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December 4, 2014

Research Notes

Pathology faculty earn multiple grants

Pitt faculty have secured  several grants this year within UPMC’s Department of Pathology:

Andrew Duncan, $2,174,309 from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH), for “Mechanisms of Polyploidy and Aneuploidy in the Liver”;

• Yuri Nikiforov, $1,568,605 from NIH, for “Translational Evaluation of Aging, Inflammation and HIV in Lung Dysfunction”;

• Alejandro Soto-Guterierrez, $1,239,952, for “Mini-livers Derived From Human iPS Cells for Modeling Steatosis and Therapy”;

• Sarah Wheeler, $460,029, for “Regulation of Metastatic Breast Cancer Dormancy Term”;

• Jennifer Picarsic, collaborating with Heth Turnquist, faculty member in surgery and immunology, as a pathology consultant on a Roche Organ Transplantation Research Foundation grant, “Prognostic Value and Function of IL-33/ST2 in Pediatric Heart Transplant Recipients With Infection,” and

• Michael Shurin, for “Microenvironmental Control of Premalignant Lesions in Ovarian Cancer.”


Improving diabetes control in world’s poorest children

A nonprofit program that brings diabetes care and education to some of the world’s poorest children has improved control of the disease, according to a Graduate School of Public Health analysis published in Diabetes Research and Clinical Practice. It is the first scientific evidence to show that improvement in long-term blood sugar control in type 1 diabetes is possible in sub-Saharan African youth.

The International Diabetes Federation Life for a Child (LFAC) program’s approach to providing care to children with type 1 diabetes in Rwanda led to major reductions in HbA1c, a long-term measure of blood sugar. The proportion of children who had an HbA1c level of more than 14 percent, a potentially lethal level, fell from 31 percent to 9 percent. The improvement was greatest in the children who had access to blood sugar testing supplies and regularly monitored their blood glucose levels.

Said senior author Trevor Orchard, epidemiology faculty member: “Type 1 diabetes can be a very difficult disease to manage, and, if not properly controlled, it is deadly. When coupled with poverty, food insecurity and severely limited health-care provision that many of the children in sub-Saharan Africa face, the need for proven programs to help these children control their diabetes becomes vital.”

Type 1 diabetes, usually diagnosed in children and young adults, happens when the body does not produce insulin, a hormone that is needed to convert sugar into energy.

LFAC supports the provision of insulin, glucose monitoring supplies, diabetes education, advice and training to children and youth with diabetes in developing countries. In Rwanda, the program provides assistance through the Association Rwandaise des Diabetiques (ARD) in the city of Kigali.

Orchard and his team followed and regularly measured the HbA1c levels in 214 people under age 25 who enrolled in the program between June 2009 and November 2010.

HbA1c develops when sugar binds to hemoglobin, a protein within red blood cells, in the blood. The higher the HbA1c, the greater the risk of developing diabetes-related complications, like heart disease, blindness and nerve damage. Those without diabetes typically have an HbA1c between 4 and 5.7 percent. For people with diabetes, an HbA1c level of less than 7 percent is considered good control.

In the Rwandan children that Orchard’s team followed, the average HbA1c initially was 11.2 percent. After two years in the program, the average fell to 9.8 percent.

Orchard became involved in the program in Rwanda in 2007 when it had only 25 children. LFAC has now enrolled more than 1,000 children and youth. Public health sends at least one graduate student every year to assist with the program and the required annual assessments of the children enrolled. Orchard and a colleague from Northwestern University also visit Rwanda regularly to help develop and provide care and education for the children.

“More work is needed,” said Orchard. “Only about 12 percent of the Rwandan children met American Diabetes Association glucose control goals, compared with 32 percent of U.S. children.”

A key part of controlling type 1 diabetes is regular blood sugar monitoring, which allows patients to adjust their insulin levels based on test results. Children who were better able to monitor their blood sugar had better HbA1c levels. In some cases, a lack of testing supplies prohibited children from testing their blood sugar as frequently as recommended.

Orchard’s team also found that, as HbA1c levels improved, high blood pressure emerged as a major problem such that over 40 percent of the youth were hypertensive.

“This is troubling,” said Orchard. “Many of our participants were very young children during the Rwandan genocide of 1994 and grew up malnourished and underweight. It is possible to attribute some of the increasing blood pressure to weight gain and rehydration after enrollment in the program. Salt also often is used in food preparation and preservation in sub-Saharan Africa, so this may be a factor as well. Unfortunately, very few participants are able to take blood pressure medication due to limited supplies and prohibitive prices.”

Orchard noted that continued study is needed to better understand the causes of the high blood pressure among the Rwandan children receiving care for type 1 diabetes, as well as to determine how best to develop a sustainable program to maintain this improved care.

Additional Pitt researchers on this project were Sara L. Marshall, Vincent C. Arena, Dorothy J. Becker, Clareann H. Bunker, Ronald E. LaPorte and Laurien Sibomana. Also contributing were researchers from LFAC, the Australian Diabetes Council and the Association Rwandaise des Diabetiques.

This work was largely funded by donations to the Life for a Child-Pitt Initiative.


Revealing barriers to public health data-sharing

Barriers to the sharing of public health data hamper decision-making efforts on local, national and global levels and stymie attempts to contain emerging global health threats, an international team led by Pitt researchers found.

The analysis, published in BMC Public Health, classifies and examines the barriers in order to open a focused international dialogue on solutions.

Said lead author Willem G. van Panhuis, faculty member in public health’s Department of Epidemiology: “Data on disease surveillance, intervention coverage, vital statistics and mortality represent some of the most widely collected but also some of the most underused data. Innovative methods for collection of new data are developed all the time, but a framework to share all these data for the global good is seriously lacking. Investments in routine data systems will better position health officials to address ongoing challenges as well as new public health threats, such as the current Ebola epidemic in West Africa.”

Van Panhuis and his team,  which included experts in ethics and law as well as public health,  identified more than 1,400 scientific publications related to public health data-sharing, ultimately winnowing them down to the 65 most relevant articles. From those, they determined 20 real or perceived barriers to data-sharing in public health and classified them into six categories: technical, motivational, economic, political, legal and ethical.

Said senior author Donald S. Burke, dean and UPMC-Jonas Salk Chair of Global Health: “These barriers and categories describe a landscape of challenges that must be addressed comprehensively, not piecemeal. We must work together as a global community to develop solutions and reap the benefits of data-sharing, which include saving lives through more efficient and effective public health programs.”

The team found that most technical, motivational and economic barriers are deeply embedded in much larger challenges of health information system capacity, particularly in low- and middle-income countries. Solutions lie in sufficiently funding such systems through international cooperation and shared development of data and infrastructure used across agencies and institutes.

The political, legal and ethical barriers will require a dialogue across international agencies that should include the World Health Organization, World Intellectual Property Organization and World Trade Organization, as well as the countries, development and funding agencies and experts in ethics and law. The team proposes the creation of a treaty for data-sharing in public health across the world, as well as a commission to monitor, mediate and facilitate data-sharing.

“Identifying and classifying these barriers was the first step toward harnessing the potential of data for a new era in population health,” said van Panhuis. “As our knowledge of these barriers increases, so will the opportunities for solutions.”

Additional Pitt researchers on this project were Proma Paul and John Grefenstette, who worked with colleagues from the University of Toronto, the Bill & Melinda Gates Foundation, the INDEPTH Network in Ghana, the University of KwaZulu-Natal in South Africa and Chatham House London.

The project was funded by the Gates Foundation and NIH.


Getting childhood cancer research to more patients

To improve information flow about childhood cancers, Jean M. Tersak, a pediatrics faculty member in the School of Medicine, has been awarded a one-year, $50,000 grant from the St. Baldrick’s Foundation.

The funding will help to support efforts to enhance website communication of research activities to make information more easily accessible to potential patients, families and referring physicians. Additionally, funding will support the transition to a new database to increase efficiency and refine the ability to query the database as a more effective tool to conduct institutional research.

According to Tersak, an oncologist in the Division of Pediatric Hematology/Oncology at Children’s Hospital, the grant “will help us to be sure that our medical treatments are more widely known and available to anyone who may need them to battle a diagnosis of cancer as a child or young adult. The grant will increase the efficiency of our program and increase awareness of novel treatments available to patients from our region and beyond.”

Tersak has a special interest in caring for survivors of childhood cancer, including evaluation for medical late effects of treatment and the quality of life in these survivors. She is involved in national research to better understand late effects, ways to prevent them and early intervention when they do occur.


Child abuse linked to poor health, unemployment later

People who currently fall into low-income and low-educational brackets are up to five times as likely to have faced abuse and adversity during childhood as people who fall into higher socioeconomic groups, according to a public health analysis of Allegheny County residents.

The findings, presented at the American Public Health Association’s (APHA) annual meeting, support the merit of whole-family programs that seek to break the cycle of adversity and negative health, economic and social outcomes that persist over generations.

Eliminating childhood abuse and adversity significantly improves health — reducing heart disease by more than 26 percent and serious mental illness by more than 41 percent, the research team determined in a separate study presented at APHA.

Said lead investigator Todd M. Bear, director of the Office of Health Survey Research in the Department of Behavioral and Community Health Sciences: “Early childhood is a sensitive period of human development when abuse or parental problems can create lasting negative consequences later in life. Our findings provide strong evidence that it is worthwhile for communities to invest in robust intervention programs that provide treatment, educational and employment opportunities and positive role models to the whole family.”

The analyses used data from the 2009-10 Allegheny County Health Survey, which interviewed 5,442 randomly selected residents.

Bear and his colleagues focused on six adverse childhood events reported by adult residents as having happened in their household when they were children: physical, sexual and emotional abuse; parental mental illness; parental substance abuse, and domestic violence.

The research team, which included experts in epidemiology and psychiatry, found that:

• Blacks had 2.5 times higher prevalence of childhood sexual abuse and greater rates of physical abuse when compared with whites.

• People with a low socioeconomic status had 1.7-4.2 times higher prevalence for each of the six adverse childhood events compared with people of higher socioeconomic status.

• People who reported they were unable to work also reported a prevalence of sexual abuse five times higher than those reporting employment.

The results are consistent with those of similar surveys conducted in other communities nationwide.

“We’ve found nothing to indicate that our findings are unique to Allegheny County,” said Bear. “These strong links between childhood adversity and poor socioeconomic status later in life, coupled with our findings that eliminating childhood abuse significantly prevents serious health consequences in adulthood, should be useful information for communities nationwide that are determining appropriate interventions to help their most vulnerable populations.”

Additional Pitt researchers on both studies were Patricia I. Documét, Michael Marshal, Ronald Voorhees and Edmund Ricci.


Preventing brain damage from rare inherited disease

Umbilical cord blood from unrelated donors can halt the progression of the neurodegenerative disease Hurler syndrome if performed before the affected child is less than 9 months old, according to a Children’s Hospital study that appears online in Annals of Neurology. The findings emphasize the need for early diagnosis of the condition, preferably through newborn screening programs.

Hurler syndrome is the most clinically severe form of an inherited disorder in which the patient lacks a key enzyme needed to break down complex sugars called glycosaminoglycans. The sugar buildup results in progressive organ deterioration and death in childhood. Affected children may not have symptoms until age 3, but the brain undergoes damage before symptoms present.

Umbilical cord blood transplantation from unrelated donors previously has been shown to improve neurological outcomes of children over 2 years of age and prolong life. Hematopoietic stem cells from the cord blood transplants provide a source for the normal enzyme that is donated to the deficient cells, decreasing the accumulation of glycosaminoglycans.

Key findings of this study show that treatment of Hurler syndrome with umbilical cord blood transplantation before 9 months of age leads to normal cognitive development. The researchers found children transplanted at 12 and 25 months of age functioned cognitively at a level 2 to 5.3 years below that of those transplanted at 4 months. Early transplantation also predicted better outcomes for language skills and adaptive behaviors.

Said Maria Luisa Escolar, pediatrics faculty member in medicine and director of the program for the study of neurodevelopment in rare disorders at Children’s Hospital: “This study highlights the importance of early detection of brain diseases in babies and infants when brain growth is the most accelerated in life, placing them at increased vulnerability for permanent damage.”

Between June 1997 and February 2013, 31 children with Hurler syndrome underwent umbilical cord blood transplantation and were evaluated every six to 12 months thereafter for an average of seven years. Median age at transplantation was 13.8 months. The youngest babies in the study were diagnosed due to family history of the condition.

“Identification of asymptomatic children through statewide newborn screening programs is the only way to diagnose early and prevent brain damage to babies with no family history of Hurler syndrome,” Escolar said.

“Unfortunately, early diagnosis is often difficult as their initial symptoms may be common in the general population,” added Escolar. “Therefore, there is a need for newborn screening for Hurler syndrome and similar neurodegenerative diseases that can identify children before symptoms appear, giving the best opportunity for prompt intervention and optimal outcomes.”

Pitt collaborators on the study were Michele Poe and Sarah Chagnon.

Support was provided by the Caterina Marcus Foundation.


Chemists developing 3-D molecule quantum repository

Remember constructing ball-and-stick models of molecules in your high school or college chemistry classes? That might soon be a thing of the past for Pitt students looking to get a three-dimensional understanding of molecular structures.

Geoffrey Hutchison and Daniel Lambrecht received a 2014 Camille and Henry Dreyfus Special Grant Program in the Chemical Sciences Award for their project, “Creating an Open Quantum Chemistry Repository.” This effort aims to create an open mobile-ready, web-based database of accurate, quantum calculations of molecules. The Pitt Quantum Repository will consist at first of 50,000-100,000 molecules and quantum chemical data. The database will grow over time to include more molecules and more computed properties.

Said Hutchison, chemistry faculty member in the Dietrich School of Arts and Sciences: “It’s chemistry in the ‘cloud.’”

Almost all areas of chemistry rely on the three-dimensional nature of molecules, including stereochemistry, symmetry, molecular interactions and reactivity. Consequently, understanding and developing intuition of molecular geometry, distances and dynamics are critical for students.

Yet topics such as chirality or basic shapes can be difficult to understand with the traditional two-dimensional depictions used in textbooks or PowerPoint slides and handouts. At the same time, students are immersed in digital media with interactive 3-D worlds of computer games and mobile devices and they have high expectations of ubiquitous and readily accessible online resources. While many online chemistry databases offer 3-D molecular shapes, few are interactive, comprehensive, well curated and maintained, user friendly and mobile ready.

The Pitt Quantum Repository will allow instructors to put “QR” barcodes on handouts or presentation slides. Students then will be able to scan the codes during a lecture, which will take them to an interactive 3-D visualization on their phone or tablet.

Said Lambrecht, faculty member in chemistry: “We may be incorporating [the quantum repository] in some lab manuals next spring. We want to start with the large lecture classes for greatest impact.”


Parental impact shown on student grades, behavior, mental health

Although students become more independent as they rise through grade levels and parent-teacher interactions typically lessen as students age, parental involvement in a child’s education during the secondary school years plays an essential role in developing positive academic, behavioral and emotional outcomes. Relations between parents and teachers are among the factors that can affect a student’s success and well-being.

These are the findings of a study by Ming-Te Wang, faculty member in psychology in education in the School of Education, published in the November/December issue of Child Development.

Wang noted that parental engagement has been widely recognized as important in the elementary school years, but up until now it has been unclear if parental involvement was as significant in secondary school.

Said Wang: “Our research has found that quality parental involvement is not as simple as more is better or less is more at any one point in a child’s life. The key findings here are that parents should always be involved, but they need to give great thought as to how they are involved and the manner in which they stay involved as the child ages.”

The study was composed of more than 1,400 families in the eastern United States. Researchers used questionnaires and interviews to gather information from a selection of teenagers in the 7th, 9th and 11th grades and their parents. African Americans comprised 56 percent of participants while European Americans made up 39 percent.

Wang’s research team assessed the impacts of five types of parental involvement on academic, behavioral and mental health outcomes: the frequency of communication between parents and teachers; the quality of communication between parents and teachers; the extent to which parents encouraged children to figure out their own solutions to homework; the structure parents established at home in the form of schedules and guidelines for studying, and the extent to which parents discussed with their children the importance of education in future success.

Key study findings include:

• Academics: all five types of parental involvement were associated with improvements in GPA from 7th to 11th grade. Additionally, the findings showed that high levels of parental structure in the home were particularly beneficial for African Americans and students from low-income families.

• Behavior: the frequency of parent-teacher communication, home structure and linking education with future success were associated with decreased overall problem behaviors for adolescents.

• Emotional outcomes: lower depressive symptoms in adolescents were linked with the quality of communication between parents and teachers, the extent to which parents challenged students to figure out their own solutions to homework and the linking of education to future success. Also, the level of parental warmth within the home played a significant role in developing emotional well-being across all races and socioeconomic backgrounds.

“Our findings highlight the importance of adapting the level and nature of parental involvement in education to adolescents’ changing psychological needs,” said Wang, who also holds a joint appointment in the Department of Psychology in the Dietrich School and is a research scientist in the Learning Research and Development Center (LRDC).

The research team also included Tara Hofkens, a graduate researcher at LRDC, and a researcher at Harvard.


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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