Financial Literacy Among Medical Trainees and Faculty: A Pilot Study.

INTRODUCTION: Medical education systems are trained to produce efficient, thorough clinicians. These programs provide limited training on personal finances. The current socioeconomic climate for medical trainees includes increasing education debt and stagnating reimbursement. We conducted a survey-based cross-sectional pilot study at an academic institution targeted at residents, fellows, and attendings of all medical specialties. Our aim was to understand baseline levels of financial literacy at different training and career stages, which can inform targeted interventions to improve this crucial aspect of physician well-being. METHODS: A survey was devised with the assistance of a certified financial planner. This survey was distributed at an academic institution targeting residents, fellows, and attendings. The survey was anonymous, and no identifying data were collected. Two reminders were sent to subjects to complete the survey. RESULTS: A total of 50 physicians completed the survey in 2021. There were eight responses from interns, 14 responses from residents (post-graduate year 2 or later), 14 responses from fellows, and nine responses from attendings. The majority of our respondents reported not having any particular financial education, and over 70% of respondents reported that their graduate education had not provided them with the tools needed for personal financial success. CONCLUSION: Financial education and financial literacy are important topics that need to be further incorporated into the medical education pathway. Physicians are not well equipped in this realm, and further training is necessary. This study provides pilot data that highlight important aspects of physician knowledge and practices in regard to finances.

Atmospheric Transport of Polycyclic Aromatic Hydrocarbons into Three Alpine Valleys: Influence of Local-Scale Wind Patterns and Chemical Partitioning.

Current understanding of atmospheric transport of polycyclic aromatic hydrocarbons (PAHs) is limited in alpine areas due to complex meteorology and topography. To better understand atmospheric transport in these areas, we measured 16 PAHs in lichens, biomonitors of atmospheric PAHs, along three transects extending from a highway into otherwise remote alpine valleys. While the valleys neighbored one another and were morphologically similar, they differed in their orientation relative to regional winds. In the valley characterized by regional winds oriented up-valley, PAH concentrations in lichens remained consistent across the transect. In the other two valleys, where regional winds were oriented down or across the valley, 3-6 ring PAHs declined rapidly with increasing distance from the highway, and PAH concentrations in the lichens declined more rapidly for higher molecular weight PAHs than lower molecular weight PAHs. We hypothesize that this trend was driven by differences in gas-particle partitioning and vegetative scavenging between PAH congeners. These results illustrate the importance of both physical transport and chemical partitioning in alpine areas where small differences in topography can lead to significant differences in chemical transport.

Molecular Glue Discovery: Current and Future Approaches.

The intracellular interactions of biomolecules can be maneuvered to redirect signaling, reprogram the cell cycle, or decrease infectivity using only a few dozen atoms. Such "molecular glues," which can drive both novel and known interactions between protein partners, represent an enticing therapeutic strategy. Here, we review the methods and approaches that have led to the identification of small-molecule molecular glues. We first classify current FDA-approved molecular glues to facilitate the selection of discovery methods. We then survey two broad discovery method strategies, where we highlight the importance of factors such as experimental conditions, software packages, and genetic tools for success. We hope that this curation of methodologies for directed discovery will inspire diverse research efforts targeting a multitude of human diseases.

A Case of Acute Motor and Sensory Axonal Neuropathy Secondary to SGN-LIV1A Therapy.

Antibody-drug conjugate therapy is rarely associated with neurologic immune-related phenomena. In this case report, we present a patient on treatment with SGN-LIV1A antibody-drug conjugate for breast cancer who developed progressive asymmetric quadriparesis, more severe in the bilateral upper extremities. Acute motor and sensory axonal neuropathy (AMSAN), a sub-variant of Guillain-Barré syndrome, was diagnosed via electro-diagnostic studies. Serological studies were significant for vitamin B1, B2 and B6 deficiencies, and cerebrospinal fluid studies were significant for albuminocytologic dissociation. The patient was treated with intravenous immunoglobulin (IVIg), B complex supplementation, and aggressive physical therapy. There was recovery of muscle strength in all extremities over the course of three months. Our case explores the biologic response to treatment of experimental immunotherapy-induced AMSAN with intravenous immunoglobulin.

Thriving in Neurology Residency: An Appreciative Inquiry Approach.

BACKGROUND AND OBJECTIVES: Enhancing resident well-being has become a top priority for medical educators as awareness of physician burnout continues to grow. Although substantial effort has been made to understand contributors to resident burnout and develop effective interventions, relatively little is known about what characterizes the opposite of burnout-that is, thriving in medical training. This phenomenologic qualitative study applies appreciative inquiry as an interview technique with the aim of characterizing self-identified experiences of thriving among residents in the Yale Neurology program. METHODS: Eight residents across all years of training in a single neurology residency participated in semi-structured appreciative interviews to identify experiences of thriving during neurology training. These interviews were transcribed and qualitatively analyzed with a phenomenologic perspective for common themes. RESULTS: Numerous themes emerged spanning personal, interpersonal, and organizational domains. Whereas some of these themes were congruent with established foundations of well-being and adult learning theory, others revealed the crucial contributions of stress and challenge to thriving. One of the strongest emergent themes was the tendency of residents to thrive during autonomous, high-challenge, high-stress situations, provided that adequate support was present and psychological safety was ensured. DISCUSSION: These findings resonate with phenomena studied in positive psychology that are not being widely applied in medical education. To the degree that conclusions are transferable to other training contexts, this study suggests an opportunity for medical educators to harness the positive aspects of stress and challenge in a supportive way that facilitates trainee well-being through experiences of thriving.

Powassan Meningoencephalitis: A Case Report Highlighting Diagnosis and Management.

Powassan virus (POWV), a rare flavivirus that may be transmitted by a tick bite, causes rare but severe cases of encephalitis, meningitis, and meningoencephalitis in humans. We present the case of a 62-year-old man with prior Lyme disease and reactive arthritis who presented to the hospital with symptoms of fever, headache, and fatigue. The patient developed rapid deterioration of mental status including profound expressive aphasia and required intubation and high-dose steroids. Cerebrospinal fluid (CSF) serologies were found to be positive for the POWV.

A System for the Evolution of Protein-Protein Interaction Inducers.

Molecules that induce interactions between proteins, often referred to as "molecular glues", are increasingly recognized as important therapeutic modalities and as entry points for rewiring cellular signaling networks. Here, we report a new PACE-based method to rapidly select and evolve molecules that mediate interactions between otherwise noninteracting proteins: rapid evolution of protein-protein interaction glues (rePPI-G). By leveraging proximity-dependent split RNA polymerase-based biosensors, we developed E. coli-based detection and selection systems that drive gene expression outputs only when interactions between target proteins are induced. We then validated the system using engineered bivalent molecular glues, showing that rePPI-G robustly selects for molecules that induce the target interaction. Proof-of-concept evolutions demonstrated that rePPI-G reduces the "hook effect" of the engineered molecular glues, due at least in part to tuning the interaction affinities of each individual component of the bifunctional molecule. Altogether, this work validates rePPI-G as a continuous, phage-based evolutionary technology for optimizing molecular glues, providing a strategy for developing molecules that reprogram protein-protein interactions.

Extensive Brainstem Posterior Reversible Encephalopathy Syndrome in a Hemodialysis Non-Adherent Patient.

Posterior reversible encephalopathy syndrome (PRES) refers to a disorder of reversible vasogenic edema caused by rapid hyperperfusion of the brain that classically involves areas supplied by the posterior circulation such as the parieto-occipital region. It may present with atypical features such as brainstem and spinal cord involvement. Common causes include renal failure, pre-eclampsia/eclampsia among pregnant women, rapid changes in systemic blood pressure, and autoimmune diseases. The most prevalent presenting signs and symptoms are encephalopathy, seizures and headache. A 64-year-old female presented to a dialysis unit after missing several sessions with twitching in her extremities and elevated blood pressure. Additionally, she recently terminated clonidine use and was likely experiencing rebound hypertension. The continuous electroencephalogram (EEG) demonstrated generalized, non-convulsive seizures. MRI findings were notable for hyperintensities in the pons, middle cerebellar peduncles, cerebellar hemispheres, and periventricular and subcortical matter with medulla and proximal spinal cord involvement. A notable clinical sequela of PRES in this patient was coma. Aggressive blood pressure control led to significant improvement and return to her neurologic baseline. PRES can present with extensive brainstem involvement with a clinical sequela of coma. Multiple underlying causes such as dialysis non-adherence and rebound hypertension following clonidine discontinuation contributed to the development of this condition in this patient.

Split T7 RNA polymerase biosensors to study multiprotein interaction dynamics.

Protein-protein interactions (PPIs) are involved in nearly all cellular processes. PPIs are particularly crucial for mediating selectivity along signaling pathways. Thus, measuring the competitive interplay between PPIs in a cell is important for both understanding fundamental cellular regulation and developing therapeutics targeting those whose dysregulation is associated with disease. A variety of split protein reporter-based tools are available to measure if two proteins interact within a cell and thereby characterize the general determinants of their interactions. PPIs, however, occur within complex networks facilitated by dynamic biophysical nuances that determine activity and selectivity. Evolved, proximity-dependent split T7 RNA polymerase (RNAP) biosensors have recently been used to perform deep mutational scanning of PPI interfaces, and to create synthetic gene circuits. In this chapter, we present the application of proximity-dependent split RNAP biosensors as a method to measure multidimensional PPIs in live cells. Orthogonal split RNAP "tags" encode each interaction in a unique RNA signal, thereby enabling the study of multiple competitive PPIs in live cells. Each unique RNA signal can be quantified via established RNA analysis methods. Herein, we provide advice and protocols to aid other researchers in using the split RNAP biosensor, focusing primarily on how to detect multiple PPIs in mammalian cells, including their dynamic interplay in the presence of small molecule inhibitors.

Bedside Teaching in Neurology.

The patient's bedside offers an ideal venue for teaching the art of clinical neurology and modeling humanism and professionalism. However, bedside teaching is underutilized in modern medical education, despite evidence that learners desire more. Logistical challenges and lack of teacher confidence are commonly cited reasons, but both can be mitigated with a deliberate approach and sufficient experience. Well-executed bedside teaching can provide lasting lessons for learners while enhancing the patient experience, without affecting the efficiency or quality care delivery. In this review, we discuss the theory and evidence to support the use of bedside teaching, and subsequently delineate a framework for designing and executing effective bedside teaching in neurology.

RNA Polymerase Tags To Monitor Multidimensional Protein-Protein Interactions Reveal Pharmacological Engagement of Bcl-2 Proteins.

We report the development of a new technology for monitoring multidimensional protein-protein interactions (PPIs) inside live mammalian cells using split RNA polymerase (RNAP) tags. In this new system, a protein-of-interest is tagged with an N-terminal split RNAP (RNAPN), and multiple potential binding partners are each fused to orthogonal C-terminal RNAPs (RNAPC). Assembly of RNAPN with each RNAPC is highly dependent on interactions between the tagged proteins. Each PPI-mediated RNAPN-RNAPC assembly transcribes from a separate promoter on a supplied DNA substrate, thereby generating a unique RNA output signal for each PPI. We develop and validate this new approach in the context of the Bcl-2 family of proteins. These key regulators of apoptosis are important cancer mediators, but are challenging to therapeutically target due to imperfect selectivity that leads to either off-target toxicity or tumor resistance. We demonstrate binary (1 × 1) and ternary (1 × 2) Bcl-2 PPI analyses by imaging fluorescent protein translation from mRNA outputs. Next, we perform a 1 × 4 PPI network analysis by direct measurement of four unique RNA signals via RT-qPCR. Finally, we use these new tools to monitor pharmacological engagement of Bcl-2 protein inhibitors, and uncover inhibitor-dependent competitive PPIs. The split RNAP tags improve upon other protein fragment complementation (PFC) approaches by offering both multidimensionality and sensitive detection using nucleic acid amplification and analysis techniques. Furthermore, this technology opens new opportunities for synthetic biology applications due to the versatility of RNA outputs for cellular engineering applications.

Tetrathiafulvalene-containing polymers for simultaneous non-covalent modification and electronic modulation of MoS2 nanomaterials.

Transition metal dichalcogenides (TMDCs) such as MoS2 comprise an important class of 2D semiconductors with numerous interesting electronic and mechanical features. Full utilization of TMDCs in materials and devices, however, necessitates robust functionalization methods. We report well-defined tetrathiafulvalene (TTF)-based polymers, exploiting synthetic routes that overcome challenges previously associated with these systems. These platforms enable basal plane coordinative interactions with MoS2, conceptually in parallel with pyrene-containing platforms for graphene and carbon nanotube modification. Not yet reported for TMDCs, these non-covalent interactions are universal and effective for MoS2 irrespective of the lattice structure, affording significantly enhanced solution stabilization of the nanosheets. Additionally, the TTF-functionalized polymers offer electronic structure modulation of MoS2 by ground state charge transfer and work function reduction, demonstrated using Kelvin probe force microscopy (KPFM). Notably, coordination and electronic effects are amplified for the TTF-polymers over TTF itself. Experiments are supported by first-principles density functional theory (DFT) calculations that probe polymer-TTF surface interactions with MoS2 and the resultant impact on electronic properties.

Regional areas and widths of the midsagittal corpus callosum among HIV-infected patients on stable antiretroviral therapies.

Recent reports suggest that a growing number of human immunodeficiency virus (HIV)-infected persons show signs of persistent cognitive impairment even in the context of combination antiretroviral therapies (cART). The basis for this finding remains poorly understood as there are only a limited number of studies examining the relationship between CNS injury, measures of disease severity, and cognitive function in the setting of stable disease. This study examined the effects of HIV infection on cerebral white matter using quantitative morphometry of the midsagittal corpus callosum (CC) in 216 chronically infected participants from the multisite HIV Neuroimaging Consortium study currently receiving cART and 139 controls. All participants underwent MRI assessment, and HIV-infected subjects also underwent measures of cognitive function and disease severity. The midsagittal slice of the CC was quantified using two semi-automated procedures. Group comparisons were accomplished using ANOVA, and the relationship between CC morphometry and clinical covariates (current CD4, nadir CD4, plasma and CSF HIV RNA, duration of HIV infection, age, and ADC stage) was assessed using linear regression models. HIV-infected patients showed significant reductions in both the area and linear widths for several regions of the CC. Significant relationships were found with ADC stage and nadir CD4 cell count, but no other clinical variables. Despite effective treatment, significant and possibly irreversible structural loss of the white matter persists in the setting of chronic HIV disease. A history of advanced immune suppression is a strong predictor of this complication and suggests that antiretroviral intervention at earlier stages of infection may be warranted.

The role of medical imaging in defining CNS abnormalities associated with HIV-infection and opportunistic infections.

In this review of the current literature, we examine the role of medical imaging in providing new and relevant information on central nervous system (CNS) injury associated with human immunodeficiency virus (HIV) infection and various clinical manifestations of this injury. Common imaging modalities used to examine CNS injury in HIV infection include structural magnetic resonance imaging, magnetic resonance spectroscopy, diffusion tensor imaging, functional MRI, and positron emissions tomography. Clinical implications for the findings are discussed for each of these modalities individually and collectively. In addition, the direction for future studies is suggested in an attempt to provide possible methods that might answer the many questions that remain to be answered on the evolution and progression of CNS injury in the context of HIV infection.

Reliability and validity of MRI-based automated volumetry software relative to auto-assisted manual measurement of subcortical structures in HIV-infected patients from a multisite study.

The automated volumetric output of FreeSurfer and Individual Brain Atlases using Statistical Parametric Mapping (IBASPM), two widely used and well published software packages, was examined for accuracy and consistency relative to auto-assisted manual (AAM) tracings (i.e., manual correction of automated output) when measuring the caudate, putamen, amygdala, and hippocampus in the baseline scans of 120 HIV-infected patients (86.7% male, 47.3+/-6.3y.o., mean HIV duration 12.0+/-6.3years) from the NIH-funded HIV Neuroimaging Consortium (HIVNC) cohort. The data was examined for accuracy and consistency relative to auto-assisted manual tracing, and construct validity was assessed by correlating automated and AAM volumetric measures with relevant clinical measures of HIV progression. When results were averaged across all patients in the eight structures examined, FreeSurfer achieved lower absolute volume difference in five, higher sensitivity in seven, and higher spatial overlap in all eight structures. Additionally, FreeSurfer results exhibited less variability in all measures. Output from both methods identified discrepant correlations with clinical measures of HIV progression relative to AAM segmented data. Overall, FreeSurfer proved more effective in the context of subcortical volumetry in HIV-patients, particularly in a multisite cohort study such as this. These findings emphasize that regardless of the automated method used, visual inspection of segmentation output, along with manual correction if necessary, remains critical to ensuring the validity of reported results.