Extramammary Paget Disease. Part II. Evidence-based Approach to Management.

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and non-invasive therapies, as well as novel approaches for advanced disease.

Extramammary Paget Disease. Part I. Epidemiology, Pathogenesis, Clinical Features, and Diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

Social justice in medical education: a student-led approach to addressing COVID-19 vaccine equity in the Hispanic/Latinx community.

The current healthcare system disproportionately affects vulnerable populations, leading to disparities in health outcomes. As a result, medical schools need to equip future physicians with the tools to identify and address healthcare disparities. The University of Nevada, Reno School of Medicine implemented a Scholarly Concentration in Medical Social Justice (SCiMSJ) program to address this issue. Three medical students joined the program and pioneered a project to address the equitable vaccine distribution within the local Hispanic/Latinx community. After identifying the disparity in vaccine uptake and high levels of vaccine hesitancy, they collaborated with local organizations to address vaccine misinformation and accessibility. They organized outreach events, provided vaccine education, and hosted a vaccine clinic at a Catholic church with a high Hispanic/Latinx congregation. Through their efforts, they administered 1,456 vaccines. The estimated economic and societal impacts of their work was 879 COVID-19 cases avoided, 5 deaths avoided, 45 life years saved, and $29,286 in economic value. The project's success highlights the effectiveness of a student-led approach to promote skill development in social justice training. Leadership skills and coalition building were crucial in overcoming resource limitations and connecting organizations with the necessary volunteer force. Building trust with the Hispanic/Latinx community through outreach efforts and addressing vaccine hesitancy contributed to the well-attended vaccine clinic. The project's framework and approach can be adopted by other medical students and organizations to address health disparities and improve health outcomes in their communities.

miR-10b-5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes.

BACKGROUND/AIM: Diabetes has substantive co-occurrence with disorders of gut-brain interactions (DGBIs). The pathophysiological and molecular mechanisms linking diabetes and DGBIs are unclear. MicroRNAs (miRNAs) are key regulators of diabetes and gut dysmotility. We investigated whether impaired gut barrier function is regulated by a key miRNA, miR-10b-5p, linking diabetes and gut dysmotility. METHODS: We created a new mouse line using the Mb3Cas12a/Mb3Cpf1 endonuclease to delete mir-10b globally. Loss of function studies in the mir-10b knockout (KO) mice were conducted to characterize diabetes, gut dysmotility, and gut barrier dysfunction phenotypes in these mice. Gain of function studies were conducted by injecting these mir-10b KO mice with a miR-10b-5p mimic. Further, we performed miRNA-sequencing analysis from colonic mucosa from mir-10b KO, wild type, and miR-10b-5p mimic injected mice to confirm (1) deficiency of miR-10b-5p in KO mice, and (2) restoration of miR-10b-5p after the mimic injection. RESULTS: Congenital loss of mir-10b in mice led to the development of hyperglycemia, gut dysmotility, and gut barrier dysfunction. Gut permeability was increased, but expression of the tight junction protein Zonula occludens-1 was reduced in the colon of mir-10b KO mice. Patients with diabetes or constipation- predominant irritable bowel syndrome, a known DGBI that is linked to leaky gut, had significantly reduced miR-10b-5p expression. Injection of a miR-10b-5p mimic in mir-10b KO mice rescued these molecular alterations and phenotypes. CONCLUSIONS: Our study uncovered a potential pathophysiologic mechanism of gut barrier dysfunction that links both the diabetes and gut dysmotility phenotypes in mice lacking miR-10b-5p. Treatment with a miR-10b-5p mimic reversed the leaky gut, diabetic, and gut dysmotility phenotypes, highlighting the translational potential of the miR-10b-5p mimic.