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BACKGROUND: To create an inclusive environment in nursing education, challenges to incorporating change must be addressed including institutional racism, power differences, privilege, and implicit biases (O'Connor et al.). This article discusses barriers that interfere with the implementation of diversity, equity, and inclusion (DEI) initiatives within schools of nursing and offers strategies for building a culture of inclusivity at academic institutions. METHOD: This article is based on factual, researched, and firsthand information. RESULTS: Administrators and stakeholders need to determine how DEI is incorporated into their institution's mission, vision, and values. Forming a DEI council that consists of equal representation from faculty, staff, and students will foster inclusiveness to incorporate DEI initiatives within schools of nursing and will allow outcomes to be measured. CONCLUSION: Barriers should be identified and removed to make schools of nursing a safe and inclusive zone for faculty, staff, and students. [J Nurs Educ. 2024;63(1):53-56.].
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Diversidad, Equidad e Inclusión , Facultades de Enfermería , Humanos , Personal Administrativo , Instituciones Académicas , EstudiantesRESUMEN
Meningioma is the most common primary brain tumor and carries a substantial risk of local recurrence. Methylation profiles of meningioma and their clinical implications are not well understood. We hypothesized that aggressive meningiomas have unique DNA methylation patterns that could be used to better stratify patient management. Samples (n = 140) were profiled using the Illumina HumanMethylation450BeadChip. Unsupervised modeling on a training set (n = 89) identified 2 molecular methylation subgroups of meningioma (MM) with significantly different recurrence-free survival (RFS) times between the groups: a prognostically unfavorable subgroup (MM-UNFAV) and a prognostically favorable subgroup (MM-FAV). This finding was validated in the remaining 51 samples and led to a baseline meningioma methylation classifier (bMMC) defined by 283 CpG loci (283-bMMC). To further optimize a recurrence predictor, probes subsumed within the baseline classifier were subject to additional modeling using a similar training/validation approach, leading to a 64-CpG loci meningioma methylation predictor (64-MMP). After adjustment for relevant clinical variables [WHO grade, mitotic index, Simpson grade, sex, location, and copy number aberrations (CNAs)] multivariable analyses for RFS showed that the baseline methylation classifier was not significant (p = 0.0793). The methylation predictor, however, was significantly associated with tumor recurrence (p < 0.0001). CNAs were extracted from the 450k intensity profiles. Tumor samples in the MM-UNFAV subgroup showed an overall higher proportion of CNAs compared to the MM-FAV subgroup tumors and the CNAs were complex in nature. CNAs in the MM-UNFAV subgroup included recurrent losses of 1p, 6q, 14q and 18q, and gain of 1q, all of which were previously identified as indicators of poor outcome. In conclusion, our analyses demonstrate robust DNA methylation signatures in meningioma that correlate with CNAs and stratify patients by recurrence risk.
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Metilación de ADN/fisiología , Epigenómica/métodos , Neoplasias Meníngeas/mortalidad , Meningioma/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Variaciones en el Número de Copia de ADN/genética , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Adulto JovenRESUMEN
IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioblastoma/diagnóstico , Glioblastoma/genética , Isocitrato Deshidrogenasa/genética , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Humanos , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Adulto JovenRESUMEN
While World Health Organization (WHO) grading of meningioma stratifies patients according to recurrence risk overall, there is substantial within-grade heterogeneity with respect to recurrence-free survival (RFS). Most meningiomas are graded according to mitotic counts per unit area on hematoxylin and eosin sections, a method potentially confounded by tumor cellularity, as well as potential limitations of accurate mitotic figure detection on routine histology. To refine mitotic figure assessment, we evaluated 363 meningiomas with phospho-histone H3 (Ser10) and determined the mitotic index (number of mitoses per 1000 tumor cells). The median mitotic indices among WHO grade I (n = 268), grade II (n = 84) and grade III (n = 11) tumors were 1, 4 and 12. Classification and regression tree analysis to categorize cut-offs identified three subgroups defined by mitotic indices of 0-2, 3-4 and ≥5, which on univariate analysis were associated with RFS (P < 0.01). In multivariate analysis, mitotic index subgrouped in this manner was significantly associated with RFS (P < 0.01) after adjustment for Simpson grade, WHO grade and MIB-1 index. Mitotic index was then examined within individual WHO grade, showing that for grade I and grade II meningiomas, mitotic index can add additional information to RFS risk. The results suggest that the use of a robust mitotic marker in meningioma could refine risk stratification.
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Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Índice Mitótico/métodos , Recurrencia Local de Neoplasia/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Supervivencia sin Enfermedad , Femenino , Histonas/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/mortalidad , Meningioma/mortalidad , Persona de Mediana Edad , Fosforilación , Valor Predictivo de las Pruebas , Tomógrafos Computarizados por Rayos X , Adulto JovenRESUMEN
Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.
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Ependimoma/fisiopatología , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias Infratentoriales/fisiopatología , Adolescente , Factores de Edad , Antígenos de Neoplasias/metabolismo , Niño , Análisis por Conglomerados , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/metabolismo , Bases de Datos Genéticas , Ependimoma/diagnóstico , Ependimoma/genética , Ependimoma/metabolismo , Femenino , Humanos , Neoplasias Infratentoriales/diagnóstico , Neoplasias Infratentoriales/genética , Neoplasias Infratentoriales/metabolismo , Estudios Longitudinales , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Reproducibilidad de los Resultados , Factores Sexuales , Análisis de Supervivencia , Adulto JovenRESUMEN
Li-Fraumeni syndrome (LFS) is a rare familial cancer syndrome characterized by early cancer onset, diverse tumor types, and multiple primary tumors. Germ-line TP53 mutations have been identified in most LFS families. A high-frequency single-nucleotide polymorphism, SNP309 (rs2279744), in MDM2 was recently confirmed to be a modifier of cancer risk in several case-series studies: substantially earlier cancer onset was observed in SNP309 G-allele carriers than in wild-type individuals by 7-16 years. However, cancer risk analyses that jointly account for measured hereditary TP53 mutations and MDM2 SNP309 have not been systematically investigated in familial cases. Here, we determined the combined effects of measured TP53 mutations, MDM2 SNP309, and gender and their interactions simultaneously in LFS families. We used the method that is designed for extended pedigrees and structured for age-specific risk models based on Cox proportional hazards regression. We analyzed the cancer incidence in 19 extended pedigrees with germ-line TP53 mutations ascertained through the clinical LFS phenotype. The dataset consisted of 463 individuals with 129 TP53 mutation carriers. Our analyses showed that the TP53 germ-line mutation and its interaction with gender were strongly associated with familial cancer incidence and that the association between MDM2 SNP309 and increased cancer risk was modest. In contrast with several case-series studies, the interaction between MDM2 SNP309 and TP53 mutation was not statistically significant in our LFS family cohort. Our results showed that SNP309 G-alleles were associated with accelerated tumor formation in both carriers and non-carriers of germ-line TP53 mutations.
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Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Síndrome de Li-Fraumeni/genética , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Assembling and interconnecting the building blocks of nanoscale devices and being able to electronically address or measure responses at the molecular level remains an important challenge for nanotechnology. Here we show the usefulness of bottom-up self-assembly for building electronic nanosensors from multiple components that have been designed to interact in a controlled manner. Cowpea mosaic virus was used as a scaffold to control the positions of gold nanoparticles. The nanoparticles were then interconnected using thiol-terminated conjugated organic molecules, resulting in a three-dimensional conductive network. Biotin molecules were attached to the virus scaffold using linkers to act as molecular receptors. We demonstrated that binding avidin to the biotin receptors on the self-assembled nanosensors causes a significant change in the network conductance that is dependent on the charge of the avidin protein.
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Técnicas Biosensibles/métodos , Comovirus , Nanopartículas del Metal , Avidina , Biotina , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Comovirus/química , Comovirus/genética , Conductividad Eléctrica , Oro , Mutación , NanotecnologíaRESUMEN
BACKGROUND: The transcription factor TCF21 is involved in mesenchymal-to-epithelial differentiation and was shown to be aberrantly hypermethylated in lung and head and neck cancers. Because of its reported high frequency of hypermethylation in lung cancer, further characterization of the stages and types of nonsmall cell lung cancer (NSCLC) that are hypermethylated and the frequency of hypermethylation and associated "second hits" were assessed. METHODS: TCF21 promoter hypermethylation in 105 NSCLC including various stages and histologies in smokers and nonsmokers was determined. In addition, TCF21 loss of heterozygosity and mutational status were examined. Twenty-two cancer cell lines from varied tissue origins were also assayed. The NSCLC results were validated and expanded by examining TCF21 immunohistochemical expression on a tissue microarray containing 300 NSCLC cases. RESULTS: Overall, 81% of NSCLC samples showed TCF21 promoter hypermethylation, and 84% showed decreased TCF21 protein expression. Multivariate analysis showed that TCF21 expression, although below normal in both histologies, was lower in adenocarcinoma than in squamous cell carcinoma and was not independently correlated with sex, smoking, and EGFR mutation status or with clinical outcome. Cell lines from other cancer types also showed frequent TCF21 promoter hypermethylation. CONCLUSIONS: Hypermethylation and decreased expression of TCF21 were tumor specific and very frequent in all NSCLCs, even early-stage disease, thus making TCF21 a potential candidate methylation biomarker for early-stage NSCLC screening. TCF21 hypermethylation in a variety of tumor cell lines suggests it may also be a valuable methylation biomarker in other tumor types.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Metilación de ADN , Neoplasias Pulmonares/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Biomarcadores de Tumor/genética , Regulación hacia Abajo , Femenino , Humanos , Inmunohistoquímica , Masculino , Regiones Promotoras GenéticasRESUMEN
The study of pediatric catatonia has not received much attention. During the last few years, progress has been made in delineating this syndrome in children and adolescents across a wide range of disorders. Catatonia is a potentially life-threatening but treatable syndrome that also occurs in children and adolescents with autistic, developmental, and tic disorders, and in its idiopathic form. In many of these cases, catatonia cannot be accounted for by an associated psychotic, affective, or medical disorder. These findings are imminently relevant for classification where catatonia is currently restricted to sections of the psychotic, affective, or medical disorders. Catatonia should always be the primary diagnosis in children, adolescents, and adults, as specific treatments for catatonia, i.e., benzodiazepines and electroconvulsive therapy, lower risk of worsening catatonia or precipitating Neuroleptic Malignant Syndrome when antipsychotic medications are used as first-line or sole treatment. The creation of a separate diagnostic class for catatonia is the safest approach to ensure proper diagnosis and treatment of this syndrome in patients of all ages and the best approach to promote research.
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Catatonia/clasificación , Catatonia/diagnóstico , Catatonia/patología , Adolescente , Catatonia/terapia , Niño , Terapia Electroconvulsiva/métodos , HumanosRESUMEN
BACKGROUND: Previous studies have shown that MDM2 SNP309 and p53 codon 72 have modifier effects on germline P53 mutations, but those studies relied on case-only studies with small sample sizes. The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 213 p53 germline mutation carriers including 168(78.9%) affected with cancer and 174 who had genotypic data. We analyzed time to first cancer using Kaplan-Meier and Cox proportional hazards methods, comparing risks according to polymorphism genotypes. For MDM2 SNP309, a significant difference of 9.0 years in the average age of cancer diagnosis was observed between GG/GT and TT carriers (18.6 versus 27.6 years, P = 0.0087). The hazards ratio was 1.58 (P = 0.03) comparing risks among individuals with GG/GT to risk among TT, but this effect was only significant in females (HR = 1.60, P = 0.02). Compared to other genotypes, P53 codon 72 PP homozygotes had a 2.24 times (P = 0.03) higher rate for time to develop cancer. We observed a multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk. The MDM4 polymorphism had no significant effects. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the MDM2 SNP309 G allele is associated with cancer risk in p53 germline mutation carriers and accelerates time to cancer onset with a pronounced effect in females. A multiplicative joint effect exists between the MDM2 SNP309 G allele and the p53 codon 72 G allele in the risk of cancer development. Our results further define cancer risk in carriers of germline p53 mutations.
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Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Neoplasias/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Proteínas de Ciclo Celular , Codón/genética , Estudios de Cohortes , Femenino , Heterocigoto , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Neoplasias/diagnóstico , Neoplasias/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Significant challenges exist in assembling and interconnecting the building blocks of a nanoscale device and being able to electronically address or measure responses at the molecular level. Here we demonstrate the usefulness of engineered proteins as scaffolds for bottom-up self-assembly for building nanoscale devices out of multiple components. Using genetically engineered cowpea mosaic virus, modified to express cysteine residues on the capsid exterior, gold nanoparticles were attached to the viral scaffold in a specific predetermined pattern to produce specific interparticle distances. The nanoparticles were then interconnected using thiol-terminated conjugated organic molecules, resulting in a three-dimensional network. Network properties were engineered by using molecular components with different I-V characteristics. Networks consisting of molecular wires alone were compared with networks containing voltage controlled molecular switches with two stable conductance states. Using such bistable molecules enabled the formation of switchable molecular networks that could be used in nanoscale memory circuits.
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Biónica/métodos , Comovirus/química , Nanopartículas del Metal/química , Nanopartículas del Metal/virología , Sitios de Unión , Materiales Biocompatibles/química , Cristalización , Conductividad Eléctrica , Oro , Intercambio Iónico , Sustancias Macromoleculares/química , Ensayo de Materiales , Microscopía de Túnel de Rastreo , Conformación Molecular , Nanotecnología/métodos , Organismos Modificados Genéticamente , Ingeniería de ProteínasRESUMEN
Colloidal gold has been coupled to a mutant cowpea mosaic virus (CPMV), which contains 60 cysteine residues on the surface. A purification process was developed to separate the gold-containing viral nanoblocks (VNBs) from the free gold. Agarose electrophoresis was utilized to separate the mixture followed by electroelution of the desired sample to recover the intact virus. Mobility of Au-VNB and free colloidal gold was facilitated by the addition of thioctic acid (TA). 30% of the gold-containing virus was recovered after electroelution as determined by absorbance measurements. Histogram analysis of transmission electron microscopy (TEM) images demonstrated the efficient separation of gold-containing virus from free gold. TEM and scanning electron microscopy (SEM) images indicated that the virus was recovered intact. Monodisperse spherical particles of nominal size of 45 nm were observed under SEM.