The Impact of Changing Step 1 to Pass/Fail Reporting on Anxiety, Learning Approaches, and Curiosity.

Purpose: Given the significance of the US Medical Licensing Exam (USMLE) Step 1 score moving from a 3-digit value to pass/fail, the authors investigated the impact of the change on students' anxiety, approach to learning, and curiosity. Method: Two cohorts of pre-clerkship medical students at three medical schools completed a composite of four instruments: the State-Trait Anxiety Inventory, the revised two-factor Study Process Questionnaire, the Interest/Deprivation Type Epistemic Curiosity Scale, and the Short Grit Scale prior to taking the last 3-digit scored Step 1 in 2021 or taking the first pass/fail scored Step 1 in 2022. Responses of 3-digit and pass/fail exam takers were compared (Mann-Whitney U) and multiple regression path analysis was performed to determine the factors that significantly impacted learning strategies. Results: There was no difference between 3-digit (n = 86) and pass/fail exam takers (n = 154) in anxiety (STA-I scores, 50 vs. 49, p = 0.85), shallow learning strategies (22 vs. 23, p = 0.84), or interest curiosity scores (median scores 15 vs. 15, p = 0.07). However, pass/fail exam takers had lower deprivation curiosity scores (median 12 vs. 11, p = 0.03) and showed a decline in deep learning strategies (30 vs. 27, p = 0.0012). Path analysis indicated the decline in deep learning strategies was due to the change in exam scoring (ß = - 2.0428, p < 0.05). Conclusions: Counter to the stated hypothesis and intentions, the initial impact of the change to pass/fail grading for USMLE Step 1 failed to reduce learner anxiety, and reduced curiosity and deep learning strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01878-w.

An integrated pre-clerkship curriculum to build cognitive medical schema: It's not just about the content.

Both physiology and pathophysiology are essential disciplines in health professional education however, clinicians do not use this knowledge in isolation. Instead, physicians use inter-disciplinary concepts embedded within integrated cognitive schema (illness scripts) established through experience/knowledge that manifest as expert-level thinking. Our goal was to develop a pre-clerkship curriculum devoid of disciplinary boundaries (akin to the physician's illness script) and enhance learners' clerkship and early clinical performance. As well as developing curricular content, the model considered non-content design elements such as learner characteristics and values, faculty and resources and the impact of curricular and pedagogical changes. The goals of the trans-disciplinary integration were to develop deep learning behaviors through, 1) developing of integrated, cognitive schema to support the transition to expert-level thinking, 2) authentic, contextualization to promote knowledge transfer to the clinical realm 3) allowing autonomous, independent learning, and 4) harnessing the benefits of social learning. The final curricular model was a case-based approach with independent learning of basic concepts, differential diagnosis and illness scripting writing, and concept mapping. Small-group classroom sessions were team-taught with basic scientists and physicians facilitating learners' self-reflection and development of clinical reasoning. Specifications grading was used to assess the products (written illness scripts and concept maps) as well as process (group dynamics) while allowing a greater degree of learner autonomy. Although the model we adopted could be transferred to other program settings, we suggest it is critical to consider both content and non-content elements that are specific to the environment and learner.

A Simple and Sustainable Exercise to Enhance Student Self-Reflection on Error-Making, Focus Support, and Guide Curricular Design.

Problem: Self-reflection is a critical component of professional development and clinical practice, but medical students' ability to self-reflect is typically limited. While inadequate self-reflection impacts future clinical decision-making, it may also adversely impact current learning through an inability to identify learning-behavior deficits. This may be exacerbated by common use of multiple-choice questions (MCQ) where incorrect responses provide less insight than other measures for students, faculty, or academic support. To address this, an Error Reflection Method (ERM) was developed to help students focus on 'why' they got an MCQ wrong rather than 'what' they got wrong, thereby promoting self-reflection and a learning-focus on assessment. Understanding students' learning-behavior deficits could also enrich engagement with academic support services and guide curricular design. Intervention: The ERM is a list of 10 common types of exam errors that were either 'test-taking' (unwitting) errors or 'learning-behavior' errors that reflected learning deficits. The ERM is simple, transferable, and sustainable, allowing longitudinal and regular monitoring of individual and collective error-making to focus support and guide curricular development. Context: Undergraduate medical students at the Virginia Tech Carilion School of Medicine, USA, used the ERM in formative assessment review sessions in pre-clinical years to select an error type that best described the cause of each incorrect response. Impact: Initial findings suggest the ERM is robust and associated with improved student performance and curricular development. Analysis of 3,775 student-identified errors showed the error types in the ERM described 96% of errors students made. Learning-behavior errors were more common (76%), but surprisingly, 19% were test-taking errors, allowing academic support to focus on test-taking skills in a population previously thought of as consummate test-takers. The most common error type reported was 'the content looked familiar but I couldn't answer the question' (32%); which we suggest is consistent with shallow learning. This finding has helped steer recent curricular development toward active and applied learning techniques. Lessons Learned: By formally and regularly identifying learning deficits, students may be more capable of addressing them and improve summative exam performance. As well as focusing academic support, understanding common student errors has been useful in guiding curricular design and content delivery. Further potential of the ERM may be realized in faculty development and directing assessment culture toward a learning focus.

Considerations for Organizing Longitudinal Delivery of Pharmacology: the Impact of Content Delivery in Context.

At Virginia Tech Carilion School of Medicine, we implemented a new strategy to organize the longitudinal delivery of pharmacology, leveraging elements of spaced repetition and spiral design. Our innovative model focused on generating cognitive frameworks in large group sessions, providing a scaffold to associate key aspects of individual drugs using specific objectives in problem-based learning. The design enhanced both student satisfaction and summative performance on pharmacology content on end of Block National Board of Medical Examiners exams. By taking a new approach, we were able to focus student learning, reduce the extraneous load and retain rigor and content volume. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01461-1.

Changing Medical Education, Overnight: The Curricular Response to COVID-19 of Nine Medical Schools.

Issue: Calls to change medical education have been frequent, persistent, and generally limited to alterations in content or structural re-organization. Self-imposed barriers have prevented adoption of more radical pedagogical approaches, so recent predictions of the 'inevitability' of medical education transitioning to online delivery seemed unlikely. Then in March 2020 the COVID-19 pandemic forced medical schools to overcome established barriers overnight and make the most rapid curricular shift in medical education's history. We share the collated reports of nine medical schools and postulate how recent responses may influence future medical education. Evidence: While extraneous pandemic-related factors make it impossible to scientifically distinguish the impact of the curricular changes, some themes emerged. The rapid transition to online delivery was made possible by all schools having learning management systems and key electronic resources already blended into their curricula; we were closer to online delivery than anticipated. Student engagement with online delivery varied with different pedagogies used and the importance of social learning and interaction along with autonomy in learning were apparent. These are factors known to enhance online learning, and the student-centered modalities (e.g. problem-based learning) that included them appeared to be more engaging. Assumptions that the new online environment would be easily adopted and embraced by 'technophilic' students did not always hold true. Achieving true distance medical education will take longer than this 'overnight' response, but adhering to best practices for online education may open a new realm of possibilities. Implications: While this experience did not confirm that online medical education is really 'inevitable,' it revealed that it is possible. Thoughtfully blending more online components into a medical curriculum will allow us to take advantage of this environment's strengths such as efficiency and the ability to support asynchronous and autonomous learning that engage and foster intrinsic learning in our students. While maintaining aspects of social interaction, online learning could enhance pre-clinical medical education by allowing integration and collaboration among classes of medical students, other health professionals, and even between medical schools. What remains to be seen is whether COVID-19 provided the experience, vision and courage for medical education to change, or whether the old barriers will rise again when the pandemic is over.

Using Near-Peer Teaching to Address Concepts of Cystic Fibrosis in Undergraduate Medical Learners.

Introduction: Cystic fibrosis (CF) is a high-yield undergraduate medical education topic that lends itself to adaptability of content. We used a CF case paired with activities to deliver content in a near-peer teaching session. First-year (M1) and second-year (M2) medical students contributed acquired knowledge of protein structure and obstructive lung disease, respectively, to generate a concept map and address discussion questions. Methods: Combined groups of M1 and M2 students reviewed a CF case and a concept map prompt. For 30 minutes, they created a concept map describing connections between molecular biology and clinical manifestations. We summarized by reviewing concept maps and discussion questions. The efficacy of the session was determined by comparing exam performance of class attenders and nonattenders (M2) and performance on questions related and unrelated to the exercise (M1). We also determined students' perception of the session and incorporation of additional core competencies. Results: M2 students' performance was 3.8% higher (p = .296) and M1 students' performance was 1.8% higher (p = .286) than their respective controls. Students commented positively on the exercise and perceived more than one core competency as part of the session. Discussion: Although there was no significant improvement in exam performance, this curriculum used near-peer teaching to reinforce previously learned material and apply recently acquired material in an engaging format without detriment to either group. This method can be adapted to different learner groups and provides an opportunity to deliver and assess other core medical competencies.

An Interactive Process for Delivering Pharmacologic Interventions for Migraine Headache to First-Year Medical Students.

Introduction: This interactive didactic session is designed for first-year medical students to explore the common clinical symptom of headache and its various management strategies. The session provides an opportunity to cover a variety of drugs, mechanisms of action, drug-drug interactions, and routes of administration in a single 50-minute time frame. Methods: Using a modified case-based approach, we designed an interactive session for 41 first-year medical students. Students prepared for the session using basic learning objectives and a table of drugs that treat headache pain. In class, we distributed a patient scenario and a series of discussion questions to explore headache management. We assessed student performance using questions purchased from the National Board of Medical Examiners and student perceptions using both qualitative and quantitative data collected from faculty and end-of-block evaluations. Results: Student performance on purchased questions related to content was significantly increased when compared to the national average (n = 5; 90.6% ± 6.0% vs. 82.6% ± 8.5%; p = .0052). Student perceptions of the overall quality of the faculty, content presentation, and material were positive (4.4 out of 5.0). Two themes emerged in the end-of-block evaluations: Students commented positively on the prereading materials, and students commented on the need to address underlying physiology associated with the discussed pharmacology. Discussion: This flexible activity can be delivered in a short time (50 minutes) by a single faculty member in a variety of curricular structures. Our data demonstrate strong student performance and suggest that incorporating additional content would enhance delivery.

Integrating Acid-Base and Metabolic Lab Panels Across Systems in an M1 Classroom Activity.

Introduction: It is important to deliver acid-base balance concepts in the context of multiple physiological systems and metabolic processes that influence acid-base homeostasis. This activity combines the interactions of the respiratory, gastrointestinal, and renal systems in conjunction with basic metabolism to generate an integrated activity for first-year medical students. Methods: We developed four concise case scenarios around various presentations of acid-base disturbance along with five sets of arterial blood gases (ABGs) and five different metabolic lab panels. M1 students were given class time to match the three different types of data in order to address how the underlying biochemistry and physiology of a scenario translated into ABG and metabolic laboratory values. Results: Although not statistically significant, the students' performance on acid-base questions was marginally higher than on standardized National Board of Medical Examiners questions on other topics covered in the same exam, and the improvement over national average scores on the same questions increased. Student evaluation of the activity was positive, with general appreciation of its application and integration of concepts. Discussion: The incorporation of this activity into the M1 year was positively received and enhanced integration of content related to acid-base balance. The activity is flexible and can be adapted to most any curricular structure, with the potential to include additional content depending on the level of the learner.

Cthrc1 lowers pulmonary collagen associated with bleomycin-induced fibrosis and protects lung function.

Idiopathic pulmonary fibrosis (IPF) involves collagen deposition that results in a progressive decline in lung function. This process involves activation of Smad2/3 by transforming growth factor (TGF)-ß and Wnt signaling pathways. Collagen Triple Helix Repeat-Containing-1 (Cthrc1) protein inhibits Smad2/3 activation. To test the hypothesis that Cthrc1 limits collagen deposition and the decline of lung function, Cthrc1 knockout (Cthrc1-/-) and wild-type mice (WT) received intratracheal injections of 2.5 U/kg bleomycin or saline. Lungs were harvested after 14 days and Bronchoalveolar lavage (BAL) TGF-ß, IL1-ß, hydroxyproline and lung compliance were assessed. TGF-ß was significantly higher in Cthrc1-/- compared to WT (53.45 ± 6.15 ng/mL vs. 34.48 ± 11.05) after saline injection. Bleomycin injection increased TGF-ß in both Cthrc1-/- (66.37 ± 8.54 ng/mL) and WT (63.64 ± 8.09 ng/mL). Hydroxyproline was significantly higher in Cthrc1-/- compared to WT after bleomycin-injection (2.676 ± 0.527 µg/mg vs. 1.889 ± 0.520, P = 0.028). Immunohistochemistry of Cthrc1-/- lung sections showed intracellular localization and activation of ß-catenin Y654 in areas of tissue remodeling that was not evident in WT Lung compliance was significantly reduced by bleomycin in Cthrc1-/- but there was no effect in WT animals. These data suggest Cthrc1 reduces fibrotic tissue formation in bleomycin-induced lung fibrosis and the effect is potent enough to limit the decline in lung function. We conclude that Cthrc1 plays a protective role, limiting collagen deposition and could form the basis of a novel therapy for pulmonary fibrosis.

Characterization of Pdgfrb-Cre transgenic mice reveals reduction of ROSA26 reporter activity in remodeling arteries.

With the intention to modulate gene expression in vascular mural cells of remodeling vessels, we generated and characterized transgenic mouse lines with Cre recombinase under the control of the platelet-derived growth factor receptor-ß promoter, referred to as Tg(Pdgfrb-Cre)(35Vli) . Transgenic mice were crossed with the Gt(ROSA)26Sor(tm1Sor) strain and examined for Cre activation by ß-galactosidase activity, which was compared with endogenous Pdgfrb expression. In addition, Pdgfrb-Cre mice were used to drive expression of a conditional myc-tagged Cthrc1 transgene. There was good overlap of ß-galactosidase activity with endogenous Pdgfrb immunoreactivity. However, dedifferentiation of vascular mural cells induced by carotid artery ligation revealed a dramatic discrepancy between ROSA26 reporter activity and Pdgfrb promoter driven Cre dependent myc-tagged Cthrc1 transgene expression. Our studies demonstrate the capability of the Pdgfrb-Cre mouse to drive conditional transgene expression as a result of prior Cre-mediated recombination in tissues known to express endogenous Pdgfrb. In addition, the study shows that ROSA26 promoter driven reporter mice are not suitable for lineage marking of smooth muscle in remodeling blood vessels.

Intracellular localization of Cthrc1 characterizes differentiated smooth muscle.

OBJECTIVE: We recently reported expression of collagen triple helix repeat containing-1 (Cthrc1) in injured arteries and proteolytic cleavage of Cthrc1 in smooth muscle cells in vitro. The present study characterizes Cthrc1 processing and determines its biological significance. METHODS AND RESULTS: Domain-specific antibodies localized full-length Cthrc1 in the cytoplasm of vascular, gastrointestinal, and uterine smooth muscle as well as in some neurons. Unlike smooth muscle alpha-actin, Cthrc1 was not expressed in the embryonic myocardium. Intracellular localization of full-length Cthrc1 was sharply reduced in dedifferentiated smooth muscle of the developing neointima despite the previously shown increase in mRNA levels with accompanying extracellular Cthrc1 immunoreactivity. Immunoblotting suggested an apparent covalent association of monomeric full-length Cthrc1 with a cytoplasmic protein present in differentiated smooth muscle. Plasmin was identified as a protease that cleaved a putative propeptide generating an N-terminally truncated form of Cthrc1 with increased inhibitory activity of procollagen synthesis. CONCLUSIONS: Our data show that the differentiated smooth muscle cell phenotype is associated with the intracellular localization of noncleaved Cthrc1 despite the presence of a signal peptide. On arterial injury, increased Cthrc1 expression with apparent extracellular localization of N-terminally truncated Cthrc1 occurs. Removal of the propeptide correlated with increased activity of the molecule.

Arabidopsis thaliana squalene epoxidase 1 is essential for root and seed development.

Squalene epoxidase converts squalene into oxidosqualene, the precursor of all known angiosperm cyclic triterpenoids, which include membrane sterols, brassinosteroid phytohormones, and non-steroidal triterpenoids. In this work, we have identified six putative Arabidopsis squalene epoxidase (SQE) enzymes and used heterologous expression in yeast to demonstrate that three of these enzymes, SQE1, SQE2, and SQE3, can epoxidize squalene. We isolated and characterized Arabidopsis sqe1 mutants and discovered severe developmental defects, including reduced root and hypocotyl elongation. Adult sqe1-3 and sqe1-4 plants have diminished stature and produce inviable seeds. The sqe1-3 mutant accumulates squalene, consistent with a block in the triterpenoid biosynthetic pathway. Therefore, SQE1 function is necessary for normal plant development, and the five SQE-like genes remaining in this mutant are not fully redundant with SQE1.

Cthrc1 is a novel inhibitor of transforming growth factor-beta signaling and neointimal lesion formation.

We identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene expressed in the adventitia and neointima on arterial injury and found that it functionally increases cell migration while reducing collagen deposition. To address the in vivo role of Cthrc1, we generated transgenic mouse lines that constitutively overexpress Cthrc1. An intercross of 2 transgenic lines produced offspring with brittle bones caused by a reduction in collagenous bone matrix. Hemizygous Cthrc1 transgenic mice developed normally but neointimal lesion formation and adventitial collagen deposition in response to carotid artery ligation were significantly reduced compared with wild-type littermates. In 75% of Cthrc1 transgenic mice, cartilaginous metaplasia of medial smooth muscle cells was observed as assessed by Alcian blue staining and expression of the chondrocyte marker collagen type II. Transforming growth factor-beta signaling was reduced in smooth muscle cells of Cthrc1 transgenic arteries, as demonstrated by reduced phospho-Smad2/3 immunoreactivity, whereas Smad signaling related to bone morphogenetic proteins was unaffected. Similarly, primary smooth muscle cells and PAC1 smooth muscle cells overexpressing Cthrc1 had reduced levels of phospho-Smad2/3 as well as procollagen. Furthermore, Cthrc1 inhibited transforming growth factor-beta-sensitive reporter constructs in smooth muscle but not endothelial cells. These data indicate that Cthrc1 is a cell-type-specific inhibitor of transforming growth factor-beta, which in turn impacts collagen type I and III deposition, neointimal formation, and dedifferentiation of smooth muscle cells.

Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1).

We recently identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene induced in adventitial fibroblasts after arterial injury. Cthrc1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. Cthrc1 is also glycosylated and retains a signal sequence consistent with the presence of Cthrc1 in the extracellular space. In injured arteries and skin wounds, we have found Cthrc1 expression to be associated with myofibroblasts and sites of collagen matrix deposition. Furthermore, we demonstrated that Cthrc1 inhibits collagen matrix deposition in vitro. Using in situ hybridization and immunohistochemistry, we characterized the expression domains of Cthrc1 during murine embryonic development and in postnatal tissues. In mouse embryos, Cthrc1 was expressed in the visceral endoderm, notochord, neural tube, developing kidney, and heart. Abundant expression of Cthrc1 was observed in the developing skeleton, i.e., in cartilage primordia, in growth plate cartilage with exclusion of the hypertrophic zone, in the bone matrix and periostium. Bones from adults showed expression of Cthrc1 only in the bone matrix and periostium while the articular cartilage lacked expression. Cthrc1 is typically expressed at epithelial-mesenchymal interfaces that include the epidermis and dermis, basal corneal epithelium, airway epithelium, esophagus epithelium, choroid plexus epithelium, and meninges. In the adult kidney, collecting ducts and distal tubuli expressed Cthrc1. Collectively, the sites of Cthrc1 expression overlap considerably with those reported for TGF-beta family members and interstitial collagens. The present study provides useful information towards the understanding of potential Cthrc1 functions.