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1.
AEM Educ Train ; 8(3): e11004, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911934

RESUMO

The Resident-Student Education Committee (RSEC) is a novel approach to integrate and expand medical student education within an emergency medicine (EM) residency at a large academic center. There is a paucity of literature on such programs and there is no documentation of longitudinal initiatives with residents serving as specialty-specific advisors to students throughout medical school. The goals of creating the RSEC were to expand and improve the student educational experiences in EM, strengthen the connection between students and EM residents, and foster resident career development through sustainable leadership and teaching opportunities. The RSEC was composed of three divisions: the Preclinical Division aimed to increase student exposure to EM through didactics, skill sessions, simulation, and shadowing; the Clinical Division intended to enhance the student experience during clinical EM rotations through simulation and skill sessions and resident-student socials; and the Mentoring Division focused on advising students applying into EM through informational panels and one-on-one resident mentorship. Outcome measures include students applying into EM residency, which saw an increase from 8.9% prior to the RSEC's creation in 2020 to 12.9% in 2023, despite a national decline in EM applicants. Survey data also indicates favorable student preclinical experiences and improved confidence in clinical skills. The RSEC model, with its structured approach, resident leadership, and clear objectives, presents a sustainable and replicable framework for other residency programs seeking to enhance medical student education and promote resident engagement in teaching. Future directions include expanding shadowing opportunities and procedural skills teaching, introducing career mentorship earlier in the medical education timeline, and tracking outcomes data for continuous assessment and improvement.

2.
AEM Educ Train ; 8(Suppl 1): S24-S35, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38774824

RESUMO

Background: Simulation-based procedural practice is crucial to emergency medicine skills training and maintenance. However, many commercial procedural models are either nonexistent or lacking in key elements. Simulationists often create their own novel models with minimal framework for designing, building, and validation. We propose two interlinked frameworks with the goal to systematically build and validate models for the desired educational outcomes. Methods: Simulation Academy Research Committee and members with novel model development expertise assembled as the MIDAS (Model Innovation, Development and Assessment for Simulation) working group. This working group focused on improving novel model creation and validation beginning with a preconference workshop at 2023 Society for Academic Emergency Medicine Annual Meeting. The MIDAS group sought to (1) assess the current state of novel model validation and (2) develop frameworks for the broader simulation community to create, improve, and validate procedural models. Findings: Workshop participants completed 17 surveys for a response rate of 100%. Many simulationists have created models but few have validated them. The most common barriers to validation were lack of standardized guidelines and familiarity with the validation process.We have combined principles from education and engineering fields into two interlinked frameworks. The first is centered on steps involved with model creation and refinement. The second is a framework for novel model validation processes. Implications: These frameworks emphasize development of models through a deliberate, form-follows-function methodology, aimed at ensuring training quality through novel models. Following a blueprint of how to create, test, and improve models can save innovators time and energy, which in turn can yield greater and more plentiful innovation at lower time and financial cost. This guideline allows for more standardized approaches to model creation, thus improving future scholarship on novel models.

3.
R I Med J (2013) ; 106(1): 14-16, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36706200

RESUMO

House fires can lead to cyanide poisoning and an associated elevated serum lactate level. Because of delays in obtaining serum cyanide levels, clinical symptoms and serum lactate are often used to guide clinical decision making and antidote administration. However, as this case report identifies, lower levels of serum lactate may in fact correlate with higher levels of serum cyanide that could benefit from treatment with an antidote.


Assuntos
Cianetos , Ácido Láctico , Lesão por Inalação de Fumaça , Humanos , Antídotos/uso terapêutico , Cianetos/intoxicação , Ácido Láctico/uso terapêutico , Lesão por Inalação de Fumaça/tratamento farmacológico
5.
PLoS One ; 9(7): e101199, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25047083

RESUMO

Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.


Assuntos
Corpo Estriado/patologia , Substância Cinzenta/patologia , Esclerose Múltipla/patologia , Adulto , Encéfalo/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
6.
Oncologist ; 19(6): 602-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24760710

RESUMO

Mutations in the IDH1 and IDH2 (isocitrate dehydrogenase) genes have been discovered across a range of solid-organ and hematologic malignancies, including acute myeloid leukemia, glioma, chondrosarcoma, and cholangiocarcinoma. An intriguing aspect of IDH-mutant tumors is the aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in these malignancies. We describe the first reported case of an IDH1 p.R132L mutation in a patient with hormone receptor-positive (HR+) breast adenocarcinoma. This patient was initially treated for locally advanced disease, but then suffered a relapse and metastasis, at which point an IDH1-R132 mutation was discovered in an affected lymph node. The mutation was subsequently found in the primary tumor tissue and all metastatic sites, but not in an uninvolved lymph node. In addition, the patient's serum and urine displayed marked elevations in the concentration of 2-HG, significantly higher than that measured in six other patients with metastatic HR+ breast carcinoma whose tumors were found to harbor wild-type IDH1. In summary, IDH1 mutations may impact a rare subgroup of patients with breast adenocarcinoma. This may suggest future avenues for disease monitoring through noninvasive measurement of 2-HG, as well as for the development and study of targeted therapies against the aberrant IDH1 enzyme.


Assuntos
Adenocarcinoma/genética , Neoplasias da Mama/genética , Isocitrato Desidrogenase/genética , Neoplasias Hormônio-Dependentes/genética , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/urina , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/urina , Feminino , Glutaratos/sangue , Glutaratos/urina , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/urina
7.
Blood ; 120(23): 4649-52, 2012 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-23074281

RESUMO

Mutations of genes encoding isocitrate dehydrogenase (IDH1 and IDH2) have been recently described in acute myeloid leukemia (AML). Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. In this prospective study, we sought to determine whether 2-HG can potentially serve as a noninvasive biomarker of disease burden through serial measurements in patients receiving conventional therapy for newly diagnosed AML. Our data demonstrate that serum, urine, marrow aspirate, and myeloblast 2-HG levels are significantly higher in IDH-mutant patients, with a correlation between baseline serum and urine 2-HG levels. Serum and urine 2-HG, along with IDH1/2-mutant allele burden in marrow, decreased with response to treatment. 2-HG decrease was more rapid with induction chemotherapy compared with DNA-methyltransferase inhibitor therapy. Our data suggest that serum or urine 2-HG may serve as noninvasive biomarkers of disease activity for IDH-mutant AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glutaratos/metabolismo , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/metabolismo , Doença Aguda , Idoso , Azacitidina/administração & dosagem , Azacitidina/análogos & derivados , Citarabina/administração & dosagem , Análise Mutacional de DNA , Decitabina , Feminino , Glutaratos/sangue , Glutaratos/urina , Células Precursoras de Granulócitos/metabolismo , Humanos , Idarubicina/administração & dosagem , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Leucemia Mieloide/genética , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Fatores de Tempo
8.
Mol Endocrinol ; 26(8): 1278-90, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22734036

RESUMO

Nuclear receptor transcriptional activity is enhanced by interaction with coactivators. The highly related nuclear receptor 5A (NR5A) subfamily members liver receptor homolog 1 and steroidogenic factor 1 bind to and activate several of the same genes, many of which are important for reproductive function. To better understand transcriptional activation by these nuclear receptors, we sought to identify interacting proteins that might function as coactivators. The LIM domain protein four and a half LIM domain 2 (FHL2) was identified as interacting with the NR5A receptors in a yeast two-hybrid screen of a human ovary cDNA library. FHL2, and the closely related FHL1, are both expressed in the rodent ovary and in granulosa cells. Small interfering RNA-mediated knockdown of FHL1 and FHL2 in primary mouse granulosa cells reduced expression of the NR5A target genes encoding inhibin-α and P450scc. In vitro assays confirmed the interaction between the FHL and NR5A proteins and revealed that a single LIM domain of FHL2 is sufficient for this interaction, whereas determinants in both the ligand binding domain and DNA binding domain of NR5A proteins are important. FHL2 enhances the ability of both liver receptor homolog 1 and steroidogenic factor 1 to activate the inhibin-α subunit gene promoter in granulosa cells and thus functions as a transcriptional coactivator. FHL2 also interacts with cAMP response element-binding protein and substantially augments activation of inhibin gene expression by the combination of NR5A receptors and forskolin, suggesting that FHL2 may facilitate integration of these two signals. Collectively these results identify FHL2 as a novel coactivator of NR5A nuclear receptors in ovarian granulosa cells and suggest its involvement in regulating target genes important for mammalian reproduction.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Células da Granulosa/metabolismo , Inibinas/genética , Proteínas com Homeodomínio LIM/metabolismo , Proteínas Musculares/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fator Esteroidogênico 1/metabolismo , Fatores de Transcrição/metabolismo , Animais , Sequência de Bases , Linhagem Celular , AMP Cíclico/metabolismo , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Inibinas/metabolismo , Proteínas com Homeodomínio LIM/genética , Camundongos , Proteínas Musculares/genética , Ovário/citologia , Ovário/metabolismo , Domínios e Motivos de Interação entre Proteínas , Interferência de RNA , Elementos de Resposta , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional , Técnicas do Sistema de Duplo-Híbrido
9.
Mol Cell Endocrinol ; 348(1): 331-8, 2012 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-21964465

RESUMO

Nuclear estrogen receptor α (ERα) regulates target gene expression in response to ligands through two distinct mechanisms: direct binding to DNA and indirect tethering through other DNA-bound transcription factors, such as AP-1. In the studies described herein, we examined the molecular mechanisms underlying the activation of ERα in the AP-1 tethering pathway by the selective estrogen receptor modulator (SERM) raloxifene (Ral). Our results with the MMP1 and PRUNE genes indicate that the c-Fos component of the AP-1 tethering factor and the c-Jun N-terminal kinase 1 (JNK1) are constitutively bound at the promoter regions prior to Ral exposure. Ral then promotes the binding of ERα at the promoter in a c-Fos-dependent manner. Interestingly, we found that JNK1 enzymatic activity is required for Ral-dependent gene activation through ERα. Our results suggest that one role for Ral-dependent recruitment of ERα to the AP-1 binding site is to stimulate JNK1 enzymatic activity. Alternatively, Ral-occupied ERα might recruit protein substrates to promoter-bound JNK1 without any change in JNK1 activity. Collectively, our studies have revealed a new role for JNK1 in determining gene regulatory outcomes by ERα.


Assuntos
Receptor alfa de Estrogênio/metabolismo , Regulação da Expressão Gênica , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Cloridrato de Raloxifeno/farmacologia , Fator de Transcrição AP-1/metabolismo , Proteínas de Transporte/genética , Estradiol/farmacologia , Receptor alfa de Estrogênio/agonistas , Feminino , Genes Reporter , Glucuronosiltransferase/genética , Células HeLa , Humanos , Luciferases/biossíntese , Luciferases/genética , Metaloproteinase 1 da Matriz/genética , Neoplasias Epiteliais e Glandulares , Monoéster Fosfórico Hidrolases , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Neoplasias do Colo do Útero
10.
Mol Endocrinol ; 20(4): 831-43, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16339274

RESUMO

Steroidogenic factor 1 (SF1) is a member of the NR5A subfamily of nuclear hormone receptors and is considered a master regulator of reproduction because it regulates a number of genes encoding reproductive hormones and enzymes involved in steroid hormone biosynthesis. Like other NR5A members, SF1 harbors a highly conserved approximately 30-residue segment called the FTZ-F1 box C-terminal to the core DNA binding domain (DBD) common to all nuclear receptors and binds to 9-bp DNA sequences as a monomer. Here we describe the solution structure of the SF1 DBD in complex with an atypical sequence in the proximal promoter region of the inhibin-alpha gene that encodes a subunit of a reproductive hormone. SF1 forms a specific complex with the DNA through a bipartite motif binding to the major and minor grooves through the core DBD and the N-terminal segment of the FTZ-F1 box, respectively, in a manner previously described for two other monomeric receptors, nerve growth factor-induced-B and estrogen-related receptor 2. However, unlike these receptors, SF1 harbors a helix in the C-terminal segment of the FTZ-F1 box that interacts with both the core DBD and DNA and serves as an important determinant of stability of the complex. We propose that the FTZ-F1 helix along with the core DBD serves as a platform for interactions with coactivators and other DNA-bound factors in the vicinity.


Assuntos
DNA/genética , DNA/metabolismo , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/metabolismo , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Proteínas de Homeodomínio/genética , Humanos , Ligação de Hidrogênio , Técnicas In Vitro , Substâncias Macromoleculares , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Eletricidade Estática , Fator Esteroidogênico 1 , Fatores de Transcrição/genética
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