’s Hospital, and the entire project was part of a Prevention Epicenter program sponsored by the Centers for Disease Control and Prevention.  Read more

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How race + TBI experience affect views of informed consent

The upcoming HBO movie of The Immortal Life of Henrietta Lacks reminds us that biomedical research has a complex legacy, when it comes to informed consent and people of color.

A paper from Emory investigators, published in AJOB Empirical Bioethicstouches on related current issues. The paper examines how race and close experience with traumatic brain injury affect study participants’ views of informed consent in clinical research.

This emerged from a study of community consultation for EFIC (exception from informed consent), in connection with a nationwide clinical trial of progesterone for traumatic brain injury (TBI). EFIC describes clinical research performed when the normal process of obtaining patients’ informed consent is not possible, because of emergency conditions such as seizures or TBI. Before such studies can be undertaken, the FDA calls for protective procedures and community consultation.

In this case, researchers surveyed 2612 people at 12 sites involved in the TBI study. The survey asked about attitudes toward the EFIC aspects of the study and also asked if they had personal experience with traumatic brain injury – either themselves or someone close to them. How that personal connection affected their responses was influenced by race.

Key paragraph from discussion:

Among white participants, increased levels of acceptance of EFIC were found among those with any connections to TBI. On the other hand, among participants identifying as black or other nonwhite races, there was decreased acceptance of EFIC enrollment among TBI patients and no increase in acceptance among those with a family member/loved one with TBI. The fact that black and white participants with no personal TBI experience or with a more distant connection to TBI had similar acceptance rates suggests that baseline acceptance of EFIC among these two groups is fairly similar and that the experience with the condition itself plays a role in driving the observed differences…

Read more

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Fecal transplant replants microbial garden

When facing a life-threatening infection, the “yuck factor” is a minor concern. Fecal microbiota transplant (FMT for short) has become an accepted treatment for recurrent Clostridium difficile infection, which can cause severe diarrhea and intestinal inflammation.

In a new video, Emory physicians Colleen Kraft and Tanvi Dhere explain how FMT restores microbial balance when someone’s internal garden has been disrupted.

C. difficile or “C diff” is a hardy bacterium that can barge into the intestines after another infection has been treated with antibiotics, when competition for real estate is low. In the last few years, doctors around the world have shown that FMT can resolve recurrent C diff infection better than antibiotics alone.

At Emory, Kraft and Dhere have performed almost 300 FMTs and report a 95 percent success rate when treating recurrent C diff. They have established a standard slate of stool donors, whose health is carefully screened.

Building on their experience with the procedure, Kraft and Dhere are studying whether FMT can head off other antibiotic-resistant infections besides C diff in kidney transplant patients. They have teamed up with infectious disease specialists Aneesh Mehta and Rachel Friedman-Moraco to conduct this study. Read more

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Meningitis bacteria adapt to STI niche — again?

A new paper in PNAS from Emory scientists highlights a neat example of bacterial evolution and adaptation related to sexually transmitted infections. Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, sometimes appears in the news because of cases on college campuses or other outbreaks.

The N meningitidis bacteria causing a recent cluster of sexually transmitted infections in Columbus, Ohio and other US cities have adapted to the urogenital environment, an analysis of their DNA shows.

Update: May 2016 Clinical Infectious Diseases paper on the same urethritis cluster.

Genetic changes make this clade look more like relatives that are known to cause gonorrhea. Some good news is that these guys are less likely to cause meningitis because they have lost their outer capsule. They have also gained enzymes that help them live in low oxygen.

The DNA analysis helps doctors track the spread of this type of bacteria and anticipate which vaccines might be protective against it. Thankfully, no alarming antibiotic resistance markers are present (yet) and currently available vaccines may be helpful. Full press release here, and information about meningococcal disease from the CDC here.

This looks like a well-worn path in bacterial evolution, since N. gonorrhoeae is thought to have evolved from N. meningitidis and there are recent independent examples of N. meningitidis adapting to the urogenital environment. 

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Three remarkable Emory case reports from #ACC17

The big news from the American College of Cardiology meeting today is about PCSK9 inhibitors, which were known to be effective at lowering LDL cholesterol, and how much they really prevent heart attacks and save lives.

Lab Land went looking off the beaten path for individual stories of Emory cardiologists saving lives and was pleased to find several. We highlight here three remarkable case reports that are being presented at the ACC meeting. We look forward to learning more about these cases.

Refractory electrical storm 

Electrical storm is life threatening and refers to a recurrent arrhythmia. The arrhythmia did not respond to drug treatment, so anesthesiologists were brought in to perform left stellate ganglion block, an injection of medication into a nerve bundle in the neck, allowing diagnosis and further treatment. It turns out the arrhythmia was caused by sarcoidosis, a rare intrusion of immune cells into the heart. [Saturday morning: Michael Lloyd, Boris Spektor]

Hormone-producing tumor + cardiomyopathy 

A 30-year old woman came to doctors with drastically impaired heart function, although she did not have a blockage of her coronary arteries or signs of damage to the heart muscle. Doctors discovered a tumor near her spine that was producing heart-distorting hormones such as epinephrine. She underwent surgery to remove the tumor. [Saturday afternoon: Stamatios Lerakis]

Giving birth unveils birth defects

Ten days after giving birth, a woman came to a hospital with chest pain. Upon cardiac catheterization, a rearrangement of her coronary arteries was discovered. It appears that the congenital defect had gone undetected until the stress of giving birth. Under medical treatment, she is asymptomatic, but she will need future monitoring and possibly a procedure to correct the artery problems. [Sunday morning: Camden Hebson]

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Direct reprogramming into endothelial cells

Direct reprogramming has become a trend in the regenerative medicine field. It means taking readily available cells, such as skin cells or blood cells, and converting them into cells that researchers want for therapeutic purposes, skipping the stem cell stage.

In a way, this approach follows in Nobel Prize winner Shinya Yamanaka’s footsteps, but it also tunnels under the mountain he climbed. Direct reprogramming has been achieved for target cell types such as neurons and insulin-producing beta cells.

Young-sup Yoon, MD, PhD

In Circulation Research, Emory stem cell biologist Young-sup Yoon, MD, PhD and colleagues recently reported converting human skin fibroblast cells into endothelial cells, which line and maintain the health of blood vessels.

Once reprogrammed, a patient’s own cells could potentially be used to treat conditions such as peripheral artery disease, or to form vascular grafts. Exactly how reprogrammed cells should be deployed clinically still needs to be worked out.

In cardiovascular disease, many clinical trials have been performed using bone marrow cells that were not reprogrammed. Emory readers may be familiar with studies conducted by Arshed Quyyumi, MD and colleagues, in which treatment was delivered after patients’ heart attacks. In those studies, sorted progenitor cells, some of which could become endothelial cells, were introduced into the heart. To provide the observed effects, the introduced cells were more likely supplying supportive growth factors.

In contrast, Yoon’s team is able to produce cells that already have endothelial character hammered into them. The authors have applied for a patent. The co-first authors were instructor Sang-Ho Lee, PhD and Changwon Park, PhD, assistant professor of pediatrics. Read more

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