Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.

Introduction: Research is an important aspect of many students’ training. However, formal research training is rarely included in curricula. Thus, we developed an online, asynchronous series of modules to introduce trainees to multiple topics that are relevant to the conduct of research. Methods: Research 101 was utilized by first-year medical students and undergraduate students conducting mentored research projects. Students’ knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with five-point Likert scaled questions, open-ended text responses, and a final quiz. Results: Pre-module survey results showed that learners felt most confident with the Conducting a literature search and Race and racism in medicine modules and least confident with the Submitting an Institutional Review Board protocol at UC module. Post-module survey responses were significantly increased compared to pre-module results for all modules and questions (p < 0.0001). The response to “The content of this module met my needs” was endorsed across all modules (84.9% “yes” responses). A final quiz of 25 multiple-choice questions was completed by 92 participants who received a median score of 21. Content analysis of open-ended post-module survey responses identified several strengths and opportunities for improvement in course content and instructional methods. Conclusions: These data demonstrate that significant learning resulted from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions. Final quiz scores were positive but also highlighted opportunity for additional trainee learning and will guide evolution of future modules.

OBJECTIVES/GOALS: The grant writing process provides investigators with critical thinking, problem solving, and communication skills, crucial for personal and professional development. However, opportunities for junior faculty to learn these skills are highly variable. Thus, we developed a grant writing program to assist in the preparation of an NIH R proposal. METHODS/STUDY POPULATION: The R Club Grant Program was implemented in 2021 for junior faculty of the University of Cincinnati’s College of Medicine and Center for Clinical & Translational Science & Training (CCTST). The program consists of a series of workshops (e.g., How to Craft a Specific Aims Page, How to Construct a Competitive R01 Proposal) utilizing examples of successful proposals and grant review criteria to demonstrate how to translate a conceptual framework into a research proposal (level 1). All participants can receive constructive feedback on a Specific Aims page from an experienced grant writer (level 2), and for a select cohort, the program provides comprehensive scientific content edits and iterative feedback on a full research proposal, with a focus on grantsmanship, presentation, and overall competitiveness (level 3). RESULTS/ANTICIPATED RESULTS: Over three NIH grant cycles, the program to date has provided 38 early-career investigators with multi-level grant writing support. All participants attended the workshops and received supporting documents, 21 received feedback on a Specific Aims page, and 6 received one-on-one writing assistance on their full research proposal. Of the 6 investigators who received the greatest level of support, 3 have received NIH scientific review, with a 66.6% funding success rate for either an original (R01, n=1) or subsequent overlapping (R35, n=1) proposal. In a survey sent to workshop attendees, 100% of respondents (n=23) reported ( Strongly Agreed or Agreed ) that the training was a worthwhile investment in their professional development and 96% stated that they will be able to apply the knowledge and skills learned. DISCUSSION/SIGNIFICANCE: Initial evaluation measures suggest that grant writing support programs have great potential to enhance funding success rates. As the program evolves it will be crucial to evaluate both qualitative and quantitative feedback measures to ensure efforts are directed to the appropriate level(s) of service to maximize the funding success of our faculty.

OBJECTIVES/GOALS: Research is an important aspect of many students’ training. However, most trainees do not complete a scholarly project, and formal research training is rarely included in a degree program’s curriculum. Thus, we developed an online, asynchronous series of modules to introduce trainees to multiple topics that are relevant to the conduct of research. METHODS/STUDY POPULATION: Research 101 was utilized by first year medical students and undergraduate students conducting mentored research projects at the University of Cincinnati College of Medicine. Students’ knowledge, confidence, and satisfaction were assessed using pre- and post-module surveys with 5-point Likert scaled questions, open-ended text responses, and a final quiz. RESULTS/ANTICIPATED RESULTS: Pre-module survey results showed that learners were most confident with the Conducting a literature search and Race and racism in medicine modules and least confident with the Submitting an Institutional Review Board (IRB) protocol at UC module. Post-module survey responses were significantly increased compared to pre-module results for all modules and questions (p < 0.0001). The response to The content of this module met my needs was endorsed across all modules (84.9% yes responses). A final quiz of 25 multiple choice questions covering content from all required modules was completed by 92 students who had a median score of 21 (range: 15 to 25). DISCUSSION/SIGNIFICANCE: These data demonstrate significant learning resulting from completion of Research 101, as post-module survey scores were significantly higher than pre-module survey scores for all modules and questions. Final quiz scores were positive but also highlighted opportunity for additional student learning and will guide evolution of future modules.