Impact of the Radiology Scholars Certificate Program: Does It Persist Years After Program Completion?

RATIONALE AND OBJECTIVE: The Radiology Scholars Certificate Program (RSCP) is an elective course for preclinical medical students which aims to improve radiology knowledge, dispel misconceptions regarding the field, and train future clinicians who have a greater understanding of the scope of the field. Previously, we have shown that students demonstrate improved knowledge of radiological topics as well as improved perception of radiology as a field after completing the program. In this study we attempt to determine whether these effects persist up to two years following program completion. MATERIAL AND METHODS: A two-part questionnaire was sent to all third- and fourth-year medical students at our institution in order to assess their objective ability to select appropriate imaging studies and interpret basic imaging findings, as well as evaluate their subjective attitudes and comfort level with radiology topics. Statistical analysis compared students who completed the RSCP to non-RSCP controls. RESULTS: A total of 54 students responded to the survey (34 had previously completed the RSCP). RSCP participants were significantly more likely to select appropriate imaging workups and correctly interpret imaging findings compared to controls (p < 0.001). Furthermore, RSCP participants reported significantly higher confidence in their ability to order imaging (p < 0.001) and significantly higher satisfaction with their radiology education (p < 0.001). RSCP participants were less likely to agree with negative stereotypes regarding radiology and reported more favorable perceptions of the field. CONCLUSION: Preclinical radiology-driven medical student education programs like the RSCP offer the potential for lasting improvements in students' understanding of and attitudes toward radiology as a field. We believe that such programs will help address challenges facing the field of radiology regarding recruitment, diversity, and interdisciplinary understanding.

BET Protein Inhibition Regulates Macrophage Chromatin Accessibility and Microbiota-Dependent Colitis.

Introduction: In colitis, macrophage functionality is altered compared to normal homeostatic conditions. Loss of IL-10 signaling results in an inappropriate chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodomain and extra-terminal domain (BET) proteins alters usage of DNA regulatory elements responsible for driving inflammatory gene expression. We determined if the BET inhibitor, (+)-JQ1, could suppress inflammatory activation of macrophages in Il10-/- mice. Methods: We performed ATAC-seq and RNA-seq on Il10-/- bone marrow-derived macrophages (BMDMs) cultured in the presence and absence of lipopolysaccharide (LPS) with and without treatment with (+)-JQ1 and evaluated changes in chromatin accessibility and gene expression. Germ-free Il10-/- mice were treated with (+)-JQ1, colonized with fecal slurries and underwent histological and molecular evaluation 14-days post colonization. Results: Treatment with (+)-JQ1 suppressed LPS-induced changes in chromatin at distal regulatory elements associated with inflammatory genes, particularly in regions that contain motifs for AP-1 and IRF transcription factors. This resulted in attenuation of inflammatory gene expression. Treatment with (+)-JQ1 in vivo resulted in a mild reduction in colitis severity as compared with vehicle-treated mice. Conclusion: We identified the mechanism of action associated with a new class of compounds that may mitigate aberrant macrophage responses to bacteria in colitis.

Toward Mail-in-Sensors for SARS-CoV-2 Detection: Interfacing Gel Switch Resonators with Cell-Free Toehold Switches.

The COVID-19 pandemic has emphasized the importance of widespread testing to control the spread of infectious diseases. The rapid development, scale-up, and deployment of viral and antibody detection methods since the beginning of the pandemic have greatly increased testing capacity. Desirable attributes of detection methods are low product costs, self-administered protocols, and the ability to be mailed in sealed envelopes for the safe analysis and subsequent logging to public health databases. Herein, such a platform is demonstrated with a screen-printed, inductor-capacitor (LC) resonator as a transducer and a toehold switch coupled with cell-free expression as the biological selective recognition element. In the presence of the N-gene from SARS-CoV-2, the toehold switch relaxes, protease enzyme is expressed, and it degrades a gelatin switch that ultimately shifts the resonant frequency of the planar resonant sensor. The gelatin switch resonator (GSR) can be analyzed through a sealed envelope allowing for assessment without the need for careful sample handling with personal protective equipment or the need for workup with other reagents. The toehold switch used in this sensor demonstrated selectivity to SARS-CoV-2 virus over three seasonal coronaviruses and SARS-CoV-1, with a limit of detection of 100 copies/µL. The functionality of the platform and assessment in a sealed envelope with an automated scanner is shown with overnight shipment, and further improvements are discussed to increase signal stability and further simplify user protocols toward a mail-in platform.

Successful Transition from Plasma Exchange to Eculizumab in Acetylcholine Receptor Antibody- and Muscle-Specific Kinase (MuSK) Antibody-Negative Myasthenia Gravis: A Case Report.

BACKGROUND The effectiveness of eculizumab (a terminal complement inhibitor) in acetylcholine receptor (AChR) antibody-negative generalized myasthenia gravis (gMG) is unknown. CASE REPORT A female patient was diagnosed with AChR-antibody and muscle-specific kinase (MuSK) antibody-negative gMG in March 2016. In January 2017, the patient was referred for plasma exchange (PLEX) because of continuing symptoms. She was also receiving azathioprine, mycophenolate mofetil, and pyridostigmine (all were continued during subsequent therapies). PLEX (5 sessions over 10 days) was initially effective, but over the following month the patient received PLEX weekly, then twice weekly, followed by 3-times weekly because of worsening symptoms. In April 2018, PLEX was reduced to twice weekly following initiation of eculizumab (weekly induction dose of 900 mg 1 day after first PLEX, plus 600 mg on the day of the second PLEX session, for 4 weeks). The patient was then stabilized on eculizumab 1200 mg every 2 weeks and the frequency of PLEX treatment was reduced, until PLEX was discontinued at Week 39 after eculizumab initiation. During eculizumab treatment, the patient's myasthenia gravis activities of daily living (MG-ADL) score decreased from 9 to 1 or 2 at most assessments, with a transient increase to 4 or 5 between Weeks 19 and 27 following less frequent eculizumab treatment. There were no eculizumab-related adverse events. CONCLUSIONS Following transition from 3-times weekly PLEX to eculizumab in a patient with treatment-refractory, AChR antibody- and MuSK antibody-negative gMG, there were clinically significant improvements in everyday activities affected by MG symptoms. Further investigation of eculizumab in antibody-negative MG is required.

Turnover in local parasite populations temporarily favors host outcrossing over self-fertilization during experimental evolution.

The ubiquity of outcrossing in plants and animals is difficult to explain given its costs relative to self-fertilization. Despite these costs, exposure to changing environmental conditions can temporarily favor outcrossing over selfing. Therefore, recurring episodes of environmental change are predicted to favor the maintenance of outcrossing. Studies of host-parasite coevolution have provided strong support for this hypothesis. However, it is unclear whether multiple exposures to novel parasite genotypes in the absence of coevolution are sufficient to favor outcrossing. Using the nematode Caenorhabditis elegans and the bacterial parasite Serratia marcescens, we studied host responses to parasite turnover. We passaged several replicates of a host population that was well-adapted to the S. marcescens strain Sm2170 with either Sm2170 or one of three novel S. marcescens strains, each derived from Sm2170, for 18 generations. We found that hosts exposed to novel parasites maintained higher outcrossing rates than hosts exposed to Sm2170. Nonetheless, host outcrossing rates declined over time against all but the most virulent novel parasite strain. Hosts exposed to the most virulent novel strain exhibited increased outcrossing rates for approximately 12 generations, but did not maintain elevated levels of outcrossing throughout the experiment. Thus, parasite turnover can transiently increase host outcrossing. These results suggest that recurring episodes of parasite turnover have the potential to favor the maintenance of host outcrossing. However, such maintenance may require frequent exposure to novel virulent parasites, rapid rates of parasite turnover, and substantial host gene flow.

Ethanol confers differential protection against generalist and specialist parasitoids of Drosophila melanogaster.

As parasites coevolve with their hosts, they can evolve counter-defenses that render host immune responses ineffective. These counter-defenses are more likely to evolve in specialist parasites than generalist parasites; the latter face variable selection pressures between the different hosts they infect. Natural populations of the fruit fly Drosophila melanogaster are commonly threatened by endoparasitoid wasps in the genus Leptopilina, including the specialist L. boulardi and the generalist L. heterotoma, and both wasp species can incapacitate the cellular immune response of D. melanogaster larvae. Given that ethanol tolerance is high in D. melanogaster and stronger in the specialist wasp than the generalist, we tested whether fly larvae could use ethanol as an anti-parasite defense and whether its effectiveness would differ against the two wasp species. We found that fly larvae benefited from eating ethanol-containing food during exposure to L. heterotoma; we observed a two-fold decrease in parasitization intensity and a 24-fold increase in fly survival to adulthood. Although host ethanol consumption did not affect L. boulardi parasitization rates or intensities, it led to a modest increase in fly survival. Thus, ethanol conferred stronger protection against the generalist wasp than the specialist. We tested whether fly larvae can self-medicate by seeking ethanol-containing food after being attacked by wasps, but found no support for this hypothesis. We also allowed female flies to choose between control and ethanol-containing oviposition sites in the presence vs. absence of wasps and generally found significant preferences for ethanol regardless of wasp presence. Overall, our results suggest that D. melanogaster larvae obtain protection from certain parasitoid wasp species through their mothers' innate oviposition preferences for ethanol-containing food sources.

Fruit flies medicate offspring after seeing parasites.

Hosts have numerous defenses against parasites, of which behavioral immune responses are an important but underappreciated component. Here we describe a behavioral immune response that Drosophila melanogaster uses against endoparasitoid wasps. We found that when flies see wasps, they switch to laying eggs in alcohol-laden food sources that protect hatched larvae from infection. This change in oviposition behavior, mediated by neuropeptide F, is retained long after wasps are removed. Flies respond to diverse female larval endoparasitoids but not to males or pupal endoparasitoids, showing that they maintain specific wasp search images. Furthermore, the response evolved multiple times across the genus Drosophila. Our data reveal a behavioral immune response based on anticipatory medication of offspring and outline a nonassociative memory paradigm based on innate parasite recognition by the host.