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Credit: Bob Wilder / University at Buffalo.
Credit: Bob Wilder / University at Buffalo.

Jacobs School researchers help identify biomarker for concussions in saliva

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Wed, Oct 21st 2020 12:40 pm

Multi-institutional study could lead to development of an objective, simple test to diagnose mild traumatic brain injury

By the University at Buffalo

In a landmark study led by Steven Hicks, M.D., Ph.D., of Penn State College of Medicine, researchers from the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, along with peers from other institutions, found a combination of biomarkers in saliva can help objectively and accurately diagnose mild traumatic brain injury.

John Leddy, M.D., clinical professor in the department of orthopaedics and director of the UB Concussion Management Clinic at UBMD Orthopaedics and Sports Medicine, and Mohammad Nadir Haider, M.D., assistant director at the clinic, served as co-authors of the prospective multicenter, caseā€control study, titled “Diagnosing mild traumatic brain injury using saliva RNA compared to cognitive and balance testing.” It was published online in Clinical and Translational Medicine on Oct. 3.

The traditional method of diagnosing mild traumatic brain injury (mTBI) involves measuring physical and cognitive changes along with symptom reports from patients. The latter is problematic because patients can purposely misrepresent their symptoms in order to speed up or slow down their return to activities.

A saliva swab, on the other hand, is a noninvasive, specific, objective and easy-to-use biological assessment tool.

“Concussions can be difficult to diagnose due to lack of objective, diagnostic testing. The diagnosis often relies on a patient’s self-reported symptoms, which are not specific to concussion,” Haider said. “This saliva test is a significant development because it can improve diagnostic accuracy, which could potentially improve clinical management.”

The other participating institutions included Adena Health System; Bridgewater College; Colgate University; the United States Army Fort Benning; Marist College; Penn State College of Medicine; New York Institute of Technology; SUNY Upstate Medical University; Temple University; and Vanderbilt University Medical Center.

Mild traumatic brain injuries are characterized by a brief alteration in mental status, post-traumatic amnesia, and often vestibular and vision abnormalities.

Nearly 3 million of these injuries occur in the U.S. each year, mostly in teens and young adults. The occurrence of mTBI in adolescents is on the rise, resulting in an increased burden on the nation’s economic and health care systems.

The study took place between April 2017 and February 2020. It included 538 participants between 5 and 66 years of age. Of this sample, 251 had a clinical diagnosis of mTBI as defined by the 2016 Concussion in Sport Group criteria. The mTBI group was compared to a control group of 287 individuals with absence of mTBI in the previous 12 weeks and clinical resolution of any previous mTBI.

Following enrollment, saliva and survey data were collected from mTBI participants across five time points: at 72 hours, four to seven days, eight 14 days, 15 to 30 days and 31 to 60 days after the initial injury. The saliva samples were collected at the various institutions and sent for analysis to Quadrant Biosciences in Syracuse.

The researchers found the combination of saliva biomarkers and patient-reported symptoms proved to be 92.5% accurate in differentiating patients with and without a concussion.

According to Haider, the group of researchers found a combination of micro RNA biomarkers in saliva that could be used to distinguish between people with mTBI/concussion and non-mTBI controls who presented with concussion-like symptoms.

“This test was compared with disorders that present with symptoms that are similar to concussion, like mood disorders, non-head-related trauma and learning disorders, and was still able to differentiate between them,” he said. “This means the test is specific as well as sensitive, making it superior to subjective symptom reports alone.”

Haider noted the results will be validated in a larger population.

Quadrant Biosciences has received a $2.3 million grant from the National Institutes of Health to develop a saliva-based microRNA diagnostic test. Quadrant will work with researchers from UB, SUNY Upstate, Arkansas Children's Hospital in Little Rock, Children’s Hospital of Michigan in Detroit, and Penn State College of Medicine.

The research will be conducted in a study of 2,500 adolescents and young adults with either a formal diagnosis of an mTBI or an overlapping medical condition.

“We are confident that an objective, rapid screen for concussion will be an important addition to concussion management protocols in the future, and we think that salivary micro RNAs have potential because they are noninvasive and relatively easy-to-use,” Haider said.

Legacy Pollutants Found in Migratory Terns in Great Lakes Region

A study concludes that PCBs, PBDEs and metabolites of DDT threaten the terns throughout their lives, from the moment they hatch

Chemicals that haven’t been manufactured in the U.S. for years or even decades are still turning up in the bodies of migratory terns in the Great Lakes region, a new study finds.

The research focused on three types of compounds: polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and the breakdown products, called metabolites, of dichlorodiphenyltrichloroethane (DDT).

Scientists discovered all three kinds of chemicals in the organs of over two-dozen common terns in breeding grounds along the Niagara River and the shore of Lake Erie. The pollutants were found at various life stages, in chicks, in juveniles and in adults.

Researchers also detected the compounds in emerald shiners, a small fish that is the terns’ primary food source in the area.

The research was published online on Sept. 3 in Environment International, and will appear in the journal’s November issue. Authors included University at Buffalo chemists Diana Aga and Steven Travis, and SUNY Buffalo State biologist Alicia Pérez-Fuentetaja.

Sales of PBDEs, a class of flame-retardants used in car seats, carpet padding, mattresses and many other household products, were phased out in the U.S. in 2013. Production of PCBs, once widely used as a coolant or insulating fluid in electrical transformers and capacitators, ended in the country in 1979. And use of DDT, an insecticide, has been prohibited in the U.S. for almost half a century, since 1972. The metabolite of DDT the team found in the birds and fish is called dichlorodiphenyldichloroethylene (DDE).

“These chemicals are still there. They don’t just go away. With PCBs, for example, they haven’t been produced in the U.S. for a long time now, but you can still find them in the environment, in sediments and in water. They don’t degrade for many years. The fish eat organisms that accumulate them, and then the birds eat the fish,” said Aga, Ph.D., Henry M. Woodburn Professor of Chemistry in the University at Buffalo College of Arts and Sciences.

“The common tern is a threatened species in New York state, and their numbers have not increased much despite state efforts to provide nesting sites and surveillance. This study shows how wildlife is affected by human pollution of aquatic systems and how the chemicals we produce can have a multigenerational effect, being passed from mothers to chicks,” said Pérez-Fuentetaja, Ph.D., professor of biology at SUNY Buffalo State and research scientist at the Great Lakes Center at SUNY Buffalo State.

The levels of PCBs and PBDEs in the birds were high enough to potentially harm the birds’ health and affect population recovery, the authors write in their paper.

Pollutants Impact Terns in Every Stage Of Life

The findings illustrate how household and industrial chemicals have become ubiquitous in the environment, where they can endure for many years, posing risks to wildlife.

In the case of terns, the threat begins from the earliest moments of their lives, even before they hatch, said Travis, the paper’s first author, who successfully defended his Ph.D. thesis at UB this fall.

He noted the smallest chicks the team studied harbored higher concentrations of the chemicals than older birds and adults, indicating the compounds are being passed from parent to progeny. To test this hypothesis, Travis has begun work on a study examining the levels of pollutants in the eggs of common terns and other wild aquatic birds.

“We see these really high concentrations in the smaller chicks, which indicates that there is maternal transfer of contaminants into the eggs,” he said.

“These substances interfere with the reproductive system and are endocrine disruptors,” Pérez-Fuentetaja said. “They tax the terns’ livers as they have to try and get rid of these pollutants, but the bioaccumulative nature of PCBs, PBDEs and DDEs means that the birds will not be able to fully detoxify themselves, and that they will pass part of their body-load to the next generation. These substances can alter development and neurological processes and could cause deformities, cancers and impaired behavior.”

The research highlights the risks associated with legacy contaminants, as well as the urgency of protecting the environment as new issues surrounding other classes of persistent chemicals, such as per- and polyfluoroalkyl substances (PFAS), emerge. Aga said that, once persistent pollutants become pervasive in water and soil, it’s very difficult to get rid of them.

The new study shows how long-banned chemicals continue to jeopardize the health of Great Lakes ecosystems.

“We can’t say that all the chemicals we’re seeing in the birds are coming from the Great Lakes, as the birds migrate and could be accumulating these compounds in other places along their migration route, too,” Travis said. “But the specific types of PCBs and PBDEs we’re seeing in the emerald shiners is similar to what we’re seeing in the birds. This pattern of chemical concentrations suggests that pollution in the Great Lakes region is the source of at least some of this contamination.”

He added, however, that, "One positive outcome of the study is that we only see the metabolite of DDT, called ‘DDE,’ in the fish. This likely indicates that there aren’t new sources of DDT being introduced to Lake Erie and the Niagara River, and that the DDT that was there is breaking down.”

The New York State Department of Environmental Conservation supported the research through collection of tern samples, which consisted of common terns that died through natural causes. The SUNY Buffalo State Great Lakes Center supported the study through collection of emerald shiners and other contributions. Additional support came from the UB Mark Diamond Research Fund and Greenway Ecological Standing Committee.

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