A longitudinal study of multicultural curriculum in medical education

OBJECTIVE: To evaluate impact a multicultural interclerkship had on students\u27 perception of knowledge, interview skills, and empathy towards serving culturally diverse populations and role student demographics played in learning. METHODS: Data extracted from students\u27 self-reported course evaluations and pre/post questionnaires during multiculturalism interclerkship across 11 academic years. Inquired students\u27 opinion about four areas: effectiveness, small group leaders, usefulness, and overall experience. Subscale and item ratings were compared using trend tests including multivariate analyses. RESULTS: During studied years, 883 students completed course evaluation with high overall mean rating of 3.08 (S = 0.45) and subscale mean scores ranging from 3.03 to 3.30. Trends in three of four subscales demonstrated clear uptrend (p \u3c 0.0001). Positive correlations between ratings of leaders and usefulness were observed (p \u3c 0.0001). Pre/post matched dataset (n = 967) indicated majority of items (19/23) had statistically significant higher post interclerkship ratings compared to pre scores with nine of 19 having statistically significant magnitudes of change. Questionnaire had high overall reliability (Cronbach alpha = 0.8), and item-to-group correlations ranged from 0.40 to 0.68 (p \u3c 0.0001). CONCLUSIONS: By increasing students\u27 exposure and interaction with diverse patients, their knowledge, attitude, and skills were increased and expanded in positive manner. These findings might inform those who are interested in enhancing this important competence. This is especially true given increasing scrutiny this global topic is receiving within and across healthcare professions around the world

Weaving The Threads of Multiculturalism Throughout Medical Education

How do medical students learn about the healthcare impact of essential multiculturalism issues in an increasingly diverse population? This study gauges student participation in a variety of multiculturalism curricula and student assessment of curriculum time devoted to multiculturalism at school versus national levels

Outcomes from an Interprofessional Educational Model for Teaching Community Health

Interprofessional team work is widely recognized as an essential component of our health care delivery system. At UMass, an interprofessional educational partnership was established with the goal of promoting interprofessional teaching to medical and nursing students in the area of community health. Presented at the UMMS Commonwealth Medicine Academic Conference, Worcester, Mass. in 2006

Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4+ T-cell repertoire selection

Human CD4+ αβ T cells are activated via T-cell receptor recognition of peptide epitopes presented by major histocompatibility complex (MHC) class II (MHC-II). The open ends of the MHC-II binding groove allow peptide epitopes to extend beyond a central nonamer core region at both the amino- and carboxy-terminus. We have previously found that these non-bound C-terminal residues can alter T cell activation in an MHC allele-transcending fashion, although the mechanism for this effect remained unclear. Here we show that modification of the C-terminal peptide-flanking region of an influenza hemagglutinin (HA305−320) epitope can alter T-cell receptor binding affinity, T-cell activation and repertoire selection of influenza-specific CD4+ T cells expanded from peripheral blood. These data provide the first demonstration that changes in the C-terminus of the peptide-flanking region can substantially alter T-cell receptor binding affinity, and indicate a mechanism through which peptide flanking residues could influence repertoire selection

Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4+ T cell immunity

CD4+ T cells recognize a broad range of peptide epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which contribute to immune memory and limit COVID-19 disease. We demonstrate that the immunogenicity of SARS-CoV-2 peptides, in the context of the model allotype HLA-DR1, does not correlate with their binding affinity to the HLA heterodimer. Analyzing six epitopes, some with very low binding affinity, we solve X-ray crystallographic structures of each bound to HLA-DR1. Further structural definitions reveal the precise molecular impact of viral variant mutations on epitope presentation. Omicron escaped ancestral SARS-CoV-2 immunity to two epitopes through two distinct mechanisms: (1) mutations to TCR-facing epitope positions and (2) a mechanism whereby a single amino acid substitution caused a register shift within the HLA binding groove, completely altering the peptide-HLA structure. This HLA-II-specific paradigm of immune escape highlights how CD4+ T cell memory is finely poised at the level of peptide-HLA-II presentation

CD4(+)CD25(+)FOXP3(+) Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer

BACKGROUND: A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients. METHODOLOGY AND PRINCIPAL FINDINGS: Treg were identified and characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group. CONCLUSIONS/SIGNIFICANCE: Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy

Seven mysteries of LAG-3: a multi-faceted immune receptor of increasing complexity

Despite three decades of research to its name and increasing interest in immunotherapies that target it, LAG-3 remains an elusive co-inhibitory receptor in comparison to the well-established PD-1 and CTLA-4. As such, LAG-3 targeting therapies have yet to achieve the clinical success of therapies targeting other checkpoints. This could, in part, be attributed to the many unanswered questions that remain regarding LAG-3 biology. Of these, we address: (i) the function of the many LAG-3-ligand interactions, (ii) the hurdles that remain to acquire a high-resolution structure of LAG-3, (iii) the under-studied LAG-3 signal transduction mechanism, (iv) the elusive soluble form of LAG-3, (v) the implications of the lack of (significant) phenotype of LAG-3 knockout mice, (vi) the reports of LAG-3 expression on the epithelium, and (vii) the conflicting reports of LAG-3 expression (and potential contributions to pathology) in the brain. These mysteries which surround LAG-3 highlight how the ever-evolving study of its biology continues to reveal ever-increasing complexity in its role as an immune receptor. Importantly, answering the questions which shroud LAG-3 in mystery will allow the maximum therapeutic benefit of LAG-3 targeting immunotherapies in cancer, autoimmunity and beyond