AIMS:Drug-loaded poly(lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a mold-less technique to investigate whether the combined delivery of both Y15 (FAK inhibitor) and metformin would result in enhanced effects on cell viability compared to the release of each drug alone for the treatment of platinum-resistant ovarian cancer (PROC). MATERIALS & METHODS:Scaffolds were fabricated using an easy and economical mold-less technique that combined PLGA and the drugs (i.e. metformin and/or Y15) in tetraglycol and injected in PBS, to form a globular morphology. RESULTS:The exposure of cells to metformin and Y15 resulted in a significantly enhanced cytotoxic efficacy compared to single-drug treatment with either metformin or Y15. When the drugs were delivered using the PLGA scaffolds, the combination of the two drugs was significantly more cytotoxic compared to scaffolds containing metformin only and Y15 only. CONCLUSIONS:The combination of metformin and Y15 can result in an increase in antitumor activity in PROC cells through apoptosis. The delivery of both drugs from the PLGA biomaterial scaffold allowed for a more enhanced combinational effect compared to the utilization of free drugs (without a scaffold) and should be further explored as a promising treatment of PROC.

Over the past 50 years, there has been increased awareness of the importance of social determinants of health (SDOH) in undergraduate medical education (UME) curricula. Since the societal guidelines and accreditation standards started to address SDOH topics, it has further evolved to recognize the impacts of SDOH on the medical outcomes for our patients. Medical schools across the United States have been integrating SDOH content across the curriculum in response to expectations from accrediting bodies, guided by national organizations, and fueled by internal efforts of curricular reform and improvement. Since its inception in 2017, our college of allopathic medicine has made SDOH a major pillar in its vertically and horizontally integrated 4-year curriculum. To evaluate the depth and breadth of SDOH integration, we searched “eMedley,” our curriculum management system, for content specifically addressing these topics. We identified various curricular activities integrating SDOH-related topics across all 4 years, including hands-on learning projects, as well as small-group discussions and large group discussions with a heavy emphasis on the clinical impact of SDOH. Based on our review of current trends and our experience, we recommend a progressive competency-based transition of SDOH learning and assessment across pre-clerkship, clerkship, and graduate medical education to ensure a meaningful longitudinal learning process.

Moral reasoning skills among medical students have regressed despite the implementation of ethics teachings in medical education curricula. This inability to retain moral reasoning capability is attributed to difficulty transitioning to the principled thinking stage of moral reasoning as well as worsening of ethical decision-making skills during clerkship education due to the “hidden curriculum.” Prior studies have examined the efficacy of individual strategies for moral education, but there is insufficient analysis comparing multiple educational interventions and moral reasoning assessment tools. The role and impact of these instruments in medical curricula for the advancement of health equity is reviewed.

Abstract Ovarian cancer is the fifth leading cause of cancer mortality among women. This high mortality rate is linked to the development of resistance to first-line chemotherapy with platinum compounds which has been attributed in part to increased activity of focal adhesion kinase (FAK). The anti-diabetic drug Metformin was previously shown to inhibit the proliferation and migration of ovarian cancer cells and thus, the combination of a FAK inhibitor, Y15, and Metformin may be a promising treatment for platinum-resistant ovarian cancer (PROC). The objective of this study was to evaluate the combination of Y15 and Metformin on PROC cell viability and the mechanism of cell death. An MTT assay was used to analyze cell viability in PROC OVCAR3 cells after 48 h of treatment by measuring the absorbance at 570 nm with a microplate reader. Western blot was used to determine the protein levels of the apoptosis marker cleaved PARP and the autophagy marker LC3B-II. The exposure of OVCAR3 platinum-resistant ovarian cancer cells to Metformin (4.5 mM) + Y15 (5.5 µM) resulted in a significantly enhanced cytotoxicity (32.6 ± 1.8%) compared to single drug treatment with either Metformin (4.5 mM) (65.0 ± 4.2%) or Y15 (5.5 µM) (66.0 ± 4.8%). A combination of Metformin (7.8 mM) + Y15 (5.5 µM) also resulted in a significantly enhanced cytotoxicity (22.8 ± 1.5%) compared to single drug treatment with either Metformin (7.8 mM) (50.7 ± 3.7%) or Y15 (5.5 µM) (66.0 ± 4.8%). Cells treated with the combination of Metformin and Y15 for 24, 48, and 72-hours showed an increase in cleaved PARP compared to the control, Metformin alone and Y15 alone. For Metformin alone, there was an increase in cleaved PARP compared to the control at all timepoints and increased from 24 hours to 72 hours. For Y15 alone, the amount of cleaved PARP was also higher compared to the control at all time points, however, decreased over time from 24 hours to 72 hours. Cells treated with Metformin, Y15, and a combination of Metformin and Y15 showed no conversion of LC3B-I to LC3B-II, which occurs during autophagy. Thus, it is concluded that the mechanism of cell death for both Metformin and Y15 is through apoptosis and not autophagy and apoptosis is enhanced with the combination of the drugs. The delivery of Metformin and Y15 can result in an additive effect on cell viability through apoptosis and can be further explored as a promising approach for the treatment of PROC. Citation Format: Manuel A. Duarte, Kristal Garcia, Marco A. Arriaga, Sue Anne Chew, Arkene S. Levy, Isabela Mendez. An evaluation of the combination of metformin and Y15 for the treatment of platinum-resistant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 954.

Core roles of medical school faculty are increasingly diverse, substantial, and evolving. In alignment with this dynamic nature of medical education, faculty effort should be accurately appraised, constantly evaluated, and rewarded to ensure faculty satisfaction and promote a culture of belonging. The study goal was to examine the imbalance in official assignments and perceptions of medical school faculty effort in various educator domains. An 80-item survey was designed to collect quantitative and qualitative measures of faculty perceptions of effort. Survey questions collected data on faculty demographics, intent to stay, and perceptions of effort in the following educator domains: teaching, educational leadership and administration, research and scholarship, and service. A mixed methods approach was utilized in data analysis. Eighty-eight complete survey responses were collected between February and May of 2022 from respondents from 27 states. There was a significant disparity between assigned and perceived effort in the educator domains of teaching, research, and service (P < 0.01). Faculty satisfaction with percent effort dedicated to teaching significantly correlated with intent to stay (P < 0.05). Satisfaction with workload assignments was higher with advanced academic rank and male gender. Qualitative analysis identified many key themes in the categories of promotion, workload, resources, and retention. Our study revealed that satisfaction with workload directly correlates with intent to stay, and principles of equitable workload distribution are violated from the perspective of the medical educator. This data provides critical information that can be used to assist medical schools in developing metrics to evaluate faculty performance in medical education and improve retention in academic medicine.

BACKGROUND/AIMS:In today's age, celiac disease (CD) is no longer solely characterized by chronic diarrhea in a malnourished child. Obesity is gradually being acknowledged as part of CD's clinical course. Both conditions have been linked to alterations of gut microbiome. Given the difficulty of strict gluten-free diet adherence, there is a need for less restrictive adjunctive therapies. We aimed to investigate the prevalence of obesity in patients diagnosed with CD with the goal of developing new therapeutic approaches. METHODS:Baseline data from the National Institute of Health's All of Us Research Program, was used to evaluate the relationship between CD and obesity. A retrospective cohort study was conducted where groups of individuals with CD and without CD were matched by age range and health surveys. Statistical analysis with odds ratios (OR) with 95% confidence intervals (CI) were reported. RESULTS:The prevalence of obesity was 32.6% in the CD group compared to 18.4% in the control group (OR, 2.111; 95% CI, 1.914-2.328; P< 0.0001). Women accounted for a greater population of patients with CD and obesity. The largest percentage of patients with CD and obesity were older than 65 years. The highest percentage of individuals in both the experimental and control groups were white, followed by African Americans. CONCLUSIONS:Our data shows a significant association between CD and increased prevalence of obesity. These results warrant further investigation into microbial changes and dietary exposures that affect the pathogenesis of both diseases.

An overarching theme in clinical literature suggests an inherent mistrust among populations of color within the healthcare system and the importance of healthcare professionals to bridge this gap in care. This is especially true when addressing cancer care in underserved populations due to mistrust in providers, diagnostic tools, and treatments. Ovarian cancer is difficult to diagnose early in all populations; however, women of color who have an intrinsic mistrust of the medical community will delay or refuse screenings or treatments that could be greatly beneficial. Similarly, although breast cancer rates are high in women of color, many are reluctant to utilize genetic screenings or counseling services due to bad experiences with healthcare, both personally and within their community. Moreover, transgender patients are at a unique disadvantage, as they face barriers to accessing culturally competent care while also being at a higher risk for developing cancer. The objective of this study was to conduct a scoping review of the literature in order to synthesize knowledge about the climate of mistrust between medical providers and racial, ethnic, and gender minorities with breast cancer and ovarian cancer. It is imperative for healthcare workers to acknowledge medical mistrust and strive to reduce internalized bias, increase their availability to patients, and ensure patients feel heard, respected, and well cared for during visits. Improving care by physicians can enhance trust between underserved communities and healthcare workers, encouraging all people to actively seek proper medical care and cancer screening, potentially resulting in a reduction of mortality and morbidity rates.

Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin’s potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome.

Impostor phenomenon (IP) is described as a pattern typified by doubting one's accomplishments and a persistent fear of being exposed as a fraud. These feelings of self-doubt are pervasive along the medical education continuum, beginning with medical students where IP has been associated with emotional stress, physical exhaustion, depression, and anxiety. We, therefore, conducted an interactive workshop with first-year medical students to educate them about the manifesting patterns and risk factors of IP and strategies to mitigate these feelings. The 60-min workshop began with participants voluntarily completing the Young Imposter Scale (YIS) followed by an interactive presentation that reviewed the literature related to IP and its prevalence in medicine. Participants were then assigned to small groups where they discussed three cases of IP in academia and the medical profession. Medical school faculty acted as facilitators and utilized pre-designed prompt questions to stimulate discussion. Students re-convened for a large group report out, where each group shared main discussion points. The session ended with facilitators discussing IP mitigation strategies that can be implemented at the individual, peer, and institutional levels. Participants were also invited to complete a post-workshop evaluation. Fifty first-year medical students participated in the session. A total of 49 (96 %) completed the YIS and post-workshop evaluation. Nineteen (40 %) participants obtained scores on the YIS to indicate a positive finding of IP. The percentage of female medical students meeting the threshold for IP was significantly higher (84 %, n = 41 vs 16 %, n = 7) than male medical students. The workshop was effective at identifying IP and associated risk factors and providing mitigation strategies, with 95.8 % of participants agreeing or strongly agreeing. In qualitative feedback, participants reported that the workshop was “very interactive”, “provided strategies to manage impostor syndrome” and “helped me become more vulnerable with my peers.” This workshop provided a novel interactive and effective method to increase medical students' awareness about IP which can be employed as a strategy to enhance student's wellness.

Objective Artificial Intelligence (AI) has made significant inroads into various domains, including medicine, raising concerns about algorithmic bias. This study investigates the presence of biases in generative AI programs, with a specific focus on gender and racial representations across 19 medical residency specialties. Methodology This comparative study utilized DALL-E2 to generate faces representing 19 distinct residency training specialties, as identified by the Association of American Medical Colleges (AAMC), which were then compared to the AAMC's residency specialty breakdown with respect to race and gender. Results Our findings reveal an alignment between OpenAI's DALL-E2's predictions and the current demographic landscape of medical residents, suggesting an absence of algorithmic bias in this AI model. Conclusion This revelation gives rise to important ethical considerations. While AI excels at pattern recognition, it inherits and mirrors the biases present in its training data. To combat AI bias, addressing real-world disparities is imperative. Initiatives to promote inclusivity and diversity within medicine are commendable and contribute to reshaping medical education. This study underscores the need for ongoing efforts to dismantle barriers and foster inclusivity in historically male-dominated medical fields, particularly for underrepresented populations. Ultimately, our findings underscore the crucial role of real-world data quality in mitigating AI bias. As AI continues to shape healthcare and education, the pursuit of equitable, unbiased AI applications should remain at the forefront of these transformative endeavors.

Three scenarios involving LGBTQI+ populations are presented. Case 1 highlights an in-class interaction between a faculty member and two students. A female-to-male transgender student is misgendered by a faculty member in front of the class, resulting in the student leaving the session. A second student acts as an ally when approached by the faculty member about the situation. Case 2 involves a professional development session focused on creating inclusive environments for LGBTQI+ students. One faculty member presents her approach of avoiding knowledge of students' personal lives as an effective tool for protecting students and faculty. Case 3 involves an inclusivity training session that doesn't connect as intended with the audience, resulting in students who are disengaged. Prompt questions promote reflection on what transpired, its impact, and institutional resources to help faculty in building inclusive environments. Readers will consider how to address what transpired both immediately and in the future.

The American Psychological Association defines racism as a construct that is ‘structural, institutional, interpersonal, and internalized.' The marginalization of persons of color due to blatant racism is a pervasive social issue that has historically held negative consequences for the health of these individuals, and evidence links racism to the higher levels of morbidity and mortality, seen especially among Blacks/African Americans (Paradies, 2015). The effort and movement to reduce marginalization of minorities through healthcare professional education is upon us. Providing health professional learners and practitioners with tools to understand manifestations and implications of racial acts and microaggressions in the healthcare setting is imperative, as is training medical professionals to recognize and mitigate their biases. This chapter highlights cases of varying levels of racism from the healthcare professionals' view and experience in the clinical setting.

Over the last 2 years in their role as a director of diversity, the author had a sense of fulfillment from hosting small group discussions with medical students on implicit bias. Many of these discussions are centered around cases they developed to mirror their own experiences. As an educator having small group discussions was important for the author. Their goal was to train well-rounded health care professionals with diverse thoughts and skills to serve everyone regardless of how they speak or where they are from. The author wanted to engage in conversations with their students and have a chance to truly observe if they understood the issue of microaggressions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

INTRODUCTION:The COVID-19 pandemic affected numerous subpopulations of people in unique ways. This study evaluated the impact of the COVID-19 pandemic on the mental health status of Broward County's aging lesbian, gay, bisexual, transgender, and queer (LGBTQ) seniors and identified strengths, weaknesses, and opportunities for interventions to enhance positive mental health outcomes. The study was performed from April 2021 through July 2021.METHODS:Online surveys measuring anxiety, depression, social support, and resilience were delivered by email to 47 residents of Wilton Manors, Florida. Study data were collected and collated using research electronic data capture tools with bivariate analysis using the Mann-Whitney test and generalized linear regression.RESULTS:Bivariate analysis showed that males scored significantly higher on the social interactions subscale of the Duke Social Support Index, indicating greater social support, yet there was not a significant difference with sexual orientation or living situation. Multivariate analysis revealed differences for several dependent variables including anxiety and depression reporting being lower in LGBTQ individuals.DISCUSSION:This study provides important insight into specific mental health challenges faced by Broward County's LGBTQ seniors, which can be applied to other LGBTQ populations across the globe.CONCLUSION:Using the results, targeted interventions can be developed to help improve mental health outcomes during periods of isolation for all individuals.

Introduction Lesbian, Gay, Bi-sexual, Transgender, Questioning, Intersex, and Asexual (LGBTQIA+) patients report experiences of discrimination within healthcare settings due to a lack of provider knowledge and biases of healthcare workers. There is an identified need among all health professions to provide more culturally competent healthcare for this community. Early interventions during healthcare profession training programs may be effective to address this need. The overall goal of this study was to assess the educational impact of an active learning session that was specifically designed to enhance LGBTQIA+ cultural competency awareness using an interprofessional setting. Methods This 2-year study involved students from 16 healthcare professional programs joining virtually to form interprofessional teams. A small group case-based learning approach was used and included pre/post-activity surveys to measure the change in student attitude and confidence, as well as the change in perception of the importance of the activity. Results Results indicate an increase in perception of importance (p < 0.005) and in overall level of confidence (p < 0.001) with respect to LGBTQIA+ issues post-session. Key themes established through the session represent an overall recognition of the importance of interprofessional education and awareness of LGBTQIA+ healthcare needs. Discussion The results demonstrate the effectiveness of a case-based approach for enhancing cultural competency awareness across different healthcare professions programs. This session also provided an interprofessional learning environment to allow multiple healthcare professions program students to interact and share perspectives. The positive impact of this intervention in a highly collaborative virtual learning environment also highlights that this immersive active learning approach that can be adopted across different programs and institutions.

Background The relevance and importance of using racial and ethnic categories in medical education is an area requiring richer discussion and engagement among all health professions educators. Objectives There is a genuine need to identify opportunities for leveraging social and structural determinants of health to address health disparities within medical education. We designed a focus session led by a team of diverse clinical and basic science faculty to analyze how medical curricula can integrate racial/ethnic identity as a clinical indicator. We sought to develop strategies to empower medical students and teachers to integrate race as a social rather than a biological construct. Methods The 90-minute focus session included an interactive presentation reviewing the literature related to the use of racial identity in medical education, small group case-based discussions in breakout rooms, a large group debrief, and an optional activity for participants to apply the knowledge gained. The study was approved by the Nova Southeastern University Institutional Review Board (IRB #: 2021-185-NSU). Results Thirty-three participants attended the session at the 2021 International Association of Medical Science Educators (IAMSE) Conference. Eleven (33%) participated in both pre-session and post-session surveys. Survey data revealed significant pre-/post-changes in the knowledge of the advantages and disadvantages of using race in medical education. Qualitative data indicated that participants acquired new knowledge related to the integration of racial identity as a clinical indicator and they were willing to incorporate strategies learned into their teaching. Conclusion Our study data suggests that this focus session equipped faculty with new knowledge and resources to effectively incorporate racial/ethnic identity into medical school curricula to increase awareness of healthcare disparities.

BACKGROUND:Current approaches for managing benzodiazepine (BZD) withdrawal symptoms are daunting for clinicians and patients, warranting novel treatment and management strategies. This review discusses the pharmacodynamic properties of BZDs, gabapentinoids (GBPs), endozepines, and novel GABAergic compounds associated with potential clinical benefits for BZD-dependent patients. The objective of this study was to review the complex neuromolecular changes occurring within the GABAergic and glutamatergic systems during the BZD tolerance and withdrawal periods while also examining the mechanism by which GBPs and alternative pharmacological therapies may attenuate withdrawal symptoms.METHODS AND RESULTS:An elaborative literature review was conducted using multiple platforms, including the National Center for Biotechnology (NCBI), AccessMedicine, ScienceDirect, pharmacology textbooks, clinical trial data, case reports, and PubChem. Our literature analysis revealed that many distinctive neuroadaptive mechanisms are involved in the GABAergic and glutamatergic systems during BZD tolerance and withdrawal. Based on this data, we hypothesize that GBPs may attenuate the overactive glutamatergic system during the withdrawal phase by an indirect presynaptic glutamatergic mechanism dependent on the α2δ1 subunit expression.CONCLUSIONS:GBPs may benefit individuals undergoing BZD withdrawal, given that the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor current significantly increases during abrupt BZD withdrawal in animal studies. This may be a conceivable explanation for the effectiveness of GBPs in treating both alcohol withdrawal symptoms and BZD withdrawal symptoms in some recent studies. Finally, natural and synthetic GABAergic compounds with unique pharmacodynamic properties were found to exert potential clinical benefits as BZD substitutes in animal studies, though human studies are lacking.

The fifth annual summer research summit organized by the Center of Excellence (COE) in Health Equity, Training and Research, Baylor College of Medicine (BCM), was held on May 17, 2022. The theme of this year’s summit was ‘Academic-Community Partnerships: Change Agents for Advancing Health Equity.’ Given the ongoing pandemic, the summit was conducted virtually through digital platforms. This program was intended for both BCM and external audiences interested in advancing health equity, diversity, and inclusion in healthcare among healthcare providers and trainees, biomedical scientists, social workers, nurses, and individuals involved in talent acquisition and development, such as hiring managers (HR professionals), supervisors, college and hospital affiliate leadership and administrators, as well as diversity and inclusion excellence practitioners. We had attendees from all regions of the United States as well as from Saudi Arabia. The content in this Book of Abstracts encapsulates a summary of the research efforts by the BCM COE scholars (which includes post-baccalaureate students, medical students, clinical fellows, and junior faculty from BCM) as well as the external summit participants. The range of topics in this year’s summit was quite diverse, encompassing disparities in relation to maternal and child health (MCH), immigrant health, cancers, vaccination uptakes, and COVID-19 infections. Various solutions were ardently presented to address these disparities, including community engagement and partnerships, improvement in health literacy, and the development of novel technologies and therapeutics. With this summit, BCM continues to build on its long history of educational outreach initiatives to promote diversity in medicine by focusing on programs aimed at increasing the number of diverse and highly qualified medical professionals ready to introduce effective and innovative approaches to reduce or eliminate health disparities. These programs will improve information resources, clinical education, curricula, research, and cultural competence as they relate to minority health issues and social determinants of health. The year’s summit was a great success! Copyright © 2022 Dongarwar et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.