A slight chill on the air and the rustling of falling leaves means it’s time to grab your favorite pumpkin spice beverage and read our latest roundup of research news. Investigators from Children’s Hospital of Philadelphia’s Center for Injury Prevention and Research shared findings in concussion research and preventing car crashes among teens. Scientists in the Raymond G. Perelman Center for Cellular and Molecular Therapeutics discovered a gene that could help guide future treatment for schizophrenia, and a pilot grant from the Center for Pediatric Clinical Effectiveness will support aims to improve pre-transplant communication with patients and their families. As you savor the last few sips from your cup, learn about CHOP researchers’ contributions to a special journal issue on baby brain development.
Pilot Study Explores Kidney Pre-transplant Evaluation and Communication
Transplant centers frequently observe significant variation in the time it takes for patients and families to complete the evaluation for kidney transplant, given its extensive nature. Adult studies have found multiple reasons for these differences, but little is understood about drivers of variation for pediatric transplant candidates. The Center for Pediatric Clinical Effectiveness (CPCE) awarded a pilot grant to Eloise Salmon, MD, fellow in Pediatric Nephrology, for a project that will bridge that knowledge gap by collecting demographic and qualitative information via surveys and semi-structured interviews with parents or caregivers of children who begin the pre-transplant evaluation at CHOP.
One of the aims of the study is to gain an understanding of how tools could support the parent/caregiver experience during the transplant evaluation process, specifically an evaluation roadmap provided to families at their first meeting with the transplant coordinator and the patient portal of the electronic medical record.
CPCE Core Faculty member Sandra Amaral, MD, MHS, and Judy Shea, PhD, professor in the Division of General Internal Medicine in the Department of Medicine at the University of Pennsylvania, are Dr. Salmon’s mentors.
Working Memory Development and Teen Crashes
Motor vehicle crashes are the leading cause of death for adolescents in the United States and abroad. Many studies cite inexperience and lack of driving skills as key contributing factors to teen driver crashes, but a new study published in JAMA Network Open conducted by Elizabeth Walshe, PhD, with colleagues at CHOP, the Annenberg Public Policy Center at the University of Pennsylvania, and the University of Oregon, suggests that brain development may also play a critical role.
In her blog about the study, Dr. Walshe, a research postdoctoral fellow at CHOP’s Center for Injury Research and Prevention (CIRP), noted this is the first paper to examine changes in cognitive development over time during adolescence and how these changes relate to the probability of crash involvement in young drivers. Her team found that teens with slower growth in working memory ability were more likely to report being involved in a crash. This points to cognitive development screening as a potential new strategy for identifying and tailoring driving interventions for teens at high risk for crashes.
“Ideally, we’d be able to offer interventions like driver training or technologies like in-vehicle alert systems to assist new drivers who need it,” Dr. Walshe said.
CHOP Scientists Identify Gene as a Master Regulator in Schizophrenia
CHOP research findings may unlock the door to future treatments for patients with schizophrenia. Using computational tools to investigate gene transcription networks in large collections of brain tissues, a scientific team identified a gene, TCF4, which acts as a master regulator of schizophrenia during early human brain development. The study appeared online in Science Advances, and its co-authors include Abolfazl Doostparast Torshizi, PhD, and Kai Wang, PhD, of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at CHOP.
“Because hundreds, or even thousands, of genes may contribute to the risk of schizophrenia, it is crucial to understand which are the most important ones, orchestrating core networks in the disease,” Dr. Wang said. “Pinpointing master regulators may help guide us toward priority targets for novel treatments in the future.”
The current study suggests paths of additional investigation. One direction, Dr. Wang said, is to use expanded datasets to explore whether other master regulators in addition to TCF4 may act in schizophrenia. If so, it may eventually be possible to classify patients with schizophrenia into subgroups more responsive to specific treatments, as is occurring in many cancers, to help implement precision medicine in psychiatric diseases. Other approaches, Dr. Doostparast added, may involve functional genomics at the level of single cells to assess the cell types most influenced by dysregulating gene expression.
The study represents one of the first successful examples of combining computational approaches and stem cell-based experimental models to disentangle complex gene networks in psychiatric diseases.
Female Athletes Delay Specialty Care Following Concussion
Researchers from the Sports Medicine Program at CHOP found that female athletes seek specialty medical treatment later than male athletes for sports-related concussions (SRC), and the ramifications of this delay could be more symptoms and longer recovery times.
The study appears in Clinical Journal of Sports Medicine, and it raises the question of whether inequities in medical and athletic trainer coverage on the sidelines are contributing to delayed identification and specialized treatment of concussion for young female athletes and, consequently, leading to more symptoms and longer recovery trajectories.
“There is speculation in the scientific community that the reasons adolescent female athletes might suffer more symptoms and prolonged recoveries than their male counterparts include weaker neck musculature and hormonal differences,” said senior author Christina Master, MD, a pediatric and adolescent primary care sports medicine specialist and senior fellow at CIRP. “We now see that delayed presentation to specialty care for concussion is associated with prolonged recovery, and that is something we can potentially address.”
The study team analyzed a dataset containing records of 192 children between 7 and 18 years of age who were diagnosed with an SRC and seen by a sports medicine specialist. Results showed girls took longer to present to specialist care (i.e., 15 days vs. nine days for boys) and had longer recovery trajectories than boys.
By looking at average-days-to-recovery for female and male patients across these outcomes, researchers found that females returned to school later, returned to exercise later, had neurocognitive recovery later, had vision and vestibular recovery later, and returned to full sport activity far later (119 vs. 45 days).
Importantly, when researchers limited the analysis to those female and male patients who presented to the specialty practice for evaluation within the first seven days of injury, the differences between males and females on all outcomes disappeared.
Hao Huang, PhD, is Lead Editor of Special Issue of NeuroImage
Hao Huang, PhD, principal investigator in the Laboratory for Neural MRI and Brain Connectivity @ CHOP and Penn, and colleagues served as guest editors for a special edition of NeuroImage, a leading journal in the field of neuroimaging. The issue, scheduled for September 2019, includes an impressive collection of works at the forefront of studying healthy and diseased baby brain development based on neuroimaging and features the findings of various CHOP researchers.
"Elucidating the ontogeny of structure, function, and physiology of the early developing brain will not only greatly advance current understanding of the general principles of normal development, but also offer insights into neural disorders," Dr. Huang wrote in the issue’s editorial.
Catch up on our headlines from our last edition of In the News:
- Cancer Drug Granted Accelerated Approval
- Welcome to Our New Chief of Infectious Diseases
- CHOP Leads Largest Genetic Study Associated With Childhood Obesity
- Improving Police Encounters for People With ASD
- Maurizio Pacifici, PhD, Featured in Q&A With IFOPA
- Findings Show Receptor Protein Promotes Stress Resilience
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