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February 7, 2013

Research Notes

Bariatric surgery patients benefit from physical activity counseling

People who lose weight with bariatric surgery may have better results if they receive counseling about increasing physical activity before and after surgery, according to research led by epidemiology faculty member Wendy C. King of the Graduate School of Public Health.

Said King: “Bariatric surgery is the most effective treatment for severe obesity. However, maintaining the resulting weight loss can be difficult. On their own, bariatric surgery patients are not likely to significantly increase their physical activity following surgery. However, with assistance, motivated patients can increase their activity level to achieve better health than with surgery alone.”

Using activity monitors that capture movement and the intensity of physical activity, King and a Brown University colleague found that, without counseling, most bariatric surgery patients are insufficiently active prior to surgery and, without support, fail to increase their physical activity substantially after surgery, despite significant weight loss and improvements in their physical function.

The researchers used previous and ongoing studies to estimate that pre- and postoperative physical activity counseling could increase the physical activity level of bariatric surgery patients by about 50 percent. Earlier research suggested that even mild increases in physical activity preoperatively could reduce surgical complications and improve healing after surgery.

“Because of patients’ health-related barriers to physical activity, clinicians may be inclined to hold off on advising their patients to become more physically active until after the surgery helps them lose weight,” King said. “However, the U.S. Department of Health and Human Services’ guidelines indicate that it is safe and beneficial for people with chronic medical conditions, such as obesity and diabetes, to be physically active according to their abilities.”

Recent studies also show that bariatric surgery patients’ postoperative physical activity levels can be increased when the patients are enrolled in exercise programs with a personal trainer or other structured support.

Despite these findings, only 22 percent of patients of bariatric surgical centers accredited by the American College of Surgeons Bariatric Surgery Center Network report having received postoperative exercise counseling.

“A major barrier to providing physical activity counseling is lack of insurance reimbursement,” King said. “However, another major barrier is lack of training and available information on what to recommend or how to effectively make recommendations, specifically to adults undergoing bariatric surgery.”

King serves on the joint committee of the American College of Sports Medicine and the American Society for Metabolic and Bariatric Surgery, working to develop the first evidence-based preoperative or postoperative physical activity guidelines for bariatric surgery patients.

To aid surgeons and clinicians in advising their bariatric surgery patients, the researchers provide guidelines on how to tailor counseling to those patients to lead safely and effectively to increases in physical activity using proven counseling strategies.

Dubbed the “Five A’s,” the strategies are to assess the patient’s physical activity experience and ability; advise the patient on its benefits; agree on physical activity goals and a plan; assist the patient with tools and resources, and arrange follow-up.

The findings, as well as recommendations on how best to tailor physical activity counseling to patients, were published in the January issue of Exercise and Sports Sciences Reviews, a publication of the American College of Sports Medicine.

The research was funded by the National Institutes of Health (NIH).

Bioengineering prof wins ophthalmology award

George Stetten, a bioengineering faculty member in the Swanson School of Engineering, has received a Research to Prevent Blindness Innovative Ophthalmic Research Award.

The award provides funding to basic scientists engaged in “innovative, out-of-the-box” research performed in collaboration with the ophthalmology department at the researcher’s home institution — in this case, in the School of Medicine.

Stetten is one of six researchers at six institutions who have received the award since 2011. He also serves on the faculty of the Carnegie Mellon University Robotics Institute and directs the Visualization and Image Analysis Laboratory and the Music Engineering Laboratory, run jointly with CMU.

New nanowires rival silicon’s properties

Jeremy Levy, a Dietrich School of Arts and Sciences faculty member in physics and astronomy, has created a new type of semiconductor nanowire with properties that rival more common silicon nanowires. These near atomic-sized wires, based on the oxide materials lanthanum aluminate and strontium titanate, have a mobility high enough to be used in modern electronics. Electron mobility is a material property that has direct influence on an electronic circuit’s speed.

Levy and colleagues began by creating oxide-based nanowires 100 nanometers wide. They found that as they decreased the size of the nanowires, the mobility increased. This is contrary to what happens in all other known materials.

The researchers produced the nanowires via a rewritable nanoelectronics platform developed in Levy’s lab that works like a microscopic Etch A Sketch, the drawing toy that initially inspired him. His technique involves a method to switch an oxide crystal between insulating and conducting states. Applying a positive voltage to the sharp conducting probe of an atomic force microscope creates conducting wires only a few nanometers wide at the interface of two insulators — a 1.2 nanometer-thick layer of lanthanum aluminate grown on a strontium titanate substrate. The conducting nanowires then can be erased with reverse voltage, rendering the interface an insulator once more.

In this recent work, Levy and colleagues created nanowires with high mobility using the same techniques and materials. In a solid-state material, for example a semiconductor or an oxide crystal, mobility relates how fast an electron will move due to an electric field. If the electrons are able to move faster, then circuits made from that material will be able to operate at faster speeds. Silicon, which is used in the majority of modern microelectronics, actually suffers from decreased mobility when formed into nanowire geometries.

Adding high mobility to a materials platform on which one can reversibly write electronic and photonic circuits with extreme nanoscale dimensions will aid future researchers in creating new kinds of devices and for investigating new kinds of physics.

Lead author on the paper, which appears in the latest issue of Nano Letters, is physics faculty member Patrick Irvin, who collaborated with Pitt students and faculty from the University of Wisconsin-Madison.

“Achilles heel” of key HIV replication protein found

School of Medicine researchers may have found an “Achilles heel” in a key HIV protein. The study, led by Thomas E. Smithgall, chair of the Department of Microbiology and Molecular Genetics, showed that targeting this vulnerable spot could stop the virus from replicating, potentially thwarting HIV infection from progressing to full-blown AIDS.

Previous research demonstrated that a small HIV protein called Nef interacts with many other proteins in infected cells to help the virus multiply and hide from the immune system. Smithgall and colleagues developed a way to track Nef activity in high-throughput drug screening protocols by linking it to an enzyme called Hck, which is activated by Nef in HIV-infected cells.

Said Smithgall: “We reasoned that agents that prevent Nef from its usual interactions with other proteins might be able to stop HIV from replicating and infecting other cells. We devised an automated screening procedure and tested nearly 250,000 compounds to find ones that could block Nef activity.”

One of the compounds they discovered, called B9, seemed particularly potent at blocking Nef. B9’s ability to prevent two Nef molecules from interacting consequently impairs its function in the viral replication process. “This pocket where B9 binds to Nef … [is an] Achilles heel that could represent a new target for HIV drugs,” Smithgall said. “Our test-tube and cell-culture experiments show that blocking this site brings HIV replication to a halt.”

The team is working with medicinal chemists at Pitt’s Drug Discovery Institute to find analogs of B9 that have therapeutic potential, and plan to assess them in animal models of HIV/AIDS.

Co-authors of the study include colleagues from microbiology and molecular genetics, structural biology, pharmaceutical sciences in the School of Pharmacy, and the University of Virginia.

The project was funded by NIH and appears in Chemistry and Biology.

Literacy coaching aids low-income students

The language and reading comprehension skills of low-income, upper elementary-school students — especially English-language learners — can improve markedly if their teachers work alongside content-specific literacy coaches to foster a more interactive learning environment during class reading assignments, according to a Pitt study.

In this three-year study, coaches were trained using an Institute for Learning professional development system called the content-focused coaching model. Coaches provide teachers with the tools they need to implement rigorous, standards-based lessons. Teachers then can use the knowledge they’ve gained to train other teachers in their schools.

Said study principal investigator Lindsay Clare Matsumura, a School of Education faculty member with the Learning Research and Development Center (LRDC): “We found that a well-structured and content-specific approach to literacy coaching shows strong evidence of being able to really make an impact on classroom text discussion and reading achievement in these upper elementary grades — a critical time for students to develop their higher-level reading skills.”

This method also strengthens adherence to the common core state standards, a national campaign aiming to increase the quality of the country’s education system.

In a group-randomized trial, Matsumura and colleagues investigated the effects of the content-focused coaching model, zeroing in on the quality of text discussions in the classroom. The researchers worked with 29 schools in a Texas district that serves a high percentage of low-income and English-language-learning students.

Coaches were placed in schools and began working with teachers on “Questioning the Author,” one approach of the content-focused coaching model in which students answer critical questions about the author and text.

Students are asked to stop throughout the reading of a book and answer thought-provoking questions. If a text is written unclearly, said Matsumura, the teacher will pause to make sure students understand what is happening and also review any unknown vocabulary.

Students’ reading scores were evaluated through a series of tests across the three years. Schools participating in the coaching intervention had a positive effect on students’ reading achievement — specifically for English-language learners, who made up 40 percent of the study’s sample.

The study, conducted with colleagues from LRDC and Western Michigan University, appeared in Learning and Instruction online in December and will appear in print there in June.

The research was supported by the Institute for Educational Sciences.

Confidence falls when people agree — but for different reasons

Research gathered during President Barack Obama’s first campaign for president has contributed to a study that examines the impact of others’ choices on our confidence in our own decisions.

Cait Poynor Lamberton, faculty member in the Joseph M. Katz Graduate School of Business and College of Business Administration, used survey data that included polling participants on their preferred 2008 presidential candidate. She and colleagues found that a person’s confidence in his or her publicly stated choices can be diminished after knowing that another person has made the same choice for different reasons.

Considering the scene on the National Mall at Obama’s second inauguration as an example of the phenomenon, Lamberton said: “If I see someone holding signs and displaying views that have nothing to do with my reasons for supporting Obama, it’ll make me question whether I really voted for the right guy — or if my reasons for doing so were completely misguided. We could call this the ‘strange bedfellows effect.’”

Lamberton and colleagues conducted surveys with undergraduate students on choosing a graduate school, a vacation destination and a presidential candidate to assess how different reasons for making the same choice can affect people’s decisions and confidence.

In the survey on choosing a presidential candidate, participants were asked individually to rank reasons why they were considering Barack Obama or the 2008 Republican nominee, Sen. John McCain, as well as their confidence in their decision.

Then, some participants were told that they would need to discuss their choice and reasons with a potential partner. They were given fabricated decisions from their potential partners, including some with reasons that were ranked in orders different from their own.

The participants then were asked to reconsider the two candidates a second time and to again rank their confidence in their choice. The participants who read the fabricated decisions from partners with different reasons for choosing the same candidate were more likely to feel less confident in their decision.

While reviewing survey results, the team found that its central observation does not hold true in private situations where individuals are not expected to explain the reasoning behind their decisions.

“In the public domain, people anticipate that they may have to defend their choices,” Lamberton said. “As such, having strong reasoning underlying their choices becomes more important to them. By contrast, many of our private decisions aren’t even based on well-articulated reasons: We choose simply based on habit or instinct, but if no one forces us to, we don’t think too carefully about our reasoning.”

The study, conducted with researchers from Ohio State University and Texas A&M University, was published in the January issue of the Journal of Consumer Psychology.

Growth halted in cancer cells: Result could be therapy

University of Pittsburgh Cancer Institute (UPCI) researchers have uncovered a technique to halt the growth of cancer cells, a discovery that may lead to a new anti-cancer therapy.

When deprived of a key protein, some cancer cells are unable to properly divide. Noted senior author Bennett Van Houten, faculty member in the Department of Pharmacology and Chemical Biology in the School of Medicine and Richard M. Cyert Professor of Molecular Pharmacology at UPCI: “This is the first time anyone has explained how altering this protein at a key stage in cell reproduction can stop cancer growth. Our hope is that this discovery will spur the development of a new type of cancer drug that targets this process and could work synergistically with existing drugs.”

All cells have a network of mitochondria, which are tiny structures inside cells that are essential for energy production and metabolism. Dynamin-related protein 1 (Drp1) helps mitochondria undergo fission, a process by which they split themselves into two new mitochondria.

In breast- or lung-cancer cells made to be deficient in Drp1, the researchers observed a huge network of highly fused mitochondria. These cancer cells appear to have stalled during a stage in cell division called G2/M. Unable to divide into new cells, the cancer growth stops.  Those cells that do try to divide literally tear their chromosomes apart, causing more stress for the cell.

“Once we revealed this process for halting cancer cell growth by knocking out Drp1, we began looking into existing compounds that might utilize a similar mechanism,” said Van Houten. “Now that we know affecting mitochondria in this manner inhibits cell growth, we could target drugs to this biological process to treat cancer.”

The researchers found a compound called Mdivi-1 that makes cancer cells behave much the way they do when deficient in Drp-1. When used in combination with cisplatin, a drug already used to treat many solid cancers, rapid cell death can be induced in a wide range of cancer cells. This means that Mdivi-1 makes cisplatin work better.

Mdivi-1 is being tested in cancer cells in a laboratory setting. Those tests show that, while the compound acts as though it is depriving cancer cells of Drp1, it is actually using a different mechanism.

Van Houten hopes to move his laboratory tests on Mdivi-1 to clinical trials. “We were on the hunt for a drug that could make cancer cells deficient in Drp1,” he said, “and, instead, we found a new cancer therapy that seems to work really well.”

Van Houten’s Pitt co-authors are Wei Qian, Serah Choi, Gregory A. Gibson and Christopher J. Bakkenist.

This research is the cover story of the February issue of the Journal of Cell Science.

NIH and the Pennsylvania Department of Health provided support for the research.


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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