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p38 MAPKs are key regulators of cellular adaptation to various stress stimuli, however, their role in mediating erythrocyte cell death and hemolysis is largely unknown. We hypothesized that activation of erythrocyte p38 MAPK is a common event in the stimulation of hemolysis, and that inhibition of p38 MAPK pathways could mitigate hemolysis in hemoglobinopathies. We exposed human erythrocytes to diamide-induced oxidative stress or to hypoosmotic shock in the presence or absence of p38 MAPK inhibitors (SCIO469, SB203580, CMPD1) and used immunoblotting to determine MAPK activity and to identify possible downstream effectors of p38 MAPK. We also evaluated the impact of p38 MAPK inhibitors on stress-induced hemolysis or hypoxia-induced sickling in erythrocytes from mouse models of sickle cell disease. We found that human erythrocytes express conventional MAPKs (MKK3, p38 MAPK, MAPKAPK2) and identified differential MAPK activation pathways in each stress condition. Specifically, p38 MAPK inhibition in diamide-treated erythrocytes was associated with decreased phosphorylation of Src tyrosine kinases and Band 3 protein. Conversely, hypoosmotic shock induced MAPKAPK2 and RSK2 phosphorylation, which was inhibited by SCIO469 or CMPD1. Relevant to hemoglobinopathies, sickle cell disease was associated with increased erythrocyte MKK3, p38 MAPK, and MAPKAPK2 expression and phosphorylation as compared with erythrocytes from healthy individuals. Furthermore, p38 MAPK inhibition was associated with decreased hemolysis in response to diamide treatments or osmotic shock, and with decreased erythrocyte sickling under experimental hypoxia. These findings provided insights into MAPK-mediated signaling pathways that regulate erythrocyte function and hemolysis in response to extracellular stressors or human diseases.

OBJECTIVE: To obtain an overview of medical student attitudes on the need for explicit consent for pelvic exams under anesthesia performed for educational purposes DESIGN: From February to October 2020, 201 medical students at a single medical school in the United States participated in a cross-sectional survey after completion of the obstetrics and gynecology clerkship. Outcome measures included endorsement of need for explicit informed consent for educational pelvic exams under anesthesia, and knowledge of informed consent processes for such exams. SETTING: University of Pittsburgh School of Medicine PARTICIPANTS: Third- and fourth-year medical students RESULTS: Overall, 75% of medical students endorsed a need for explicit informed consent for educational pelvic exams under anesthesia, which extended to prostate, rectal, and breast exams under anesthesia. Additionally, 45% and 77% of these participants indicated that consent for educational pelvic exams under anesthesia should take the form of a separate signature line on the surgical consent form and/or a verbal form, respectively. Only 40% of students correctly identified institutional policy for obtaining informed consent for educational pelvic exams under anesthesia. Rotation with the oncologic surgical service (p=0.02) and correct identification of institutional informed consent policies (p=0.002) were associated with decreased perceptions of the importance of explicit informed consent for educational pelvic exams under anesthesia. CONCLUSIONS: Medical students at the institution studied largely support explicit informed consent for educational pelvic and other sensitive exams under anesthesia, but a knowledge gap on institutional informed consent policy exists. Medical students support increased transparency and bodily autonomy. Due to the agreement of patients and medical students and the ethical rationale for this position, it may be appropriate for physicians and institutions to consider new processes of obtaining explicit informed consent for pelvic exams under anesthesia by medical students. COMPETENCIES: Interpersonal and Communication Skills (ICS), Professionalism

BackgroundHydroxychloroquine (HCQ) is widely used in the treatment of malaria, rheumatologic disease such as lupus, and most recently, COVID-19. These uses raise concerns about its safe use in the setting of glucose-6-phosphate dehydrogenase (G6PD) deficiency, especially as 11% of African American men carry the G6PD A- variant. However, limited data exist regarding the safety of HCQ in this population.Study design and methodsRecently, we created a novel "humanized" mouse model containing the G6PD deficiency A- variant (Val68Met) using CRISPR technology. We tested the effects of high-dose HCQ administration over 5 days on hemolysis in our novel G6PD A- mice. In addition to standard hematologic parameters including plasma hemoglobin, erythrocyte methemoglobin, and reticulocytes, hepatic and renal function were assessed after HCQ.ResultsResidual erythrocyte G6PD activity in G6PD A- mice was ~6% compared to wild-type (WT) littermates. Importantly, we found no evidence of clinically significant intravascular hemolysis, methemoglobinemia, or organ damage in response to high-dose HCQ.ConclusionsThough the effects of high doses over prolonged periods was not assessed, this study provides early, novel safety data of the use of HCQ in the setting of G6PD deficiency secondary to G6PD A-. In addition to novel safety data for HCQ, to our knowledge, we are the first to present the creation of a "humanized" murine model of G6PD deficiency.

ObjectiveSexual health is important to quality of life; however, the sexual health of gynecologic cancer patients is infrequently and inadequately addressed. We sought to understand patient experiences and preferences for sexual health care to help inform strategies for improvement.Methods/MaterialsAn anonymous, cross-sectional survey of outpatient gynecologic cancer patients at a large academic medical center was performed as part of a larger study examining patient and caregiver needs. The survey explored patient-provider discussions about sexuality across 3 domains (experiences, preferences, barriers) and 4 phases of cancer care (diagnosis, treatment, treatment completion, follow-up). Age, relationship status, sexual activity, and cancer type were recorded.ResultsMean age was 63 years. Most patients had ovarian cancer (38%) or endometrial cancer (32%). Thirty-seven percent received treatment within the last month, 55% were in a relationship, and 35% were sexuality active. Thirty-four percent reported sexuality as somewhat or very important, whereas 27% felt that it was somewhat or very important to discuss. Importance of sexuality was associated with age, relationship status, and sexual activity but not cancer type. Fifty-seven percent reported never discussing sexuality. Age was associated with sexuality discussions, whereas relationship status, sexual activity, and cancer type were not. The most common barrier to discussion was patient discomfort. Follow-up was identified as the best time for discussion. Sexuality was most often discussed with a physician or advanced practice provider and usually brought up by the provider.ConclusionsDemographic predictors of importance of sexuality to the patient are age, relationship status, and sexual activity. Providers primarily use age as a proxy for importance of sexuality; however, relationship status and sexual activity may represent additional ways to screen for patients interested in discussing sexual health. Patient discomfort with discussing sexuality is the primary barrier to sexual health discussions, and awareness of this is key to developing effective approaches to providing sexual health care.