Student-Led Efforts to Advance Anti-Racist Medical Education.

Over the past decade, medical schools across the United States have increasingly dedicated resources to advancing racial and social justice, such as by supporting diversity and inclusion efforts and by incorporating social medicine into the traditional medical curricula. While these changes are promising, the academic medicine community must apply an anti-racist lens to every aspect of medical education to equip trainees to recognize and address structural inequities. Notably, organizing and scholarly work led by medical students has been critical in advancing anti-racist curricula. In this article, the authors illustrate how student activism has reshaped medical education by highlighting examples of student-led efforts to advance anti-racist curricula at Harvard Medical School (HMS) and at the University of California, San Francisco (UCSF) School of Medicine. HMS students collaborated with faculty to address aspects of existing clinical practice that perpetuate racism, such as the racial correction factor in determining kidney function. They also responded to the existing curricula by noting missed opportunities to discuss structural racism, and they planned supplemental sessions to address these gaps. At UCSF, students identified specific avenues to improve the rigor of social medicine courses and developed new curricula to equip students with skills to confront and work to dismantle racism. The authors describe how HMS students, in an effort to improve the learning environment, developed a workshop to assist students in navigating microaggressions and discrimination in the clinical setting. At UCSF, students partnered with faculty and administration to advocate pass/fail grading for clerkships after university data revealed racial disparities in students' clerkship assessments. In reviewing these examples of students' advocacy to improve their own curricula and learning environments, the authors aim to provide support for students and faculty pursuing anti-racist curricular changes at their own institutions.

Mechanism of EBV inducing anti-tumour immunity and its therapeutic use.

Tumour-associated antigens (TAAs) comprise a large set of non-mutated cellular antigens recognized by T cells in human and murine cancers. Their potential as targets for immunotherapy has been explored for more than two decades1, yet the origins of TAA-specific T cells remain unclear. While tumour cells may be an important source of TAAs for T cell priming2, several recent studies suggest that infection with some viruses, including Epstein-Barr virus and influenza virus can elicit T cell responses against abnormally expressed cellular antigens that function as TAAs3,4. However, the cellular and molecular basis of such responses remains undefined. Here we show that expression of the Epstein-Barr virus signalling protein LMP1 in B cells provokes T cell responses to multiple TAAs. LMP1 signalling leads to overexpression of many cellular antigens previously shown to be TAAs, their presentation on major histocompatibility complex classes I (MHC-I) and II (MHC-II) (mainly through the endogenous pathway) and the upregulation of costimulatory ligands CD70 and OX40L, thereby inducing potent cytotoxic CD4+ and CD8+ T cell responses. These findings delineate a mechanism of infection-induced anti-tumour immunity. Furthermore, by ectopically expressing LMP1 in tumour B cells from patients with cancer and thereby enabling them to prime T cells, we develop a general approach for rapid production of autologous cytotoxic CD4+ T cells against a wide range of endogenous tumour antigens, such as TAAs and neoantigens, for treating B cell malignancies. This work stresses the need to revisit classical concepts concerning viral and tumour immunity, which will be critical to fully understand the impact of common infections on human health and to improve the rational design of immune approaches to treatment of cancers.

Racial Discrimination in the Life Course of Older Adults Experiencing Homelessness: Results from the HOPE HOME Study.

Over 2.5 million people experience homelessness yearly in the United States. Black persons are overrepresented by three-fold among those experiencing homelessness but little research has examined the relationship between race and homelessness. We aimed to understand the relationship between race and the experience of homelessness for older adults. We used grounded theory methodology to analyze in-depth qualitative interviews (n = 65) of persons experiencing homelessness. We recruited participants who were enrolled in two sub-studies of the Health Outcomes of People Experiencing Homelessness in Older Middle AgE (HOPE HOME) Study in Oakland California. We identified two major themes within interviews with Black participants (n=52) related to race: (1) participants experienced overt racial discrimination in early life and (2) structural racism precipitated and perpetuated adult homelessness. Further, we identified sub-themes of structural racism that contributed to participants becoming or staying homeless: criminal justice discrimination, employment discrimination, exposure to violence, premature death, and limited family wealth. We developed a theoretical model of how these elements of structural racism may increase susceptibility to homelessness. These relationships between racial discrimination and homelessness may serve as targets for policies aimed at preventing homelessness.

Medical Training in the Maelstrom: The Call to Physician Advocacy and Activism in Turbulent Times.

In this Invited Commentary, the author probes current events overlapping with his early medical education for unwritten lessons. Today's generation of trainees studies the careful application of science to suffering in the roiling context of resurgent white supremacy, anti-immigrant hatred, climate disasters, contentious public health epidemics, and attacks on the structures undergirding access to health care for millions. The author reflects on the connections between sociopolitical events and his own experiences, as well as those of his classmates, friends, and family members. These experiences, he argues, have galvanized his and his fellow medical students' commitment to decency, truth, diversity, and equity. He concludes that, in the current climate, the practice of healing is inextricably tied to the social and political context, such that advocacy and activism have become essential to a career in medicine.

Noninvasive imaging technologies for cutaneous wound assessment: A review.

The ability to phenotype wounds for the purposes of assessing severity, healing potential and treatment is an important function of evidence-based medicine. A variety of optical technologies are currently in development for noninvasive wound assessment. To varying extents, these optical technologies have the potential to supplement traditional clinical wound evaluation and research, by providing detailed information regarding skin components imperceptible to visual inspection. These assessments are achieved through quantitative optical analysis of tissue characteristics including blood flow, collagen remodeling, hemoglobin content, inflammation, temperature, vascular structure, and water content. Technologies that have, to this date, been applied to wound assessment include: near infrared imaging, thermal imaging, optical coherence tomography, orthogonal polarization spectral imaging, fluorescence imaging, laser Doppler imaging, microscopy, spatial frequency domain imaging, photoacoustic detection, and spectral/hyperspectral imaging. We present a review of the technologies in use or development for these purposes with three aims: (1) providing basic explanations of imaging technology concepts, (2) reviewing the wound imaging literature, and (3) providing insight into areas for further application and exploration. Noninvasive imaging is a promising advancement in wound assessment and all technologies require further validation.

Examination of the Early Diagnostic Applicability of Active Dynamic Thermography for Burn Wound Depth Assessment and Concept Analysis.

Despite advances in perfusion imaging, burn wound imaging technology continues to lag behind that of other fields. Quantification of blood flow is able to predict time for healing, but clear assessment of burn depth is still questionable. Active dynamic thermography (ADT) is a noncontact imaging modality capable of distinguishing tissue of different thermal conductivities. Utilizing the abnormal heat transfer properties of the burn zones, we examined whether ADT was useful in the determination of burn depth in a model of early burn wound evaluation. Duroc pigs (castrated male; n = 3) were anesthetized, and two burns were created with an aluminum billet at 3 and 12 seconds. These contact times resulted in superficial partial and deep partial thickness burn wounds, respectively. ADT and laser Doppler imaging (LDI) imaging were performed every 30 minutes postburn for a total of five imaging sessions ending 150 minutes postburn. For ADT, imaging excitation was performed for 42-120 seconds with dual quartz-infrared lamps, and subsequent infrared image capture was performed for 300 seconds. MATLAB-assisted image analysis was performed to determine burn zone region of interest thermal relaxation and characteristic patterns. LDI was performed with a moorLDI system, and biopsies were captured for histology following the 150-minute imaging session. Both ADT and LDI imaging modalities are able to detect different physical properties at 30, 60, 90 120, and 150 minutes postburn with statistical significance (P < 0.05). Resultant ADT cooling curves characterize greater differences with greater stimulation and a potentially more identifiable differential cooling characteristic. Histological analysis confirmed burn depth. This preliminary work confirms that ADT can measure burn depth and is deserving of further research either as a stand-alone imaging technology or in combination with a device to assess perfusion.

A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar.

Using a validated swine model of human scar formation, hyperpigmented and hypopigmented scar samples were examined for their histological and optical properties to help elucidate the mechanisms and characteristics of dyspigmentation. Full-thickness wounds were created on the flanks of red Duroc pigs and allowed to heal. Biopsies from areas of hyperpigmentation, hypopigmentation, and uninjured tissue were fixed and embedded for histological examination using Azure B and primary antibodies to S100B, HMB45, and α-melanocyte-stimulating hormone (α-MSH). Spatial frequency domain imaging (SFDI) was then used to examine the optical properties of scars. Hyperpigmentation was first noticeable in healing wounds around weeks 2 to 3, gradually becoming darker. There was no significant difference in S100B staining for the presence of melanocytes between hyperpigmented and hypopigmented scar samples. Azure B staining of melanin was significantly greater in histological sections from hyperpigmented areas than in sections from both uninjured skin and hypopigmented scar (P < .0001). There was significantly greater staining for α-MSH in hyperpigmented samples compared with hypopigmented samples (P = .0121), and HMB45 staining was positive for melanocytes in hyperpigmented scar. SFDI at a wavelength of 632 nm resulted in an absorption coefficient map correlating with visibly hyperpigmented areas of scars. In a red Duroc model of hypertrophic scar formation, melanocyte number is similar in hyperpigmented and hypopigmented tissues. Hyperpigmented tissues, however, show a greater amount of melanin and α-MSH, along with immunohistochemical evidence of stimulated melanocytes. These observations encourage further investigation of melanocyte stimulation and the inflammatory environment within a wound that may influence melanocyte activity. Additionally, SFDI can be used to identify areas of melanin content in mature, pigmented scars, which may lead to its usefulness in wounds at earlier time points before markedly apparent pigmentation abnormalities.

Staphylococcal superantigens and toxins are detectable in the serum of adult burn patients.

Bacterial infection in burn patients is still a devastating contributor to morbidity and mortality. Little is known regarding the presence of staphylococcal toxins in the burn-injured patient. The aim of this study was to characterize the prevalence of several of these toxins and their relationship to clinical metrics and mortality in burn patients. Levels of exotoxins staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B, toxic shock syndrome toxin 1 (TSST-1), and α-hemolysin were assayed from the serum of 207 adult burn patients aged 16-92 years. Clinical, demographic, and microbiological data from these patients were then compared to toxin levels. Staphylococcal exotoxins α-hemolysin and SEA were present in 45% and 25% of the population, respectively. Bacterial cultures concomitantly showed a high prevalence of Staphylococcus aureus in 48% of patients, of which 59% were methicillin resistant. Several metrics may be predictive of high toxin concentrations of α-hemolysin and TSST-1 and SEA including burn size, length of stay, and bacteremia. Mortality associations indicated that burn size, bacteremia, age, and the presence of α-hemolysin and SEA may be predictors of mortality. A high prevalence of staphylococcal toxin α-hemolysin and superantigens TSST-1 and SEA can be found in the circulation of the adult burn population. The presence of these toxins may contribute to the morbidity and mortality of the burn patient.

Regional neurovascular inflammation and apoptosis are detected after electrical contact injury.

High-voltage electrical injuries are a devastating form of trauma often treated in burn centers. Examining superficial wounds alone may lead to an inaccurate assessment of local, regional, and systemic severity of injury. In this work, the neurovasculature at sites regionally distinct from the contact wound were assessed for cellular pathology. Nine male Sprague-Dawley rats subjected to 1000 V direct-current shocks were separated into three groups: high-shock (>10-second contact), low-shock (<4-second contact), and control. Injury video was captured with a forward-looking infrared camera, and a thermal excitation analysis was performed. The neurovascular bundles from the iliofemoral region to the distal posterior tibial region were dissected from the hind limbs of the shocked animals and stained by immunohistochemistry for antibodies specific to apoptosis (APO) 1, caspase-3, activating transcription factor 3, high-mobility group box-1, granulocyte-macrophage colony-stimulating factor and interleukin-6. Real-time reverse-transcription polymerase chain reaction was used to quantify differential transcript levels of superoxide dismutases 1, 2, and 3 and heat-shock protein 70 from peripheral blood mononuclear cells and liver tissue. Finally, a protein array was used to identify key inflammatory cytokines in blood plasma. Significant dose-dependent trends were identified in apoptotic markers as well as inflammatory markers in both arterial and nerve tissues. Although arterial tissue exhibited a gradual decline in these markers proximally from the wound site, nerve tissue maintained a constant level at every location. Transcript analysis revealed an up-regulation of extracellular superoxide dismutase, and down-regulation of heat-shock protein 70, whereas plasma inflammatory cytokine levels indicated no significant changes. Thermal excitation analysis revealed a linear temperature increase, with a dose-dependent thermal maximum. In this study the authors have shown that neurovascular APO and inflammation are present at locations extremely proximal to electrical injury contact sites and this appears to be dose-dependent. Nerve tissue APO and inflammation may extend farther proximally than the iliofemoral region, and multiple proapoptotic mechanisms may be activated. No systemic inflammatory response was indicated in this study.