Apolipoprotein (apo) E is an exchangeable apolipoprotein that plays an integral role in cholesterol transport in the plasma and the brain. It is also associated with protein misfolding or amyloid proteopathy of the beta amyloid peptide (Abeta) in Alzheimer's disease (AD) and cerebral amyloid angiopathy. The C-terminal domain (CT) of apoE encompasses two types of amphipathic alpha helices: a class A helix (residues 216-266) and a class G* helix (residues 273-299). This domain also harbors high-affinity lipoprotein binding and apoE self-association sites that possibly overlap. The objective of this study is to examine if the neurotoxic oligomeric Abeta interacts with apoE CT and if this association affects the lipoprotein binding function of recombinant human apoE CT. Site-specific fluorescence labeling of single cysteine-containing apoE CT variants with donor probes were employed to identify the binding of Abeta bearing an acceptor probe by intermolecular fluorescence resonance energy-transfer analysis. A higher efficiency of energy transfer was noted with probes located in the class A helix than with those located in the class G* helix of apoE CT. In addition, incubation of apoE CT with Abeta severely impaired the lipid binding ability and the overall amount of lipid-associated apoE CT. However, when apoE CT is present in a lipid-bound state, Abeta appears to be localized within the lipid milieu of the lipoprotein particle and not associated with any specific segments of the protein. When our data are taken together, they suggest that Abeta association compromises the fundamental lipoprotein binding function of apoE, which may have implications not only in terms of amyloid buildup but also in terms of the accumulation of cholesterol at extracellular sites.

Introduction: Social Contexts in Medicine (SCIM) is an 18-month program that connects medical students, patients, and physicians for a longitudinal learning experience. SCIM was developed for first-and secondyear medical students and seeks to supplement students' biomedical education with practical experiences built around community and continuity. The program increases students' awareness of, and skills to address, social determinants of health via a seminar series, a home visit program, and a mentoring component. Methods: The program begins with a seminar series covering communication skills and the basics of social determinants of health, providing the foundation for successful home visits. Students are then paired with a patient for home visits to learn firsthand about the complex social factors that affect health and illness, patient participation in health care systems, and the doctor-patient relationship. In conjunction with the home visits, students obtain guidance from a physician mentor. Results: The SCIM program has been successful during its first 3 years at our institution. Analysis of changes in student attitudes using Crandall's Medical Student Attitudes Toward the Underserved survey has shown that SCIM students develop more positive attitudes toward the underserved than do their peers completing traditional clinic-based preceptorships. Additionally, in student surveys, the average response to the statement "I learned something valuable I would not have otherwise learned in my classes" has been 4.5 out of 5. Discussion: These findings suggest that the SCIM model contributes to medical education by broadening students' understanding about the influence of social factors on health and disease.

Limited research has examined the ways in which public health training programs equip students to address health disparities affecting the lesbian, gay, bisexual, and transgender (LGBT) community and other sexual and gender minority (SGM) populations. This study outlines the availability of public health curricula on SGM health topics, and the prevalence of LGBT and SGM-inclusive institutional support services across CEPH-accredited U.S. schools of public health. Content analysis of all course offerings related to gender and sexuality revealed a limited focus on sexual and gender minority health: just 4.7% of courses contained keywords indicating that LGBT or SGM health topics were covered. Similar analysis of institutional support services available at U.S. schools of public health found that only 25% of schools had LGBT student organizations, and just 19% had an office of diversity that specifically advertised LGBT or SGM-inclusive programming or services on the institution's Web site. Finally, only two of 52 schools offered an educational certificate centered on LGBT health. These findings illustrate a significant need for enhanced curricular content and institutional support services that equip public health students to address SGM health disparities. Improvement in this area may encourage future health care professionals to work to reduce these disparities, to improve SGM persons' experiences in health care settings, and to generate further research in this area.

Members of the lesbian, gay, bisexual, transgender, and queer community experience marginalization, bias, and discrimination, including in the world of academic medicine. People who are transgender and nonbinary (TGNB) experience further marginalization compared with individuals who are lesbian, gay, bisexual, and queer. According to a recent survey, more than half of medical students who are TGNB chose not to disclose their gender identities during training due to fears of discrimination, feeling a lack of support, and concerns about future career options. Academic medicine has historically pathologized TGNB individuals, perpetuating discrimination structurally and reinforcing discriminatory behaviors of peers and faculty. In this Perspective, the authors provide a comprehensive overview of the challenges that administrators and educators face in creating a learning environment that is inclusive of TGNB trainees. They outline opportunities for change and provide strategies to address administrative and educational challenges, including those related to institutional climate, policies, data collection, physical spaces, health care, curriculum, mentoring, and the evaluation of TGNB trainees. Finally, the authors issue a call to action for medical educators and administrators to create environments in which trainees who are TGNB can fulfill their educational mission: to learn the practice of medicine.