A Guiding Model for Undergraduate Medical Education Well-Being Programs.

ABSTRACT: Most medical schools have instituted undergraduate medical education (UME) well-being programs in recent years in response to high rates of medical student distress, but there is currently significant variability in the structure of UME well-being programs and limited guidance on how to best structure such programs to achieve success. In this article, the authors, all leaders of medical student well-being programs at their home institutions and members of the Association of American Medical Colleges Group on Student Affairs Committee on Student Affairs Working Group on Medical Student Well-Being between 2019 and 2023, offer guidance to the national community on how best to structure a UME well-being program. They use the current literature and their professional experiences leading well-being efforts at 7 different institutions to review the case for addressing medical student well-being, propose a guiding model, and make recommendations for strategies to implement this model.The proposed guiding model emphasizes the importance of the learning environment and efficiency of learning to medical student well-being, as well as personal resilience. Based on this model, the authors recommend specific and tangible well-being strategies to implement systemic interventions to improve the learning environment, efficiency of learning, and personal resilience, including: formalizing the well-being program; hiring qualified, dedicated, and empowered well-being leadership with clear responsibilities; acting as a central hub for resources and as a liaison with mental health care; and establishing robust program evaluation methods.

Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster.

Mammalian sex determination is controlled by antagonistic gene cascades operating in embryonic undifferentiated gonads. The expression of the Y-linked gene SRY is sufficient to trigger the testicular pathway, whereas its absence in XX embryos leads to ovarian differentiation. Yet, the potential involvement of non-coding regulation in this process remains unclear. Here we show that the deletion of a single microRNA cluster, miR-17~92, induces complete primary male-to-female sex reversal in XY mice. Sry expression is delayed in XY knockout gonads, which develop as ovaries. Sertoli cell differentiation is reduced, delayed and unable to sustain testicular development. Pre-supporting cells in mutant gonads undergo a transient state of sex ambiguity which is subsequently resolved towards the ovarian fate. The miR-17~92 predicted target genes are upregulated, affecting the fine regulation of gene networks controlling gonad development. Thus, microRNAs emerge as key components for mammalian sex determination, controlling Sry expression timing and Sertoli cell differentiation.

Sindbis Virus Vaccine Platform: A Promising Oncolytic Virus-Mediated Approach for Ovarian Cancer Treatment.

This review article provides a comprehensive overview of a novel Sindbis virus vaccine platform as potential immunotherapy for ovarian cancer patients. Ovarian cancer is the most lethal of all gynecological malignancies. The majority of high-grade serous ovarian cancer (HGSOC) patients are diagnosed with advanced disease. Current treatment options are very aggressive and limited, resulting in tumor recurrences and 50-60% patient mortality within 5 years. The unique properties of armed oncolytic Sindbis virus vectors (SV) in vivo have garnered significant interest in recent years to potently target and treat ovarian cancer. We discuss the molecular biology of Sindbis virus, its mechanisms of action against ovarian cancer cells, preclinical in vivo studies, and future perspectives. The potential of Sindbis virus-based therapies for ovarian cancer treatment holds great promise and warrants further investigation. Investigations using other oncolytic viruses in preclinical studies and clinical trials are also presented.

Psychological Burden of Systemic Racism-Related Distress in New York City Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: Little is known about the relationship among systemic racism, psychological symptoms (depression, anxiety, and/or post-traumatic stress disorders), and burnout in healthcare workers (HCWs). OBJECTIVE: To determine whether distress related to awareness of systemic racism contributes to psychological symptoms and/or burnout in HCWs. We explored whether this form of racism-related distress may moderate the relationship between race, ethnicity, psychological symptoms, and burnout. DESIGN: A cross-sectional survey was conducted from November 19, 2020, through January 11, 2021. Statistical analysis was conducted from May 3, 2022, to June 15, 2022. PARTICIPANTS: Frontline HCWs at an urban tertiary care hospital in New York City. MAIN MEASURES: Distress related to awareness of systemic racism (SR) and racial disparities in COVID-19 outcomes (RD), psychological symptoms, and burnout. KEY RESULTS: Two thousand one of 4654 HCWs completed the survey (response rate 43.0%). Most HCWs reported experiencing distress related to awareness of systemic racism (1329 [66.4%]) and to racial disparities in COVID-19 outcomes (1137 [56.8%]). Non-Hispanic Black participants (SR odds ratio (OR) 2.84, p < .001; RD OR 2.34, p < .001), women (SR OR 1.35, p = .01; RD OR 1.67, p < .001), and those with history of mental illness (SR OR 2.13, p < .001; RD OR 1.66, p < .001) were more likely to report SR- and RD-related distress, respectively. HCWs who experienced "quite-a-bit to extreme" SR-related distress were more likely to screen positive for psychological symptoms (OR 5.90, p < .001) and burnout (OR 2.26, p < .001). CONCLUSIONS: Our findings suggest that distress related to awareness of systemic racism, not race/ethnicity, was associated with experiencing psychological symptoms and burnout in HCWs. As the medical community continues to critically examine the role of systemic racism in healthcare, our work is a first step in characterizing its toll on the psychological well-being of HCWs.

Channeling the Natural Properties of Sindbis Alphavirus for Targeted Tumor Therapy.

Sindbis alphavirus vectors offer a promising platform for cancer therapy, serving as valuable models for alphavirus-based treatment. This review emphasizes key studies that support the targeted delivery of Sindbis vectors to tumor cells, highlighting their effectiveness in expressing tumor-associated antigens and immunomodulating proteins. Among the various alphavirus vectors developed for cancer therapy, Sindbis-vector-based imaging studies have been particularly extensive. Imaging modalities that enable the in vivo localization of Sindbis vectors within lymph nodes and tumors are discussed. The correlation between laminin receptor expression, tumorigenesis, and Sindbis virus infection is examined. Additionally, we present alternative entry receptors for Sindbis and related alphaviruses, such as Semliki Forest virus and Venezuelan equine encephalitis virus. The review also discusses cancer treatments that are based on the alphavirus vector expression of anti-tumor agents, including tumor-associated antigens, cytokines, checkpoint inhibitors, and costimulatory immune molecules.

Glutathione Peroxidase gpx1 to gpx8 Genes Expression in Experimental Brain Tumors Reveals Gender-Dependent Patterns.

Extensive research efforts in the field of brain tumor studies have led to the reclassification of tumors by the World Health Organization (WHO) and the identification of various molecular subtypes, aimed at enhancing diagnosis and treatment strategies. However, the quest for biomarkers that can provide a deeper understanding of tumor development mechanisms, particularly in the case of gliomas, remains imperative due to their persistently incurable nature. Oxidative stress has been widely recognized as a key mechanism contributing to the formation and progression of malignant tumors, with imbalances in antioxidant defense systems being one of the underlying causes for the excess production of reactive oxygen species (ROS) implicated in tumor initiation. In this study, we investigated the gene expression patterns of the eight known isoforms of glutathione peroxidase (GPx) in brain tissue obtained from male and female control rats, as well as rats with transplacental ethyl nitrosourea (ENU)-induced brain tumors. Employing the delta-delta Ct method for RT-PCR, we observed minimal expression levels of gpx2, gpx5, gpx6, and gpx7 in the brain tissue from the healthy control animals, while gpx3 and gpx8 exhibited moderate expression levels. Notably, gpx1 and gpx4 displayed the highest expression levels. Gender differences were not observed in the expression profiles of these isoforms in the control animals. Conversely, the tumor tissue exhibited elevated relative expression levels in all isoforms, except for gpx4, which remained unchanged, and gpx5, which exhibited alterations solely in female animals. Moreover, except for gpx1, which displayed no gender differences, the relative expression values of gpx2, gpx3, gpx6, gpx7, and gpx8 were significantly higher in the male animals compared to their female counterparts. Hence, the analysis of glutathione peroxidase isoforms may serve as a valuable approach for discerning the behavior of brain tumors in clinical settings.

Racial & ethnic differences in mental health outcomes and risk factors among frontline healthcare workers during the COVID-19 pandemic.

OBJECTIVE: To examine racial/ethnic differences in mental health outcomes and risk factors during the COVID-19 pandemic among frontline healthcare workers (FHCWs). METHODS: A survey was conducted on FHCWs at a large metropolitan hospital during winter 2021. Depression, anxiety, and post-traumatic stress symptoms, demographic characteristics, and COVID-19-related occupational factors were assessed. Multivariable logistic regression examined factors associated with screening positive for psychiatric symptoms and their interactions with race/ethnicity. RESULTS: Of 1437 FHCWs, 762 (53.0%) self-identified as white, 451 (31.4%) as Asian, 118 (8.2%) as Black, and 106 (7.4%) as Latinx. Black FHCWs had a higher prevalence of screening positive for depression (18.6%) than other groups (6.6%-11.7%, p < .05). Significant risk factors by race/ethnicity interactions indicated that having cared for patients who died from COVID-19 increased risk of psychiatric symptoms among white and Black individuals, having to make difficult decisions prioritizing patients increased risk most significantly among white and Asian individuals, and working more hours increased risk most significantly among Latinx individuals. CONCLUSION: Results suggest that occupational stressors may have differential impacts on mental health among racial/ethnic groups of FHCWs. Findings provide insight on subgroups with increased vulnerability to certain risk factors and inform interventions to improve mental health in diverse FHCWs.

Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03

Background Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. Methods We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. Results From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors” (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43–22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99–36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. Conclusion Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857) (AU)

Low- and Negative-Pressure Hydrocephalus: New Report of Six Cases and Literature Review.

Low- or very-low-pressure hydrocephalus is a serious and rare phenomenon, which is becoming better known since it was first described in 1994 by Pang and Altschuler. Forced drainage at negative pressures can, in most cases, restore the ventricles to their original size, thus achieving neurological recovery. We present six new cases that suffered this syndrome from 2015 to 2020: two of them after medulloblastoma surgery; a third one as a consequence of a severe head trauma that required bifrontal craniectomy; another one after craniopharyngioma surgery; a fifth one with leptomeningeal glioneuronal tumor; and, finally, a patient with a shunt for normotensive hydrocephalus. Before the development of this condition, four of them had mid-low-pressure cerebrospinal fluid (CSF) shunts. Four patients required cerebrospinal fluid (CSF) drainage at negative pressures oscillating from zero to -15 mmHg by external ventricular drainage until ventricular size normalized, followed by the placement of a new definitive low-pressure shunt, one of them to the right atrium. The duration of drainage in negative pressures through external ventricular drainage (EVD) ranged from 10 to 40 days with concomitant intracranial pressure monitoring at the neurointensive care unit. Approximately 200 cases of this syndrome have been described in the literature. The causes are varied and superimposable to those of high-pressure hydrocephalus. Neurological impairment is due to ventricular size and not to pressure values. Subzero drainage is still the most commonly used method, but other treatments have been described, such as neck wrapping, ventriculostomy of the third ventricle, and lumbar blood patches when associated with lumbar puncture. Its pathophysiology is not clear, although it seems to involve changes in the permeability and viscoelasticity of the brain parenchyma together with an imbalance in CSF circulation in the craniospinal subarachnoid space.

Applying Kern's Model to the Development and Evaluation of Medical Student Well-Being Programs.

The Liaison Committee on Medical Education (LCME) requires that well-being programs must be "effective." Yet most medical schools do not robustly assess their well-being programs. Most evaluate their programs using one question on the Association of American Medical College's annual Graduation Questionnaire (AAMC GQ) survey for fourth-year students on their satisfaction with well-being programs, which is inadequate and nonspecific and only assesses a specific time in training. In this perspective, we, as members of the AAMC Group on Student Affairs (GSA) - Committee on Student Affairs (COSA) Working Group on Medical Student Well-being, suggest adapting Kern's 6-step approach to curriculum development as an effective framework to guide the development and evaluation of well-being programs. We suggest strategies for applying Kern's steps to well-being programs, with attention to conducting needs assessments, identifying goals, implementation, and evaluation and feedback. While each institution will have unique goals emerging from their needs assessment, we put forth five common medical student well-being goals as examples. Applying a rigorous and structured approach to developing and evaluating undergraduate medical education well-being programs will involve defining a guiding philosophy and clear goals and implementing a strong assessment strategy. This Kern-based framework can help schools meaningfully assess the impact of their initiatives on student well-being.

Longitudinal Mental Health Outcomes of Third-year Medical Students Rotating Through the Wards During COVID-19.

This study investigated third year medical students' psychological well-being during clinical rotations at Mount Sinai hospitals in New York City during the COVID-19 pandemic. All students (n = 147) starting rotations (psychiatry, surgery, obstetrics-gynecology, neurology, pediatrics, and medicine) could participate in quarterly, online, anonymous surveys comprised of validated screeners for: psychological symptoms, risk, coping, and protective factors, demographics, COVID-19 worries, and stressful clerkship-related events. Associations between variables were examined with Chi-squared, Fisher's exact, t-, Wilcoxon Rank Sum, one-way ANOVA, and McNemar tests. Significant univariate predictors of psychological distress were included in stepwise multivariable linear regression models. The baseline survey was completed by 110 (74.8%) students; ninety-two (62.6%) completed at least one other survey. During the year, 68 (73.9%) students screened positive for depression, anxiety, or PTSD. The prevalence of psychiatric symptoms peaked in June 2020 without significant changes in average scores over time. COVID-19 worries decreased over time but did not influence psychological symptoms at year-end. Eighty-three students (90.2%) experienced stressful clerkship-related events, which were traumatic and/or COVID-19-related for 26 (28.3%) and 22 students (24.0%), respectively. Baseline psychological distress, childhood emotional abuse, and resilience predicted depression, anxiety, and/or PTSD by year-end. This study highlights the importance of recognizing psychological distress and implementing interventions to support students' well-being.

Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03.

BACKGROUND: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. METHODS: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. RESULTS: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. CONCLUSION: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). GOV IDENTIFIER: NCT01584297.

Tumor glioneuronal leptomeníngeo difuso: diagnóstico y tratamiento con un caso ilustrativo / Diffuse leptomeningeal glioneuronal tumor: A review of diagnosis and management with an illustrative case

El tumor glioneuronal leptomeníngeo difuso es una entidad infrecuente, con un curso indolente; fue descrito en la clasificación de los tumores del sistema del sistema nervioso central de la OMS 2016. Presentamos el caso de un varón de 11 años que comienza con un cuadro clínico inespecífico de cefalea, dolor lumbosacro e hidrocefalia comunicante. En el curso clínico aparecen crisis epilépticas con lesiones nodulares en RM craneal; fue diagnosticado de meningitis tuberculosa y tratado con tuberclostáticos. Ante un deterioro clínico progresivo, a pesar del tratamiento, y empeoramiento de los hallazgos en RM craneoespinal, se le realiza biopsia cerebral y de leptomeninges que confirma el diagnóstico de tumor glioneuronal leptomeníngeo difuso. El tumor glioneuronal leptomeníngeo difuso debe incluirse en el diagnóstico diferencial de los cuadros que se presentan con hidrocefalia comunicante y lesiones leptomeníngeas. Se precisa un diagnóstico histológico precoz mediante biopsia para establecer un tratamiento adecuado (AU)

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are a rare indolent neoplasm described in the 2016 WHO classification of tumors of the central nervous system (CNS). We describe a case of an 11 year old boy who initially presented intermittent headache, low back pain and communicating hydrocephalus, misdiagnosed as having tuberculous meningitis. Further clinical deterioration with seizures was observed and follow-up MRI showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain and leptomeninges revealed a diffuse leptomeningeal glioneuronal tumor. DLGNT should be considered in the differential diagnosis of conditions presenting as communicating hydrocephalus with nodular lesions and leptomeningeal enhancement. A timely histologic diagnosis through a biopsy of the brain is necessary to confirm the diagnosis (AU)

Sox9 Is Required for Nail-Bed Differentiation and Digit-Tip Regeneration.

The nail organ is a specialized appendage in which several ectodermal tissues coordinately function to sustain nail growth, a process that is coupled to digit regeneration. In this study, we show that the transcription factor Sox9 is expressed in several cell populations in the mouse digit tip. We found a SOX9+ cell population in the nail bed, and genetic lineage tracing showed that this is a transient cell population differentiated from matrix nail stem cells. In the absence of Sox9, nail matrix stem cells fail to differentiate into epithelial nail-bed cells and proliferate, thus expanding distally and following the corneocyte fate, which results in outlandishly large fingernails. In addition, the tip of the underlying terminal phalanx undergoes bone regression. Sox9-lineage tracing also revealed the existence of a continuous cell supply from a Sox9-expressing population residing in the basal layers to the entire hyponychium epidermis. Furthermore, digit-tip regeneration is compromised in Sox9-knockout mice, revealing an essential role for the gene during this process. These results will contribute to understand the cellular and molecular basis of mammalian nail organ homeostasis and disease and digit-tip regeneration and will help to design new treatment strategies for patients with nail diseases or amputation.

We Get by With a Little Help From Our PEERS: The Practice Enhancement, Engagement, Resilience, and Support Program for Building Community and Well-Being in Medical Education.

PROBLEM: Physician distress is a growing national problem that begins in medical school. Solutions that teach well-being concepts and coping skills during medical school and throughout medical training are needed. APPROACH: The Practice Enhancement, Engagement, Resilience, and Support (PEERS) program was designed at the Icahn School of Medicine at Mount Sinai (ISMMS) in 2017 as a longitudinal program for medical students to process challenges and learn evidence-based coping strategies in a supportive group setting. The curriculum comprises 10 small-group sessions incorporating principles of mindfulness, positive psychology, cognitive behavioral therapy, and dialectical behavioral therapy. Students remain with the same group of approximately 8 students throughout the PEERS program, which spans all 4 years of medical school. As an established part of the core medical school curriculum, PEERS centers physician well-being as an essential clinical skill for providing sustainable, high-quality patient care. OUTCOMES: Now in its fourth year, PEERS is recognized as an effective, sustainable intervention to support trainee well-being. Cross-sectional survey data collected in 2020 reveal that PEERS has effectively established a space for emotional support and community building among peers and mentors. The program has successfully garnered institutional and administrative support, including protected curricular time and dedicated faculty leadership. NEXT STEPS: PEERS continues to evolve, incorporating feedback in real time to reflect the changing landscape of medical education, particularly in the era of remote learning. Given the demand for well-being initiatives throughout the Mount Sinai Health System, PEERS programming is being adapted and implemented across various residency, fellowship, and graduate school programs at ISMMS with the support of Mount Sinai's Office of Well-Being and Resilience and the Office of Graduate Medical Education. The PEERS program offers an evidence-based, trainee-led model that can be flexibly implemented at medical training programs across the country to support trainee well-being.

Diffuse leptomeningeal glioneuronal tumor: A review of diagnosis and management with an illustrative case.

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are a rare indolent neoplasm described in the 2016 WHO classification of tumors of the central nervous system (CNS). We describe a case of an 11 year old boy who initially presented intermittent headache, low back pain and communicating hydrocephalus, misdiagnosed as having tuberculous meningitis. Further clinical deterioration with seizures was observed and follow-up MRI showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain and leptomeninges revealed a diffuse leptomeningeal glioneuronal tumor. DLGNT should be considered in the differential diagnosis of conditions presenting as communicating hydrocephalus with nodular lesions and leptomeningeal enhancement. A timely histologic diagnosis through a biopsy of the brain is necessary to confirm the diagnosis.

Posttraumatic growth among health care workers on the frontlines of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has led to significant mental health consequences for frontline health care workers (FHCWs). However, no known study has examined the prevalence, determinants, or correlates of posttraumatic growth (PTG) in this population. METHODS: Data were analyzed from a prospective cohort of FHCWs at an urban tertiary care hospital in New York City (NYC). Assessments were conducted during the spring 2020 pandemic peak (Wave 1) and seven months later (Wave 2). Multivariable logistic regression analyses were conducted to identify Wave 1 sociodemographic, occupational, and psychosocial factors associated with PTG at Wave 2, and the association between aspects of PTG with burnout and pandemic-related PTSD symptoms at Wave 2. RESULTS: A total 76.8% of FHCWs endorsed moderate or greater PTG; the most prevalent domains were increased appreciation of life (67.0%), improved relationships (48.7%), and greater personal strength (44.1%). Non-White race/ethnicity, greater levels of positive emotions, pandemic-related PTSD symptoms, dispositional gratitude, and feelings of inspiration were independently associated with PTG. At Wave 2, endorsement of spiritual growth during the pandemic was associated with 52% and 44% lower odds of screening positive for pandemic-related PTSD symptoms and burnout, respectively; greater improvement in relationships was associated with 36% lower odds of screening positive for burnout. LIMITATIONS: Single institution study and use of self-report instruments. CONCLUSIONS: Nearly 4-of-5 FHCWs report pandemic-related PTG, driven largely by salutogenic factors assessed during the pandemic surge. Interventions to bolster these factors may help promote PTG and mitigate risk for burnout and pandemic-related PTSD symptoms in this population.

The Psychiatric Burden on Medical Students in New York City Entering Clinical Clerkships During the COVID-19 Pandemic.

For medical students first entering the clinical space in July 2020, the unique challenges related to the coronavirus pandemic threatened to amplify the psychological distress associated with clerkship rotations. This study aimed to characterize the mental health of third-year medical students starting clinical clerkships in the midst of a pandemic by assessing symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) as well as risk, coping, and protective factors associated with psychological outcomes. Of 147 third-year medical students at the Icahn School of Medicine at Mount Sinai in New York City, 110 (75%) participated in this prospective survey-based study with 108 included in the final analysis. 43 (39.8%) respondents screened positive for symptoms of either MDD, GAD, or PTSD. Multiple regression analyses revealed that greater overall symptom severity was associated with more avoidant coping, more traumatic events witnessed, poorer student and leisure functioning, lower trait emotional stability, and lower social support. Worries related to COVID-19 did not significantly influence outcome variables. To better understand the role of the pandemic on psychological outcomes in third-year medical students, additional research should focus on the trajectory of these outcomes over the year during the coronavirus pandemic.

Social Determinants, Risk Factors, and Needs: A New Paradigm for Medical Education.

COVID-19 and the escalation of racism and bias that has come in its wake have had a devastating impact on health professions students. In addition to academic challenges and personal health risks, aspects of students' lives that have often gone unnoticed or inadequately addressed have come to light. Financial constraints that impact access to housing and food, neighborhood safety in light of the spike in hate crimes, and the bias inherent in the continuum from premedical education to undergraduate and graduate medical education are some examples. The authors believe that to better understand students' lived experiences and determine how to best support them, the social determinants of health framework should be applied. This framework, the social determinants of education, encompasses concepts such as social risk factors and social needs in an effort to focus more intentionally on what can be done at a policy, institutional, and individual level. In response to the pandemic, the authors expanded their appreciation of students' risk factors and needs by advancing the scope and refining the definitions of 3 key determinants: from well-being to the power of individual and communal resilience, from equity to centering racial justice, and from student health to public health and infection prevention. The authors propose applying this same paradigm to the lived experiences of staff in medical education, whose needs are often neglected in favor of students and faculty, and who, in many cases, were the most negatively impacted by COVID-19 of all the constituents in an academic health center.

Potent and Targeted Sindbis Virus Platform for Immunotherapy of Ovarian Cancer.

Our laboratory has been developing a Sindbis viral (SV) vector platform for treatments of ovarian and other types of cancers. In this study we show that SV.IL-12 combined with an agonistic OX40 antibody can eliminate ovarian cancer in a Mouse Ovarian Surface Epithelial Cell Line (MOSEC) model and further prevent tumors in mice rechallenged with tumor cells after approximately 5 months. Treatment efficacy is shown to be dependent upon T-cells that are transcriptionally and metabolically reprogramed. An influx of immune cells to the tumor microenvironment occurs. Combination of sequences encoding both IL-12 and anti-OX40 into a single SV vector, SV.IgGOX40.IL-12, facilitates the local delivery of immunoregulatory agents to tumors enhancing the anti-tumor response. We promote SV.IgGOX40.IL-12 as a safe and effective therapy for multiple types of cancer.