Role of renin angiotensin system inhibitors and metformin in Glioblastoma Therapy: a review.

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.

Integrating the Teaching and Assessment of Moral Reasoning into Undergraduate Medical Education to Advance Health Equity.

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.

Impostor phenomenon: Prevalence among 1st year medical students and strategies for mitigation.

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.

What Goes In, Must Come Out: Generative Artificial Intelligence Does Not Present Algorithmic Bias Across Race and Gender in Medical Residency Specialties.

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.

Mental Health Effects of the COVID-19 Pandemic on Aging Lesbian, Gay, Bisexual, Transgender, and Queer Populations.

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.

A health care experience from an immigrant educator.

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).

Application of gabapentinoids and novel compounds for the treatment of benzodiazepine dependence: the glutamatergic model.

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.

Racial Identity and Relevance in Teaching Clinical Skills and Diagnostic Medicine: A Small/Pilot Focus Session to Engage Medical Educators.

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.

Role and significance of c-KIT receptor tyrosine kinase in cancer: A review.

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.

Inclusive LGBTQIA+ healthcare: An interprofessional case-based experience for cultural competency awareness.

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.

Attitudes and Knowledge of Medical Students Towards Healthcare for Lesbian, Gay, Bisexual, and Transgender Seniors: Impact of a Case-Based Discussion With Facilitators From the Community.

BACKGROUND:  Lesbian, gay, bisexual, and transgender (LGBT) seniors are generally a medically underserved population that faces unique healthcare challenges. When compared to younger patients, LGBT seniors are at a greater risk for social isolation and have higher rates of smoking, disability, physical and mental distress, and lack of access to healthcare services. They are often reluctant to discuss their sexual orientations and gender identities with healthcare providers due to fear of discrimination and receiving inferior care based on prior unsatisfactory experiences with untrained or insensitive healthcare providers. Furthermore, recent research has revealed that only about 50% of primary care providers indicated confidence in providing culturally competent LGBT healthcare, highlighting the need for more LGBT proficiency training in medical school curricula. OBJECTIVES: The aim of this study was to provide early intervention training to first-year medical students regarding best practices for equitable healthcare for LGBT seniors through integrative, small group, case-based discussions. The impact of this activity on the knowledge and attitudes of medical students regarding LGBT healthcare was also assessed. METHODS: First-year medical students participated in a two-hour small group, case-based discussion. Each group consisted of seven to eight students with one of seven facilitators who were invited members of the LGBT community. Students were provided with two clinical case scenarios related to treatment of LGBT senior patients. Students were given a pre/post-session knowledge and attitude survey to assess the impact of the session on their attitudes and understanding of the importance of providing equitable healthcare to LGBT patients. A rubric was also used by facilitators to evaluate level of student engagement and professionalism. RESULTS: A total of 51 first-year medical students attended the session and 38 (74.5%) completed the pre/post surveys. There was diverse representation in our student demographic with 5.2% of respondents identifying as LGBT. Survey results showed a significant increase in knowledge confidence and attitudes following the session. Students' attitudes regarding determinants of health status changed significantly for nine of the 13 (69%) survey items. In addition, their confidence in knowledge regarding healthcare barriers, health issues, and practices for LGBT culturally competent care significantly increased post-session. Data from our assessment rubrics also show that students were highly professional and engaged with the LGBT facilitators. CONCLUSION: Our study provides some evidence that case-based training of medical students regarding issues that affect health of LGBT seniors can improve attitudes and sensitize them to the unique needs of this population. Through this activity, the students indicated their desire to learn more about the topics covered and to receive further training in this field of study. While the study was somewhat limited by a small participant number, the significance of the data demonstrates the effectiveness of the approach involving members of the LGBT community as facilitators. Future work with these students as part of a longitudinal curriculum will include additional LGBT proficiency training to be offered in the subsequent blocks of instruction. Additionally, this intervention could potentially be adapted by other medical schools.

Strategies to better treat glioblastoma: antiangiogenic agents and endothelial cell targeting agents.

Glioblastoma multiforme (GBM) is the most prevalent and aggressive form of glioma, with poor prognosis and high mortality rates. As GBM is a highly vascularized cancer, antiangiogenic therapies to halt or minimize the rate of tumor growth are critical to improving treatment. In this review, antiangiogenic therapies, including small-molecule drugs, nucleic acids and proteins and peptides, are discussed. The authors further explore biomaterials that have been utilized to increase the bioavailability and bioactivity of antiangiogenic factors for better antitumor responses in GBM. Finally, the authors summarize the current status of biomaterial-based targeting moieties that target endothelial cells in GBM to more efficiently deliver therapeutics to these cells and avoid off-target cell or organ side effects.

A Call to Action: Preventing Opioid and Substance Abuse in South Florida Youth.

Description The opioid crisis poses a substantial threat to youth throughout the nation. This crisis has been exacerbated by the COVID-19 pandemic, reversing some of the positive national trends in the fight against the opioid epidemic. Some risk factors for youth opioid use have been identified nationally. The South Florida tri-county region of Miami-Dade, Broward and Palm Beach is a culturally distinct region which may not follow national trends and likely has unique risk and protective factors. To address the concerning spike in youth opioid use in South Florida, a community coalition was formed to identify factors unique to South Florida and create a plan for early awareness and prevention.

The Application of Biomaterials in the Treatment of Platinum-Resistant Ovarian Cancer.

More than 70 % of women with ovarian cancer are diagnosed with advanced-stage disease, which is initially treated with cytoreductive surgery, and combination chemotherapy with platinum-based compounds. Most patients initially respond to platinum-based therapy, but eventually up to 80 % of this responsive cohort becomes refractory due to the development of platinum resistance. This review discusses current and potential therapeutic approaches that exploit biomaterial-based applications to combat platinum resistance either by enhancing the delivery of platinum-based drugs or prodrugs, delivering other toxic non-platinum-based bioactive factors (by themselves or in combination with platinum-based drugs) or by delivering other bioactive factors that re-sensitize resistant ovarian cancer cells to these drugs. The types of materials that are used, the bioactive factors applied (i.e., drug or gene delivery), and the specific agents that are employed to target these types of cancer cells are discussed. We conclude that the unique attributes of biomaterial-based applications can be further explored toward overcoming platinum-resistant ovarian cancer as monotherapy, or in combination with other treatment strategies.

Focal Adhesion Kinase in Ovarian Cancer: A Potential Therapeutic Target for Platinum and Taxane-Resistant Tumors.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase, which is an essential player in regulating cell migration, invasion, adhesion, proliferation, and survival. Its overexpression and activation have been identified in sixty-eight percent of epithelial ovarian cancer patients and this is significantly associated with higher tumor stage, metastasis, and shorter overall survival of these patients. Most recently, a new role has emerged for FAK in promoting resistance to taxane and platinum-based therapy in ovarian and other cancers. The development of resistance is a complex network of molecular processes that make the identification of a targetable biomarker in platinum and taxane-resistant ovarian cancer a major challenge. FAK overexpression upregulates ALDH and XIAP activity in platinum-resistant and increases CD44, YB1, and MDR-1 activity in taxaneresistant tumors. FAK is therefore now emerging as a prognostically significant candidate in this regard, with mounting evidence from recent successes in preclinical and clinical trials using small molecule FAK inhibitors. This review will summarize the significance and function of FAK in ovarian cancer, and its emerging role in chemotherapeutic resistance. We will discuss the current status of FAK inhibitors in ovarian cancers, their therapeutic competencies and limitations, and further propose that the combination of FAK inhibitors with platinum and taxane-based therapies could be an efficacious approach in chemotherapeutic resistant disease.

6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant.

BACKGROUND: 6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200-250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). RESULTS: Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 +/- 0.2 mm to 1.0 +/- 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 +/- 0.6 mm to 0.8 +/- 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 +/- 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. CONCLUSION: From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats.