These authors contributed equally to this work Affiliations:Abstract Pediatric brain tumor survivors experience significant cognitive sequelae from their diagnosis and treatment. The exact mechanisms of these injuries are poorly understood, and validated predictors of cognitive outcome are lacking. The current study aims to determine if there are abnormalities in functional brain network organization and cognitive performance in pediatric brain tumor patients, measured via resting state functional magnetic resonance imaging (rsfMRI) and the NIH Toolbox Cognition Battery, respectively. Further, we assess potential relationships between changes in brain network architecture and behavior in the patients.Patients ages 4-18 years old with diagnosis of a brain tumor underwent awake rsfMRI during regularly scheduled clinical imaging and were tested with the NIH Toolbox Cognition Battery. Overall, functional brain network organization was significantly different in patients compared to age-and sex-matched healthy controls (p < 0.001).Network integrity within the dorsal attention network was particularly affected, with 86% of patients having connectivity strength 2+ SD below the mean of controls (p < 0.0001).Moreover, cognitive testing of patients demonstrated significant impairments in multiple domains, including attention (p < 0.05, FDR corrected). Finally, a significant amount of variance of age-adjusted total composite scores from the Toolbox was explained by changes in segregation between the dorsal attention and default mode networks as well as sex (R 2 = 0.52, p < 0.05). Pediatric brain tumor patients demonstrated statistically significant deficits in multiple cognitive domains and multiple abnormalities in brain network architecture.Thus, rsfMRI may provide insight into neural systems that underlie these changes in cognitive function, suggesting that these metrics may serve as a biomarker for cognitive performance.

INTRODUCTION: Survivors of pediatric brain tumors experience significant cognitive deficits from their diagnosis and treatment. Mechanisms of cognitive injury are poorly understood, and predictors of long-term outcome are lacking. Large-scale, distributed brain systems provide a window into brain organization and function that may yield insight into these mechanisms and outcomes. Recent evidence suggests that systems-level changes are related to cognitive performance across the lifespan. Here, we evaluated brain network architecture, cognitive performance, and brain-behavior relationships in pediatric brain tumor patients. METHODS: Forty-nine patients (ages 7-18y.o.) with any brain tumor diagnosis underwent resting state functional Magnetic Resonance Imaging (rsfMRI) during regularly scheduled clinical visits. All patients were tested with the NIH Toolbox Cognition Battery. One-hundred thirty-nine age- and sex-matched typically developing children were used as controls. All data were processed to minimize artifactual sources of variance. Functional brain networks were created for each patient via rsfMRI data from 300 regions of interest that sample the whole brain. Multilinear models were implemented to examine brain-behavior relationships, while accounting for demographic and clinical factors. RESULTS: Functional network organization was significantly altered in patients compared to controls (p&lt;0.001). Network organization was more affected in patients who received whole-brain radiation therapy than those who did not (t=2.52, p&lt;0.015). Patients demonstrated significant impairments in multiple domains of cognitive performance, e.g. attention (p&lt;0.0001). Weak relationships were found between cognitive performance and network organization, none of which survived multiple comparison correction. CONCLUSIONS: Brain network architecture is significantly altered in pediatric brain tumor patients. Whole-brain radiation was related to the largest changes. Most network and cognitive changes were significant with large effect sizes, yet brain-behavior relationships were weak. Our results suggest that systems-level changes in brain organization may provide insight into long-term changes in brain function in pediatric brain tumor patients.

Introduction: Cigarette smoking is a significant public health issue, and the primary cause of preventable health problems in the Greater Toronto Area (GTA). Nevertheless, the prevalence of adolescent smoking remains high. Our proposed study aims to investigate the effectiveness of school-based educational programs in reducing adolescent smoking rates in the GTA. It will compare the results of weekly integrated education sessions offered throughout a school term to more focused, discrete sessions offered at two different points in the term at 10 secondary schools in the GTA. The findings will help inform potential policy and curricular changes to promote smoking cessation among current and future youth. Methods: This study utilizes an experimental quantitative research design. Multi-stage cluster sampling will be used. 10 schools will be selected, with 20 students being recruited per school. The intervention group will receive a school-based education program for smoking cessation, lasting an academic semester. The control group will receive an educational session at the beginning and end of the semester. The inclusion criteria is as follows: participants must be (a) adolescents aged 12-17 and attending an accredited primary or secondary school, (b) living in the GTA, and (c) current daily smokers. The Fagerström Test for Nicotine Dependence (FTND) and biochemical tests will be used to collect pertinent data about smoking cessation rates. Abstinence will also be assessed using the Russell Standard. Results: The study will use statistical tests to compare the proportion of students in the intervention group who quit smoking to the control group. The primary outcome measures will be 4-week and 6-month abstinence counts and nicotine dependency as measured by the FTND. The analysis will be conducted using IBM SPSS ver. 29. Discussion: The results of this study will provide valuable insight into the effectiveness of educational programs in promoting smoking cessation among youth, which will inform the design of future school-based interventions. Additionally, the study will help to understand adolescent smoking patterns, which can be used to guide public health policies. Conclusion:The results will have the potential to inform future education and public health strategies for encouraging adolescent smoking cessation.

decrease the incidence and severity of late effects. The purpose of this study is to report mature clinical outcomes, including disease control and late toxicity, for pediatric patients treated with PRT for medulloblastoma. Materials/Methods: 180 patients with standard, intermediate (large cell/ anaplastic histology but otherwise standard risk) or high risk medulloblastoma were treated with surgery, adjuvant PRT, and chemotherapy at an institution between February 2002 and November 2016. Patients underwent craniospinal irradiation of 18-36 Gy radiobiological equivalents (GyRBE) at 1.8 GyRBE per fraction followed by a boost dose to the whole posterior fossa or tumor bed. 131 (72.8%) patients were enrolled on a prospective clinical trial. Event Free Survival (EFS) and Overall Survival (OS) was assessed using the Kaplan Meier Method. The cumulative incidence of brainstem injury and secondary malignancies was also evaluated. Results: The median follow up was 8.1 years (1-16.3). The median age at start of PRT was 8.1 years (2.5-24.1). The percentage of patients undergoing a gross total resection (GTR) or near-GTR/NTR, subtotal resection (STR), and biopsy only was 88.3%, 11.1%, and 0.6%, respectively. 58.3% of patients were categorized as standard risk and 41.7% of patients as intermediate/high risk. The 7-year EFS and OS for the entire cohort was 76.9% and 80.5%, respectively. The 7-year EFS and OS was 85.1% and 87.5% for the standard risk cohort and 65.4% and 70.5% for intermediate/ high risk patients. On univariate analysis, intermediate/high risk disease (HR: 2.0; p Z 0.02) was associated with inferior EFS, while anaplastic subtype (HR: 1.9; p Z 0.07) trended towards worse EFS. The 7-year cumulative incidence of both secondary tumors and brainstem injury was 2.0%. Conclusion: PRT for medulloblastoma is effective, with disease control in our cohort comparable to other published data. Furthermore, it is associated with low rates of grade II or higher brainstem injury and secondary malignancies. Strategies to improve survival outcomes for high risk patients are needed.

Vibrio parahaemolyticus (V. para) is a Gram‐negative, halophilic bacteria that causes acute gastroenteritis in humans upon consumption of contaminated seafood. The V. para life cycle is facilitated by an array of virulence factors, including two type III secretion systems (T3SS). T3SS‐mediated translocation of effectors into host cells is dependent on delivery of each effector to the base of the T3SS needle by a chaperone. VopR is an effector secreted by the first V. para T3SS (T3SS1) that uses an N‐terminal PIP2 –binding domain (BPD) to localize to the plasma membrane and induces host cell rounding through an unknown catalytic mechanism. We hypothesize that VP1684, encoded by a gene directly upstream of vopR in the V. para genome, is the cognate chaperone of VopR, and that the BPD also constitutes the chaperone‐binding domain. Through affinity column purification coupled with FPLC filtration we demonstrate that VP1684 forms a homodimer in solution much like other T3SS effector chaperones, which corroborates bioinformatics analyses indicating that VP1684 shares conserved biochemical properties with T3SS effector chaperones. We also show that VP1684 forms a stable complex with VopR. Moreover, we reveal through confocal microscopy of HeLa cells infected with V. para that the VopR‐mediated cell rounding phenotype is VP1684‐dependent. Finally, we show via increases in host cell cAMP levels by translocated cyaA‐tagged effectors that the translocation of VopR into the host cell by T3SS1 also depends on the presence of VP1684. Taken together, these data suggest that VP1684 is acting as the previously unidentified cognate chaperone for VopR, and as a necessary factor in effector translocation plays a significant role in V. para pathogenicity.Support or Funding InformationThis work was funded by the HHMI, National Institutes of Health (NIH) grant R01‐AI056404, NIH grant 5T32AI007520‐20, the Welch Foundation grant I‐1561, and Once Upon a Time&[hellip]Foundation. STARS program funding provided by the state of Texas.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.