Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

Objectives/Goals: This study tests how fiber microstructural integrity and myelination levels within the cingulum connectome are associated with information processing speed (IPS) in relapsing-remitting multiple sclerosis (RRMS). We investigate the functional impact of structural coherence, myelin content, and white matter hyperintensities (WMH) load on IPS. Methods/Study Population: Data from 63 RRMS and 25 healthy controls (HC) were used. We hypothesize that the structural integrity of the cingulum bundle and its structural network – or connectome – is distinctly associated with IPS function in people with RRMS (vs. HC) due to myelin-related plasticity across the wiring. Using diffusion spectrum imaging and high-resolution tract segmentation, we constructed individualized white matter connectomes. Diffusion quantitative anisotropy (QA) and myelin fractions (MWF) were used to quantify structural coherence and myelination. WMH load was measured with T2-FLAIR imaging. Bayesian–Pearson correlations, mixed-linear, and moderation models explored how fiber-specific QA, MWF, and WMH load relate to IPS function in RRMS, as measured by Symbol Digit Modalities Test (SDMT). Results/Anticipated Results: We theorize that (1) QA in the cingulum connectome correlates with SDMT performance dimensionally, indicating that structural coherence in the white matter supports IPS function among both groups; (2) increased myelination will strengthen the positive association between QA and SDMT scores, suggesting that connectome-specific myelin content facilitates IPS; (3) conversely, WMH load within the cingulum connectome is expected to inversely correlate with SDMT scores, reflecting the detrimental impact of lesion burden on IPS function; (4) myelination in specialized tracts within the cingulum connectome play a compensatory role to support IPS function in the RRMS group. These investigations can offer a mechanistic clue to potential neuroplastic targets for cognitive interventions in MS. Discussion/Significance of Impact: By linking white matter integrity to cognitive function at the connectome level, this study can support neuroregenerative strategies to mitigate cognitive burden in RRMS. Our findings may advance understanding of how structural coherence, tract myelination, and WMH affect IPS, shaping personalized prognostic and therapeutic interventions.

Objectives/Goals: Early childhood obesity is a major concern for Latin American children in the U.S., with gut barrier dysfunction as a key risk factor. Diet plays a role in gut development, but few studies have focused on Latin American infants. Our objective is to identify culturally relevant introductory foods that promote in vitro gut barrier development and function. Methods/Study Population: Pooled human milk (2.5 mL) from 6-month postpartum Hispanic mothers was combined with fruit and vegetable baby food products (2.5 g) and subjected to a 3-phase in vitro digestion system that simulates oral, gastric, and intestinal digestion. Digesta products were then anaerobically fermented for 24-hours using human stool inoculum, centrifuged, and filter sterilized. Intestinal epithelial cells (Caco-2, ATCC) were grown to confluence on 0.4 μm polystyrene transwell inserts using a DMEM + 10% FBS medium and allowed to differentiate for 21-days. Highly differentiated monolayers were treated with a 1:4 dilution of fermenta with medium in triplicate. The cell experiment was conducted twice. Cell layer integrity was measured using transepithelial electrical resistance (TEER) 24- and 48-hours after treatment. Results/Anticipated Results: Dietary intake data from the What We Eat in America database indicated that the top 3 fruit and vegetable exposures for infants with Mexican or Hispanic ethnicity were banana, apple, and carrot. Commercial baby food purees of these fruits and vegetables, in addition to baby foods with blueberry and spinach (Natural for Baby, Gerber Products Company) were acquired for digestion and fermentation experiments. Caco-2 cell experiments with these foods are ongoing. We expect Caco-2 monolayer incubated with fermenta from human milk and fruit or vegetables will have greater TEER values due to increased integrity of the cell layer as compared to those with breast milk alone. We also expect that exposure to fruit and vegetable fermenta will increase gene expression of tight junctions compared to exposure to media and human milk. Discussion/Significance of Impact: Using an in vitro digestion and fermentation system coupled with cell culture studies, we are identifying cellular mechanisms that link individual fruits and vegetables to gut barrier function. This will support translational work focused on mitigating obesity development in vulnerable populations.

Starting in late September 1872, horses started falling ill with a severe respiratory complaint in the countryside about a dozen miles north of Toronto, Ontario. Veterinary experts swiftly diagnosed the malady, which paralyzed street transportation, commerce, and everyday life in Toronto itself during the first weeks of October, as influenza. Over the next year, an equine plague that most contemporaries referred to as the epizootic—and which I call the Great Horse Flu in the book I am completing on this outbreak—spread throughout southern Canada, every reach of the United States, and parts of Cuba, Mexico, and Central America. The novel influenza virus responsible for this outbreak sickened between ninety and ninety-nine percent of horses, donkeys, and mules across this vast swath of the northern Americas.1 Our best guess is that the Great Horse Flu killed between one and four percent of the equines it afflicted—a case fatality rate roughly not unlike those recorded by the Great Influenza Pandemic of 1918–1920 and the COVID Pandemic. In less than a year, an estimated 112,500 to 554,000 horses and ponies perished alongside tens or hundreds of thousands of mules and donkeys.2