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1.
Prev Med Rep ; 28: 101864, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35774855

RESUMO

E-cigarette use among youth remains a significant public health concern. In 2018, The Real Cost campaign began disseminating messages about the harms of vaping, primarily using digital media. We sought to determine the prevalence of aided recall of The Real Cost e-cigarette prevention ads and identify potential differences by participant characteristics. Participants were a nationally representative sample of adolescents living in United States (US) households recruited by the National Opinion Research Center (NORC) at the University of Chicago's AmeriSpeak panel in September and October of 2020. A total of 623 adolescents completed the survey. Analyses were weighted to represent the distribution of youth in the US, and effect sizes for individual characteristics were estimated using an adjusted marginalized two-part model. Seventy-one percent of adolescents recalled at least one of the five The Real Cost e-cigarette prevention ads, with individual ad recall ranging from a low of 38.8% (for Magic) to a high of 50.1% (for Narrative). Adjusted estimates of aided recall identified significantly higher recall among Black adolescents and those that used social media at medium or high frequencies (p < 0.05). Results support ongoing efforts by the FDA to reach youth with e-cigarette prevention messages using primarily digital media.

2.
Mol Cell ; 82(13): 2443-2457.e7, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35613620

RESUMO

RAF protein kinases are effectors of the GTP-bound form of small guanosine triphosphatase RAS and function by phosphorylating MEK. We showed here that the expression of ARAF activated RAS in a kinase-independent manner. Binding of ARAF to RAS displaced the GTPase-activating protein NF1 and antagonized NF1-mediated inhibition of RAS. This reduced ERK-dependent inhibition of RAS and increased RAS-GTP. By this mechanism, ARAF regulated the duration and consequences of RTK-induced RAS activation and supported the RAS output of RTK-dependent tumor cells. In human lung cancers with EGFR mutation, amplification of ARAF was associated with acquired resistance to EGFR inhibitors, which was overcome by combining EGFR inhibitors with an inhibitor of the protein tyrosine phosphatase SHP2 to enhance inhibition of nucleotide exchange and RAS activation.


Assuntos
Neurofibromina 1 , Proteínas Proto-Oncogênicas A-raf , Proteínas Ativadoras de ras GTPase , Receptores ErbB/genética , Receptores ErbB/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Neurofibromina 1/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas A-raf/metabolismo , Transdução de Sinais , Proteínas Ativadoras de ras GTPase/metabolismo
3.
Hum Pathol ; 101: 40-52, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360491

RESUMO

The current World Health Organization classification does not distinguish transitional cell carcinoma of the ovary (TCC) from conventional tubo-ovarian high-grade serous carcinoma (HGSC), despite evidence suggesting improved prognosis for patients with TCC; instead, it is considered a morphologic variant of HGSC. The immunohistochemical (IHC) markers applied to date do not distinguish between TCC and HGSC. Therefore, we sought to compare the proteomic profiles of TCC and conventional HGSC to identify proteins enriched in TCC. Prognostic biomarkers in HGSC have proven to be elusive, and our aim was to identify biomarkers of TCC as a way of reliably and reproducibly identifying patients with a favorable prognosis and better response to chemotherapy compared with those with conventional HGSC. Quantitative global proteome analysis was performed on archival material of 12 cases of TCC and 16 cases of HGSC using SP3 (single-pot, solid phase-enhanced, sample preparation)-Clinical Tissue Proteomics, a recently described protocol for full-proteome analysis from formalin-fixed paraffin-embedded tissues. We identified 430 proteins that were significantly enriched in TCC over HGSC. Unsupervised co-clustering perfectly distinguished TCC from HGSC based on protein expression. Pathway analysis showed that proteins associated with cell death, necrosis, and apoptosis were highly expressed in TCCs, whereas proteins associated with DNA homologous recombination, cell mitosis, proliferation and survival, and cell cycle progression pathways had reduced expression. From the proteomic analysis, three potential biomarkers for TCC were identified, claudin-4 (CLDN4), ubiquitin carboxyl-terminal esterase L1 (UCHL1), and minichromosome maintenance protein 7 (MCM7), and tested by IHC analysis on tissue microarrays. In agreement with the proteomic analysis, IHC expression of those proteins was stronger in TCC than in HGSC (p < 0.0001). Using global proteomic analysis, we are able to distinguish TCC from conventional HGSC. Follow-up studies will be necessary to confirm that these molecular and morphologic differences are clinically significant.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias Ovarianas/diagnóstico , Feminino , Humanos , Proteômica/métodos
4.
Am J Epidemiol ; 187(11): 2460-2469, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383261

RESUMO

The National Cancer Institute developed the Health Disparities Calculator (HD*Calc) to facilitate research on health disparities. HD*Calc calculates multiple measures of health disparities using data collected from population-based disease surveillance systems, such as cancer registries. In this paper, we extend the use of HD*Calc to complex survey data by developing plug-in point estimators and Taylor linearization variance estimators that consider complex designs: stratification, multistage clustering, and differential weighting. Our simulation indicates that the plug-in estimators are approximately unbiased and the Taylor linearization variance estimators are accurate. Using 2011-2016 data from the National Health and Nutrition Examination Survey, we demonstrate the use of these estimators in evaluating socioeconomic disparities in the prevalence of child and adolescent (ages 2-18 years) obesity in the United States. Statistical software has been developed for ease of disparity analyses using complex survey data.


Assuntos
Interpretação Estatística de Dados , Projetos de Pesquisa Epidemiológica , Disparidades nos Níveis de Saúde , Adolescente , Criança , Pré-Escolar , Coleta de Dados , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Obesidade Infantil/epidemiologia , Vigilância da População/métodos , Fatores Socioeconômicos , Estados Unidos/epidemiologia
5.
World Neurosurg ; 104: 788-794, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28559083

RESUMO

OBJECTIVE: To investigate potential effect of sacrifice of the superior petrosal vein (SPV) on postoperative complications after microvascular decompression (MVD). METHODS: Retrospective review of 98 consecutive patients undergoing MVD of cranial nerve V was performed. Frequency of division of the SPV during surgery was recorded, and postoperative complications and imaging were recorded and analyzed. In patients with complications, the specific anatomic variation of the superior petrosal venous complex was noted. RESULTS: Of 98 patients undergoing MVD, 83 (84.7%) had sacrifice of the SPV at the time of surgery, 12 (12.2%) had the SPV preserved, and 3 (3.1%) were revision operations. Four patients (4.8%) had complications deemed to be attributable to venous insufficiency or congestion. These included sigmoid sinus thrombosis with coincident cerebellar hemorrhage, midbrain and pontine infarction, hemiparesis with midbrain and pontine edema, and facial paresis with ischemia in the middle cerebellar peduncle. None of the patients with preserved SPV were symptomatic or had imaging changes consistent with venous congestion. CONCLUSIONS: Sacrifice of the SPV is often performed during MVD. This is associated with a complication rate that is significant in frequency and severity compared with preserving the vein. SPV sacrifice should be limited to cases where it is deemed absolutely necessary for successful cranial nerve decompression.


Assuntos
Veias Cerebrais/cirurgia , Cirurgia de Descompressão Microvascular/métodos , Síndromes de Compressão Nervosa/cirurgia , Complicações Pós-Operatórias/etiologia , Doenças do Nervo Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Veias Cerebrais/diagnóstico por imagem , Cavidades Cranianas/diagnóstico por imagem , Cavidades Cranianas/cirurgia , Eletrocoagulação , Feminino , Humanos , Hiperemia/diagnóstico por imagem , Hiperemia/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Doenças do Nervo Trigêmeo/diagnóstico por imagem , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/etiologia
7.
World Neurosurg ; 84(4): 1147-60, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26072457

RESUMO

Aneurysmal subarachnoid hemorrhage (SAH) remains an important health issue in the United States. Despite recent improvements in the diagnosis and treatment of cerebral aneurysms, the mortality rate following aneurysm rupture. In those patients who survive, up to 50% are left severely disabled. The goal of preventing the hemorrhage or re-hemorrhage can only be achieved by successfully excluding the aneurysm from the circulation. This article is a comprehensive review by contemporary vascular neurosurgeons and interventional neuroradiolgists on the modern management of cerebral aneurysms.


Assuntos
Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/terapia , Procedimentos Neurocirúrgicos/métodos , Aneurisma Roto/cirurgia , Gerenciamento Clínico , Humanos , Aneurisma Intracraniano/mortalidade , Qualidade de Vida , Instrumentos Cirúrgicos
8.
Neurosurg Focus ; 22(2): E3, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17628897

RESUMO

The authors report on a 63-year-old man initially admitted to an outside hospital for altered mental status and respiratory distress. A head computed tomography scan disclosed a right frontal cystic mass, suspected to be a neoplasm. An open biopsy was performed at an outside institution, and on visualization of the cyst, an aneurysm was found incidentally. Postoperatively, an angiogram and magnetic resonance image confirmed the presence of a distal right M1 segment aneurysm. The patient was transferred to our institution where, in addition to the middle cerebral artery lesion, a right anterior choroidal artery aneurysm was found intraoperatively; the necks of both aneurysms were clipped successfully. A review of the literature revealed 14 additional cases of intracranial aneurysms associated with arachnoid cysts. Data in the present report highlight the importance of considering an intracystic aneurysm in the differential diagnosis when reviewing cases that involve a cystic mass with a mural nodule. The authors provide a comprehensive summary of documented cases of aneurysms associated with arachnoid cysts. In addition, they include a discussion of prevailing thoughts on the origin and evolution of arachnoid cysts.


Assuntos
Cistos Aracnóideos/diagnóstico , Aneurisma Intracraniano/diagnóstico , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico , Cistos Aracnóideos/patologia , Angiografia Cerebral/métodos , Humanos , Aneurisma Intracraniano/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos
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