Jefferson Investigates: Improving Physical Activity in TBI Patients, Analyzing Small RNA in Psychiatric Illness, Fighting Post-Surgical Infection

Traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases. Physical activity decreases this risk through improving cognitive health. In a new study, Amanda Rabinowitz, PhD, and her team at Jefferson Moss Rehabilitation Research Institute developed an approach to increase physical activity in TBI patients to decrease cognitive decline.

“Traditional exercise programs for TBI patients are ‘one size fits all,’ making it difficult for people with varying injury severity to benefit,” says Tessa Hart, PhD, first author on the study, published in Frontiers in Rehabilitation Sciences. “Our program is designed to meet people where they are, regardless of the type of brain injury.”

In their program, a therapist works virtually with TBI patients to develop physical activity goals, ranging from gardening to going to the gym. Regular text messages from a chatbot, RehaBot, remind patients to complete their physical activity.

“Patients we’ve interviewed see the value in the study and are excited to continue. No one has dropped out either,” Dr. Hart says. “The program has the potential to help people with TBI develop long-lasting, healthy physical activity habits to improve cognitive function.”

The team plans to use a smartwatch tracker to measure the impact of improved physical activity, emotional function, sleep and pain management. Dr. Hart says, “Everyone with TBI is unique, with their own unique set of challenges and goals. We wanted our approach to be just as unique, and hope patients will experience success.”

“The more we learn about the science behind TBI, the more evidence we have that we can improve a wide variety of issues people with TBI struggle with,” says Dr. Rabinowitz, who is also part of Sidney Kimmel Medical College.

Dr. Rabinowitz and Dr. Hart are still recruiting for this clinical trial; click here for more information.

By Moriah Adde

For decades, scientists studying brain disorders have focused almost exclusively on proteins and the genes encoding them. Now, new research from Thomas Jefferson University’s Computational Medicine Center suggests that several classes of small regulatory molecules, fittingly known as small RNAs, may play a much larger role in schizophrenia and bipolar disorder, and in a healthy brain, than previously thought.

In a study recently published in Translational Psychiatry, a team led by Isidore Rigoutsos, PhD, took a comprehensive look at small RNAs in brain samples from people with schizophrenia, bipolar disorder and individuals without psychiatric illness. Their goal was to find out what kind of small RNAs are active in the brain, and whether their levels change in disease.

“Little attention had been paid to small RNAs in these disorders,” says Dr. Rigoutsos, “even though small RNAs help control numerous processes by modulating the abundance of genes.” One well-known group, called microRNAs, had been studied but not extensively. “If you only look at one class, you may be missing important regulatory events.”

To capture the broader picture, researchers used deep sequencing and specialized computational tools developed in the Rigoutsos lab. This allowed them to analyze multiple classes of small RNAs at once, and they found that microRNAs account for just over half of all small RNAs in the brain. The remainder comes from the other classes the Rigoutsos team studies. The team found that these other RNAs may regulate critical processes in schizophrenia and bipolar disorder, as well as in healthy brains.

Also, a surprising pattern emerged when the team separated participants by age. The small RNA profiles of young patients looked substantially different than those of healthy, young people. Yet, those differences disappeared when the researchers compared the profiles from the brains of older patients with those from older individuals without mental illness. “It turns out that the differences in the small RNA populations happen early on in patients’ lives,” Dr. Rigoutsos says.

The findings highlight the growing importance of data-driven, collaborative science. “To understand complex disease,” Dr. Rigoutsos continues, “we need to study all the molecules that are present and work across disciplines.”

By Roni Dengler

Nearly one in 10 people who are implanted with a surgical fix to their spine will develop a serious bacterial infection, despite prophylactic antibiotic treatment. In a new study, researchers at Thomas Jefferson University have engineered a device they hope will help prevent this devastating complication.

Current practice includes applying antibiotics on wounded areas at the end of an orthopedic surgery, says Flemming Forsberg, PhD, professor of radiology and expert in ultrasound physics. The problem is that the protection wanes over hours, and any surviving bacteria can still ravage the area. Dr. Forsberg, Dr. Noreen Hickok from orthopedic surgery and their team have been developing a tiny repository of antibiotics that could be put in the surgical site and activated with ultrasound two to three days later — when the prophylactic drugs have petered out. Such a device would help doctors deliver a one-two punch against troublesome bacteria.

The team first explored materials that would be stable enough to hold a reservoir of drugs for several days and also weak enough to break open with ultrasound. MD-PhD student Selin Isguven Billmyer, first author of the study, spent years testing materials and shapes of receptacles. However, when tested in freely moving laboratory animals, the reservoir broke open too soon. She went back to the figurative drawing board to find a shape that would perform better. The design holds promise for clinical use in spinal surgeries.

A related antibiotic reservoir has been tested in knee surgery, and one of the Sidney Kimmel Medical College team members. radiology researcher Lauren Delaney, PhD, recently received NIH funding to conduct a multicenter clinical trial.

This iterative testing cycle is common practice in the Forsberg laboratory, which includes engineers, scientists and physicians. “We test new engineering ideas, we get clinicians’ feedback, and then we try to implement,” he says. Getting his team’s good ideas into the clinic is always the goal, in the vein of translational science. Dr. Forsberg says, “I can get the two sides to talk to each other, so we focus on moving solutions to real problems into clinical practice.”

By Jill Adams