New treatment possible for gum disease?

The red, swollen and painful gums and bone destruction of periodontal disease could be treated by beckoning the right kind of immune system cells to the inflamed tissues, according to an animal study conducted by Pitt researchers. Their findings, published this week in the early online version of the Proceedings of the National Academy of Sciences, offer a new therapeutic paradigm for a condition that afflicts 78 million people in the U.S. alone.

Periodontal disease currently is treated by keeping oral bacteria in check with daily brushing and flossing as well as regular professional deep cleaning with scaling and root planing, which remove tartar above and below the gum line. In some hard-to-treat cases, antibiotics are given.

These strategies of mechanical tartar removal and antimicrobial delivery aim to reduce the amount of oral bacteria on the tooth surface, explained co-author and co-investigator Charles Sfeir, director, Center for Craniofacial Regeneration and faculty member in periodontics and oral biology in the School of Dental Medicine.

“Currently, we try to control the buildup of bacteria so it doesn’t trigger severe inflammation, which could eventually damage the bone and tissue that hold the teeth in place,” Sfeir said. “But that strategy doesn’t address the real cause of the problem, which is an overreaction of the immune system that causes a needlessly aggressive response to the presence of oral bacteria. There is a real need to design new approaches to treat periodontal disease.”

In the healthy mouth, a balance exists between bacteria and the immune system response to forestall infection without generating inflammation, said senior author Steven Little, chair of the Department of Chemical and Petroleum Engineering in the Swanson School of Engineering. But in many people, a chronic overload of bacteria sets up the immune system to stay on red alert, harming the oral tissues while it attempts to eradicate germs.

“There is a lot of evidence now that shows these diseased tissues are deficient in a subset of immune cells called regulatory T-cells, which tells attacking immune cells to stand down, stopping the inflammatory response,” Little said. “We wanted to see what would happen if we brought these regulatory T-cells back to the gums.”

To do so, the researchers developed a system of polymer microspheres to slowly release a chemokine, or signaling protein, called CCL22 that attracts regulatory T-cells, and placed tiny amounts of the paste-like agent between the gums and teeth of animals with periodontal disease. The team found that even though the amount of bacteria was unchanged, the treatment led to improvements of standard measures of periodontal disease, including decreased pocket depth and gum bleeding, reflecting a reduction in inflammation as a result of increased numbers of regulatory T-cells. MicroCT-scanning showed lower rates of bone loss.

“Mummified remains from ancient Egypt show evidence of teeth scraping to remove plaque,” Little noted. “The tools are better and people are better trained now, but we’ve been doing much the same thing for hundreds of years. Now, this homing beacon for Treg cells, combined with professional cleaning, could give us a new way of preventing the serious consequences of periodontal disease by correcting the immune imbalance that underlies the condition.”

Next steps include developing the immune modulation strategy for human trials.

In addition to Sfeir and Little, Pitt members of the research team included Andrew J. Glowacki, Sayuri Yoshizawa and Siddharth Jhunjhunwala. Researchers from Sao Paulo University in Brazil also participated.

The project was funded by National Institutes of Health, the Wallace H. Coulter Foundation, the Camille and Henry Dreyfus Foundation, the Arnold and Mabel Beckman Foundation and the Commonwealth of Pennsylvania.

Low vitamin D may trigger preterm births

African-American and Puerto Rican women who have low levels of vitamin D during pregnancy are more likely to go into labor early and give birth to preterm babies, according to research led by the Graduate School of Public Health.

The study is the largest to date to look at the association between vitamin D and preterm birth.

Said lead author Lisa Bodnar, epidemiology faculty member: “Vitamin D is unique in that while we get it from our diets, our primary source is our body making it from sunlight. Previous studies using conservative definitions for vitamin D deficiency have found that nearly half of black women and about 5 percent of white women in the United States have vitamin D concentrations that are too low.”

Among nonwhite mothers, the incidence of spontaneous, preterm birth — naturally going into labor two or more weeks before the 37 weeks of pregnancy considered full-term — decreased by as much as 30 percent as vitamin D levels in the blood increased.

Bodnar and her co-authors did not find a similar relationship between maternal vitamin D levels and preterm birth in white women.

“We were concerned that finding this association only in nonwhite women meant that other factors we did not measure accounted for the link between low vitamin D levels and spontaneous preterm birth in black and Puerto Rican mothers,” said Bodnar. Her team accounted for the expected influence of discrimination and socioeconomic position, as well as fish intake and physical activity. “Even after applying these methods, vitamin D deficiency remained associated with spontaneous preterm birth.”

A novel part of the study was the availability of information from placental examinations. The researchers found that vitamin D deficiency was most strongly related to preterm births with damage to the placenta caused by inflammation. They used a sample of more than 700 cases of preterm birth and 2,600 full-term births collected by the Collaborative Perinatal Project, which was conducted in 12 U.S. medical centers from 1959 to 1965. The blood samples collected by the project were well preserved and able to be tested for vitamin D levels 40 years later.

“It is critical to repeat this study in a modern sample,” said Bodnar, noting that pregnant women today smoke less, have less sun-exposure and receive more vitamin D in their foods than the mid-century cohort. “Further, it is especially important to understand how vitamin D influences preterm birth among black mothers. Vitamin D supplementation could be an easy way to reduce the high rates of preterm birth in this group.”

Pitt co-authors on this research included Alison D. Gernand, Janet M. Catov and W. Tony Parks. Researchers from Ohio State and McGill University also contributed.

The research was supported by the National Institutes of Health (NIH) and appears in the American Journal of Epidemiology.

Local attitudes mixed on environment

Long after the decline of southwestern Pennsylvania’s steel industry, pollution levels in the region continue to be unhealthy by U.S. Environmental Protection Agency standards. Yet 65 percent of the region’s citizens view air quality as a minor problem or not a problem at all.

These are some of the findings released from the Pittsburgh Regional Environment Survey, conducted by PittsburghTODAY and the University Center for Social and Urban Research. The survey queried more than 800 citizens in the seven-county Pittsburgh Metropolitan Statistical Area on their views and behaviors related to the environment. The results provide an extensive profile of the region’s environment-related behaviors and views on such issues as air and water quality, climate change and Marcellus Shale drilling.

According to Douglas Heuck, director of PittsburghTODAY, key survey findings include:

• Climate change: 64 percent of citizens describe climate change as a severe or moderate problem; 55 percent of the region’s residents believe human activities are the root cause, while 40 percent believe climate change is the result of natural conditions.

• Economy and the environment: More than 55 percent of citizens say protecting the environment should be a priority over energy production, even at the risk of limiting the nation’s supply of coal, natural gas or oil. Nearly 80 percent view natural gas drilling in the Marcellus Shale as a significant or moderate economic opportunity for the region; at the same time, 59 percent believe it poses a significant or moderate threat to public health and the environment.

• Energy-saving actions and behaviors: 95 percent of citizens regularly turn off lights and electronics in unoccupied rooms, 74 percent make a conscious effort to take short showers, 63 percent turn down the thermostat when asleep or away from home during winter, and 42 percent say they reduced car trips by carpooling, taking public transportation or walking in the past year.

• Governmental policy: 78 percent of citizens believe that government should be most responsible for solving Pennsylvania’s environmental issues. More than 30 percent believe environmental regulations strengthen job growth, while 28 percent believe regulations weaken growth.

• Parks and recreation: Nearly 75 percent give the quality of the region’s public parks and trails high marks; 12 percent rate them as “excellent,” while another 63 percent grade them as “very good” or “good.”

Additional data and statistics from the Pittsburgh Regional Environment Survey are available at pittsburghtoday.org/special_reports.html.

Improving heart disease risk assessment

Physicians caring for people with Type 1 diabetes might be better able to determine their patients’ chances of developing heart disease if they include their levels of protective antioxidants in the assessment, according to a new study from the public health school.

The study, funded by NIH, was published in the November issue of Diabetes Care. It relied on data from “Pittsburgh Epidemiology of Diabetes Complications,” a historical prospective investigation of childhood onset Type 1 diabetes cases diagnosed, or seen within one year of diagnosis, at Children’s Hospital between 1950 and 1980.

Said lead author Tina Costacou, an epidemiology faculty member: “Currently in clinical practice, physicians assess a patient’s risk factors for developing a disease to determine what, if any, preventative measures to take. In our study, we found that the risk of people with Type 1 diabetes developing heart disease is better predicted by looking at the ratio of factors representing protection (for example, antioxidants) to those representing harm (for example, oxidative stress levels). Currently, doctors most commonly determine heart disease risk by looking at the level of harmful risk factors alone, which may not give an accurate picture of the person’s risk.”

In a statistical analysis over time, it appeared that patients with higher levels of oxidative stress (measured with a urine test) who also had higher levels of a form of the antioxidant vitamin E (measured with a blood test) had a lower risk of developing heart disease compared to those with higher levels of oxidative stress and lower levels of protective antioxidants.

Thus, although both patient groups had higher levels of oxidative stress, they actually were at a different risk of developing heart disease, and only those with the lower levels of antioxidants may need additional treatment to try to prevent heart disease from developing.

“This improved way of determining risk is not necessarily limited to the hypothesis of oxidative stress and antioxidants in terms of heart disease development,” said Costacou. “It could be expanded to other risk/protective factors and other pathologic conditions. If further supportive data are published, it may one day become possible to better classify a person’s disease risk and individualize treatment based on simultaneous assessment of risk and protective factors.”

Epidemiology co-authors were Trevor J. Orchard, Robert W. Evans and Gerald L. Schafer.

PSC gets $7.6 million NSF grant

The National Science Foundation (NSF) has approved a grant to Pittsburgh Supercomputing Center (PSC) to develop a prototype Data Exacell (DXC), a next-generation system for storing, handling and analyzing vast amounts of data. The $7.6-million, four-year grant will allow PSC to design, build, test and refine DXC in collaboration with selected scientific research projects that face unique challenges in working with and analyzing “big data,” under PSC scientific director Michael Levine.

Big data is a broad field including challenges from both traditional high-performance computing and other fields of research that depend on methodologies more focused on data collection and analysis than on computation. These fields not only require very large amounts of data (the European Bioinformatics Institute alone now stores 20 petabytes of life sciences data) but also require access methods and performance beyond the capability of traditional large data stores. The DXC project will directly address these required enhancements.

Said Nick Nystrom, director of strategic applications at PSC: “What’s needed is a distributed, integrated system that allows researchers to collaboratively analyze cross-domain data without the performance roadblocks that are typically associated with big data. One result of this effort will be a robust, multifunctional system for big data analytics that will be ready for expansion into a large production system.”

The core of the DXC will be SLASH2, PSC’s production software for managing and moving big data. It is currently represented by the Data Supercell (DSC), a 4-petabyte, disk-based, production storage system that combines archival-quality storage with access times comparable to data stored on a user’s own computer and able to support remote access. DXC will incorporate updated, DSC-type storage and high-performance analysis resources, both existing and new.

DXC will concentrate primarily on enhancing essential functionality for conducting data-intensive research. Said J. Ray Scott, PSC director of systems and operations: “The Data Exacell will have a heavy focus on how the system will be used. We’ll start with a targeted set of users who will get results but who are experienced enough to help us work through the challenges of making it production quality.”

PSC external collaborators from a variety of fields will work closely with the center’s scientists to ensure the systems applicability to existing problems and its ability to serve as a model for future systems. The collaborating fields are expected to include genomics, radio astronomy, analysis of multimedia data and others.

A third of homicides may be preventable

More than 30 percent of the homicides in Pittsburgh in 2012 likely were related to peer violence, not gang activity, and are the type of crime most readily prevented by early intervention, according to a new report by the public health school’s community violence prevention project.

The group’s research indicates that 19 percent of the 42 homicides in the city last year were due to peer violence and not gang-related; another 12 percent were identified as possibly related to peer violence.

Peer violence is defined as a purposeful, self-motivated conflict stemming from drugs, money or perceived disrespect between two individuals who know each other.

Gang activity involves leadership and internal organization, and often is associated with conflicts over neighborhoods, or “turfs.”

Said Steven Albert, chair of the Department of Behavioral and Community Health Sciences: “Casual observers often confuse gang violence and peer violence. Peer violence may have different contributing factors and requires different interventions.”

Added Richard Garland, visiting instructor in the Department of Behavioral and Community Health Sciences and co-author of the report: “Peer violence could involve a disagreement over a girl, or money or even a pair of shoes. The Pittsburgh gangs of the 1990s barely exist anymore. The leaders are in jail — or dead.”

Using data from the Pittsburgh Initiative to Reduce Crime (PIRC), Allegheny County Jail, Allegheny County Department of Human Services, Allegheny County Adult and Juvenile Probation and the Allegheny County Medical Examiner’s Office, researchers studied all 42 homicides that occurred within the city of Pittsburgh in 2012 to identify their root cause and patterns. In 95 percent of the homicides, the cause of death was a gunshot wound.

In addition to the homicides where peer violence was a possible motive, researchers found the following:

• 28 percent of all homicide victims were killed during illegal transactions (for example, a drug deal gone bad, or a home invasion).

• In another 23 percent, the victim was an unintended target.

• 7 percent occurred due to gang violence.

• 3 percent were related to child abuse.

• 7 percent could not be determined.

Researchers also found homicides disproportionately affected certain groups and areas:

• 93 percent of all homicide victims were male.

• 83 percent were African Americans.

• 36 percent were ages 18-25.

• 43 percent of the homicides took place in Pittsburgh Police Zone 5 — East Liberty, Garfield, Lincoln-Lemington, Larimer and Homewood.

Information beyond a victim’s gender, race, age and location from these reports was very limited, so researchers gathered additional information by attending community and coalition meetings, conducting informal interviews and engaging in community outreach.

“We need programs that will get these young men safely through the ‘killing years,’” said Garland. According to the U.S. Centers for Disease Control and Prevention, the risk of becoming a victim of gun violence is highest from ages 15 to 24.

The researchers recommend engaging individuals and families at risk for violence in nontraditional settings, including emergency room trauma departments.

Said Albert: “A specialized team of trained peer mentors can meet with family members in the waiting room. It’s a way to drive home the potential outcomes of gun violence.”

All four hospitals providing level 1 trauma services in Allegheny County have agreed to host the program.

The research was funded by the Richard King Mellon Foundation.

Grant to create network targeting most-impacted autism patients

Psychiatry faculty member Carla Mazefsky is a co-investigator on a two-year, $1.2 million grant to develop a nationwide collaborative to study children who are most severely affected by autism, directed by Spring Harbor Hospital in Westbrook, Maine, and the Maine Medical Center Research Institute.

The Autism and Developmental Disorders Inpatient Research Collaborative is made up of specialized inpatient child psychiatry units that exclusively serve children with autism and other developmental disorders.

The network will seek to better understand the characteristics and complex challenges faced by these children and their families, with the goal of developing improved treatment protocols. The network also will provide an opportunity to gain new insights into the genetic pathways that underlie language impairments, intelligence and psychiatric illness in autism.

The study is being funded by the Simons Foundation and the NLM Family Foundation.

Grant creates tool to spot network glitches

The Web10G Project has received a $178,000 Software Development for Cyberinfrastructure (SDCI) supplemental award from NSF to develop a “dashboard” that will allow users of computer networks to identify when and where a networking problem is slowing or blocking their access.

Web10G, funded by an earlier SDCI grant, is a collaboration between Pittsburgh Supercomputing Center (PSC) — Pitt’s joint effort with Carnegie Mellon and Westinghouse Electric Co. —  and the National Center for Supercomputing Applications.

Said Chris Rapier, PSC network applications engineer: “We’ve found that a lot of network users either have unrealistically high expectations or unrealistically low expectations for network performance. Web10G has produced 127 different instruments that report on what’s going on with the network connection, ways in which it might be failing and ways in which it might be improved. With the supplemental grant, we’re going to automate that process to let users know what’s reasonable and then help them work with their network operations teams to actually get the performance they need.”

Web10G and the new tool target an unintended consequence of TCP/IP, the first set of rules to help make an electronically interconnected world work on a massive scale.

Andrew K. Adams, PSC senior network engineer, said: “The primary protocol used on the Internet, TCP/IP, actually hides everything that happens from the end user.” That structure helped the Internet to grow and independent applications to be developed, but networking glitches essentially were invisible, even to the people who run the networks.

“One of the big issues you have with network problems is that they all basically look the same,” Rapier said. “Either you can’t connect or the connection is really slow.”

Web10G and its predecessor, Web100, allowed the collaborators in essence to open up TCP/IP and acquire data about the network, making it a standard part of the Linux operating system favored by researchers. The new grant will allow the Web10G researchers to develop a simple tool to make those data useful to nontechnical users. The team envisions a kind of dashboard, possibly including the equivalent of a speedometer and warning lights.

Web100, which involved the same collaborating institutions as well as the National Center for Atmospheric Research, also created networking tools such as automatic received buffer tuning, which allows today’s network connections to adjust automatically to maximize network throughput.

“That actually became a part of every major operating system,” Rapier said. “It was a huge win; we’d like to see the same adoption level for Web10G.”

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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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