Using a boundary crossing lens to understand basic science educator and clinical educator collaboration in instructional design.

PURPOSE: Collaborations between basic science educators (BE) and clinical educators (CE) in medical education are common and necessary to create integrated learning materials. However, few studies describe experiences of or processes used by educators engaged in interdisciplinary teamwork. We use the lens of boundary crossing to explore processes described by BE and CE that support the co-creation of integrated learning materials, and the impact that this work has on them. MATERIALS AND METHODS: We conducted qualitative content analysis on program evaluation data from 27 BE and CE who worked on 12 teams as part of a multi-institutional instructional design project. RESULTS: BE and CE productively engaged in collaboration using boundary crossing mechanisms. These included respecting diverse perspectives and expertise and finding efficient processes for completing shared work that allow BE and CE to build on each other's contributions. BE and CE developed confidence in connecting clinical concepts with causal explanations, and willingness to engage in and support such collaborations at their own institutions. CONCLUSIONS: BE and CE report the use of boundary crossing mechanisms that support collaboration in instructional design. Such practices could be harnessed in future collaborations between BE and CE.

Development and Implementation of a Medical School Course Integrating Basic, Clinical, and Health Systems Sciences.

OBJECTIVE: In recent years, significant steps have been made in integrating basic science and clinical medicine. There remains a gap in adding the third pillar of education: health systems science (HSS). Core clerkships represent an ideal learning venue to integrate all three. Students can experience the value of integrating basic science as they learn clinical medicine in environments where HSS is occurring all around them. METHODS: We outline the creation of Sciences and Art of Medicine Integrated (SAMI), a course that runs parallel with the clerkship year and integrates basic science and HSS with clinical medicine. A complete description of the planning and implementation of SAMI is provided. We include the participants and educational setting, the goals and objectives, and the structure of each session. To encourage the integration of basic science, HSS, and clinical medicine, students utilize a series of tools, described in detail. Examples of each tool are provided utilizing a case of a patient presenting with obstructive sleep apnea. RESULTS: We successfully implemented this course with positive reception from students. CONCLUSION: This course represents a step not only toward the integration of HSS with basic science and clinical medicine but also an advancement in training future clinicians to provide high-value care. Future curricular development must consider the validation of a measure of clinical reasoning that assesses a student's ability to think in a cognitively integrated fashion about basic science, HSS, and clinical medicine demonstrated by enhanced justification of clinical reasoning and a more holistic approach to planning patient care.

An Institutional Evaluation of Race and Ethnic Diversity in Pre-clerkship Lectures.

The goal of this project was to assess the current state of racial and ethnic presentation in medical pedagogy using the pre-clerkship curriculum at Case Western Reserve University School of Medicine (CWRU SOM). We systematically reviewed 20,630 slides across the basic sciences curriculum from 2020 to 2022 for references to race, ethnicity, or photos of people of color. Results showed that race and ethnicity are overwhelmingly used as biological constructs and references lack appropriate historical context. In addition, this project constructed learning objectives that provide suggestions to shift medical discourse on race and ethnicity from contemplation to a state of solution.

Preparing Students to Deliver Care to Diverse Populations.

The purpose of this study was to increase student exposure to diverse patients using patient ID cards in problem-based learning (PBL) at Case Western Reserve University (CWRU). The pre-clerkship curriculum capitalizes on facilitated small-group, case-based discussions to promote inquiry and learning of the foundational sciences. Quantitative and qualitative results supported a finding of added value to case-discussions and the humanization of case-patients. The inclusion of the patient ID cards resulted in most students indicating that it helped them learn about and prepare to care for their future population of diverse patients. The patient ID cards will allow us to develop specific learning objectives about the demographics to increase learning about diverse patient care. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01648-0.

"Flipped" clinical rotations: A novel approach.

BACKGROUND: Near the beginning of the COVID-19 pandemic in the United States, medical students were pulled out of all in-person patient care activities. This resulted in massive disruption to the required clinical rotations (clerkships), necessitating creative curricular solutions to ensure continued education for medical students. APPROACH: In response to the lockout, our school adopted a "flipped" clinical rotations model that assigned students to remote learning activities prior to in-person patient care activities. This approach allowed students to continue their clinical education virtually with a focus on knowledge for practice while awaiting return to the shortened in-person portions of their rotation. In planning the modified clinical curriculum, educational leaders adhered to several guiding principles including ensuring flexible remote curricular components that would engage students in active learning, designating that no rotation would be completely virtual, and completing virtual educational activities and standardised exams before students returned to in-person experiences. EVALUATION: End of rotation evaluations and standardised exam scores were analysed to determine the effectiveness of this model. Despite the disruption associated with the pandemic and the rapid implementation of the "flipped" rotations, students continued to rate the overall experiences as highly as traditional clinical rotations. Students also performed similarly on standardised exams when compared to cohorts from other classes at the same experience level. IMPLICATIONS: While borne out of necessity during a pandemic, the lessons learned from our implementation of a "flipped" rotations model can be applied to address problems of capacity and clinical preparedness in the clinical setting.

Early Medical Students' Experiences as System Navigators: Results of a Qualitative Study.

PURPOSE: To explore how early meaningful experiential learning in community settings impacted medical students' application of systems thinking, their perceptions of systems navigation, and their professional identity as health system change agents. METHODS: Following an immersive Health Systems Science course, first-year medical students partnered with veterans or newly arrived refugee families and served as health system patient navigators embedded within primary care teams for a year. Across two cohorts, fifty-six students participated in the elective. Three voluntary focus groups were conducted each year for a total of six groups with 50 patient navigator students. Inductive content analysis of focus group transcripts was conducted. RESULTS: Qualitative analysis produced three major themes: program impact on students, student impact on patients, and student perceptions of the role of healthcare providers. Students reported a rich understanding of social determinants of health. By improving patient awareness of health and well-being, building capacity to understand medical issues, and increasing medication adherence through teaching, students recognized their impact on patient care. The importance of interprofessional collaboration with social workers also emerged and helped shape students' understanding of how they as physicians are part of a coordinated team working toward better patient care. CONCLUSION: The Case Western Reserve University WR2 curriculum teaches students how to address complex determinants of health and how to consider their role in dynamic health systems. This study highlights rich themes that emerged from students as they recognized the context that creates health for both individuals and communities. It underscores the role of such experiences in reinforcing systems thinking and development of change agency, both contributing to their professional identity formation as physicians.

Thinking Slow More Quickly: Development of Integrated Illness Scripts to Support Cognitively Integrated Learning and Improve Clinical Decision-Making.

Illness scripts describe the mental model used by experienced clinicians to store and recall condition-specific knowledge when making clinical decisions. Studies demonstrate that novice clinicians struggle to develop and apply strong illness scripts. We developed the Integrated Illness Script and Mechanism of Disease (IIS-MOD) map framework to address this challenge.

The educators' experience: Learning environments that support the master adaptive learner.

BACKGROUND: The Master Adaptive Learner (MAL) theoretical framework describes an integrated approach to learning that combines features of educational theory on self-regulated learning and aspects of quality improvement. In order to develop MAL students, it is important to pay attention to the learning environment. PURPOSE: To describe educators' perspectives about the learning environment needed to promote the development of master adaptive learners. METHODS: Thematic analysis of reports by medical educators who were workshop participants at a national presentation on creating effective learning environment to develop MAL in undergraduate medical education. RESULTS: Three themes educators considered important in the development of the Master Adaptive Learner were Adaptive Educator, Support for Learning, and Institutional Commitment. These findings suggest that in order to support the MAL, an educational setting should provide faculty who can be flexible and adapt to the developing MAL, learning experiences that support active learning, focused on groups as well as developing individual learners. Leaders in the educational setting should demonstrate a commitment to creating a culture to support learning and provide appropriate resources to that end. CONCLUSION: Learning environments to develop master adaptive learners need to have adaptive educators, teaching, learning, and institutional culture to support challenge and grow Master Adaptive Learners.

Evaluating the Anatomage Table Compared to Cadaveric Dissection as a Learning Modality for Gross Anatomy.

The purpose of this study was to compare the effectiveness and qualitative experience of learning gross anatomy of the pelvis and perineum (P/P) and musculoskeletal system (MSK) via cadaveric dissection to learning these same anatomical regions using the Anatomage table. The Anatomage table is an anatomical visualization system that projects male and female gross anatomical structures from human cadavers onto a life-sized touchscreen table. A crossover design was implemented. Four volunteer dissection groups, consisting of four students each, were randomly assigned to dissect P/P on the Anatomage table and MSK (upper and lower limb) not on the cadaver lab or vice versa. Participating students completed surveys before and after each lab, formative quizzes following each lab, and summative final practical exams on both the Anatomage table and in the cadaver lab. Results indicated that when studying on the Anatomage table, students were more excited before and after labs and perceived a greater degree of learning. The groups did not demonstrate a significant difference in P/P knowledge based on quiz results; however, the Anatomage group had a significantly higher mean score on quizzes in MSK anatomy. Finally, the practical exam results suggest that for some anatomical regions, students may perform similarly regardless of the modality on which they were instructed.

Learning to balance efficiency and innovation for optimal adaptive expertise.

It is critical for health professionals to continue to learn and this must be supported by health professions education (HPE). Adaptive expert clinicians are not only expert in their work but have the additional capacity to learn and improve in their practices. The authors review a selective aspect of learning to become an adaptive expert: the capacity to optimally balance routine approaches that maximize efficiency with innovative ones where energy and resources are used to customize actions for novel or difficult situations. Optimal transfer of learning, and hence the design of instruction, differs depending on whether the goal is efficient or innovative practice. However, the task is necessarily further complicated when the aspiration is an adaptive expert practitioner who can fluidly balance innovation with efficiency as the situation requires. Using HPE examples at both the individual and organizational level, the authors explore the instructional implications of learning to shift from efficient to innovative expert functioning, and back. They argue that the efficiency-innovation tension is likely to endure deep into the future and therefore warrants important consideration in HPE.

Motor and non-motor features of Parkinson's disease in LRRK2 G2019S carriers versus matched controls.

INTRODUCTION: LRRK2 G2019S mutation carriers with Parkinson's disease (PD) have been generally indistinguishable from those with idiopathic PD, with the exception of variable differences in some motor and non-motor domains, including cognition, gait, and balance. LRRK2 G2019S is amongst the most common genetic etiologies for PD, particularly in Ashkenazi Jewish (AJ) populations. METHODS: This cross-sectional data collection study sought to clarify the phenotype of LRRK2 G2019S mutation carriers with PD. Primary endpoints were the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA). Other motor and non-motor data were also assessed. The Mann-Whitney U Test was utilized to compare LRRK2 G2019S carriers with PD (LRRK2+) with non-carrier PD controls who were matched for age, gender, education, and PD duration. Survival analyses and log rank tests were utilized to compare interval from onset of PD to development of motor and non-motor complications. RESULTS: We screened 251 subjects and 231 completed the study, of whom 9 were LRRK2+, including 7 AJ subjects. 22.73% of AJ subjects with a family history of PD (FH) and 12.96% of AJ subjects without a FH were LRRK2+. There were no significant differences between the 9 LRRK2+ subjects and 19 matched PD controls in MDS-UPDRS, MoCA, or other motor and non-motor endpoints. CONCLUSION: Prevalence of the LRRK2 G2019S mutation in AJ and non-AJ subjects in our study population in Cleveland, Ohio was comparable to other clinical studies. There were no significant motor or non-motor differences between LRRK2+ PD and matched PD controls.

Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, caused by the degeneration of the dopaminergic neurons in the substantia nigra. Mutations in PARK7 (DJ-1) result in early onset autosomal recessive PD, and oxidative modification of DJ-1 has been reported to regulate the protective activity of DJ-1 in vitro. Glutathionylation is a prevalent redox modification of proteins resulting from the disulfide adduction of the glutathione moiety to a reactive cysteine-SH, and glutathionylation of specific proteins has been implicated in regulation of cell viability. Glutaredoxin 1 (Grx1) is the principal deglutathionylating enzyme within cells, and it has been reported to mediate protection of dopaminergic neurons in Caenorhabditis elegans; however many of the functional downstream targets of Grx1 in vivo remain unknown. Previously, DJ-1 protein content was shown to decrease concomitantly with diminution of Grx1 protein content in cell culture of model neurons (SH-SY5Y and Neuro-2A lines). In the current study we aimed to investigate the regulation of DJ-1 by Grx1 in vivo and characterize its glutathionylation in vitro. Here, with Grx(-/-) mice we provide show that Grx1 regulates protein levels of DJ-1 in vivo. Furthermore, with model neuronal cells (SH-SY5Y) we observed decreased DJ-1 protein content in response to treatment with known glutathionylating agents, and with isolated DJ-1 we identified two distinct sites of glutathionylation. Finally, we found that overexpression of DJ-1 in the dopaminergic neurons partly compensates for the loss of the Grx1 homologue in a C. elegans in vivo model of PD. Therefore, our results reveal a novel redox modification of DJ-1 and suggest a novel regulatory mechanism for DJ-1 content in vivo.

The roles of redox enzymes in Parkinson's disease: Focus on glutaredoxin.

Parkinson's disease (PD) results from the loss of dopaminergic neurons in the substantia nigra portion of the midbrain, and represents the second most common neurodegenerative disease in the world. Although the etiology of PD is currently unclear, oxidative stress and redox dysfunction are generally understood to play key roles in PD pathogenesis and progression. Aging and environmental factors predispose cells to adverse effects of redox changes. In addition to these factors, genetic mutations linked to PD have been observed to disrupt the redox balance. Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with autosomal dominant PD, and several of these mutations have also been shown to increase the levels of reactive oxygen species in cells. Anti-oxidant proteins are necessary to restore the redox balance and maintain cell viability. Over the past decade studies have started to demonstrate the critical importance for redox proteins mediating neuronal protection in models of PD. This commentary briefly describes some of the factors hypothesized to contribute to PD, specifically regarding the redox changes that occur in PD. Dysregulation of redox proteins in PD is highlighted by some of the work detailing the roles of peroxiredoxin-3 and thioredoxin-1 in models of PD. In an attempt to generate novel therapies for PD, several potent inhibitors of LRRK2 have been developed. The use of these compounds, both as tools to understand the biology of LRRK2 and as potential therapeutic strategies is also discussed. This mini-review then provides a historical prospective on the discovery and characterization of glutaredoxin (Grx1), and briefly describes current understanding of the role of Grx1 in PD. The review concludes by highlighting our recent publication describing the novel role for Grx1 in mediating dopaminergic neuronal protection both in vitro and in vivo.

Identifying Gaps in the Cultural Competence/Sensitivity Components of an Undergraduate Medical School Curriculum: A Needs Assessment.

Physicians and other health care workers are increasingly being called upon to bridge the cultural differences that may exist between themselves and their patients. Adequate cross-cultural education is essential if existing health care disparities are to be reduced. We conducted a needs assessment to identify gaps in the cultural competence/sensitivity components of the undergraduate medical school curriculum at Case Western Reserve University School of Medicine. The 2011 study was designed (1) to assess how first and second year medical school students perceive the adequacy of the medical school curriculum with respect to issues of diversity and (2) the extent to which first and second year medical students believe that an understanding of issues relating to patient culture are important to the provision of effective patient care. Student perspectives were assessed through a web-based anonymous survey of all first year (n = 167) and all second year (n = 166) medical school students, two focus groups (total n = 14) and a Problem-based Case Inquiry Group exercise (n = 6), both with second year students. A substantial proportion of participating first and second year medical students do not believe that self-reflection regarding one's own cultural biases is important to one's performance as a physician, do not view an understanding of diverse patient cultural beliefs as important or very important in the provision of effective patient care, and are uncomfortable with and unsure about how to approach culture-related issues arising in patient care. The inclusion of specified elements--increased contact with diverse patients, more comprehensive resources, increased opportunities to practice communication skills and engage in self-reflection--may be critical to heighten student awareness of and comfort in interacting with diverse populations. Our findings are relevant to the development of medical school curricula designed to improve physician understanding of and responsiveness to diverse patient populations and efforts to reduce health disparities.

Glutaredoxin deficiency exacerbates neurodegeneration in C. elegans models of Parkinson's disease.

Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic neurons. Although the etiology of PD remains incompletely understood, oxidative stress has been implicated as an important contributor in the development of PD. Oxidative stress can lead to oxidation and functional perturbation of proteins critical to neuronal survival. Glutaredoxin 1 (Grx1) is an evolutionally conserved antioxidant enzyme that repairs protein oxidation by reversing the oxidative modification of cysteine known as S-glutathionylation. We aimed to explore the regulatory role of Grx1 in PD. We first examined the levels of Grx1 in postmortem midbrain samples from PD patients, and observed that Grx1 content is decreased in PD, specifically within the dopaminergic neurons. We subsequently investigated the potential role of Grx1 deficiency in PD pathogenesis by examining the consequences of loss of the Caenorhabditis elegans Grx1 homolog in well-established worm models of familial PD caused by overexpression of pathogenic human LRRK2 mutants G2019S or R1441C. We found that loss of the Grx1 homolog led to significant exacerbation of the neurodegenerative phenotype in C. elegans overexpressing the human LRRK2 mutants. Re-expression in the dopaminergic neurons of the active, but not a catalytically inactive form of the Grx1 homolog rescued the exacerbated phenotype. Loss of the Grx1 homolog also exacerbated the neurodegenerative phenotype in other C. elegans models, including overexpression of human α-synuclein and overexpression of tyrosine hydroxylase (a model of sporadic PD). Therefore, our results reveal a novel neuroprotective role of glutaredoxin against dopaminergic neurodegeneration in models of familial and sporadic PD.

Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent known cause of late-onset Parkinson's disease (PD). To explore the therapeutic potential of small molecules targeting the LRRK2 kinase domain, we characterized two LRRK2 kinase inhibitors, TTT-3002 and LRRK2-IN1, for their effects against LRRK2 activity in vitro and in Caenorhabditis elegans models of LRRK2-linked neurodegeneration. TTT-3002 and LRRK2-IN1 potently inhibited in vitro kinase activity of LRRK2 wild-type and mutant proteins, attenuated phosphorylation of cellular LRRK2 and rescued neurotoxicity of mutant LRRK2 in transfected cells. To establish whether LRRK2 kinase inhibitors can mitigate pathogenesis caused by different mutations including G2019S and R1441C located within and outside of the LRRK2 kinase domain, respectively, we evaluated effects of TTT-3002 and LRRK2-IN1 against R1441C- and G2019S-induced neurodegeneration in C. elegans models. TTT-3002 and LRRK2-IN1 rescued the behavioral deficit characteristic of dopaminergic impairment in transgenic C. elegans expressing human R1441C- and G2019S-LRRK2. The inhibitors displayed nanomolar to low micromolar rescue potency when administered either pre-symptomatically or post-symptomatically, indicating both prevention and reversal of the dopaminergic deficit. The same treatments also led to long-lasting prevention and rescue of neurodegeneration. In contrast, TTT-3002 and LRRK2-IN1 were ineffective against the neurodegenerative phenotype in transgenic worms carrying the inhibitor-resistant A2016T mutation of LRRK2, suggesting that they elicit neuroprotective effects in vivo by targeting LRRK2 specifically. Our findings indicate that the LRRK2 kinase activity is critical for neurodegeneration caused by R1441C and G2019S mutations, suggesting that kinase inhibition of LRRK2 may represent a promising therapeutic strategy for PD.

Dysregulation of glutathione homeostasis in neurodegenerative diseases.

Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, and Friedreich's ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated.