NMR and EPR reveal a compaction of the RNA-binding protein FUS upon droplet formation.

Many RNA-binding proteins undergo liquid-liquid phase separation, which underlies the formation of membraneless organelles, such as stress granules and P-bodies. Studies of the molecular mechanism of phase separation in vitro are hampered by the coalescence and sedimentation of organelle-sized droplets interacting with glass surfaces. Here, we demonstrate that liquid droplets of fused in sarcoma (FUS)-a protein found in cytoplasmic aggregates of amyotrophic lateral sclerosis and frontotemporal dementia patients-can be stabilized in vitro using an agarose hydrogel that acts as a cytoskeleton mimic. This allows their spectroscopic characterization by liquid-phase NMR and electron paramagnetic resonance spectroscopy. Protein signals from both dispersed and condensed phases can be observed simultaneously, and their respective proportions can be quantified precisely. Furthermore, the agarose hydrogel acts as a cryoprotectant during shock-freezing, which facilitates pulsed electron paramagnetic resonance measurements at cryogenic temperatures. Surprisingly, double electron-electron resonance measurements revealed a compaction of FUS in the condensed phase.

Perceived Barriers to Career Advancement: Medical Students and Resident Physicians.

BACKGROUND: The path to becoming a physician is challenging, with various barriers influencing medical student and resident physician residency and fellowship training career decisions. Studies comparing perceived obstacles at disparate training levels are limited and given these obstacles are dynamic, studies are frequently needed to evaluate perceived barriers to pursuing residency specialty or fellowship of interest for physician trainees. OBJECTIVE: To evaluate and compare perceived barriers to obtaining residency specialty or fellowship of choice for medical students and resident physicians, respectively. METHODS: A Likert scale survey assessing perceived barriers was administered via the listservs of medical schools and organizations in 2021. Differences in the Likert scale score mean between medical students and resident physicians were measured with student t-tests (2-sided). RESULTS: A total of 404 medical trainees participated (301 medical students and 103 resident physicians). Medical students indicated lack of opportunity to obtain alpha omega alpha membership as the most crucial perceived barrier (mean Likert scale score ± standard deviation, 4.01±1.97), followed by USMLE Step 1 score (3.92±1.89) and lack of home program in specialty/fellowship of interest (3.62±1.85). Similarly, resident physicians implicated the lack of a home program in a specialty/fellowship of interest as the most prominent barrier (3.48±1.78), followed by lack of connections/networking (3.17±1.50) and probability of matching (3.14±1.44). CONCLUSIONS: The lack of a home program was an important barrier to pursuing a specialty or fellowship of choice for both medical students and resident physicians, respectively, and may have been heightened during the COVID-19 pandemic. J Drugs Dermatol. 2023;22(11):e17-e20    doi:10.36849/JDD.7005e.

Underrepresented Groups and Perceived Educational Barriers for Residency and Fellowship Success.

BACKGROUND: The study aimed to compare barriers perceived by medical students and resident physicians identifying as of underrepresented groups in medicine (UIM) and/or as sexual and gender minorities (SGM) to individuals not identifying with these groups, especially for trainees with an interest in dermatology. METHODS: Cross-sectional survey of medical students and resident physicians based in the United States from February 2021 to July 2021, with subgroup analysis of trainees with interest in dermatology. FINDINGS: Among trainees interested in dermatology, the most notable barriers for the UIM group were 1) lack of home program in specialty/fellowship of interest (4.71±1.73); 2) lack of connections/networking opportunities (4.14±1.29); 3) lack of opportunity to obtain AOA membership (4.00±1.96); 4) obtaining mentorship (4.00±1.47); and lack of diversity in specialty/fellowship of interest (3.93±1.14). CONCLUSIONS AND RELEVANCE: Increasing focused mentorship programs and fostering environments that embrace diversity are key to reducing perceived barriers for minority candidates. J Drugs Dermatol. 2023;22(12):1210-1215. doi:10.36849/JDD.7528R1.

Emerging Intralesional Treatments for Plantar Warts: A Systematic Review.

BACKGROUND: Therapies for plantar warts remain subjective and unclear, which has led to continual pursuit of an optimal treatment. As a consequence, many intralesional therapies have emerged over the last decade. This warrants a systematic review from a clinical lens which provides updates on intralesional treatment options for plantar warts from the last decade. METHODS: A PubMed/MEDLINE literature search was performed, in accordance with PRISMA reporting guidelines for systematic reviews. Original peer-reviewed articles on safety/efficacy of intralesional plantar wart treatments, published from January 2012 to January 2021, were considered for inclusion. RESULTS: Twenty-6 studies were included and the following intralesional modalities were identified (median cure rates): vitamin D3 (80%), bleomycin (74%), 5-fluorouracil (59%), Candida antigen (66%), zinc sulfate (70%), and purified protein derivative (67%). CONCLUSION: Intralesional vitamin D3, in particular, demonstrated promising results as a potential second- or even first-line agent although not accessible in the United States. Candida antigen and bleomycin are less effective than intralesional vitamin D3, but given their greater accessibility and superiority to cryotherapy, should continue to be considered for treating recalcitrant plantar warts. Moreover, the quadrivalent human papillomavirus (HPV) vaccine, showing success in case reports, warrants further attention for both the treatment and prevention of plantar warts. J Drugs Dermatol. 2022;21(12):1322-1329. doi:10.36849/JDD.6735.

A Step-by-Step Guide to Study Protein-RNA Interactions.

Protein-RNA complex formation is at the center of RNA metabolism and leads to the modulation of protein and RNA functions. We propose here a step-by-step guide to investigate these interactions including the identification of the protein and RNA parts involved in complex formation, the determination of the affinity of the complex and the characterization of the protein-RNA interface at amino acid and nucleotide level. Moreover, we briefly review the methods that are the most often used to obtain this information using primarily examples from our lab and finally mention what we perceive as the next challenges in the field.

Post-COVID-19 Syndrome Clinical Pathway for the US Veterans Health Administration.

The Department of Veterans Health Affairs (VHA) has launched 22 multispecialty post-COVID-19 clinics across the US for the growing number of veterans experiencing long-term sequelae after acute COVID-19 infection. While evidence-based treatments for this syndrome are under investigation, there is a critical need to establish and disseminate clinical pathways (CPWs) based on knowledge and experience gained in those clinics. This VHA CPW is intended to guide primary care clinicians who care for patients experiencing dyspnea and/or cough during post-COVID-19 syndrome (PCS), which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID-19. This effort will help guide and standardize the care of veterans across the VHA, improve health outcomes, and effectively utilize health care resources. This article summarizes our stepwise diagnostic approach for patients presenting with PCS dyspnea and/or cough in primary care; it also highlights teleconsultation and telerehabilitation as opportunities to reach those in rural areas or with transportation barriers and improve reach for specialized services.

Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing.

The human prototypical SR protein SRSF1 is an oncoprotein that contains two RRMs and plays a pivotal role in RNA metabolism. We determined the structure of the RRM1 bound to RNA and found that the domain binds preferentially to a CN motif (N is for any nucleotide). Based on this solution structure, we engineered a protein containing a single glutamate to asparagine mutation (E87N), which gains the ability to bind to uridines and thereby activates SMN exon7 inclusion, a strategy that is used to cure spinal muscular atrophy. Finally, we revealed that the flexible inter-RRM linker of SRSF1 allows RRM1 to bind RNA on both sides of RRM2 binding site. Besides revealing an unexpected bimodal mode of interaction of SRSF1 with RNA, which will be of interest to design new therapeutic strategies, this study brings a new perspective on the mode of action of SRSF1 in cells.

The use of technology for urgent clinician to clinician communications: a systematic review of the literature.

OBJECTIVE: Urgent clinician-clinician communications require routes of contact that are fast and dependable, and allow for the exchange of complex information. Despite the increasing focus on improving healthcare delivery systems over the past decade, few studies have examined the role of technology in clinician-clinician communication. The aim of this study was to review the literature examining the role of devices and technology in facilitating urgent clinician-clinician communication to identify critical areas for future research. MATERIALS AND METHODS: A search of Pub Med was performed using the terms (((("Critical Care"[Mesh] OR "urgent")))) AND (((hospital communication systems[MeSH Terms]) OR health communication[MeSH Terms]) OR interdisciplinary communication[MeSH Terms]). Commentaries and editorials were excluded. RESULTS: The initial search returned 272 articles, which were reviewed to identify articles describing: (1) the role of technological support or devices in clinician-clinician communication, (2) technology-based interventions that improved clinician-to-clinician communication in hospitals or acute care facilities related to critically ill patients, or (3) critical information exchange. A total of 16 articles were included in the final review. These were grouped into three categories: alphanumeric pagers, cellular and smart telephones, and novel uses of technology. DISCUSSION: Breakdowns in clinician-clinician communication are complex and cannot be solved through the implementation of devices or technologically advanced systems alone. It is essential to understand the correlation between emerging technologies, a demanding workload, and clinician-clinician interaction. Enhanced communication of clinical ideas, opportunities for team discussion, and a sense of partnership and support require not just increased information, but enhanced delivery.