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February 9, 2012

Research Notes

Mitral repair safe for seniors

A study that analyzed valve mitral repair operations in people over age 65 has found the surgery to be a safe treatment option for older patients who have a leaking mitral valve. Leaking, or mitral regurgitation, can limit long-term life expectancy and reduce quality of life due to its secondary effects.

Young patients with mitral regurgitation have their valves repaired as a first course of treatment but, for elderly patients, current guidelines call for medical treatments to be tried first because advanced age was believed to put these patients at high risk for complications and little was known about their long-term outcomes. Mitral valve repair often was done in the elderly only after symptoms worsened.

Lead author Vinay Badhwar, a faculty member in cardiothoracic surgery and co-director of the UPMC Center for Mitral Valve Disease, presented the findings at a recent meeting of The Society of Thoracic Surgeons.

Based on an analysis of clinical data from the society’s Adult Cardiac Surgery Database matched to longitudinal claims data from the Centers for Medicare and Medicaid Services, the study identified 14,604 mitral valve repair operations. The cases were studied for mortality, mitral reoperation and readmissions for heart failure, bleeding and stroke. Researchers found 2.6 percent of the patients died during or soon after surgery. Survival during followup was 74 percent. After adjusting for the statistical impact of late mortality, the researchers found that mitral repair was durable, with reoperation occurring in only 5 percent of cases.

The study was supported by The Society of Thoracic Surgeons Research Center through the Adult National Cardiac Database and the Duke Clinical Research Institute.

Online hookah ads studied

Of the growing number of businesses promoting hookah tobacco smoking on the Internet, fewer than 1 percent included a tobacco-related warning on the first page of their web sites, according to a School of Medicine study available online in the American Journal of Preventive Medicine.

The study also found that, while cigarette-related web pages often are required to verify users’ ages, none of the hookah tobacco web pages required any type of age verification.

Researchers say the findings suggest more health education may be valuable in countering misinformation about smoking tobacco through hookahs.

Principal investigator Brian Primack, a faculty member in medicine and pediatrics, said many web sites stated or implied that smoking tobacco through the pipes was safer than cigarette smoking. In fact, only 26 percent of the web sites included the word “tobacco” on their opening web pages.

“Hookah tobacco smoking is growing in popularity in the United States, but many people are unaware of the health risks. It’s believed that one session of smoking tobacco through a hookah can deliver about 50-100 times the smoke volume, 40 times the tar and twice the nicotine usually delivered by a single cigarette,” Primack said. “Hookah smoking has been linked to serious diseases like cancer and cardiovascular disease, and people should be aware of these risks.”

The researchers examined the contents of 144 United States-based web sites that promote hookah-smoking establishments. Many of the hookah businesses had similar characteristics that glamorized hookah tobacco smoking as a fun, social activity: 79 percent served food, 41 percent served alcohol, 53 percent offered dancing and 37 percent offered live music. Many also had a social media presence, with 31 percent having Facebook pages and 15 percent using Twitter.

“Many people seem to have the misconception there is no tar or nicotine associated with this type of tobacco use. I think we need to step up our educational efforts to help them understand what the risks may be,” Primack said.

Pitt collaborators included Kristen R. Rice, Ariel S. Shensa, Mary V. Carroll and Erica J. DePenna of medicine.

The study was funded by the National Cancer Institute.

Tumor growth, suppression protein found

Researchers at the School of Medicine and University of Pittsburgh Cancer Institute (UPCI) have identified a protein that governs a key molecule involved in orchestrating the balance between tumor growth and tumor suppression. The findings, published in Molecular Cell, reveal a regulatory pathway that could provide new targets for future cancer treatment.

Kruppel-like factor 4 (KLF4) is one of four molecules known to play an important role in transforming the body’s mature cells back into stem cells, said senior author Yong Wan, a faculty member in the Department of Cell Biology and UPCI. “This molecule has been shown in other studies to encourage tumor growth in some cases, such as breast cancer, but to suppress it in others, such as gastrointestinal cancer,” he said. “We wanted to learn how that was possible.”

The researchers found that a protein made by the von Hippel-Lindau gene (pVHL) binds to KLF4 and triggers a biochemical pathway that leads to KLF4’s degradation. Wan noted that KLF4 determines cell fate by activating or inhibiting a network of genes involved in cellular functions. High pVHL shortens the lifespan of KLF4. If it is low, KLF4 lasts longer, with a consequent impact on the number of cells. “In colon cancer cells, pVHL levels are high and KLF4 is low, which suggest promotion of tumor cell growth,” he said.

“But our other research shows that in breast cancer, KLF4 is high. The abnormal proteins produced by cancer cells could be influencing this pathway, so we are working to better understand these processes.” Learning more about the role of pVHL, KLF4 and other proteins that interact with them also could lead to new cancer drugs, the researchers said.

Pitt co-authors included Armin M. Gamper, Xinxian Qiao and Liyong Zhang of the Department of Cell Biology and UPCI.

The research was funded by grants from the National Institutes of Health and the American Cancer Society.

Jewish studies program grant received

Pitt’s Jewish studies program has been awarded a grant from the Association for Jewish Studies for public programming in 2012-13.

The grant will fund lectures, workshops and panel discussions between September 2012 and May 2013 on the topic of “Squirrel Hill, the Jewish Community of Pittsburgh and American Urban History.”

Lung cancer grant awarded

The Bonnie J. Addario Lung Cancer Foundation (BJALCF) has awarded radiology faculty member Jiantao Pu $50,000 as part of more than $1 million in 2012 lung cancer research grants.

Pu’s project, “Diagnosis-by-Search: Enabling Early Detection & Accurate Diagnosis of Lung Cancer,” aims to develop a novel computer-aided diagnosis paradigm.

CT scans can identify small nodules that could indicate early lung cancer, but further testing often is needed to determine whether a suspicious nodule is malignant or benign. Those tests can be invasive and bring unnecessary cost, worry and risk to patients, Pu stated in his grant application.

“We propose to develop and test a novel diagnosis paradigm by searching similar cases from an available database with verified diagnosis information and use them as a reference for accurate diagnosis,” Pu stated.

Such a tool could improve doctors’ performance in early detection and accurate diagnosis of lung cancer and accelerate understanding of the mechanisms that underlie the disease.

BJALCF is a philanthropic organization devoted to eradicating lung cancer through research, early detection, education and treatment. Its research grants are directed toward immediate results-oriented projects or programs with the potential to catalyze progress through early detection, genetic testing, drug discovery and patient-focused outcomes.

Digital nanofixes proposed

Inspired by the ability of white blood cells to heal wounds on-site, a team of researchers from Pitt and the University of Massachusetts-Amherst have proposed a “repair-and-go” approach to fixing malfunctions caused by nanoscale scratches or cracks on any digital device or part before it hits store shelves.

Their work was published in Nature Nanotechnology, available online at

“Anything that’s a machine with a surface is affected by these small-scale cracks,” said Anna Balazs, Distinguished Professor of Chemical and Petroleum Engineering and co-investigator on the project. “These are surfaces that play a role in almost anything, especially functionality.”

Balazs and Pitt colleagues conceived a theoretical “repair-and-go” method in which a flexible microcapsule filled with a solution of nanoparticles would be applied to a damaged surface. It then would repair defects by releasing nanoparticles into them.

Using nanoparticles and droplets of oil stabilized with a polymer surfactant — compounds that lower the surface tension of a liquid — the UMass team actualized the theory, showing that these microcapsules found the cracks and delivered the nanoparticle contents into them.

Balazs proposed that manufacturers use this method as a last step in the building process.

“The repair-and-go method can extend the lifetime of any system or device,” she said. “Additionally, it could be used as a repair method after a crack has been found.”

German Kolmakov of the Department of Chemical and Petroleum Engineering was among the paper’s co-authors.

More-porous materials designed

Pitt researchers have identified an approach to building porous materials that could ease the delivery of drugs into the human body and better control the storage of gas molecules. Their work appears in Nature Communications.

Working with metal-organic frameworks — crystalline compounds made from metal-cluster vertices linked together by organic molecules to form porous structures — researchers addressed changing the size of the vertex (the metal cluster) rather than the length of the organic molecule links, which resulted in the largest metal organic framework pore volume reported to date.

Principal investigator Nathaniel L. Rosi, a faculty member in chemistry, said, “Think of this the way you imagine Tinkertoys. The metal clusters are your joints, and the organic molecules are your linkers. In order to build a highly open structure with lots of empty space, you can increase the linker length or you can increase the size of the joint. We developed chemistry to make large joints, or vertices, and showed that we could link these together to build a material with extraordinarily large pores for this class of materials.

“Essentially, we’re like architects. We first make a blueprint for a target material, and we then select our building blocks for construction,” he said. “We develop methods for designing structures and controlling the assembly of these structures on a molecule-by-molecule basis.”

The new approach could have an impact on storing large quantities of gas such as carbon dioxide or methane, an important development for alternative energy, or large amounts of drug molecules, which could impact the drug-delivery field, researchers said.

Other Pitt co-authors were Jihyun An, who received her PhD in chemistry in 2011, and Joanne I. Yeh of the Department of Structural Biology.

The team’s research has been supported in part by the American Chemical Society Petroleum Research Fund.

Solar power grant awarded

In an effort to help advance the use of solar power, the U.S. Department of Energy (DOE) has awarded $315,697 to a coalition of private and public organizations — including the Congress of Neighboring Communities (CONNECT) program of the Center for Metropolitan Studies in Pitt’s Graduate School of Public and International Affairs — to help standardize and streamline ordinances and processes for the installation of solar power in southwestern Pennsylvania.

DOE’s Rooftop Solar Challenge, part of an initiative to make solar power cost-competitive with other forms of energy by the end of the decade, awarded a total of $12 million to 22 teams across the country to help increase solar power installation in homes and businesses in communities and reduce administrative costs for installing the systems.

According to DOE, reducing the installed cost of solar energy systems by 75 percent could drive widespread large-scale adoption of solar power, fortifying U.S. leadership in the global clean energy race while spurring new industries and job creation across the nation.

CONNECT partnered with the Citizens for Pennsylvania’s Future’s Three Rivers Solar Source project, the City of Pittsburgh, Allegheny County, the Southwestern Pennsylvania Commission, Solar Unified Network of Western Pennsylvania and the Green Building Alliance.

Twenty-three local municipalities are participating in the grant’s initiative.

AOPA funds knee research

The American Orthotic and Prosthetic Association has awarded two years of funding for a project by Department of Bioengineering faculty members Rakie Cham and April Chambers.

Funding began Dec. 1 for their project, “Microprocessor Knee — Non-Microprocessor Knee Comparative Effectiveness.”

Military research funding continues

A team of Pitt researchers led by Scott Lephart, chair of the School of Health and Rehabilitation Sciences Department of Sports Medicine and Nutrition, recently was awarded a $5.6 million grant to continue their Naval Special Warfare study of strategies to mitigate musculoskeletal injuries and optimize physical readiness of military personnel.

Research with the Department of Defense since 2006 includes studying injury prevention and human performance, including two research projects with Naval Special Warfare and the Army 101st Airborne Division.

The project is slated to begin additional U.S. Special Operations Command research including Army Special Operations Command, Air Force Special Operations Command and a third Naval Special Warfare study.

Preventive blood thinners may aid cancer patients

Preventive use of blood thinners, or anticoagulants, in people receiving outpatient treatment for cancer could prevent the development of blood clots and improve quality of life, according to a study led by medical school faculty member Margaret Ragni of the Division of Hematology/Oncology. Results were presented recently at the annual meeting of the American Society of Hematology.

“Blood clots are a major cause of cancer patient deaths, but the current standard of care is to use anticoagulants in cancer patients only when they are hospitalized, undergo surgery or develop a clot,” said Ragni.

“We wanted to find out whether giving anticoagulants preventively would stop clots from forming and improve health outcomes and quality of life. We found not only could this approach improve patient outcomes, it also appears to be cost-effective.”

Ragni and her team constructed a model using data from published studies to determine if the research intervention warrants a clinical trial. The model evaluated the cost and effectiveness of preventive anticoagulant use in cancer patients with no history of blood clots in the following clinical states: bleeding; new clots; cancer recurrence, and death.

“Because a significant percentage of cancer patients suffer from blood clots, it makes sense to examine whether or not preventive anticoagulation could work. When you take into consideration all of the benefits, balanced with the cost of the drug, this approach could be practice-changing,” said Ragni.

The study was sponsored by the Hemophilia Center of Western Pennsylvania, where Ragni is medical director.

UCSUR: area population rising

A study by Pitt’s University Center for Social and Urban Research (UCSUR) has found that more people moved into the seven-county Pittsburgh metropolitan area than those who moved out in 2009 and 2010.

Chris Briem, UCSUR regional economist, said, “This turnaround and moderate migration into the region is consistent with our long-range forecasts for this economy. Pittsburgh has fared much better through the recent recession than it has in past economic downturns.”

Briem noted that by some measures Pittsburgh’s labor force is doing better than the labor force nationally.

“The Pittsburgh region’s unemployment rate has been below the national unemployment rate for five straight years. It’s likely some folks are looking to Pittsburgh for job market opportunities that don’t exist elsewhere,” Briem added.

The report used IRS migration data, which draws from administrative records such as income tax returns to produce statistics on the movement of people between counties and across the nation.

The Pittsburgh metropolitan area is made up of Allegheny, Armstrong, Beaver, Butler, Fayette, Washington and Westmoreland counties.


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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