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.

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.

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.

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.

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.

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.

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.

LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1.

The leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of autosomal-dominant Parkinson disease (PD). Mitochondrial dysfunction represents a critical event in the pathogenesis of PD. We demonstrated that wild-type (WT) LRRK2 expression caused mitochondrial fragmentation along with increased mitochondrial dynamin-like protein (DLP1, also known as DRP1), a fission protein, which was further exacerbated by expression of PD-associated mutants (R1441C or G2019S) in both SH-SY5Y and differentiated primary cortical neurons. We also found that LRRK2 interacted with DLP1, and LRRK2-DLP1 interaction was enhanced by PD-associated mutations that probably results in increased mitochondrial DLP1 levels. Co-expression of dominant-negative DLP1 K38A or WT Mfn2 blocked LRRK2-induced mitochondrial fragmentation, mitochondrial dysfunction and neuronal toxicity. Importantly, mitochondrial fragmentation and dysfunction were not observed in cells expressing either GTP-binding deficient mutant LRRK2 K1347A or kinase-dead mutant D1994A which has minimal interaction with DLP1 and did not increase the mitochondrial DLP1 level. We concluded that LRRK2 regulates mitochondrial dynamics by increasing mitochondrial DLP1 through its direct interaction with DLP1, and LRRK2 kinase activity plays a critical role in this process.

Does using artificial intelligence assistance accelerate skill decay and hinder skill development without performers' awareness?

Artificial intelligence in the workplace is becoming increasingly common. These tools are sometimes used to aid users in performing their task, for example, when an artificial intelligence tool assists a radiologist in their search for abnormalities in radiographic images. The use of artificial intelligence brings a wealth of benefits, such as increasing the efficiency and efficacy of performance. However, little research has been conducted to determine how the use of artificial intelligence assistants might affect the user's cognitive skills. In this theoretical perspective, we discuss how artificial intelligence assistants might accelerate skill decay among experts and hinder skill acquisition among learners. Further, we discuss how AI assistants might also prevent experts and learners from recognizing these deleterious effects. We then discuss the types of questions: use-inspired basic cognitive researchers, applied researchers, and computer science researchers should seek to answer. We conclude that multidisciplinary research from use-inspired basic cognitive research, domain-specific applied research, and technical research (e.g., human factors research, computer science research) is needed to (a) understand these potential consequences, (b) design artificial intelligence systems to mitigate these impacts, and (c) develop training and use protocols to prevent negative impacts on users' cognitive skills. Only by answering these questions from multidisciplinary perspectives can we harness the benefits of artificial intelligence in the workplace while preventing negative impacts on users' cognitive skills.

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.

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.

"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.

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.

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.

LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease.

Mutations in LRRK2 are thus far the most frequent known cause of autosomal dominant and idiopathic Parkinson's disease (PD) with prevalent mutations being found within the GTPase (R1441C/G) and kinase (G2019S) domains. Previous in vitro studies have revealed that R1441C and G2019S mutations are associated with increased kinase activity. To better understand LRRK2-linked PD pathogenesis in vivo, we have generated transgenic C. elegans overexpressing human LRRK2 wild type, R1441C and G2019S in dopaminergic (DA) neurons. Overexpression of these LRRK2 proteins causes age-dependent DA neurodegeneration, behavioral deficits, and locomotor dysfunction that are accompanied by a reduction of dopamine levels in vivo. In comparison, R1441C and G2019S mutants cause more severe phenotypes than the wild type protein. Interestingly, treatment with exogenous dopamine rescues the LRRK2-induced behavioral and locomotor phenotypes. In contrast, expression of the GTP binding defective mutant, K1347A, or knockout of the C. elegans LRRK2 homolog, LRK-1, prevents the LRRK2-induced neurodegeneration and behavioral abnormalities. Hence, our transgenic LRRK2 C. elegans models recapitulate key features of PD including progressive neurodegeneration, impairment of dopamine-dependent behavior and locomotor function, and reduction in dopamine levels. Furthermore, our findings provide strong support for the critical role of GTPase/kinase activity in LRRK2-linked pathologies. These invertebrate models will be useful for studying pathogenesis of PD and for development of potential therapeutics for the disease.

Leucine-rich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have recently been linked to autosomal dominant, late-onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multidomain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease-associated mutations are found throughout the multidomain structure of the protein. LRRK2, however, is unique among the PD-causing genes, because a missense mutation, G2019S, is a frequent determinant of not only familial but also sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. In this Mini-Review, we look at the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2.

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.

The Roc domain of leucine-rich repeat kinase 2 is sufficient for interaction with microtubules.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the leading cause of genetically inherited Parkinson's disease (PD). Although this multidomain protein has been shown to have both GTPase and kinase activities through the Roc and MAPKKK domains, respectively, the protein-protein interactions and pathways involved in LRRK2-mediated signaling remain elusive. Utilizing a combination of protein pull-down assays, mass spectrometry, Western blotting, and immunofluorescence microscopy, this study identifies and describes the interaction between LRRK2 and microtubules. The Roc or GTPase-like domain of LRRK2 is sufficient for interaction with alpha/beta-tubulin heterodimers. This interaction occurs in a guanine nucleotide-independent manner, suggesting that tubulin might not be an effector of the LRRK2 GTPase domain. The R1441C pathogenic mutation, located within the Roc domain, retains interaction with alpha/beta-tubulin heterodimers, suggesting that disruption of this interaction likely is not the mechanism whereby the R1441C mutation leads to disease. At a subcellular level, endogenous LRRK2 protein was found to colocalize with alpha/beta-tubulin in primary hippocampal neurons. These findings are significant in that they link LRRK2 with microtubules, a structural component of the cell that is critically involved in the pathogenesis of several neurodegenerative diseases, including PD.

Population medicine in a curricular revision at Case Western Reserve.

Inclusion of population medicine in a medical school curriculum has received growing attention. Recently, the Association of American Medical Colleges has highlighted this issue through support of the Regional Medicine and Public Health Education Centers initiative. The Case Western Reserve University School of Medicine joined this consortium while implementing a new curriculum in which population medicine would be an underlying theme woven with the classic science elements of disease. The organization for the first two years of the new curriculum, which was implemented in 2006, is a six-block structure during which the basic sciences are learned with key concepts of population medicine woven throughout. The focus for this article is Block One, in which population medicine is the major emphasis of the introduction to medicine. The first week, students learn social determinants, impact on communities, and social aspects of diabetes mellitus, even before addressing a patient's clinical presentation. Emphasis on student-centered learning is undertaken as part of the new curriculum, using a series of weekly, case-based, small-group sessions. This type of group learning is used throughout Block One as students encounter key components of population medicine. A thesis requirement was also introduced as a mechanism to emphasize research with opportunities for research in population medicine as well as other medical sciences. A variety of mechanisms are described to measure the outcomes of Block One.