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1.
West J Emerg Med ; 24(4): 728-731, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37527382

RESUMO

INTRODUCTION: The Standardized Letter of Evaluation (SLOE) is designed to assist emergency medicine (EM) residency programs in differentiating applicants and in selecting those to interview. The SLOE narrative component summarizes the student's clinical skills as well as their non-cognitive attributes. The purpose of this qualitative investigation was to explore how students described in the SLOE as quiet are perceived by faculty and to better understand how this may impact their residency candidacy. METHODS: This retrospective cohort study included all SLOEs submitted to one EM residency program during one application cycle. We analyzed sentences in the SLOE narrative describing students as "quiet," "shy," and/or "reserved." Using grounded theory, thematic content analysis with a constructivist approach, we identified five mutually exclusive themes that best characterized the usage of these target words. RESULTS: We identified five themes: 1) quiet traits portrayed as implied-negative attributes (62.4%); 2) quiet students portrayed as overshadowed by more extraverted peers (10.3%); 3) quiet students portrayed as unfit for fast-paced clinical settings (3.4%); 4) "quiet" portrayed as a positive attribute (10.3%); and 5) "quiet" comments deemed difficult to assess due to lack of context (15.6%). CONCLUSION: We found that quiet personality traits were often portrayed as negative attributes. Further, comments often lacked clinical context, leaving them vulnerable to misunderstanding or bias. More research is needed to determine how quiet students perform compared to their non-quiet peers and to determine what changes to instructional practices may support the quiet student and help create a more inclusive learning environment.


Assuntos
Medicina de Emergência , Internato e Residência , Humanos , Estudos Retrospectivos , Estudantes , Medicina de Emergência/educação , Percepção
2.
West J Emerg Med ; 24(2): 259-263, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36976603

RESUMO

INTRODUCTION: The Standardized Letter of Evaluation (SLOE) is an emergency medicine (EM)-specific assessment designed to help EM residency programs differentiate applicants. We became interested in SLOE-narrative language referencing personality when we observed less enthusiasm for applicants described as "quiet" in their SLOEs. In this study our objective was to compare how quiet-labeled, EM-bound applicants were ranked compared to their non-quiet peers in the global assessment (GA) and anticipated rank list (ARL) categories in the SLOE. METHODS: We conducted a planned subgroup analysis of a retrospective cohort study of all core EM clerkship SLOEs submitted to one, four-year academic EM residency program in the 2016-2017 recruitment cycle. We compared SLOEs of applicants who were described as "quiet," "shy," and/or "reserved" - collectively referred to as "quiet" - to SLOEs from all other applicants, referred to as "non-quiet." We compared frequencies of quiet to non-quiet students in GA and ARL categories using chi-square goodness-of-fit tests with a rejection criteria (alpha) of 0.05. RESULTS: We reviewed 1,582 SLOEs from 696 applicants. Of these, 120 SLOEs described quiet applicants. The distributions of quiet and non-quiet applicants across GA and ARL categories were significantly different (P < 0.001). Quiet applicants were less likely than non-quiet applicants to be ranked in the top 10% and top one-third GA categories combined (31% vs 60%) and more likely to be in the middle one-third category (58% vs 32%). For ARL, quiet applicants were also less likely to be ranked in the top 10% and top one-third categories combined (33% vs 58%) and more likely to be in the middle one-third category (50% vs 31%). CONCLUSION: Emergency medicine-bound students described as quiet in their SLOEs were less likely to be ranked in the top GA and ARL categories compared to non-quiet students. More research is needed to determine the cause of these ranking disparities and address potential biases in teaching and assessment practices.


Assuntos
Medicina de Emergência , Internato e Residência , Humanos , Estudos Retrospectivos , Estudantes , Medicina de Emergência/educação , Idioma
3.
ACS Chem Biol ; 12(4): 1001-1010, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28191924

RESUMO

The use of coumarin caged molecules has been well documented in numerous photocaging applications including for the spatiotemporal control of Cre-estrogen receptor (Cre-ERT2) recombinase activity. In this article, we report that 4-hydroxytamoxifen (4OHT) caged with coumarin via a conventional ether linkage led to an unexpected photo-Claisen rearrangement which significantly competed with the release of free 4OHT. The basis for this unwanted reaction appears to be related to the coumarin structure and its radical-based mechanism of uncaging, as it did not occur in ortho-nitrobenzyl (ONB) caged 4OHT that was otherwise linked in the same manner. In an effort to perform design optimization, we introduced a self-immolative linker longer than the ether linkage and identified an optimal linker which allowed rapid 4OHT release by both single-photon and two-photon absorption mechanisms. The ability of this construct to actively control Cre-ERT2 mediated gene modifications was investigated in mouse embryonic fibroblasts (MEFs) in which the expression of a green fluorescent protein (GFP) reporter dependent gene recombination was controlled by 4OHT release and measured by confocal fluorescence microscopy and flow cytometry. In summary, we report the implications of this photo-Claisen rearrangement in coumarin caged compounds and demonstrate a rational linker strategy for addressing this unwanted side reaction.


Assuntos
Cumarínicos/química , Fotoquímica , Tamoxifeno/análogos & derivados , Animais , Células Cultivadas , Cromatografia Líquida/métodos , Cinética , Camundongos , Moduladores Seletivos de Receptor Estrogênico/química , Análise Espectral/métodos , Tamoxifeno/química
4.
Nature ; 531(7595): 513-7, 2016 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-26982733

RESUMO

Lung metastasis is the lethal determinant in many cancers and a number of lines of evidence point to monocytes and macrophages having key roles in its development. Yet little is known about the immediate fate of incoming tumour cells as they colonize this tissue, and even less known about how they make first contact with the immune system. Primary tumours liberate circulating tumour cells (CTCs) into the blood and we have developed a stable intravital two-photon lung imaging model in mice for direct observation of the arrival of CTCs and subsequent host interaction. Here we show dynamic generation of tumour microparticles in shear flow in the capillaries within minutes of CTC entry. Rather than dispersing under flow, many of these microparticles remain attached to the lung vasculature or independently migrate along the inner walls of vessels. Using fluorescent lineage reporters and flow cytometry, we observed 'waves' of distinct myeloid cell subsets that load differentially and sequentially with this CTC-derived material. Many of these tumour-ingesting myeloid cells collectively accumulated in the lung interstitium along with the successful metastatic cells and, as previously understood, promote the development of successful metastases from surviving tumour cells. Although the numbers of these cells rise globally in the lung with metastatic exposure and ingesting myeloid cells undergo phenotypic changes associated with microparticle ingestion, a consistently sparse population of resident conventional dendritic cells, among the last cells to interact with CTCs, confer anti-metastatic protection. This work reveals that CTC fragmentation generates immune-interacting intermediates, and defines a competitive relationship between phagocyte populations for tumour loading during metastatic cell seeding.


Assuntos
Movimento Celular , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Pulmão/imunologia , Pulmão/patologia , Metástase Neoplásica/imunologia , Metástase Neoplásica/patologia , Animais , Capilares/patologia , Linhagem Celular Tumoral , Linhagem da Célula , Células Dendríticas/citologia , Células Dendríticas/imunologia , Feminino , Genes Reporter/genética , Humanos , Pulmão/irrigação sanguínea , Pulmão/citologia , Neoplasias Pulmonares/patologia , Masculino , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Microscopia Confocal , Células Mieloides/citologia , Células Neoplásicas Circulantes/patologia
5.
Biochemistry ; 51(40): 7863-72, 2012 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-22978677

RESUMO

The virus-host cell fusion process is mediated by a membrane anchored viral fusion protein that inserts its hydrophobic fusion peptide into the plasma membrane of the host cell, initiating the fusion reaction. Therefore, fusion peptides are an important functional constituent of the fusion proteins of enveloped viruses. In this work, we characterize the fusion peptide or VT18 (V(84)YPFMWGGAYCFCDAENT(101)) of Chikungunya virus (CHIKV) using NMR and fluorescence spectroscopy in zwitterionic lipid environments. Our results demonstrate that the VT18 peptide is able to induce liposome fusions in a pH independent manner and interacts with the zwitterionic lipid vesicles. The NMR derived three-dimensional structure of VT18, in solution of dodecylphosphocholine (DPC) micelles, is typified by extended or ß-type conformations for most of the residues, whereby residues M88-W89-G90-G91 adopt a type I ß-turn conformation. Strikingly, the aromatic side chains of residues Y85, F87, Y93, and F95 in the VT18 structure are found to be well-packed forming an aromatic core. In particular, residue F87 is situated at the center of the aromatic core establishing a close proximity with other aromatic side chains. Further, the aromatic core residues are also involved in packing interactions with the side chains of residues M88, C94. Paramagnetic relaxation enhancement NMR, using spin labeled doxyl lipids, indicated that the aromatic core residues of VT18 are well inserted into the micelles, whereas the polar residues at the C-terminus may be surface localized. The atomic resolution structure and lipid interactions of CHIKV fusion peptide presented here will aid to uncover the fusion mechanism by the type II viral fusion proteins.


Assuntos
Vírus Chikungunya/metabolismo , Micelas , Proteínas Virais de Fusão/química , Sequência de Aminoácidos , Vírus Chikungunya/genética , Concentração de Íons de Hidrogênio , Lipídeos/química , Lipossomos/química , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Espectrometria de Fluorescência , Proteínas Virais de Fusão/metabolismo , Internalização do Vírus
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