BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation.

The mitochondrial pathway of apoptosis is initiated by mitochondrial outer membrane permeabilization (MOMP). The BCL-2 family effectors BAX and BAK are thought to be absolutely required for this process. Here, we report that BCL-2 ovarian killer (BOK) is a bona fide yet unconventional effector of MOMP that can trigger apoptosis in the absence of both BAX and BAK. However, unlike the canonical effectors, BOK appears to be constitutively active and unresponsive to antagonistic effects of the antiapoptotic BCL-2 proteins. Rather, BOK is controlled at the level of protein stability by components of the endoplasmic reticulum (ER)-associated degradation pathway. BOK is ubiquitylated by the AMFR/gp78 E3 ubiquitin ligase complex and targeted for proteasomal degradation in a VCP/p97-dependent manner, which allows survival of the cell. When proteasome function, VCP, or gp78 activity is compromised, BOK is stabilized to induce MOMP and apoptosis independently of other BCL-2 proteins.

Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death.

During apoptosis, the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases. Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell, leading to rapid caspase activation and apoptosis. Using a new imaging approach, we demonstrate that MOMP is not an all-or-nothing event. Rather, we find that a minority of mitochondria can undergo MOMP in a stress-regulated manner, a phenomenon we term "minority MOMP." Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death. Instead, this caspase activity leads to DNA damage that, in turn, promotes genomic instability, cellular transformation, and tumorigenesis. Our data demonstrate that, in contrast to its well-established tumor suppressor function, apoptosis also has oncogenic potential that is regulated by the extent of MOMP. These findings have important implications for oncogenesis following either physiological or therapeutic engagement of apoptosis.

Gender Distribution of Emergency Medicine Podcast Speakers.

STUDY OBJECTIVE: Over the past 2 decades, podcasting has become an easy and inexpensive way to disseminate information. Given the increasing importance of podcasts in medicine and medical education, it is important to understand the current status of diverse voices on podcasts. The primary objective of this study was to describe the distribution of women and men as hosts and guest speakers among 3 popular emergency medicine podcasts across a 10-year period. The secondary objective was to evaluate the association between host gender and speaker gender. METHODS: We performed a retrospective cohort study of the gender distribution of hosts and guest speakers among 3 popular emergency medicine podcasts from July 2011 to June 2021. Data were extracted and their gender determined using pronouns listed in their faculty profiles or using Genderize. The data were presented descriptively using subanalyses by year and the type of speaker. We calculated the odds ratio (OR) with 95% confidence interval (CI) for the likelihood of a single host predicting a speaker's gender. RESULTS: We identified 2,834 podcasts (n=5,962 speakers), with 964 (16.2%) women and 4,996 (83.8%) men speakers. Among hosts, 10.2% were women and 89.8% were men, whereas among guest speakers, 23.4% were women and 76.5% were men. The distribution of women speakers increased from 9.1% in 2011 to 23.1% in 2021. Having a woman host had an OR of 2.40 (95% CI 1.72 to 3.34) for having a woman guest speaker, whereas having a man host had an OR of 0.42 (95% CI 0.30 to 0.58) for having a woman guest speaker. CONCLUSION: Among the 3 popular emergency medicine podcasts, there are few women speakers, hosts, and guest speakers; however, the proportion has risen over the past 10 years.

Sex Distribution of Editorial Board Members Among Emergency Medicine Journals.

STUDY OBJECTIVE: Previous studies have demonstrated that a sex disparity exists in the editorial boards of select specialties. However, there are limited data with respect to emergency medicine. We seek to determine the sex distribution of editors in chief and editorial board members among emergency medicine journals. METHODS: In this cross-sectional survey, we compiled a list of all emergency medicine journals, using the Scimago Journal & Country Rank on August 13, 2019. We excluded journals that were no longer published, were not emergency medicine journals, had rotating editorial boards for each issue, or had no first names listed. We obtained the sex and editorial board role by using publicly available data on the journal Web sites. We assigned sex according to knowledge of the member or his or her online faculty profile and used the Genderize program (Genderize.io, Roskilde, Denmark) when sex could not be determined with the above-mentioned approach. We report descriptive statistics for the categoric data, stratified by position (editor in chief, editorial board member, social media editor, resident/fellow member) and country. RESULTS: We identified 73 journals in Scimago; 37 met inclusion criteria, with data available to determine the sex in 99.5% of cases. There were 46 total editors in chief, with only 4 (8.7%) being women. Of 1,477 total editorial board members, only 241 were women (16.3%), with a range of 0% to 33.3% per journal. We found that 28.6% of social media editors (2/7) at 4 journals and 70% of resident or fellow editors (7/10) at 5 journals were women. CONCLUSION: There is a notable sex disparity among emergency medicine journals' editors in chief and editorial board members. Efforts should be made to improve sex distribution among editorial boards.

Peek at the glass ceiling: gender distribution of leadership among emergency medicine residency programs.

BACKGROUND: A gender gap in faculty rank at academic institutions exists; however, data among graduate medical education (GME) programmes are limited. There is a need to assess gender disparities in GME leadership, as a lack of female leadership may affect recruitment, role modelling and mentorship of female trainees. This cross-sectional study aimed to describe the current state of gender in programme leadership (department chair, programme director (PD), associate/assistant PD (APD) and clerkship director (CD)) at accredited Emergency Medicine (EM) programmes in the USA to determine whether a gender gap exists. METHODS: A survey was distributed to EM residency programmes in the USA assessing demographics and gender distribution among programme leadership. If no response was received, information was collected via the programme's website. Data were organised by position, region and length of the programme. We obtained data on the number of female EM physicians in practice and in training/fellowship in 2017 from the Association of American Medical Colleges. Data analysis was completed using descriptive statistics and χ2 analysis. RESULTS: Of the 226 programmes contacted, 148 responded to the survey (66.3%). Among US EM residency programmes, 11.2% of chairs, 34.6% of PDs, 40.5% of APDs and 46.5% of CDs are women. The percentage of female chairs is significantly lower than the percentage of women in practice or in training in EM. The percentage of female PDs did not differ from the percentage of women in practice or in training in EM. The percentage of female APDs and CDs was significantly higher than the percentage of women in practice but did not differ from the percentage in training. There was wide variability across regions. Four-year programmes had more women in PD and APD positions compared with 3-year programmes (p=0.01). CONCLUSIONS: While the representation of women in educational roles is encouraging, the number of women holding the rank of chairperson remains disproportionately low. Further studies are needed to evaluate reasons for this and strategies to increase gender equality in leadership roles.

What Emergency Medicine Rewards: Is There Implicit Gender Bias in National Awards?

STUDY OBJECTIVE: Multiple studies have demonstrated a gender gap in the percentage of women recognized in national awards, but to our knowledge this gap has not been studied within emergency medicine. This study is designed to evaluate the presence of a gender gap in female representation in awards from national emergency medicine organizations in the United States and Canada. METHODS: The awards from 5 national organizations during the past 5 years were reviewed. We developed a data extraction tool to identify and categorize the awards and recipients. Data were grouped according to gender distribution and assessed with respect to emergency medicine organization, year of award, category of award, and career phase specified by award. RESULTS: The overall percentage of female awardees across all 5 organizations from 2014 to 2018 was 28%. Only 16% of all named awards were named after women, and female awardees were more likely to be recognized early in their career for advocacy and work pertaining to the advancement of women, whereas men were favored for awards recognizing mentorship and organizational contributions. CONCLUSION: Emergency medicine is unique among other specialties in that the percentage of women represented in national awards (28%) closely mirrors the overall representation of women in emergency medicine (27.6% in the United States, 31% in Canada). This is in contrast to the documented leadership gap in academic medicine and emergency medicine, which may reflect a lag time between receiving national awards and earning academic and professional promotion. Although some organizations had significantly lower representation of female awardees, the overall trends indicate that women have closed the gender gap in award representation. This may signal a forthcoming change in other domains with established gaps in emergency medicine; specifically, in leadership and pay.

The BCL-2 family reunion.

B cell CLL/lymphoma-2 (BCL-2) and its relatives comprise the BCL-2 family of proteins, which were originally characterized with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis. Current observations expand BCL-2 family function to include numerous cellular pathways. Here we will discuss the mechanisms and functions of the BCL-2 family in the context of these pathways, highlighting the complex integration and regulation of the BCL-2 family in cell fate decisions.

The current landscape of emergency medicine resident scheduling.

Background: The Accreditation Council for Graduate Medical Education (ACGME) and Residency Review Committee oversee resident physician work hours with additional specifics for U.S. emergency medicine (EM) residency programs. While there are maximum work hours, the regulatory bodies do not describe minimum work hours to achieve competency, leading to variable scheduling practices. This study aimed to understand the current landscape of U.S. EM residency scheduling given the expansion of programs, evolution of policies, and increased emphasis on wellness. Methods: We conducted a cross-sectional study to assess current strategies of U.S. EM residency scheduling. The RedCap survey was sent to all ACGME-accredited EM residency programs across the United States via individualized emails between January 10, 2023, and March 15, 2023. Data were combined using Microsoft Excel. Results: A total of 138 of 278 (50%) programs responded to the survey. A total of 73.2% of programs were using thirteen 28-day blocks with the remainder using twelve 1-month blocks or reported "other" block scheduling. The number of blocks in the ED increases with each postgraduate year (PGY). For PGY-1 through PGY-3, the most commonly used shift duration was 9 h. The mean total shifts per ED block and hours worked per ED block are as follows: 19 shifts and 185.1 h (PGY-1), 18.2 shifts and 173.9 h (PGY-2), 17.3 shifts and 163.6 h (PGY-3), and 14.8 shifts and 157.2 h (PGY-4). Programs provide a median for 4 weeks of vacation per year of residency. Conclusions: Given the expansion of U.S. EM residency programs, we reevaluated the landscape of resident scheduling. We described scheduling patterns related to night shifts, vacations, requested time off, conference coverage, charting time, and circadian rhythms. Programs should utilize these data as a starting point for setting a clinical experience for their residents.

Australian Youth Mental Health and Climate Change Concern After the Black Summer Bushfires.

Climate change and its effects present notable challenges for mental health, particularly for vulnerable populations, including young people. Immediately following the unprecedented Black Summer bushfire season of 2019/2020, 746 Australians (aged 16-25 years) completed measures of mental health and perceptions of climate change. Results indicated greater presentations of depression, anxiety, stress, adjustment disorder symptoms, substance abuse, and climate change distress and concern, as well as lower psychological resilience and perceived distance to climate change, in participants with direct exposure to these bushfires. Findings highlight significant vulnerabilities of concern for youth mental health as climate change advances.

Why take the risk? Exploring the psychosocial determinants of floodwater driving.

As anthropogenic climate change progresses, there is an increasing need for individuals to make appropriate decisions regarding their approach to extreme weather events. Natural hazards are involuntary risk environments (e.g., flooded roads); interaction with them cannot be avoided (i.e., a decision must be made about how to engage). While the psychological and sociocultural predictors of engagement with voluntary risks (i.e., risk situations that are sought out) are well-documented, less is known about the factors that predict engagement with involuntary risk environments. This exploratory study assessed whether mental health (depression, anxiety, and stress symptoms), personality traits, and cultural worldviews combine to predict engagement with involuntary risk, using the situation of floodwater driving. An Australian sample (N = 235) was assessed via questionnaire and scenario measures. Results were analyzed in a binomial logistic regression assessing which individual factors predicted decision-making in a proxy floodwater driving scenario. Agreeableness and gender were individually significant predictors of floodwater driving intention, and four factors (named "affect," "progressiveness," "insightfulness," and "purposefulness") were derived from an exploratory factor analysis using the variables of interest, though only two ("progressiveness" and "insightfulness") predicted floodwater driving intention in an exploratory binomial logistic regression. The findings highlight the need for further research into the differences between voluntary and involuntary risk. The implication of cultural worldviews and personality traits in interaction with mental health indicators on risk situations is discussed.

Distribution of core content coverage among three popular emergency medicine podcasts: A 10-year analysis.

Objective: Podcasts are increasingly utilized as educational tools within emergency medicine (EM). As EM residency programs seek to incorporate asynchronous educational material, it is important to ensure we are covering the full breadth of EM core content. This study sought to describe the distribution of EM core content among three popular EM podcasts. Methods: We performed a retrospective study of the distribution of podcast topics among three popular EM podcasts from July 2011 to June 2021. We evaluated the podcast episode content and alignment with the EM core content, as defined by the Model of the Clinical Practice of Emergency Medicine (MCPEM) and American Board of Emergency Medicine (ABEM) examination distribution. Data are presented descriptively. Results: We identified 2759 podcast episodes, consisting of 7413 total topics and 2498.7 hours of content. The most frequently covered topics were "signs, symptoms, and presentations" (20.1% of total hours vs. 7.9% of MCPEM and 10.0% of ABEM exam) and "procedures and skills integral to the practice of emergency medicine" (14.8% of total hours vs. 8.1% of MCPEM and 8.0% of ABEM exam). The least frequently covered topics was were "immune system disorders"(0.5% of total hours vs. 2.0% of MCPEM and 2.0% of ABEM exam),"environmental disorders"(0.8% of total hours vs. 2.4% of MCPEM and 2.0% of ABEM exam), "obstetrics and gynecology" (1.0% of total hours vs. 5.4% of MCPEM and 3.0% of ABEM exam), and "cutaneous disorders" (0.9% of total hours vs. 4.3% of MCPEM and 3.0% of ABEM exam). Conclusions: Our findings suggest an imbalance of MCPEM core content in three popular EM podcasts.

Holistic Review, Mitigating Bias, and Other Strategies in Residency Recruitment for Diversity, Equity, and Inclusion: An Evidence-based Guide to Best Practices from the Council of Residency Directors in Emergency Medicine.

Advancement of diversity, equity, and inclusion (DEI) in emergency medicine can only occur with intentional recruitment of residency applicants underrepresented in medicine (UIM). Shared experiences from undergraduate and graduate medical education highlight considerations and practices that can contribute to improved diversity in the resident pool, such as holistic review and mitigating bias in the recruitment process. This review, written by members of the Council of Residency Directors in Emergency Medicine (CORD) Best Practices Subcommittee, offers best practice recommendations for the recruitment of UIM applicants. Recommendations address pre-interview readiness, interview approach, and post-interview strategies that residency leadership may use to implement holistic review and mitigate bias for recruitment of a diverse class.

Physician Pipeline and Pathway Programs: An Evidence-based Guide to Best Practices for Diversity, Equity, and Inclusion from the Council of Residency Directors in Emergency Medicine.

Improving the diversity and representation in the medical workforce requires intentional and deliberate efforts to improve the pipeline and pathway for underrepresented in medicine (UIM) applicants. Diversity enhances educational experiences and improves patient care and outcomes. Through a critical review of the literature, in this article we offer evidence-based guidelines for physician pipeline and pathway programs (PP). Recommendations are provided regarding considerations on the types of programs and surrounding implementation to ensure a sound infrastructure and framework. We believe this guide will be valuable for all leaders and faculty members seeking to grow the UIM applicant pool in our efforts to advance diversity, equity, and inclusion within medicine.

Faculty Recruitment, Retention, and Representation in Leadership: An Evidence-Based Guide to Best Practices for Diversity, Equity, and Inclusion from the Council of Residency Directors in Emergency Medicine.

Improving the recruitment, retention, and leadership advancement of faculty who are under-represented in medicine is a priority at many academic institutions to ensure excellence in patient care, research, and health equity. Here we provide a critical review of the literature and offer evidence-based guidelines for faculty recruitment, retention, and representation in leadership. Recommendations for recruitment include targeted recruitment to expand the candidate pool with diverse candidates, holistic review of applications, and incentivizing stakeholders for success with diversity efforts. Retention efforts should establish a culture of inclusivity, promote faculty development, and evaluate for biases in the promotion and tenure process. We believe this guide will be valuable for all leaders and faculty members seeking to advance diversity, equity, and inclusion in their institutions.

Gender differences in emergency medicine standardized letters of evaluation.

Objectives: The Standardized Letter of Evaluation (SLOE) is a vital portion of any medical student's emergency medicine (EM) residency application. Prior literature suggests gender bias in EM SLOE comparative ranking, but there is limited understanding of the impact of gender on other SLOE components. The study objective was to evaluate the presence of gender differences in the 7 Qualifications for EM (7QEM), Global Assessment (GA), and anticipated Rank List (RL) position. A secondary objective was to evaluate the gender differences in 7QEM scores and their link to GA and anticipated RL position. Methods: We performed a cross-sectional study using SLOEs from a subset of United States applicants to three EM residency programs during the 2019-2020 application cycle. We collected self-reported demographics, 7QEM scores, GA, and anticipated RL position. We utilized linear regression analyses and repeated measures ANOVA to evaluate if the relationship between the 7QEM scores, GA score, and anticipated RL position was different for men and women. Results: 2103 unique applicants were included (38.6% women, 61.4% men), with 4952 SLOEs meeting inclusion criteria. The average QEM (2.51 vs. 2.39; p < 0.001), GA (2.68 vs. 2.48; p < 0.001), and RL (2.68 vs. 2.47; p < 0.001) scores were statistically higher for women than men. When exploring the relationship between the 7QEM and GA, Ability to communicate a caring nature to patients was not found to be a statistically significant predictor for men, but it was for women. When exploring the relationship between 7QEM and RL, Commitment to EM was not a significant predictor for men, but it was for women. Conclusions: Women scored higher than men on the 7QEM, GA, and anticipated RL position on SLOEs. The 7QEM scores factored differently for men and women.

Ethnic and Racial Differences in Ratings in the Medical Student Standardized Letters of Evaluation (SLOE).

Background: The Standardized Letter of Evaluation (SLOE) stratifies the assessment of emergency medicine (EM) bound medical applicants. However, bias in SLOE, particularly regarding race and ethnicity, is an underexplored area. Objective: This study aims to assess whether underrepresented in medicine (UIM) and non-UIM applicants are rated differently in SLOE components. Methods: This was a cross-section study of EM-bound applicants across 3 geographically distinct US training programs during the 2019-2020 application cycle. Using descriptive and regression analyses, we examine the differences between UIM applicants and non-UIM applicants for each of the SLOE components: 7 qualifications of an EM physician (7QEM), global assessment (GA) rating, and projected rank list (RL) position. Results: Out of a combined total of 3759, 2002 (53.3%) unique EM-bound applicants were included. UIM applicants had lower ratings for each of the 7QEM questions, GA, and RL positions. Compared to non-UIM applicants, only some of the 7QEM components: "Work ethic and ability to assume responsibility," "Ability to work in a team, and "Ability to communicate a caring nature," were associated with their SLOE. "Commitment to EM" correlated more with GA for UIM than for non-UIM applicants. Conclusions: This study shows a difference in SLOE rating, with UIM applicants receiving lower ratings than non-UIM applicants.

Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis.

In addition to its classical role in apoptosis, accumulating evidence suggests that caspase-2 has non-apoptotic functions, including regulation of cell division. Loss of caspase-2 is known to increase proliferation rates but how caspase-2 is regulating this process is currently unclear. We show that caspase-2 is activated in dividing cells in G1-phase of the cell cycle. In the absence of caspase-2, cells exhibit numerous S-phase defects including delayed exit from S-phase, defects in repair of chromosomal aberrations during S-phase, and increased DNA damage following S-phase arrest. In addition, caspase-2-deficient cells have a higher frequency of stalled replication forks, decreased DNA fiber length, and impeded progression of DNA replication tracts. This indicates that caspase-2 protects from replication stress and promotes replication fork protection to maintain genomic stability. These functions are independent of the pro-apoptotic function of caspase-2 because blocking caspase-2-induced cell death had no effect on cell division, DNA damage-induced cell cycle arrest, or DNA damage. Thus, our data supports a model where caspase-2 regulates cell cycle and DNA repair events to protect from the accumulation of DNA damage independently of its pro-apoptotic function.

A national assessment of residency wellness initiatives in emergency medicine.

BACKGROUND: Wellness is increasingly recognized as an important component of graduate medical education. However, there are limited data regarding how wellness initiatives are enacted in practice. This study aimed to survey emergency medicine (EM) residency programs to identify current, previous, and planned wellness initiatives as well as barriers to implementation and resources utilized. METHODS: This was a cross-sectional survey study performed from November 2019 through January 2020. A literature search was performed to identify existing published wellness interventions and existing barriers, and these interventions and barriers were compiled to create a survey. The survey was piloted among five program directors and assistant program directors in person with feedback directly incorporated into the survey. The survey was sent to program leadership at all 223 Accreditation Council for Graduate Medical Education-accredited EM residency programs across the United States. RESULTS: Of the programs surveyed, 95 (42.6%) were included. The most common current wellness interventions reported were resident retreats (91%), group events (90%), formal mentorship (74%), and wellness committees (66%). Reported factors that contributed to the successful implementation of wellness interventions were faculty involvement (78%), resident involvement (78%), department chair support (51%), institutional support (44%), and financial support (36%). Lack of financial support (65%) and limited time (62%) were the most commonly reported barriers that prevented the implementation of wellness interventions. CONCLUSIONS: Resident wellness is an important aspect of residency training. Survey respondents generally perceived that wellness interventions were associated with wellness improvement. Successful programs have financial, institutional, and chair support.