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University of Pittsburgh

July 25, 2013

Research Notes

Poor sleep in pregnancy can cause complications

Poor sleep quality and quantity during pregnancy can disrupt normal immune processes and lead to lower birth weights and other complications, a School of Medicine study finds. Women with depression also are more likely than non-depressed women to suffer from disturbed sleep and to experience immune system disruption and adverse pregnancy outcomes.

Said Michele Okun, psychiatry faculty member and lead author of the report: “Our results highlight the importance of identifying sleep problems in early pregnancy, especially in women experiencing depression, since sleep is a modifiable behavior. The earlier that sleep problems are identified, the sooner physicians can work with pregnant women to implement solutions.”

Adequate and high-quality sleep is essential for a healthy immune system. Pregnancy often is associated with changes in sleep patterns, including shortened sleep, insomnia symptoms and poor sleep quality. These disturbances can exacerbate the body’s inflammatory responses and cause an overproduction of cytokines, which act as signal molecules that communicate among immune cells.

While cytokines are important for numerous pregnancy-related processes, excess cytokines can attack and destroy healthy cells and cause destruction of tissue in pregnant women, thereby inhibiting the ability to ward off disease. For expectant mothers, excess cytokines also can disrupt spinal arteries leading to the placenta, cause vascular disease, lead to depression and cause pre-term birth.

Previous studies conducted postpartum have shown higher inflammatory cytokine concentrations among women who experienced adverse pregnancy outcomes such as preeclampsia and pre-term birth. While infection accounts for half of these adverse outcomes, researchers discovered that behavioral processes such as disturbed sleep also may play a role, given the relationship between sleep disturbance and immune function. Furthermore, higher concentrations of inflammatory cytokines also are found in depressed individuals.

The study is the first to evaluate all factors — inflammatory cytokines, depression and insomnia — and their possible combined effect on pregnant women. The study examined nearly 170 women, both depressed and not depressed, at 20 weeks of pregnancy and analyzed their sleep patterns and cytokine production levels over the course of 10 weeks, since pregnancy-related physiological adaptations are in flux prior to 20 weeks.

The findings reveal that women with depression and poor sleep are at greatest risk for adverse birth-related outcomes. Cytokine levels may be one biological pathway through which this is accomplished, particularly with regard to pre-term birth.

The study also concluded that any shift in immunity, such as poor sleep and/or depression, could set the stage for increased risk for adverse outcomes; that at 20 weeks, depressed pregnant women have higher levels of inflammatory cytokines compared to non-depressed women, and at 30 weeks of pregnancy, differences in cytokines among depressed and non-depressed women were negligible, likely because as pregnancy progresses, levels of cytokines normally increase.

The study was published this month in Psychosomatic Medicine.
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Swanson center awards funds

The Center for Medical Innovation (CMI) in the Swanson School of Engineering announced five awards in its 2013 round-1 pilot funding program for early stage medical technology research and development. This year’s awardees include projects ranging from the creation of a prototype surgical implant for vocal cord paralysis to the development of a small, implantable device that uses Doppler technology to monitor blood flow from inside the body.

Said CMI executive director Alan D. Hirschman: “Since our goal is to help new biomedical technologies get ready for eventual commercialization, we take a close look at which applications are most likely and most ready to move to the next level of funding and development.”

CMI funds applied technology projects that are in the early stages of development, with the goal of ultimately transitioning the work to clinical adoption. Proposals are evaluated on the basis of scientific merit, technical and clinical relevance, potential health-care impact and significance, experience of the investigators and potential to obtain further financial investment to translate the particular solution to health care. Funding ranges between $10,000-$25,000 per award for a total this round of $95,000.

• The project “Universal Bio-Thyroplant for Medialization Thyroplasty” will develop and test a prototype surgical implant for treatment of vocal cord paralysis under the research team of James J. Jaber, otolaryngology; April Chambers, bioengineering, and Peter Wipf, chemistry and pharmacy sciences.

• “Non-invasive Quantification of ACL Function With an iPad App” will develop and evaluate image-processing software for quantitative pre- and post-operative assessment of the anterior cruciate ligament (ACL) in the knee. The research team is composed of Volker Musahl, orthopaedic surgery and bioengineering; Richard E. Debski, bioengineering and orthopaedic surgery, and James J. Irrgang, orthopaedic surgery and the School of Health and Rehabilitation Sciences.

Neil Gildener-Leapman, otolaryngology, and Youngjae Chun, industrial engineering, received funding for “Prosthetic Device for Treatment of Dysphagia,” which will design and develop a device for use by patients with severe dysphagia or by patients who have undergone surgical removal of the tongue.

• The project “Precision Graft™: Next Generation Fat Harvest and Transfer Device for Reconstructive and Aesthetic Surgeries” aims to design, develop and test a new cannula to improve the efficiency, cost and efficacy of adipose tissue harvest and transfer procedures. It is led by the team of J. Peter Rubin and Lauren Kokai, plastic surgery; Mark Gartner, bioengineering, and Kacey Marra, surgery and  bioengineering.

• Funding for “Wireless Implantable Blood Flow Monitoring Device” was awarded to Michael Gimbel, surgery, and faculty from electrical and computer engineering: Ervin Sejdic, Marlin H. Mickle and Michael A. Rothfuss. The project will develop an ultra-small implantable Doppler blood flow monitoring technology with multiple applications, including the monitoring of surgical flap viability and the integrity of intravascular stents.
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Prof honored for social media privacy research

Adam J. Lee, faculty member in the Department of Computer Science, Dietrich School of Arts and Sciences, has received an Early Career Development Award from the National Science Foundation.

Lee’s five-year, $545,623 award will be used to design computer tools that enable daily social media users to better understand the interplay between security, privacy and utility within the context of their online interactions. The foundation’s CAREER program supports groundbreaking research by junior faculty members who demonstrate great understanding of their fields.

Said Lee: “Most systems deployed today have inherent security/privacy limitations. However, it’s tough for people who use these systems to understand the implications of the actions that they take online. For example, ‘checking in’ at my neighborhood pub in order to get a free Guinness seems like a great idea, until I realize that the pub is using this information to profile my activities, and I could inadvertently be tarnishing my social image with certain groups of people.”

The grant also will aid in the development of educational materials for two undergraduate courses — one for computer science majors and one for non-majors — that explore the social, technical and privacy implications of an increasingly digitized society.
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Chem prof wins $1.35 million NIH grant

W. Seth Horne, chemistry faculty member in the Dietrich school, has received a grant from the National Institutes of Health (NIH) for his project,  “Molecular Mimics of Protein Tertiary Folding From Primary Sequence Information.”

The five-year, $1.35 million award is funded by the National Institute of General Medical Sciences. The research aims to develop new strategies for mimicking chemical protein function, aiming to improve biological stability in the human body. Horne will use natural proteins to design molecules that have similar biological effects.

Along with funding research to develop the foundational technology, the grant will support work toward biomedical applications related to cancer detection and malaria. The work on cancer diagnostics will be performed in collaboration with Jan Pilch, faculty member in medicine’s Department of Urology.
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Fu, resident honored

Freddie Fu, medicine faculty member in the Department of Orthopaedic Surgery, and Carola Van Eck, an orthopaedic resident, are part of a research team that has been given the Jack Hughston Award for the outstanding sports-medicine paper of 2012 published in the American Journal of Sports Medicine.

In the paper, Fu, Van Eck and three researchers from Slovenia — principal investigator Mohsen Hussein, Andrej Cretnik and Dejan Dinevski — concluded that anatomic reconstruction techniques of the knee’s ACL were superior to reconstructing the ACL using non-anatomical drilling techniques. Fu traveled to the Artros Center for Orthopaedic Surgery and Sports Medicine in Ljubljana, Slovenia, to collaborate with Hussein, formerly a UPMC sports medicine research fellow.

The award was presented this month during the American Orthopaedic Society for Sports Medicine convention.

Additional honors received by Pitt faculty include the Young Investigator Grant, given to Pitt resident Ermias Abebe for his proposed study on ligament and meniscus injuries and how their treatment affects the knee joints, and the T. David Sisk Award for excellence in original research, given to a research team led by former Pitt faculty member Constance Chu, now at Stanford, and including Christian Coyle, Sarah Henry, Amgad Haleem and Michael O’Malley. The award recognized their ACL study published in 2012 in Sports Health: A Multidisciplinary Approach.
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New stroke rehab method tested

Elizabeth Skidmore, occupational therapy faculty member in the School of Health and Rehabilitation Sciences, received a grant from the National Center for Medical Rehabilitation Research to study the effect of early intervention in cognitive disability in stroke rehabilitation.

One-third to one-half of acute strokes result in new cognitive impairments, with individuals sustaining significant disability in daily tasks. This loss of independence is costly because individuals with stroke-related cognitive impairments require more rehabilitation and more resources to support their living than individuals who sustain stroke without cognitive impairments.

The best time to initiate rehabilitation is in the acute phase of recovery. The proposed study examines the efficacy of a new program, Adapting Daily Activity Performance Through Strategy Training after Stroke (ADAPTS), which can be delivered during acute rehabilitation.

ADAPTS teaches individuals with stroke-related cognitive impairments to identify and prioritize problematic daily activities, identify the barriers impeding activity performance, generate and evaluate strategies to address these barriers and generalize their learning through iterative practice.

Thus, ADAPTS teaches a process that can be applied to a person’s daily activities long after rehabilitation is completed. The primary aim of this randomized controlled trial is to examine the efficacy of ADAPTS for promoting independence among adults with stroke-related cognitive impairments engaged in acute rehabilitation. It also will explore changes in cognitive operations attributed to ADAPTS.

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PSC seeks better memory systems

The Pittsburgh Supercomputing Center (PSC) and Numascale AS, whose products support the construction of low-cost, scalable-server computer systems, are investigating the applicability of Numascale systems to the many research projects requiring more directly addressable memory than is readily available on single, commodity, multi-socket, large memory servers.

The field of supercomputing is well known for engineering extreme processing speeds but, increasingly, researchers’ calculations are limited not by the speed of processing but access to and efficient use of vast amounts of data. Application areas that require very large memories include natural language processing, multi-organism genomics and quantum chemistry. Having large amounts of data in directly addressable memory avoids time-consuming disk input/output and allows for more productive programming.

Using Numascale systems allows users to operate in familiar programming and runtime environments, which eliminates the need for explicit message passing and significantly reduces the overall time from idea to solution for a number of important applications in many scientific fields.
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Dendritic cell therapy could help kidney transplants

A single systemic dose of special immune cells prevented rejection for almost four months in a preclinical animal model of kidney transplantation, according to School of Medicine researchers.
Organ transplantation has saved many lives, but at the cost of sometimes lifelong requirements for powerful immunosuppressive medication that can have serious side effects. Scientists have sought ways to encourage the organ recipient’s immune system to accept or tolerate the donor organ.

Said senior investigator Angus Thomson, faculty member in surgery and immunology: “This study shows it is possible to prepare the patient’s immune system for a donor kidney by administering specially treated immune cells from the donor in advance of the transplant surgery.”

The researchers generated immune cells called dendritic cells (DCs) from the blood of rhesus macaques that later would provide a kidney to recipient monkeys. Dendritic cells are known to be key regulators of the immune system by showing antigens to T-cells to either activate them against the foreign protein or to suppress the T-cell response. The researchers treated the donor DCs in the lab to prevent them from fully maturing and having the capacity to trigger an immune reaction against foreign proteins.

One week before having a kidney transplant, recipient monkeys received a single infusion of treated DCs. Another group of monkeys was transplanted without receiving the cells, but both groups were given the same regimen of immunosuppression drugs, a modified protocol for experimental purposes that eventually results in donor organ rejection.

The donor kidney was rejected in about 40 days among animals that got only the drugs, but survived for about 113 days in the group that had a prior infusion of treated DCs.

Said lead author Mohamed Ezzelerab, surgery faculty member: “The results indicate that we achieved immune system regulation without side effects of the DCs, but better yet, the monkeys were healthier from a clinical perspective. They maintained a better weight, had less protein in the urine and fewer signs of kidney damage than the other group. Ultimately, all these factors played a role in prolonging organ survival in the group that received DC therapy.”

Co-authors of the paper included researchers from the Thomas E. Starzl Transplantation Institute and the departments of surgery, immunology, medicine and pathology. The project was funded by NIH and was published in the online version of the American Journal of Transplantation.
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State wine industry has room to grow

A report on the Pennsylvania wine industry found that the industry has capacity for growth.

The report by Shailendra Gajanan, Pitt-Bradford faculty member in economics, and James Dombrosky, former UPB faculty member, notes that Pennsylvania’s wine industry currently operates at only 76 percent of capacity and could achieve economies of scale by increasing its production.

Gajanan and Dombrosky compared practices, results, funding streams, regulations and marketing efforts with those in Ohio, Maryland, Virginia, North Carolina and New York. The researchers found that some of the limitations on growth are the laws and policies that limit the amount of Pennsylvania wines sold by the state Liquor Control Board-run stores. They noted that it is uncertain how the possible privatization of liquor sales in Pennsylvania would affect the wine industry, but lifting a prohibition against shipping wine to Pennsylvania would allow wineries to ship out of Pennsylvania.

Currently, 81 percent of all Pennsylvania wine is sold directly by wineries to wine outlets and tourists. Gajanan and Dombrosky recommended that the state consider designating any revenues from shipping wine out of state to wine research and marketing; encouraging increased signage for wine trails and regions; enacting policies to facilitate increased sales of local wines at state-run liquor stores, and providing incentives for wineries to use Pennsylvania grapes.

The report was commissioned by the Center for Rural Pennsylvania, a state legislative agency.
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SAD sufferers get sleep help

For those with seasonal affective disorder (SAD), sleeplessness is routine. Pitt researchers report that individuals with SAD — a winter depression that leads to loss of motivation and interest in daily activities — have misconceptions about their sleep habits similar to those of insomniacs.

Primary investigator Kathryn Roecklein, psychology faculty member in the Dietrich School of Arts and Sciences, along with researchers from the School of Medicine and Reyerson University, investigated why, according to a previously published sleep study by the University of California-Berkeley, individuals with seasonal affective disorder incorrectly reported that they slept four more hours a night in the winter.

Roecklein and her team interviewed 147 adults between the ages of 18 and 65 living in the Pittsburgh metropolitan area during the winters of 2011 and 2012.

Data were collected through self-reported questionnaires and structured clinical interviews in which participants were asked such questions as: “In the past month, have you been sleeping more than usual?” and “How many hours, on average, have you been sleeping in the past month? How does that compare to your normal sleep duration during the summer?”

To understand participants’ ideas about sleep, Roecklein’s team asked them to respond to questions such as “I need at least eight hours of sleep to function the next day” and “Insomnia is dangerous for health” on a scale from 0 to 7, where 7 means “strongly agree” and 0 means “disagree completely.”

Roecklein and her team found that SAD participants’ misconceptions about sleep were similar to the “unhelpful beliefs” or personal misconceptions about sleep that insomniacs often hold. Due to depression, individuals with SAD, like those with insomnia, may spend more time resting in bed, but not actually sleeping, leading to misconceptions about how much they sleep. These misconceptions, said Roecklein, play a significant role in sleep cognition for those with seasonal affective disorder.

Roecklein’s research data suggest that addressing, understanding and managing these “unhelpful beliefs” about sleep by way of psychotherapy could lead to improved treatments for seasonal affective disorder. One of the most effective treatment options for insomnia, said Roecklein, is cognitive behavioral therapy for insomnia (known as CBT-I), which aims to help people take control of their thinking to improve their sleep habits as well as mood, behavior and emotions.

Roecklein’s next research project aims to improve treatment for seasonal affective disorder by studying light perception and biological clock synchronization. Light from the environment synchronizes internal biological rhythms with the timing of dawn and dusk, which naturally changes with the seasons.

This synchronization allows people to be awake and alert during the day and to sleep at night. Roecklein will examine whether people with seasonal affective disorder perceive this light from the environment differently because of changes in the function of neurological pathways from the eye to the brain. This could help uncover reasons why people suffer from seasonal affective disorder and could suggest new treatment options.

Researchers included psychiatry faculty Peter L. Franzen and Brant P. Hasler of the School of Medicine and psychology graduate student Patrica M. Wong.

The paper was published online in the Journal of Affective Disorders and partially supported by NIH.
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Weight loss doesn’t prevent heart attacks, strokes in diabetics

Weight loss among patients with Type 2 diabetes resulted in no difference in heart attacks and strokes when compared with a control group, according to a Pitt study.

Conducted at Pitt and at clinical facilities throughout the United States, the clinical trial investigated the effects on rates of cardiovascular disease of an intensive lifestyle intervention program intended to achieve and maintain weight loss in overweight or obese people with Type 2 diabetes. Begun in 2001, the trial enrolled more than 5,000 people at 16 clinical centers.

Principal investigator John Jakicic, chair of the Department of Health and Physical Activity in the School of Education and director of the Physical Activity and Weight Management Research Center, with other Pitt colleagues comprised the national Look AHEAD (Action for Health in Diabetes) research group, which carried out the study.

The study found that weight loss among members of the study’s intensive lifestyle intervention group, provided with a program of weight management and increased physical activity, resulted in no difference in heart attacks and strokes when compared with the study’s control group, which was provided with only general health information and social support.

The effect of the intervention program on weight loss, however, was significant: Participants in the intervention group lost 8.7 percent of their initial body weight after one year of the study versus 0.7 percent among the control group’s members; the intervention group also maintained a greater weight loss, 6 percent of their initial weight, versus 3.5 percent for the control group, at the study’s conclusion.

The Look AHEAD study is the first to achieve such sustained weight loss. A weight loss of 5 percent or more in short-term studies is considered to be clinically significant and has been shown to improve control of blood pressure, blood sugar, cholesterol and other risk factors. Comparable weight loss can also help prevent the development of Type 2 diabetes in overweight and obese adults.

Said Jakicic: “While the findings from the Look AHEAD study did not support that engagement in a weight- loss intervention was effective for reducing the onset of cardiovascular disease incidence or mortality, this does not mean that overweight adults with diabetes should not lose weight and become more physically active. Rather, there is an overwhelming amount of evidence from this study to date that has shown that weight loss and physical activity were associated with numerous other health benefits.

“These include improving physical function and quality of life, reduction in risk factors such as lipids and blood pressure with less reliance on medication, better diabetes control with less reliance on medication, improved sleep, psychological and emotional health benefits, and many others. Thus, adults with diabetes can begin to realize many of these health benefits with even modest reductions in body weight and modest increases in physical activity.”

Research conducted at Pitt’s General Clinical Research Center and Clinical Translational Research Center was funded by a Clinical and Translational Science Award and an NIH grant. The results were published online in June in The New England Journal of Medicine.
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Student engagement found more complex

A student who shows up on time for school and listens respectfully in class might appear fully engaged to outside observers, including teachers.

But other measures of student engagement, including the student’s emotional and cognitive involvement with the course material, may tell a different story — one that could help teachers recognize students who are becoming less invested in their studies, according to co-author Ming-Te Wang, faculty member in the School of Education and in psychology in the Dietrich school.

More importantly for educators, the study suggests that student engagement, which is essential for success in school, is malleable and can be improved by promoting a positive school environment. The result paves the way for future work to offer teachers diagnostic tools for recognizing disengagement, as well as strategies for creating a school environment more conducive to student engagement.

Said Wang: “Enhancing student engagement has been identified as the key to addressing problems of low achievement, high levels of student misbehavior, alienation and high dropout rates. When we talk about student engagement, we tend to talk only about student behavior. But … that doesn’t tell us the whole story. Emotion and cognition are also very important.”

The study, co-authored with a University of Michigan researcher, is among the first attempts by researchers to use data to explore a multidimensional approach to the question of student engagement. In the past, only behavioral measures of student engagement, such as class attendance, turning in homework on time, and classroom participation, had been evaluated when gauging student engagement. By conducting a study linking students’ perceptions of the school environment with behavior, the authors have provided one of the first pieces of empirical research supporting the viability of the multidimensional perspective, which previously had been largely theoretical.

The researchers designed a 100-question survey that includes the evaluation of emotional engagement and cognitive engagement. Sample survey questions that tested emotional engagement in classes across all subject areas asked students to agree or disagree with statements such as “I find schoolwork interesting” and “I feel excited by the work in school.” Sample questions concerning cognitive engagement asked students to provide ratings to questions like “How often do you make academic plans for solving problems?” and “How often do you try to relate what you are studying to other things you know about?”

Using the survey, the researchers conducted a two-year longitudinal study, tracking approximately 1,200 Maryland students from seventh through eighth grade. The authors also measured students’ perceptions of their environment by having them answer questions in five areas: school structure support, which gauged the clarity of teacher expectations; provision of choice, which assessed students’ opportunities to make learning-related decisions; teaching for relevance, which evaluated the frequency of activities deemed relevant to students’ personal interests and goals; students’ perceptions of the emotional support offered by teachers, and students’ perceptions of how positive their relationships were with fellow students.

The authors found that students who felt that the subject matter being taught and the activities provided by their teachers were meaningful and related to their goals were more emotionally and cognitively engaged than were their peers. Adding measures of emotional and cognitive engagement could broaden researchers’ perspectives on student engagement in future work in this area.

Also among the paper’s main findings is that the school environment can and should be changed if it is impeding student engagement.

A positive and supportive school environment is marked, Wang said, by “positive relationships with teachers and peers. Schools must provide opportunities for students to make their own choices. But they also must create a more structured environment so students know what to do, what to expect, from school.” Wang also noted, however, that there is no “one size fits all” strategy to the problem of student engagement.

“Usually people say, ‘Yes, autonomy is beneficial. We want to provide students with choices in school,’” Wang said. “This is the case for high achievers, but not low achievers. Low achievers want more structure, more guidelines.”

As a result, Wang said, teachers must take into account individual variation among students in order to fulfill the needs of each student.

The study will appear in the December 2013 print issue of Learning and Instruction. It appeared online in that publication in May and was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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