EIN2-directed histone acetylation requires EIN3-mediated positive feedback regulation in response to ethylene.

Ethylene is an important phytohormone with pleotropic roles in plant growth, development, and stress responses. ETHYLENE INSENSITIVE2 (EIN2) mediates the transduction of the ethylene signal from the endoplasmic reticulum membrane to the nucleus, where its C-terminus (EIN2-C) regulates histone acetylation to mediate transcriptional regulation by EIN3. However, no direct interaction between EIN2-C and EIN3 has been detected. To determine how EIN2-C and EIN3 act together, we followed a synthetic approach and engineered a chimeric EIN2-C with EIN3 DNA-binding activity but lacking its transactivation activity (EIN2C-EIN3DB). The overexpression of EIN2C-EIN3DB in either wild-type or in the ethylene-insensitive mutant ein3-1 eil1-1 led to a partial constitutive ethylene response. Chromatin immunoprecipitation sequencing showed that EIN2C-EIN3DB has DNA-binding activity, indicating that EIN3DB is functional in EIN2C-EIN3DB. Furthermore, native EIN3 protein levels determine EIN2C-EIN3DB binding activity and binding targets in a positive feedback loop by interacting with EIN2C-EIN3DB to form a heterodimer. Additionally, although EIN3 does not direct affect histone acetylation levels in the absence of EIN2, it is required for the ethylene-induced elevation of H3K14Ac and H3K23Ac in the presence of EIN2. Together, we reveal efficient and specific DNA-binding by dimerized EIN3 in the presence of ethylene to mediate positive feedback regulation, which is required for EIN2-directed elevation of histone acetylation to integrate into an EIN3-dependent transcriptional activation.

An evidence review of face masks against COVID-19.

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people ("source control") with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

Trends in Residency Academic Productivity of Ophthalmic Plastic and Reconstructive Surgery Fellows Between 2012 and 2019.

PURPOSE: To characterize research productivity of ophthalmic plastic and reconstructive surgery (OPRS) fellows during residency. METHODS: A database was compiled of OPRS fellows listed on the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Annual Fall Scientific Symposium program books who began their fellowship between 2012 and 2019. PubMed was searched for all publications published between July 1st of the year they began residency and September 30th of the year they began fellowship training. Bibliometric variables captured for each fellow included: the number of publications, first-author publications, and ophthalmology-related publications. RESULTS: A total of 197 OPRS fellows who began their fellowship training between 2012 and 2019 published a mean (± SD) of 2.42 ± 2.80 publications, 1.43 ± 1.85 first-author publications, and 2.33 ± 2.74 ophthalmology-related publications during residency. Linear regression revealed that the number of publications ( P < 0.001), first-author publications ( P < 0.001), and ophthalmology-related publications ( P < 0.001) that OPRS fellows published during residency have all significantly increased over the time assessed. CONCLUSIONS: The academic productivity of OPRS fellows during residency was quantified through bibliometric analysis to establish a national benchmark for the benefit of both prospective applicants and program directors. Residency research output of OPRS fellows has significantly increased between 2012 and 2019. Since ASOPRS program requirements necessitate academic productivity and thesis completion, publication records and involvement in research become valuable considerations when evaluating fellowship applicants. The knowledge of what accepted fellows have published provides the opportunity to make historical comparisons and may prove useful in the evaluation of the competitiveness of a given year's applicant pool.

Risk Factors for Multiple Sclerosis Development After Optic Neuritis Diagnosis Using a Nationwide Health Records Database.

Multiple sclerosis (MS) is an autoimmune demyelinating disease that often initially presents with optic neuritis (ON). Little is known about the demographic factors and familial histories that may be associated with the development of MS after a diagnosis of ON. We utilised a nationwide database to characterise specific potential drivers of MS following ON as well as analyse barriers to healthcare access and utilisation. The All of Us database was queried for all patients who were diagnosed with ON and for all patients diagnosed with MS after an initial diagnosis of ON. Demographic factors, family histories, and survey data were analysed. Multivariable logistic regression was performed to analyse the potential association between these variables of interest with the development of MS following a diagnosis of ON. Out of 369,297 self-enrolled patients, 1,152 were identified to have a diagnosis of ON, while 152 of these patients were diagnosed with MS after ON. ON patients with a family history of obesity were more likely to develop MS (obesity odd ratio: 2.46; p < .01). Over 60% of racial minority ON patients reported concern about affording healthcare compared with 45% of White ON patients (p < .01). We have identified a possible risk factor of developing MS after an initial diagnosis of ON as well as alarming discrepancies in healthcare access and utilisation for minority patients. These findings bring attention to clinical and socioeconomic risk factors for patients that could enable earlier diagnosis and treatment of MS to improve outcomes, particularly in racial minorities.

Correction: Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain.

[This corrects the article DOI: 10.1371/journal.pbio.2001882.].

Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 is highly selective for the inhibition of PCSK9 translation. The mechanism of action employed by PF-06446846 reveals a previously unexpected tunability of the human ribosome that allows small molecules to specifically block translation of individual transcripts.

A novel pattern of germ cell divisions in the production of hymenopteran insect eggs.

Egg development is a defining process of reproduction in higher eukaryotes. In the fruit fly, Drosophila melanogaster, this process begins with four mitotic divisions starting from a single germ cell, producing a cyst of 16 cystocytes; one of these cells will become the oocyte and the others supporting nurse cells. These mitotic divisions are exceptional because cytokinesis is incomplete, resulting in the formation of cytoplasmic bridges known as ring canals that interconnect the cystocytes. This organization allows all cystocytes to divide synchronously during each mitotic round, resulting in a final, power-of-2 number of germ cells. Given that numerous insects obey this power-of-2 rule, we investigated if strict cell doubling is a universal, underlying cause. Using confocal microscopy, we found striking departures from this paradigm in three different power-of-2 insects belonging to the Apocrita suborder (ants, bees and wasps). In these insects, the earliest-formed cystocytes cease to divide during the latter mitotic cycles while their descendants undergo further division, thereby producing a 'radial' direction of division activity. Such cystocyte division patterns that depart from strict cell doubling may be 'fine-tuned' in order to maintain a final, power-of-2 germ cell number.

Education and Misinformation: Exploring Ophthalmology Content on TikTok.

INTRODUCTION: With the continuous rise of social media usage, more patients are looking online for health-related information. TikTok is one of the fastest-growing video-based social media platforms, but the quality of its ophthalmologic content, at a comprehensive level, has not been previously analyzed. We aim to explore and characterize popular ophthalmology content on TikTok, including the presence of misinformation. METHODS: Between April 16 and May 22, 2023, 37 different ophthalmology-relevant hashtags were queried on TikTok, and the top 20 most-liked videos per hashtag were analyzed. The quality of educational videos was graded on understandability and actionability using the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V). Trends in creator identity, content type, engagement metrics, misinformation presence, and TikTok verification status were also assessed. RESULTS: The 37 ophthalmology-related hashtags yielded 723 videos comprising 3.806 billion views. A minority of videos were created by ophthalmologists (16.9%) and eyecare providers (35.1%), while the majority were created by non-healthcare providers (55.0%). The most common types of videos identified were primarily related to personal experiences (35.8%) and education (38.0%). Amongst educational videos, mean PEMAT-A/V understandability and actionability scores were 88.1% and 50.6%, respectively. Misinformation was found in 5.4% of all videos, comprising 4.8% of all likes, 4.7% of all comments, and 11.7% of all bookmarks. Its presence was significantly correlated with content created by non-healthcare providers (p < 0.001) and received a disproportionately higher percentage of bookmarks. CONCLUSIONS: This was the largest, most comprehensive evaluation of ophthalmologic content on TikTok. A significant portion of popular ophthalmologic content on TikTok is created by non-eyecare providers and contains misinformation. Our findings confirm the need for ophthalmologists to create more engaging, actionable, and factual educational content to combat misinformation adoption.

Assessment of Medical Student Research Mentorship in Radiation Oncology.

Purpose: Mentored medical student (MS) research opportunities in radiation oncology (RO) provide in-depth exposure to the specialty and may promote greater interest in a career in RO. Many radiation oncologists conduct research; however, the extent to which they directly engage MSs in their research is unknown. The purpose of this study was to characterize MS authorship in American Society for Radiation Oncology (ASTRO) journals. Methods and Materials: The byline and abstract of all scientific articles (ie, clinical, basic science, training/education) and case reports published from 2019 to 2021 in the International Journal of Radiation Oncology, Biology, and Physics; Practical Radiation Oncology; and Advances in Radiation Oncology were reviewed. Characteristics of MSs and senior authors are reported. Results: A total of 105 of 1785 articles (5.8%) included an MS author, among which 72 (68.6%) were clinical, 13 training/education (12.4%), 12 case reports (11.4%), and 8 basic science (7.6%). MS authors were more common for publications in Advances in Radiation Oncology (9.0%) than Practical Radiation Oncology (6.4%) or the International Journal of Radiation Oncology, Biology, and Physics (4.2%; P = .002). There were 125 unique MS authors from 72 institutions, among which 40 were first author (32.0%), 28 second author (22.4%), and 57 third (or higher) author (45.6%). There were 88 unique senior authors from 55 institutions, among which 10 (11.3%) were on 2 or more MS publications, and 57 (64.7%) shared the same institution as the MS. The median number of articles per mentor institution was 1 (interquartile range, 1-2), and the mentor institutions in the upper quartile in terms of number of MS publications accounted for 53 (50.5%) of all MS publications. Conclusions: Few publications in American Society for Radiation Oncology journals include MS authors with mentorship disproportionately from a small number of academic faculty at select institutions. These findings suggest that there is great potential for radiation oncologists to proactively engage more students in their work.

Protocol for in vivo elimination of avian auditory hair cells, multiplexed mRNA detection, immunohistochemistry, and S-phase labeling.

The avian inner ear can naturally regenerate sensory hair cells and is therefore an ideal candidate for investigating mechanisms leading to hair cell regeneration and functional recovery. Here, we present a surgical protocol for eliminating auditory hair cells via sisomicin injection into the lateral semicircular canal. We describe steps for multiplex mRNA detection in chicken basilar papilla and utricle sections. We then detail procedures for integrating immunohistochemistry for concurrent mRNA and protein visualization, complemented by S-phase labeling with EdU. For complete details on the use and execution of this protocol, please refer to Benkafadar et al., Benkafadar et al., Sato et al., Janesick et al., Scheibinger et al.1,2,3,4,5.

Characterization of Research Mentorship During Medical School for Future Radiation Oncology Trainees.

Purpose: Medical student access to radiation oncology (RO) research opportunities is important for stimulating interest in the specialty. The purpose of this study was to assess the publication record during medical school of students who ultimately matched in RO, to characterize the source(s) of their RO mentorship relative to other specialties. Methods and Materials: We performed web-based searches to identify manuscripts published during medical school (defined as being published from January 2016 to December 2019) for all RO residents with postgraduate year 2 status in 2020 to 2021. Students with a PhD degree and international graduates were excluded. Characteristics of these publications, the student, and the primary mentor, were assessed. Results: A total of 435 publications were authored by the 148 included residents. In total, 115 (78%) attended a medical school with an affiliated RO residency program. The median number of publications per student was 2 (interquartile range, 1-4), and students' median byline author position was 2 (interquartile range, 1-4). In total, 351 publications (80.7%) were on a cancer-related topic, with 234 (53.8%) published in oncology-oriented journal, and 96 (22.0%) published in RO-oriented journals. There were 294 unique mentors, with 70 mentors (24%) on 2 or more student publications. Most mentors (n = 187, 64%) shared the same institution as the student. Mentors were most commonly radiation oncologists/radiation biologists/medical physicists (n = 153, 52.6%), surgical subspecialists (n = 53, 21%), and medical oncologists (n = 18, 6.2%). Students working with primary RO mentors were more likely to publish in an oncology-oriented journal (79.1% vs 18.2%, P < .01) or RO-oriented journal (36.2% vs 2.2%, P < .01), compared with students working with non-RO mentors, respectively. A higher percentage of publications with RO mentors occurred in the last 2 years of medical school compared with the first 2 years (64.0% vs 40.9%, respectively, P < .01). Conclusions: Approximately one-half of student publications among future RO residents are published in nononcology journals, and result from mentoring relationships with non-RO physicians.

Patient Opinions and Side Effects Before and After General Anesthesia for Surgery.

As the number of surgical procedures performed the world over continues to increase, so does the number of anesthetic procedures needed for those surgeries to occur. While much thought and research has been focused on the perspective of the anesthesiologist, little has been explored from the perspective of the patient receiving anesthesia. The purpose of this study was to explore the general public's opinions and experiences of general anesthesia, as well as any change in their perception after having undergone a procedure requiring it. We decided that further inquiry into the subject was warranted, and we decided to run an online Qualtrics survey in order to make that inquiry. The key takeaway from our online anonymous survey shows that there is a significant amount of anxiety related to anesthesia, but that most people specify a large decrease in said anxiety after having undergone the procedure. Noticeably, people were made more comfortable by discussing anesthesia with people who had lived through the experience, and people believed they would be significantly comforted by the presence of therapy animals prior to beginning their procedures. We hope that our exploratory research will promote future research into this topic in order to improve the healthcare outcomes of a significant number of patients. We believe that this data has opened up many potential avenues for further exploration and research, as well as potentially being able to guide surgical practice.

A Descriptive Survey Investigating the Impact of the COVID-19 Pandemic on the Public's Perception of Healthcare Professionals.

The COVID-19 pandemic brought immense attention to the healthcare system and its workers. While much research has been completed about the effects of COVID-19 on the healthcare system, little exists about how the opinions of patients have been altered by this pandemic. We decided to further investigate how the public opinion of healthcare workers (HCWs) has changed to better understand how best we can serve society. The key takeaway from the data was that both the levels of perceived trustworthiness and respectability of healthcare workers decreased following the pandemic. Data showed that the level of perceived respectability decreased from an average of 7.84 to 7.30 and the level of perceived trustworthiness from 7.38 to 6.54, all of these values out of 10. While these changes were not enormous, they demonstrate a striking trend and were found to be significant through a paired t-test. Finally, respondents were also queried about their level of desire in pursuing healthcare as a career field and overwhelmingly there was little interest, with an average level of 1.24 out of 10. We believe our data and results show important trends that all HCWs should be aware of; notably decreasing interest in the field, reduced trust, and decrease in respect, all of which will require further study and analysis. We must consider the current environment in which small mistakes or mistrust can have grave consequences on public health and patient compliance. In addition, the lack of interest in joining the medical community is concerning considering the large efflux of workers leaving the profession. Future studies could focus on how to increase trust in HCWs or attract more people to the healthcare field.

Analysis of Research Productivity of Orthopedic Surgery Residency Applicants.

Background Orthopedic surgery has become an increasingly competitive specialty. With a pass-fail Step 1, an even greater emphasis on research has been placed to allow candidates to better distinguish themselves. This study analyzes the scholarly activity of accepted orthopedic residency applicants during medical school, assessing what factors, including the novel altmetric attention score, may be associated with greater research productivity. Methods A list of orthopedic residency programs was obtained from the Electronic Residency Application Service (ERAS). A total of 688 orthopedic residents from 180 programs who matriculated in 2020 from allopathic medical schools were identified. Resident demographic information and bibliometric data (total publications, orthopedic-related publications, h-index, and altmetric score) of publications published from July 1, 2016, to September 1, 2020, were collected. Descriptive statistics were calculated. Kruskal-Wallis tests analyzed the association between medical school characteristics and research productivity using Stata® 17.0 (StataCorp LLC, College Station, Texas). Results Postgraduate-Year-3 orthopedic residents (N=688) published 2,600 articles during medical school, averaging 3.8 articles per resident. The residents from a top 25 medical school for research had publication counts, altmetric scores, and h-indices, on average, that were higher than those from non-top 25 medical schools for research. Over 150 residents had no publications, and ~10 residents had more than 30 publications. Conclusions The results illustrate that medical school research status influences the research productivity of applicants. Also, given the average number of publications, most research listed on applications are abstracts and presentations. Utilization of the altmetric score may not yet be the best way of examining research experience because orthopedic applicants do not appear to use social networks for academic research.

A Patient With Pelizaeus-Merzbacher Disease Caused by a c.67G>A Mutation in the PLP1 Gene.

Pelizaeus-Merzbacher disease is a tremendously rare genetic disorder caused by a mutation on the X chromosome. The mutation affects a gene critical to white matter myelination and results in significant neurological issues. Here, we present one such case of a child diagnosed with Pelizaeus-Merzbacher disease. A relatively normal gestation and birth belied the underlying issue until he presented to the emergency department a month after birth with seizure-like activity and failure to thrive. After intensive evaluation and treatment, the patient was diagnosed with the illness and received surgery to place a tracheostomy and a gastrostomy tube to treat the stridor and failure to thrive caused by his illness. After approximately a month and a half of inpatient treatment, the patient was able to be discharged home in stable condition.

Intraoperative Complications During Orthopaedic Spinal Surgery in a Polypharmacy Patient With Multiple Comorbidities.

Orthopedic spinal surgeries, such as laminectomies or decompressions, have the potential to significantly increase quality of life for patients suffering from a spectrum of health issues ranging from neuropathy to chronic pain. Patients suffering from neurological symptoms such as weakness or neuropathy may lose significant function and become unable to perform the activities of daily living, however these delicate surgical interventions also come with significant risks to the health and well-being of those same patients. This is especially true with patients who have predisposing health conditions. Here, we discuss the effects of surgery on a patient with severe obesity, multiple confounding pre-existing conditions, and significant polypharmacy. An initially unremarkable spinal laminectomy and decompression surgery resulted in severe intraoperative complications that necessitated direct admission to the intensive care unit for significant post-operative management before he was able to be discharged safely. Although not a case of incredible rarity, we hope it can contribute to the growing body of data about the role of predisposing health conditions and polypharmacy in calculating and understanding the risks of orthopaedic surgery.