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September 29, 2011

Research Notes

Diabetics’ family planning studied

Women with diabetes are less likely than women without chronic diseases to get contraceptive counseling or use reversible contraceptives, according to a study led by a School of Medicine researcher published online in the Journal of General Internal Medicine.

The study’s authors say family planning services are critical for diabetic women because babies born to diabetics who become pregnant when their blood sugar is uncontrolled have an increased risk of birth defects.

The study also found that diabetic women are more likely to be surgically sterilized than similarly aged women without chronic conditions.

This finding highlights the need for diabetic women to receive more information about highly effective contraceptives, such as intrauterine devices (IUDs), said lead author Eleanor Bimla Schwarz, a faculty member in medicine, epidemiology, gynecology and reproductive sciences and a UPMC physician. Such contraceptives allow women time to control their blood sugars and increase the chance a woman will have a healthy baby when she wants one.

Researchers examined the medical records of 8,182 insured women with diabetes and 122,921 insured women who had no chronic conditions between January 2006 and June 2007. More than half, or 52 percent, of the women with diabetes had not received any contraceptive services compared to 38 percent of women without chronic conditions.

“Many clinicians remain unaware of the range of contraceptive options that can be safely used when diabetes complicates a woman’s life. Just because diabetic women can’t take birth control pills doesn’t mean that surgical sterilization is their only choice,” said Schwarz, who also is an investigator at the Magee-Womens Research Institute. “IUDs, for example, are a great choice for women with diabetes. They are super-safe, as effective as having your tubes tied and are reversible.”

The study was funded in part by the National Institute of Child Health and Human Development and Bayer HealthCare Pharmaceutical.

GERD test, surgery aids lung patients

Surgery to correct gastroesophageal reflux disease (GERD) can preserve lung function in patients with end-stage pulmonary disease both before and after transplantation, according to a new study from the School of Medicine.

The findings, published recently in the Archives of Surgery, suggest that esophageal testing should be performed more frequently among these patients to determine if anti-reflux surgery is needed.

Many end-stage lung disease patients, particularly those with idiopathic pulmonary fibrosis or cystic fibrosis, have GERD, and the reflux problem is very common after lung transplantation, said faculty member Blair Jobe of the Department of Cardiothoracic Surgery.

Also, GERD has been associated with bronchiolotis obliterans syndrome (BOS), which is a progressive impairment of airflow that is a leading cause of death after lung transplantation. Its cause is not yet known.

“It’s possible that reflux, which is due to a weak sphincter between the stomach and esophagus, allows acid and other gastric juices to leak back not only into the esophagus, but also to get aspirated in small amounts into the lungs,” Jobe said. “That micro-aspiration could be setting the stage for the development of BOS.”

Lead author Toshitaka Hoppo, a faculty member in the Department of Cardiothoracic Surgery, stressed the importance of esophageal testing for reflux in patients with end-stage pulmonary disease. “Almost one-half of the patients in our series did not have symptoms but were having clinically silent exposure to gastric fluid. Based on this finding, there should be a very low threshold for esophageal testing in this patient population,” he noted.

For the study, Jobe’s team reviewed medical charts of 43 end-stage lung disease patients with documented GERD, 19 of whom were being evaluated for lung transplant and 24 who already had undergone transplantation.

All the patients were on GERD medications at the time they were evaluated for anti-reflux surgery (ARS), which prevents fluid from leaking back into the esophagus. Prior to ARS, nearly half of the patients had either no or mild symptoms of GERD and only a fifth had the typical symptoms of heartburn and regurgitation.

The researchers found that nearly all measures of lung function improved after ARS in both the pre- and post-transplant groups. There also were fewer episodes of acute rejection and pneumonia after ARS in the post-transplant group. “The surgery appeared to benefit even those who hadn’t yet had a transplant,” Jobe noted. “Given the shortage of donor organs, ARS might help preserve the patient’s own function and buy some more time.”

Pitt co-authors of the paper included Christian Bermudez, Veronica Jarido, James D. Luketich, Arjun Pennathur, Norihisa Shigemura and Yoshiya Toyoda of cardiothoracic surgery and Maria Crespo, Matthew Morrell and Joseph Pilewski of the Department of Medicine.

Big grant advances tiny computing research

Pitt is the lead institution on a $1.8 million grant from the National Science Foundation and the Nanoelectronics Research Initiative (NRI) of the Semiconductor Research Corp. to bring a new kind of computer out of the lab and into the real world. The four-year grant, titled “Scalable Sensing, Storage and Computation With a Rewritable Oxide Nanoelectronics Platform,” also involves researchers from the University of Wisconsin and Northwestern University.

The goal of the group, led by Jeremy Levy of physics and astronomy, is to transform the way computing is done.

Levy and his team have invented a tiny Etch-A-Sketch-like tool less than four nanometers wide that draws and erases minuscule “wires” on a surface by switching an oxide crystal between insulating and conducting states. Electronic circuits can be “written” and “erased” at scales approaching two nanometers — the distance between atoms.

This grant addresses key scientific and technological challenges that, if overcome, could replace conventional electronics made from silicon devices. “The question is, once you’ve pushed silicon to its limit, is there going to be another system to do computation?” said Levy. “That’s really what we’ve been granted funding to explore. We’re trying to break down the major barriers that are potential show-stoppers that would otherwise make it difficult to turn these new types of devices into real, useful things.”

In 2008, Levy and colleagues reported in Science that they had made a transistor with elements that were five interatomic distances wide. “These are really, really small transistors,” Levy emphasized. “We believe that they behave in a fundamentally different way from normal transistors.”

Today’s computers use digital logic — a fixed architecture of ones and zeros, which may not be ideal for new materials. “We want the material to tell us the best way it can do computation, rather than trying to impose an old architecture that was really designed for another type of material,” he said.

The materials the research team will be working with are part of a family known as complex oxides. This class of materials shares many of the semiconducting properties of silicon, but has a wealth of other properties that makes them interesting for computing, storage and sensing applications. The principal material the researchers wish to study is a sandwich of two such oxides: a thick layer of strontium titanate with a 1.2-nanometer layer of lanthanum aluminate.

Another issue Levy is studying is the amount of power that devices consume as they get smaller. Not only is making computing more energy efficient good for the environment, it’s also practical. “What we’re interested in doing is trying to see if we can create info processing much closer to the fundamental limits,” Levy said. “We know we can make things small; the question is can we make them small and not heat up to the temperature of the sun?”

The grant also includes an outreach component. Faculty member Chandralekha Singh of physics and astronomy is leading a new “OnRamp” education program that targets specific difficulties that students have in their subdiscipline while beginning their research careers. Graduate students help develop research-based learning modules, which are shared with a broader research community—“putting a ramp there to smooth out the bumps in the road so that people can get moving with research faster,” she said.

For more information on Levy’s research, visit

Engineering awarded Coulter grant of $3.54 million

The Swanson School of Engineering’s Department of Bioengineering has received a five-year, $3.54 million grant from the Wallace H. Coulter Foundation.

Pitt is one of only five universities nationwide to receive the foundation’s Coulter Translational Partnership II Award, which will fund research that employs engineering techniques to develop improvements in health care, with the ultimate goal of accelerating the introduction of new technologies into patient care.

The award will be supplemented by $1.5 million in matching funds from the School of Medicine, the Swanson school and the Office of Technology Management.

Harvey Borovetz, chair of the Department of Bioengineering as well as the Robert L. Hardesty Professor in the School of Medicine’s Department of Surgery and deputy director of the Artificial Organs and Medical Devices division of the McGowan Institute for Regenerative Medicine, will be the principal investigator and one of three co-leaders for the Coulter program at Pitt. Rounding out the leadership team for Pitt’s Coulter program are Stephen Badylak, a faculty member in the School of Medicine’s Department of Surgery and director of tissue engineering in the McGowan Institute, and Marc Malandro, director of the Office of Technology Management (OTM) and associate vice chancellor for technology management and commercialization.

Pratap Khanwilkar will serve as the Coulter program director and visiting professor in the Swanson school’s bioengineering department and as an executive-in-residence at OTM. Khanwilkar, who most recently was an adjunct bioengineering professor at the University of Utah for 28 years, is the founder of six medical device product/service companies.

The $3.54 million award is part of a second phase of program development from the Coulter Foundation. In its first phase, the foundation awarded a total of $50 million in translational partnership awards in 2004 to 11 U.S. universities. That funding has resulted in an additional $300 million in investments to further the development and market applications of the various projects initiated as a result of the 11 Coulter-funded programs.

The Coulter Foundation also has agreed to fund seven of those first-phase programs with an additional $10 million.

Similar long-term funding could be made to Pitt and the other second-phase recipients based upon their ability to meet Coulter’s metrics for measurable outcomes and secure matching funds.

Galactic collision shaped Milky Way

A team of astronomy researchers say that the Milky Way galaxy’s spiral arms likely were formed by a collision with the Sagittarius Dwarf galaxy.

The conclusion, reported in the journal Nature, is based on supercomputer simulations by Christopher W. Purcell, a postdoctoral research associate in the Department of Physics and Astronomy and colleagues from the University of California and Florida Atlantic University.

Their paper “presents a new and somewhat unexpected way of thinking about why the galaxy we live in looks the way it does,” said Purcell. “Cosmologically speaking, it demonstrates the idea that relatively small impacts like this can have a dramatic impact on the structure of galaxies throughout the universe.”

This idea had been assumed theoretically but never demonstrated.

With supercomputers, astronomers can recreate a small-scale simulation or model of distant, violent events that occurred over billions of years, and observe that model in sped-up time, in order to make predictions that can be tested by actual observations of the universe.

Purcell’s simulations revealed that even more important than the stars of the Sagittarius Dwarf was its halo of invisible “dark matter,” equal in mass to all the stars in the Milky Way.

Visible matter makes up less than 5 percent of the universe, while nearly a quarter of the universe is made of transparent dark matter. Its existence is felt only through its gravitational influence. It is now known that every galaxy resides at the center of a giant halo of dark matter several times larger in radius and many times greater in mass.

“When all the dark matter smacked into the Milky Way, 80-90 percent of it was stripped off,” Purcell said. That first impact — more than two billion years ago — produced instabilities that quickly were amplified, eventually forming the spiral arms and ring structures in the outskirts of Earth’s own galaxy.

Conventional wisdom has been that the Milky Way was relatively unperturbed for the past several million years and its spiral arms were just a result of the Milky Way disk evolving in isolation.

Since the Sagittarius Dwarf was discovered, astronomers have tried to match up debris from that galaxy to what they saw in the universe. In 2003, infrared telescopes and supercomputers that traced the orbital motions of its stars has revealed that the Sagittarius Dwarf actually had collided with the Milky Way twice — once 1.9 billion years ago and again 900 million years ago.

“But what those collisions did to the Milky Way hadn’t been simulated at all,” said Purcell. “Ours was the first ever to try to do that.”

They found that the collision set up instabilities — fluctuations in density of stars — in the flat disk of the rotating Milky Way. The galaxy rotates faster toward its center than toward its edges, so those instabilities were stretched and sheared, leading to the formation of spiral arms.

The simulations also revealed that the impact gave rise to ring-like structures found at the edges of the galaxy.

The second impact affected the Milky Way less, giving rise only to milder, less dense spiral-creating waves, because the Sagittarius Dwarf had by then lost most of its dark matter mass. Without the dark matter to hold the dwarf galaxy together, its visible stars began to be pulled apart by the Milky Way’s huge gravitational field and tidal forces.

“The dominant cosmology in astrophysics is one that’s very violent on small scales. Galaxies like the Milky Way are constantly being bombarded by these small dwarf galaxies. It had not been appreciated prior to our work just how dramatic those impacts could be on the stellar disk itself,” said Purcell. “We expected to find some more subtle signatures of an impact like this — a flare in the outer disk, like bell-bottom jeans. We expected to see some mild morphological changes to the Milky Way. But we did not expect to see a spiral structure begin to emerge as a result of these impacts. That was something we didn’t foresee.”

Today, long streamers of stars from the dismembered dwarf galaxy arch over and around the Milky Way, and “right now, billions and billions of dark matter particles from the Sagittarius Dwarf are raining down onto the Earth,” said Purcell. “Meantime, the sun itself is revolving around the center of the Milky Way galaxy in a complex and still-evolving system of multiple spiral arms.”

A third impact is in the galaxy’s future, Purcell said. “We can tell when we look toward the center of the Milky Way. Immediately on the opposite side of us, we can see this blob of stars crashing into the southern face of the disk from beneath. We can measure the velocities of these stars. We know that the dwarf galaxy is just about to smash the disk — in only another 10 million years.”

Women’s depression modeled

School of Medicine researchers have discovered molecular-level changes in the brains of women with major depressive disorder and have recreated them in a mouse model that could enhance future research on depression. Their results were published online in Molecular Psychiatry.

Although women are twice as likely as men to develop depression and have more severe and frequent symptoms, very little research has focused on them or been conducted in other female animals, noted senior author Etienne Sibille of psychiatry.

“It seemed to us that if there were molecular changes in the depressed brain, we might be able to better identify them in samples that come from females,” he said. “Indeed, our findings give us a better understanding of the biology of this common and often debilitating psychiatric illness.”

The researchers examined post-mortem brain tissue samples of 21 women with depression and 21 similar women without a history of depression. Compared to their counterparts, the depressed women had a pattern of reduced expression of certain genes, including the one for brain-derived neurotrophic factor (BDNF), and of genes that typically are present in particular subtypes of brain cells, or neurons, that express the neurotransmitter gamma-aminobutyric acid (GABA). These findings were observed in the amygdala, which is a brain region that is involved in sensing and expressing emotion.

In the next part of the project, the researchers tested mice engineered to carry different mutations in the BDNF gene to see its impact on the GABA cells. They found two mutations that led to the same deficit in the GABA subtype and that also mirrored other changes seen in the human depressed brain.

Sibille noted that researchers long have suspected that low levels of BDNF play a role in the development of depression; there also is a hypothesis that reduced GABA function is a key factor.

“Our work ties these two concepts together because we first show that BDNF is indeed low in depression and second, that low BDNF can influence specific GABA cells in a way that reproduces the biological profile we have observed in the depressed brain,” he said.

The team is continuing to explore the molecular pathway between BDNF and GABA and others that could be important in depression.

Pitt co-authors included Xingbin Wang of the Graduate School of Public Health and David Lewis of psychiatry.

The study was funded by the National Institute of Mental Health.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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