25 research outputs found
Measuring deliberate reflection in residents: validation and psychometric properties of a measurement tool
PURPOSE: Reflective capacity is the ability to understand critical analysis of knowledge and experience to achieve deeper meaning. In medicine, there is little provision for post-graduate medical education to teach deliberate reflection. The feasibility, scoring characteristics, reliability, validation, and adaptability of a modified previously validated instrument was examined for its usefulness assessing reflective capacity in residents as a step toward developing interventions for improvement.
METHODS: Third-year residents and fellows from four anesthesia training programs were administered a slightly modified version of the Reflection Evaluation for Learners\u27 Enhanced Competencies Tool (REFLECT) in a prospective, observational study at the end of the 2019 academic year. Six written vignettes of imperfect anesthesia situations were created. Subjects recorded their perspectives on two randomly assigned vignettes. Responses were scored using a 5-element rubric; average scores were analyzed for psychometric properties. An independent self-report assessment method, the Cognitive Behavior Survey: Residency Level (rCBS) was used to examine construct validity. Internal consistency (ICR, Cronbach\u27s alpha) and interrater reliability (weighted kappa) were examined. Pearson correlations were used between the two measures of reflective capacity.
RESULTS: 46/136 invited subjects completed 2/6 randomly assigned vignettes. Interrater agreement was high (k = 0.85). The overall average REFLECT score was 1.8 (1-4 scale) with good distribution across the range of scores. ICR for both the REFLECT score (mean 1.8, sd 0.5; α = 0.92) and the reflection scale of the rCBS (mean 4.5, sd 1.1; α = 0.94) were excellent. There was a significant correlation between REFLECT score and the rCBS reflection scale (r = .44, p \u3c 0.01).
CONCLUSIONS: This study demonstrates feasibility, reliability, and sufficiently robust psychometric properties of a modified REFLECT rubric to assess graduate medical trainees\u27 reflective capacity and established construct/convergent validity to an independent measure. The instrument has the potential to assess the effectiveness of interventions intended to improve reflective capacity
Lower extremity soft tissue reconstruction and amputation rates in patients with open tibial fractures in Sweden during 1998–2010
Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.
Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses
Cancer immunoediting by the innate immune system in the absence of adaptive immunity
Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2, and RAG2x γc mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2x γc mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting
Chronic Viral Infection and Primary Central Nervous System Malignancy
Primary central nervous system (CNS) tumors cause significant morbidity and mortality in both adults and children. While some of the genetic and molecular mechanisms of neuro-oncogenesis are known, much less is known about possible epigenetic contributions to disease pathophysiology. Over the last several decades, chronic viral infections have been associated with a number of human malignancies. In primary CNS malignancies, two families of viruses, namely polyomavirus and herpesvirus, have been detected with varied frequencies in a number of pediatric and adult histological tumor subtypes. However, establishing a link between chronic viral infection and primary CNS malignancy has been an area of considerable controversy, due in part to variations in detection frequencies and methodologies used among researchers. Since a latent viral neurotropism can be seen with a variety of viruses and a widespread seropositivity exists among the population, it has been difficult to establish an association between viral infection and CNS malignancy based on epidemiology alone. While direct evidence of a role of viruses in neuro-oncogenesis in humans is lacking, a more plausible hypothesis of neuro-oncomodulation has been proposed. The overall goals of this review are to summarize the many human investigations that have studied viral infection in primary CNS tumors, discuss potential neuro-oncomodulatory mechanisms of viral-associated CNS disease and propose future research directions to establish a more firm association between chronic viral infections and primary CNS malignancies
Measuring deliberate reflection in residents: validation and psychometric properties of a measurement tool
Abstract Purpose Reflective capacity is “the ability to understand critical analysis of knowledge and experience to achieve deeper meaning.” In medicine, there is little provision for post-graduate medical education to teach deliberate reflection. The feasibility, scoring characteristics, reliability, validation, and adaptability of a modified previously validated instrument was examined for its usefulness assessing reflective capacity in residents as a step toward developing interventions for improvement. Methods Third-year residents and fellows from four anesthesia training programs were administered a slightly modified version of the Reflection Evaluation for Learners’ Enhanced Competencies Tool (REFLECT) in a prospective, observational study at the end of the 2019 academic year. Six written vignettes of imperfect anesthesia situations were created. Subjects recorded their perspectives on two randomly assigned vignettes. Responses were scored using a 5-element rubric; average scores were analyzed for psychometric properties. An independent self-report assessment method, the Cognitive Behavior Survey: Residency Level (rCBS) was used to examine construct validity. Internal consistency (ICR, Cronbach’s alpha) and interrater reliability (weighted kappa) were examined. Pearson correlations were used between the two measures of reflective capacity. Results 46/136 invited subjects completed 2/6 randomly assigned vignettes. Interrater agreement was high (k = 0.85). The overall average REFLECT score was 1.8 (1–4 scale) with good distribution across the range of scores. ICR for both the REFLECT score (mean 1.8, sd 0.5; α = 0.92) and the reflection scale of the rCBS (mean 4.5, sd 1.1; α = 0.94) were excellent. There was a significant correlation between REFLECT score and the rCBS reflection scale (r = .44, p < 0.01). Conclusions This study demonstrates feasibility, reliability, and sufficiently robust psychometric properties of a modified REFLECT rubric to assess graduate medical trainees’ reflective capacity and established construct/convergent validity to an independent measure. The instrument has the potential to assess the effectiveness of interventions intended to improve reflective capacity
Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance
Cells undergoing xenobiotic or oxidative stress activate the transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2), which initiates an intrinsic “stress surveillance” pathway. We recently found that the cytokine IL-17D effects a form of extrinsic stress surveillance by inducing antitumor immunity, but how IL-17D is regulated remains unknown. Here, we show that Nrf2 induced IL-17D in cancer cell lines. Moreover, both Nrf2 and IL-17D were induced in primary tumors as well as during viral infection in vivo. Expression of IL-17D in tumors and virally infected cells is essential for optimal protection of the host as il17d−/− mice experienced a higher incidence of tumors and exacerbated viral infections compared to wild-type (WT) animals. Moreover, activating Nrf2 to induce IL-17D in established tumors led to natural killer cell-dependent tumor regression. These data demonstrate that Nrf2 can initiate both intrinsic and extrinsic stress surveillance pathways and highlight the use of Nrf2 agonists as immune therapies for cancer and infection
Recommended from our members
Cancer immunoediting by the innate immune system in the absence of adaptive immunity.
Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3'methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2(-/-), and RAG2(-/-)x γc(-/-) mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2(-/-)x γc(-/-) mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting