Diversity trends in traumatic brain injury clinical trials in the United States.

BACKGROUND: This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. METHODS: ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002-2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. RESULTS: About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). CONCLUSION: Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

Association between specific types of parent stressors and fast-food consumption among parents and children.

INTRODUCTION: Although stress has been associated with eating behaviors, such as overeating and eating less healthy foods, the relationships between specific types of parent stressors and fast-food consumption in parents and young children have not been well studied. We hypothesized that parent perceived stress, parenting stress, and household chaos would be positively associated with fast-food consumption for parents and their young children. METHODS: Parents of 2-5 year olds and with Body Mass Index >27 kg/m2 (N = 234, parent mean age: 34.3 (±5.7); child age: 44.9 (±13.8) months; 65.8 % from two parent households) completed surveys on parent perceived stress, parenting stress, household chaos, and their fast-food intake and that of their child. RESULTS: In separate regression models, controlling for covariates, parent perceived stress (ß = 0.21, p < 0.01; R2 = 0.10, p < 0.01), parenting stress (ß = 0.26, p < 0.01; R2 = 0.13, p < 0.01), and household chaos (ß = 0.25, p < 0.01; R2 = 0.12, p < 0.01) were each significantly associated with parent fast-food consumption, and separately with child fast-food consumption [Parent perceived stress (ß = 0.05, p = 0.02; R2 = 0.14, p < 0.01); parenting stress (ß = 0.14, p = 0.03; R2 = 0.14, p < 0.01); parent fast-food consumption (ß = 0.40, p < 0.01; R2 = 0.27, p < 0.01)]. However, combined final models showed parenting stress (p < 0.01) as the only significant predictor of parent fast-food consumption, which in turn was the only significant predictor of child fast-food consumption (p < 0.01). DISCUSSION: The findings support the inclusion of parenting stress interventions that target fast-food eating behaviors in parents, which may in turn, reduce fast-food intake in their young children.

Neurointerventional Radiology: History, Present and Future.

Neurointerventional Radiology (NIR), encompassing neuroendovascular surgery, endovascular neurosurgery, and interventional neurology, is an innovative and rapidly evolving multidisciplinary specialty focused on minimally invasive therapies for a wide range of neurological disorders. This review provides a comprehensive overview of NIR, discussing the three routes into the field, highlighting their distinct training paradigms, and emphasizing the importance of unified approaches through organizations like the Society of Neurointerventional Surgery (SNIS). The paper explores the benefits of co-managed care and its potential to improve patient outcomes, as well as the role of interdisciplinary collaboration and cross-disciplinary integration in advancing the field. We discuss the various contributions of neurosurgery, radiology, and neurology to cerebrovascular surgery, aiming to inform and educate those interested in pursuing a career in neurointervention. Additionally, the review examines the adoption of innovative technologies such as robotic-assisted techniques and artificial intelligence in NIR, and their implications for patient care and the future of the specialty. By presenting a comprehensive analysis of the field of neurointervention, we hope to inspire those considering a career in this exciting and rapidly advancing specialty, and underscore the importance of interdisciplinary collaboration in shaping its future.

MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53.

Although the number of proteins effectively targeted for posttranslational degradation by PROTAC has grown steadily, the number of E3 ligases successfully exploited to accomplish this has been limited to the few for which small-molecule ligands have been discovered. Although the E3 ligase MDM2 is bound by the nutlin class of small-molecule ligands, there are few nutlin-based PROTAC. Because a nutlin-based PROTAC should both knockdown its target protein and upregulate the tumor suppressor p53, we examined the ability of such a PROTAC to decrease cancer cell viability. A nutlin-based, BRD4-degrading PROTAC, A1874, was able to degrade its target protein by 98% with nanomolar potency. Given the complementary ability of A1874 to stabilize p53, we discovered that the nutlin-based PROTAC was more effective in inhibiting proliferation of many cancer cell lines with wild-type p53 than was a corresponding VHL-utilizing PROTAC with similar potency and efficacy to degrade BRD4. This is the first report of a PROTAC in which the E3 ligase ligand and targeting warhead combine to exert a synergistic antiproliferative effect. Our study highlights the untapped potential that may be unlocked by expanding the repertoire of E3 ligases that can be recruited by PROTAC. SIGNIFICANCE: These findings present the first BRD4-targeting MDM2-based PROTAC that possesses potent, distinct, and synergistic biological activities associated with both ends of this heterobifunctional molecule.