Changing the Clock in Medical Education: Addressing Physician Shortages and Patient Outcomes.

Despite the shortage of physicians in the United States, there is no consensus among medical educators as to how to address the nation's unmet needs. A growing but unfulfilled argument is to revisit the configuration of medical education and the time required to complete medical training. Pilot programs, such as shortened programs or advancement-in-place structures to accelerate the practice capability of trainees, have been attempted. This manuscript addresses underlying economic and human considerations that medical educators must reconcile, drawing on lessons from international educational structures, as we advance toward a system that supports the needs of the communities that our graduates will serve.

Three-dimensional modeling in anatomy-Tool or terror?

Three-dimensional (3D) modeling is a recent, innovative approach to teaching anatomy. There is little literature, however, to suggest how 3D modeling is best used to teach students and whether or not students can gain the same level of understanding as they might use more traditional, hands-on, teaching methods. This study evaluated the use of a 3D modeling software in both a flipped classroom curriculum and as an active learning tool in comparison to traditional, physical model-based teaching. Pre- and post-course content-based assessments were used to evaluate students' learning. Our findings indicated no significant difference between standard and flipped classroom learning; however, the students who used 3D modeling software as an active learning tool significantly underperformed students in the standard group (F(2,1060) = 112.43, p < 0.0001). These findings suggest that these technologies may not yet be useful as a primary means of instruction. Possible explanations may include cognitive overload in navigating the system, intrinsic limitations of the software, or other factors. Further development and research of these technologies is necessary prior to their adoption into teaching practices in anatomy.

Outcomes of the Internal Medicine Supplemental Application: Preliminary Data on the 2022-2023 Match.

INTRODUCTION: Preference signaling (program signals and geographic preference divisions) was introduced as a component of the supplemental application for internal medicine applicants applying to programs within the United States (USA) during the 2021-22 cycle. These signals were intended to address application inflation by allowing applicants to express interest in and increase their likelihood of receiving interviews from their top programs. There is little published data, however, to describe the impact of preference signaling on the likelihood of receiving interviews from a program. This study thus sought to analyze, in a small subset of US applicants, whether preference signals were associated with a higher likelihood of obtaining a residency interview. METHODS: A survey was distributed in March 2023 to US MD seniors from the four allopathic medical schools in North Carolina who applied to categorical internal medicine residency programs during the 2022-23 application cycle. The survey was developed by the research team to provide respondents with the opportunity to report data from the electronic residency application service (ERAS) application and provide data on interviews received, actions taken throughout the application season, and outcomes of the National Residency Match Program (NRMP) using a combination of free response and multiple choice questions. RESULTS: Forty-seven out of a total of 85 contacted (55%) applicants completed some or all of the survey. Of those who completed the entirety of the survey, 39 (82.98%) completed the supplemental portion of the application and the available preference signaling. Applicants in this study were 2.95 (Odds ratio, 95% confidence interval [CI] 2.20 - 3.97, p<0.01) times as likely to receive an interview invitation from a program if they used a program signal. Applicants were 1.75 (odds ratio, 95% CI 1.38 - 2.21, p<0.01) times as likely to receive an interview invitation from a program in an indicated geographic preference division. Forty-seven percent (95% CI 31 - 64%) matched to a program they had sent a program signal to, and 97% (95% CI 78 - 100%) matched to a program in an indicated geographic preference division. CONCLUSIONS: The program signals and geographic preference division components of the supplemental application increased the likelihood of receiving an interview invitation but did not have a clear impact on match outcomes. Further research with larger sample sizes will be necessary to determine how these signals actually modify the outcomes of the NRMP.

Multisystem Inflammatory Syndrome in Children: Two Years' Worth of Learning.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening sequela of SARS-CoV-2 infection. Limited data are available regarding risk-stratification or long-term outcomes in MIS-C. This study sought to determine associations between serologic markers and severity of illness and understand long-term cardiac outcomes. This series includes 46 cases (mean age 8.1 years; 63.0% male) of MIS-C. Pearson's chi-squared analysis showed an erythrocyte sedimentation rate (ESR) greater than 30 mm/h and 50 mm/h were disproportionately associated with pediatric intensive care unit (PICU) admission (χ2 = 4.44, P = .04) and use of vasopressors (χ2 = 6.06, P = .01), respectively. Ferritin less than 175.6 ng/mL was associated with use of vasopressors (χ2 = 5.28, P = .02). There was a negative correlation between ESR and ejection fraction (EF) (r = -0.39, P = .009). Most patients with abnormal echocardiograms had resolution of abnormalities within 30 days. Therefore, inflammatory markers may be helpful in predicting which patients may require specific interventions or experience cardiac dysfunction, but MIS-C does not appear to be associated with complications at 1 year.

Twelve Tips for using Learning Curves in Health Professions Education Research.

Learning curves can be used to design, implement, and evaluate educational interventions. Attention to key aspects of the method can improve the fidelity of this representation of learning as well as its suitability for education and research purposes. This paper addresses when to use a learning curve, which graphical properties to consider, how to use learning curves quantitatively, and how to use observed thresholds to communicate meaning. We also address the associated ethics and policy considerations. We conclude with a best practices checklist for both educators and researchers seeking to use learning curves in their work.

Multivariate Modeling of Student Performance on NBME Subject Exams.

Aim This study sought to determine whether it was possible to develop statistical models which could be used to accurately correlate student performance on clinical subject exams based on their National Board of Medical Examiner (NBME) self-assessment performance and other variables, described below, as such tools are not currently available.  Methods Students at a large public medical school were provided fee vouchers for NBME self-assessments before clinical subject exams. Multivariate regression models were then developed based on how self-assessment performance correlated to student success on the subsequent subject exam (Medicine, Surgery, Family Medicine, Obstetrics-Gynecology, Pediatrics, and Psychiatry) while controlling for the proximity of the self-assessment to the exam, USMLE Step 1 score, and the academic quarter. Results The variables analyzed satisfied the requirements of linear regression. The correlation strength of individual variables and overall models varied by discipline and outcome (equated percent correct or percentile, Model R2 Range: 0.1799-0.4915). All models showed statistical significance on the Omnibus F-test (p<0.001). Conclusion The correlation coefficients demonstrate that these models have weak to moderate predictive value, dependent on the clinical subject, in predicting student performance; however, this varies widely based on the subject exam in question. The next step is to utilize these models to identify struggling students to determine if their use reduces failure rates and to further improve model accuracy by controlling for additional variables.

Reflections on Part-Time Residency Training, 15-25 Years Later: A Qualitative Study on Wellness and Career Impact.

Phenomenon: While part-time clinical work options are popular for physicians, part-time residency training is uncommon. Some residency training programs have offered trainees the option to complete their training on a modified schedule in the past. These part-time tracks often involved extending training in order to complete equivalent hours on a part-time basis. Having experience with trainees in such programs, we sought to explore the impact of completing residency training part-time on the professional and private lives of physicians. Approach: Between 2019 and 2020, we conducted interviews with physicians who completed portions of their residency training part-time between 1995 and 2005 in our institution's pediatrics, combined medicine-pediatrics, and family medicine programs. Findings: Seven female physicians who completed at least some portion of residency part-time were interviewed. To better characterize their experiences, we chose phenomenology as our analytic framework. Members of the research team independently coded each interview and met to resolve conflicts. Codes were then combined and discussed to determine four overarching themes as reasons and benefits of part-time training: The pursuit of extended-time training, logistics, effects on career trajectory, and wellness. These themes highlighted the utility of part-time training and the need for programmatic support to ensure their success. Insights: Based on our findings, adaptability for training and a sense of agency from their part-time experiences persisted throughout interviewees' careers. Each felt empowered to make career choices that fit their personal and professional needs. These findings suggest further investigation into the benefits of offering time-variable training in residency programs.

What Makes a Near-Peer Learning and Tutoring Program Effective in Undergraduate Medical Education: a Qualitative Analysis.

Peer tutoring can benefit both learners and peer teachers that are distinct from the learning that occurs in expert-guided learning environments. This study sought to evaluate the peer tutoring program at a large public medical school to determine the strengths and weaknesses of a near-peer tutoring program and its benefits beyond students' typical classroom-based learning. This was a survey-based study of learners and tutors participating in the peer tutoring program. Fifty-six learners and 20 tutors participated in the survey; most learners received tutoring in the preclinical phase of the curriculum. Narrative responses were thematically analyzed to identify themes for both groups. Learners' responses about the benefit of the near-peer tutoring program were in three primary categories: creating a safe learning environment, direct coaching skills, and pitfalls around the need for individualized direction. Tutors' responses about what made a successful tutoring relationship centered around crucial activities used to engage with learners, beneficial intrinsic qualities of learners such as motivation, and qualifications of tutors that were most helpful such as knowledge base. Peer tutoring programs should emphasize individualized feedback for learners that focuses on metacognitive, content-based, and socio-emotional support. In doing so, such programs can provide a well-structured approach to improve learner success. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01680-0.

A 5-year-old with new-onset diabetes presenting with ketoacidosis, acute pancreatitis, and renal failure.

A 5-year-old girl presented to the emergency room with altered mental status secondary to severe diabetic ketoacidosis due to new-onset GAD65 antibody positive, type 1 diabetes mellitus. On hospital day 0, she developed anuria, shock, and hypertriglyceridemia-associated acute pancreatitis. Following intravenous insulin therapy, the patient's ketoacidosis improved. Her other complications persisted for several days and improved only with significant fluid resuscitation and supportive interventions, including intubation, thoracostomy, and vasopressors. This case underscores the importance of recognizing the early warning signs of diabetic ketoacidosis and reviews how to appropriately manage its associated life-threatening complications.

Ultrasound as a Learning Tool in Bachelor-Level Anatomy Education.

Point of care ultrasound (POCUS) has become an increasingly common diagnostic tool in the clinical environment. As a result, it is being used earlier for medical students in Undergraduate Medical Education (UME) as a learning tool for the basic sciences including gross anatomy. There is little literature, however, to support its utility for basic science education in students currently seeking a bachelor's degree. This study consisted of fourteen currently enrolled bachelor students with previous instruction in human anatomy and physiology. Students participated in an ultrasound didactic and an interactive ultrasound experience with volunteers. Before and after this session, students were asked to complete an assessment measuring their spatial understanding of the human anatomy and their ability to locate structures using ultrasound. Wilcoxon's signed-rank tests comparing assessment scores showed significant improvement on both portions of the assessment. Based on this improvement, we suggest that ultrasound is a valid educational tool which can be used at the bachelor-level to effectively enhance students' learning of anatomy and provide hands on experience with modern technology. Further research with larger samples will be necessary to determine whether it would supplement or replace more traditional teaching modalities.

Light-Activated Control of Translation by Enzymatic Covalent mRNA Labeling.

Activation of cellular protein expression upon visible-light photocleavage of small-molecule caging groups covalently attached to the 5' untranslated region (5' UTR) of an mRNA was achieved. These photocleavable caging groups are conjugated to in vitro transcribed mRNA (IVT-mRNA) through RNA transglycosylation, an enzymatic process in which a bacterial tRNA guanine transglycosylase (TGT) exchanges a guanine nucleobase in a specific 17-nucleotide motif (Tag) for synthetic pre-queuosine1 (preQ1 ) derivatives. The caging groups severely reduce mRNA translation efficiency when strategically placed in the 5' UTR. Using this method, we demonstrate the successful spatiotemporal photoregulation of gene expression with single-cell precision. Our method can be applied to therapeutically relevant chemically modified mRNA (mod-mRNA) transcripts. This strategy provides a modular and efficient approach for developing synthetic gene regulatory circuits, biotechnological applications, and therapeutic discovery.

Site-Specific Covalent Conjugation of Modified mRNA by tRNA Guanine Transglycosylase.

Modified mRNA (mod-mRNA) has recently been widely studied as the form of RNA useful for therapeutic applications due to its high stability and lowered immune response. Herein, we extend the scope of the recently established RNA-TAG (transglycosylation at guanosine) methodology, a novel approach for genetically encoded site-specific labeling of large mRNA transcripts, by employing mod-mRNA as substrate. As a proof of concept, we covalently attached a fluorescent probe to mCherry encoding mod-mRNA transcripts bearing 5-methylcytidine and/or pseudouridine substitutions with high labeling efficiencies. To provide a versatile labeling methodology with a wide range of possible applications, we employed a two-step strategy for functionalization of the mod-mRNA to highlight the therapeutic potential of this new methodology. We envision that this novel and facile labeling methodology of mod-RNA will have great potential in decorating both coding and noncoding therapeutic RNAs with a variety of diagnostic and functional moieties.

Fluorescent turn-on probes for wash-free mRNA imaging via covalent site-specific enzymatic labeling.

Investigating the many roles RNA plays in cellular regulation and function has increased demand for tools to explore RNA tracking and localization within cells. Our recently reported RNA-TAG (transglycosylation at guanine) approach uses an RNA-modifying enzyme, tRNA-guanine transglycosylase (TGT), to accomplish covalent labeling of an RNA of interest with fluorescent tracking agents in a highly selective and efficient manner. Unfortunately, labeling by this method currently suffers from a high nonspecific fluorescent background and is currently unsuitable for imaging RNA within complex cellular environments. Herein we report the design and synthesis of novel fluorogenic thiazole orange probes that significantly lower nonspecific binding and background fluorescence and, as a result, provide up to a 100-fold fluorescence intensity increase after labeling. Using these fluorogenic labeling agents, we were able to image mRNA expressed in Chinese Hamster Ovary cells in a wash-free manner.

Developing a Fluorescent Toolbox To Shed Light on the Mysteries of RNA.

Technologies that detect and image RNA have illuminated the complex roles played by RNA, redefining the traditional and superficial role first outlined by the central dogma of biology. Because there is such a wide diversity of RNA structure arising from an assortment of functions within biology, a toolbox of approaches have emerged for investigation of this important class of biomolecules. These methods are necessary to detect and elucidate the localization and dynamics of specific RNAs and in doing so unlock our understanding of how RNA dysregulation leads to disease. Current methods for detecting and imaging RNA include in situ hybridization techniques, fluorescent aptamers, RNA binding proteins fused to fluorescent reporters, and covalent labeling strategies. Because of the inherent diversity of these methods, each approach comes with a set of strengths and limitations that leave room for future improvement. This perspective seeks to highlight the most recent advances and remaining challenges for the wide-ranging toolbox of technologies that illuminate RNA's contribution to cellular complexity.

A Bioorthogonal Near-Infrared Fluorogenic Probe for mRNA Detection.

There is significant interest in developing methods that visualize and detect RNA. Bioorthogonal template-driven tetrazine ligations could be a powerful route to visualizing nucleic acids in native cells, yet past work has been limited with respect to the diversity of fluorogens that can be activated via a tetrazine reaction. Herein we report a novel bioorthogonal tetrazine uncaging reaction that harnesses tetrazine reactivity to unmask vinyl ether caged fluorophores spanning the visible spectrum, including a near-infrared (NIR)-emitting cyanine dye. Vinyl ether caged fluorophores and tetrazine partners are conjugated to high-affinity antisense nucleic acid probes, which show highly selective fluorogenic reactivity when annealed to their respective target RNA sequences. A target sequence in the 3' untranslated region of an expressed mRNA was detected in live cells employing appropriate nucleic acid probes bearing a tetrazine-reactive NIR fluorogen. Given the expansion of tetrazine fluorogenic chemistry to NIR dyes, we believe highly selective proximity-induced fluorogenic tetrazine reactions could find broad uses in illuminating endogenous biomolecules in cells and tissues.

Site-Specific Covalent Labeling of RNA by Enzymatic Transglycosylation.

We demonstrate the site-specific incorporation of nucleobase derivatives bearing fluorophores or affinity labels into a short RNA stem loop recognition motif by exchange of a guanine residue. The RNA-TAG (transglycosylation at guanosine) is carried out by a bacterial (E. coli) tRNA guanine transglycosylase (TGT), whose natural substrate is the nitrogenous base PreQ1. Remarkably, we have successfully incorporated large functional groups including biotin, BODIPY, thiazole orange, and Cy7 through a polyethylene glycol linker attached to the exocyclic amine of PreQ1. Larger RNAs, such as mRNA transcripts, can be site-specifically labeled if they possess the 17-nucleotide hairpin recognition motif. The RNA-TAG methodology could facilitate the detection and manipulation of RNA molecules by enabling the direct incorporation of functional artificial nucleobases using a simple hairpin recognition element.

Electrochemical Control of Rapid Bioorthogonal Tetrazine Ligations for Selective Functionalization of Microelectrodes.

We demonstrate that bioorthogonal tetrazine ligations can be utilized to rapidly modify electrode surfaces, both with redox probes and enzymes. Furthermore, we show that the redox-active nature of 1,2,4,5-tetrazines can be exploited to gain electrochemical control over surface modification. To our knowledge this is the first demonstration of controlling a tetrazine ligation by changing the redox state of one of the reactants. We utilize the redox-switchable feature of tetrazine ligations for the site-selective functionalization of a 10 µm spaced interdigitated array of microelectrodes. In addition, we were able to achieve potential controlled ligation of the redox enzyme horseradish peroxidase to a macroscopic planar electrode. The rapid kinetics, bioorthogonal reactivity, and electrochemical control provided by tetrazine ligations should lead to numerous applications related to electrode functionalization.

Interactions of AsCy3 with cysteine-rich peptides.

There is great interest in fluorogenic compounds that tag biomolecules within cells. Biarsenicals are fluorogenic compounds that become fluorescent upon binding four proximal Cys thiols, a tetracysteine (Cys(4)) motif. This work details interactions between the biarsenical AsCy3 and Cys(4) peptides. Maximal affinity was observed when two Cys-Cys pairs were separated by at least 8 amino acids; the highest affinity ligand bound in the nanomolar concentration range (K(app) = 43 nM) and with a significant (3.2-fold) fluorescence enhancement.