For Aging Research and Equity: Lessons Learned in Undergraduate Research Education.

Mentoring underrepresented students in aging research during the COVID-19 pandemic affords many opportunities for innovation and learning, for both students and program leaders. Here, we describe lessons learned from an Advancing Diversity in Aging Research (ADAR) program at a women-centered, minority-serving undergraduate institution. We share program elements and assessment results related to scholars' education in aging, support through community-building and mentorship, and research experiences in gerosciences. Notably, we highlight lessons learned for retaining and training undergraduate students as graduate school-ready researchers: 1) draw students into a community focused on social justice, 2) show students that geroscience is inclusive and integrative, 3) model professionalism with flexibility, 4) keep open lines of communication, and 5) build a team of mentors around each scholar. By sharing insights from our community of practice in geroscience research and education, we hope to model best practices for URM student support in aging research.

Identifying gaps in parental support for families of children with hypoplastic left heart syndrome.

PURPOSE: The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome. DESIGN AND METHODS: Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings. RESULTS: Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team's open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team's anticipation of parental emotional needs and provision of coping resources (p = 0.003). CONCLUSIONS: Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience. PRACTICE IMPLICATIONS: Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.

Opportunities to strengthen aging curricula across the health professions.

The rapidly aging population of the United States presents an urgent need for healthcare professionals trained in Gerontology, rooted in a holistic framework of health across the lifespan, and sustained by interprofessional collaborative practice. Institutions of higher education can meet this demand by aligning their curriculum and co-curriculum to train health sciences students in the increasingly important field of Gerontology. This IPEP guide will outline lessons learned at one University based on program director insight into aging-related courses, experiential training, and research opportunities. The lessons described here provide insight for other faculty and program directors on the current state of aging-related education and how to move from aging-related to aging-rich education in an interprofessional way.

Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.

BACKGROUND: Through genome-wide transcriptional comparisons, this study interrogates the capacity of in vitro differentiation of induced pluripotent stem cells (iPSCs) to accurately model pathogenic signatures of developmental cardiac defects. METHODS AND RESULTS: Herein, we studied the molecular etiology of cardiac defects in Nos3(-/-) mice via transcriptional analysis of stage-matched embryonic tissues and iPSC-derived cells. In vitro comparisons of differentiated cells were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3(-/-) transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic tissues and ex vivo iPSC-derived cells. In particular, up-regulation of glucose metabolism (p-value=3.95×10(-12)) and down-regulation of fatty acid metabolism (p-value=6.71×10(-12)) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived differentiated cells. CONCLUSIONS: The in vitro concordance of early Nos3(-/-) disease signatures supports the utility of iPSCs as a cellular model of developmental heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of congenital cardiac pathogenesis.

Understanding faculty perspectives of supports and barriers to interprofessional collaboration within a clinical scholars program: A qualitative study.

AIM: This study explores the faculty perspective of an interprofessional clinical scholars program to identify recommendations for strengthening team collaboration between academia and clinical practice. BACKGROUND: Interprofessional evidence-based practice, pairing higher education and clinical practice, is a critical part of nursing education. DESIGN: This qualitative study consisted of two phases of participant engagement, in both data collection and data analysis. METHODS: Specifically, faculty participated in a focus group discussion followed by a card sort of initial codes. RESULTS: The major themes identified are Unifying the Team and Navigating Layers of Challenge, encompassing concepts of teamwork and programmatic context that supported or disrupted interprofessional collaboration. This study affirms the importance of role clarity, connectedness, intentionality and continuity within clinical teams. Moreover, faculty identified barriers to teamwork based on workload, leadership turnover and constraining environmental forces. CONCLUSIONS: Recommendations for effective teamwork in an interprofessional setting will strengthen future collaboration between higher education and clinical settings.

Case-Based Learning in Translational Biomedical Research Education: Providing Realistic and Adaptive Skills for Early-Career Scientists.

PROBLEM: Case-based learning is an established means of educating students in law, business, and medicine; however, this methodology is not often applied to educating translational biomedical researchers. The application of case-based learning to translational biomedical research education allows scholars to actively engage with real-world material and apply their newfound knowledge as it is acquired. APPROACH: Through the Mayo Clinic Center for Clinical and Translational Science (CCaTS), three courses were delivered in 2009-2017 which emphasized case-based learning in clinical and translational science, entrepreneurship, and individualized medicine. Quantitative measures collected in student course reviews upon course completion were analyzed. Additionally, products arising from each course were identified, including publications and startups pitched. OUTCOMES: Analyses demonstrate that case-based learning techniques are well suited to graduate biomedical research education. Furthermore, case studies can be employed throughout the entire clinical and translational spectrum, from basic and preclinical work through to clinical and population-based learning. NEXT STEPS: Within CCaTS, next steps include creating case-based courses in regulatory and team science to continue to allow scholars to learn and apply these critical skills to real-world material. The goal is to continue to provide immersive training opportunities in areas of clinical and translational science that cannot be readily learned in a traditional lecture-based class setting.

Promoting international collaboration and creativity in doctoral students.

Staff from the Mayo Clinic in the US and the Karolinska Institute in Sweden describe a joint transatlantic course intended to broaden the horizons of the next generation of researchers in the field of regenerative medicine.

Mapping transcriptome profiles of in vitro iPSC-derived cardiac differentiation to in utero heart development.

The dataset includes microarray data (Affymetrix Mouse Genome 430 2.0 Array) from WT and Nos3(-/-) mouse embryonic heart ventricular tissues at 14.5 days post coitum (E14.5), induced pluripotent stem cells (iPSCs) derived from WT and Nos3(-/-) mouse tail tip fibroblasts, iPSC-differentiated cardiomyocytes at Day 11, and mouse embryonic stem cells (mESCs) and differentiated cardiomyocytes as positive controls for mouse iPSC differentiation. Both in utero (using embryonic heart tissues) and in vitro (using iPSCs and differentiated cells) microarray datasets were deposited to the NCBI Gene Expression Omnibus (GEO) database. The deposited data in GEO include raw microarray data, metadata for sample source information, experimental design, sample and data processing, and gene expression matrix. The data are available under GEO Access Number GSE69317 (GSE69315 for tissue sample microarray data, GSE69316 for iPSCs microarray data, http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE69317).

Induced pluripotent stem cells for cardiovascular disease: from product-focused disease modeling to process-focused disease discovery.

Induced pluripotent stem (iPS) cell technology offers an unprecedented opportunity to study patient-specific disease. This biotechnology platform enables recapitulation of individualized disease signatures in a dish through differentiation of patient-derived iPS cells. Beyond disease modeling, the in vitro process of differentiation toward genuine patient tissue offers a blueprint to inform disease etiology and molecular pathogenesis. Here, we highlight recent advances in patient-specific cardiac disease modeling and outline the future promise of iPS cell-based disease discovery applications.

Human umbilical cord blood-derived mononuclear cells improve murine ventricular function upon intramyocardial delivery in right ventricular chronic pressure overload.

INTRODUCTION: Stem cell therapy has emerged as potential therapeutic strategy for damaged heart muscles. Umbilical cord blood (UCB) cells are the most prevalent stem cell source available, yet have not been fully tested in cardiac regeneration. Herein, studies were performed to evaluate the cardiovascular safety and beneficial effect of mononuclear cells (MNCs) isolated from human umbilical cord blood upon intramyocardial delivery in a murine model of right ventricle (RV) heart failure due to pressure overload. METHODS: UCB-derived MNCs were delivered into the myocardium of a diseased RV cardiac model. Pulmonary artery banding (PAB) was used to produce pressure overload in athymic nude mice that were then injected intramyocardially with UCB-MNCs (0.4×10^6 cells/heart). Cardiac functions were then monitored by telemetry, echocardiography, magnetic resonance imaging (MRI) and pathologic analysis of heart samples to determine the ability for cell-based repair. RESULTS: The cardio-toxicity studies provided evidence that UCB cell transplantation has a safe therapeutic window between 0.4 to 0.8 million cells/heart without altering QT or ST-segments or the morphology of electrocardiograph waves. The PAB cohort demonstrated significant changes in RV chamber dilation and functional defects consistent with severe pressure overload. Using cardiac MRI analysis, UCB-MNC transplantation in the setting of PAB demonstrated an improvement in RV structure and function in this surgical mouse model. The RV volume load in PAB-only mice was 24.09±3.9 compared to 11.05±2.09 in the cell group (mm3, P-value<0.005). The analysis of pathogenic gene expression (BNP, ANP, Acta1, Myh7) in the cell-transplanted group showed a significant reversal with respect to the diseased PAB mice with a robust increase in cardiac progenitor gene expression such as GATA4, Kdr, Mef2c and Nkx2.5. Histological analysis indicated significant fibrosis in the RV in response to PAB that was reduced following UCB-MNC's transplantation along with concomitant increased Ki-67 expression and CD31 positive vessels as a marker of angiogenesis within the myocardium. CONCLUSIONS: These findings indicate that human UCB-derived MNCs promote an adaptive regenerative response in the right ventricle upon intramyocardial transplantation in the setting of chronic pressure overload heart failure.