Translation of Raman micro-spectroscopy into the clinic for bladder cancer diagnosticsviaurine cytology.
Forty-one endomyocardial biopsies of the right interventricular septum have been investigated in 24 immunosuppressed patients after orthotopic heart transplantation. Monoclonal antibodies 27E10, 25F9, and RM3/1, which react with different macrophage phenotypes, and antisera MRP-8 and MRP-14, specific for proteins expressed on endothelial and monocyte cell surfaces in inflammation as well as markers for CD4+ and CD8+ T-lymphocytes, were employed in an indirect immunoperoxidase staining technique. This methodology permits more physiological recognition of the inflammatory process within the myocardium. It was possible to verify and to distinguish acute early, late and down-regulatory stages of inflammation in 33 biopsies (80%). No evidence of inflammation was found in seven biopsies (17%). Conventional histopathology with haematoxylin-eosin and Masson's trichrome was performed simultaneously, and demonstrated inflammation to be present in 23 of 41 biopsies (56%). An important findings is that CD4+ and CD8+ lymphocytes were absent in 15 of 41 specimens (37%) although there was inflammation proven by the presence of different macrophage phenotypes. The results indicate the necessity of long-term serial investigations of the physiological role of specific inflammatory macrophage phenotypes during the rejection process. It is concluded that the phenotyping of macrophage and endothelial cell differentiation antigens offers a sensitive approach to assess diagnosis of myocardial inflammation as a consequence of ongoing rejection in cardiac allografts.
Bone morphogenetic protein (BMP) signaling is important for correct lung morphogenesis, and there is evidence of BMP signaling reactivation in lung diseases. However, little is known about BMP signaling patterns in healthy airway homeostasis and inflammatory airway disease and during epithelial repair. In this study, a rhesus macaque (Macaca mulatta) model of allergic airway disease was used to investigate BMP signaling throughout the airways in health, disease, and regeneration. Stereologic quantification of immunofluorescent images was used to determine the expression of BMP receptor (BMPR) Ia and phosphorylated SMAD (pSMAD) 1/5/8 in the airway epithelium. A pSMAD 1/5/8 expression gradient was found along the airways of healthy juvenile rhesus macaques (n = 3, P < 0.005). Membrane-localized BMPRIa expression was also present in the epithelium of the healthy animals. After exposure to house dust mite allergen and ozone, significant down-regulation of nuclear pSMAD 1/5/8 occurs in the epithelium. When the animals were provided with a recovery period in filtered air, proliferating cell nuclear antigen, pSMAD 1/5/8, and membrane-localized BMPRIa expression were significantly increased in the epithelium of conducting airways (P < 0.005). Furthermore, in the asthmatic airways, altered BMPRIa localization was evident. Because of the elevated eosinophil presence in these airways, we investigated the effect of eosinophil-derived proteins on BMPRIa trafficking in epithelial cells. Eosinophil-derived proteins (eosinophil-derived neurotoxin, eosinophil peroxidase, and major basic protein) induced transient nuclear translocation of membrane-bound BMPRIa. This work mapping SMAD signaling in the airways of nonhuman primates highlights a potential mechanistic relationship between inflammatory mediators and BMP signaling and provides evidence that basal expression of the BMP signaling pathway may be important for maintaining healthy airways.
Introduction Systemic racism impacts personal and community health; however, education regarding its role in perpetuating healthcare inequity remains limited in medical curricula. This study implemented and evaluated the impact of a student-led anti-racism programme on medical students’ perceptions of racial bias in medicine, awareness of, and confidence to advocate against racism in medicine. Method A total of 543 early stage medical students were invited to participate in the programme. Participants were assigned readings and videos exploring racial injustice in medicine and attended a virtual small-group discussion facilitated by faculty and students. Online surveys were used to collect pre- and post-programme data using Likert scales for response items. Open-ended questions were independently reviewed by three authors using reflexive thematic analysis. Results Sixty-three early-stage medical students enrolled in the programme, of which 42 completed the pre-programme survey. There was a 76% ( n = 32) response rate for the post-programme survey. The majority of students (60%, n = 25) had no previous education about racism in medicine. From pre- to post-programme, there was a significant change in students’ perceived definition of race from genetic, biological, geographical, and cultural factors to socio-political factors ( P < 0.0001). Significant increases in almost all factors assessing student awareness of racism and confidence to advocate against racism were observed. Student-identified barriers to discussing racism included lack of education and lived experience, fear of starting conflict and offending others. All survey respondents would recommend this programme to peers and 69% ( n = 32) engaged in further topical self-directed education. Conclusion This simple and reproducible programme improved awareness and confidence to advocate against racism in medicine and resulted in a change in opinion regarding race-based medical practice. These findings are in line with best practice towards addressing racial bias in medicine, decolonizing medical curricula and strengthening anti-racism teaching of future physicians.
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