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1.
Rev. lasallista investig ; 18(2): 105-124, jul.-dic. 2021. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1365854

RESUMO

Resumen Introducción: El comienzo del año 2020 llegó acompañado de una pandemia causada por el virus denominado SARS-CoV-2. Con las medidas de distanciamiento social implementadas para evitar la propagación de este virus, se presentan problemáticas de salud mental, como ansiedad, depresión, etc., trayendo como consecuencia una necesidad de atención a pacientes a distancia. Dadas las cifras alarmantes de incidencias de suicidio en la sociedad actual, aunadas a estas medidas de distanciamiento, son requeridas herramientas de apoyo para identificar individuos en riesgo de cometer suicidio. Objetivo: Proponer y evaluar una nueva metodología para calcular riesgo de suicidio en usuarios de Twitter, apoyándose en el análisis de emociones. Materiales y Métodos: Usando modelos de aprendizaje estadístico (supervisado y no supervisado), la metodología propuesta identifica el nivel de riesgo en el texto analizado de 77 tuits de usuarios regulares y de figuras políticas en México y Latinoamérica. Resultados: Se encontró que, al comparar los métodos utilizados, el porcentaje de coincidencia en clasificación es cercano al 96 %, siendo los métodos supervisado no paramétrico y no supervisado los que detectaron los niveles extremos de riesgo al suicidio. Conclusiones: la metodología propuesta es una herramienta que puede ser de gran apoyo para especialistas del área de salud mental al ayudar a identificar, de manera masiva, la presencia de indicios de enfermedades mentales, para su subsecuente diagnóstico.


Abstract Introduction: The beginning of 2020 was accompanied by a pandemic caused by the virus called SARS-CoV-2. With social distancing measures implemented to prevent the spread of this virus, mental health problems arose, such as anxiety, depression, etc., resulting in a need for telemedicine. Given the alarming numbers of suicide incidences in today's society, coupled with these distancing measures, support tools are required to identify individuals at risk of committing suicide. Objective: To propose and evaluate a new methodology to calculate suicide risk in Twitter users, based on the analysis of emotions. Materials and Methods: Using statistical learning models (supervised and unsupervised), the proposed methodology identifies the level of risk in the analyzed text of 77 tweets from regular users and political figures in Mexico and Latin America. Results: It was found that, when comparing the methods used, the percentage of coincidence in classification is close to 96%, being the supervised non-parametric and unsupervised methods those that detected the extreme levels of suicide risk. Conclusions: the proposed methodology is a tool that can be of great support for specialists in the mental health area by helping to identify, in a massive way, the presence of signs of mental illness, for its subsequent diagnosis.


Resumo Introdução: O início de 2020 foi acompanhado por uma pandemia causada pelo vírus denominado SARS-CoV-2. Com as medidas de distanciamento social implantadas para prevenir a propagação desse vírus, surgem problemas de saúde mental, como ansiedade, depressão, etc., resultando na necessidade de atendimento remoto ao paciente. Dados os números alarmantes de incidentes de suicídio na sociedade atual, juntamente com essas medidas de distanciamento, ferramentas de apoio são necessárias para identificar indivíduos em risco de suicídio. Objetivo: propor e avaliar uma nova metodologia para calcular o risco de suicídio em usuários do Twitter, a partir da análise das emoções. Materiais e Métodos: Usando modelos estatísticos de aprendizagem (supervisionados e não supervisionados), a metodologia proposta identifica o nível de risco no texto analisado de 77 tweets de usuários regulares e figuras políticas no México e na América Latina. Resultados: Verificou-se que, na comparação dos métodos utilizados, o percentual de coincidência na classificação é próximo a 96%, sendo os métodos não paramétricos supervisionados e não supervisionados aqueles que detectaram os níveis extremos de risco de suicídio. Conclusões: A metodologia proposta é uma ferramenta que pode ser de grande apoio aos especialistas da área de saúde mental por ajudar a identificar, de forma massiva, a presença de indícios de doença mental, para seu posterior diagnóstico.

2.
Mol Cancer Res ; 5(12): 1263-75, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18171984

RESUMO

Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the beta-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.


Assuntos
Adenoma/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Adenoma/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Filogenia , RNA Mensageiro/metabolismo , Transcrição Gênica
3.
Int J Cancer ; 118(8): 1937-40, 2006 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-16287072

RESUMO

In 10-30% of patients with classical familial adenomatous polyposis (FAP) and up to 90% of those with attenuated (<100 colorectal adenomas; AFAP) polyposis, no pathogenic germline mutation in the adenomatous polyposis coli (APC) gene can be identified (APC mutation-negative). Recently, biallelic mutations in the base excision repair gene MYH have been shown to predispose to a multiple adenoma and carcinoma phenotype. This study aimed to (i) assess the MYH mutation carrier frequency among Swiss APC mutation-negative patients and (ii) identify phenotypic differences between MYH mutation carriers and APC/MYH mutation-negative polyposis patients. Seventy-nine unrelated APC mutation-negative Swiss patients with either classical (n=18) or attenuated (n=61) polyposis were screened for germline mutations in MYH by dHPLC and direct genomic DNA sequencing. Overall, 7 (8.9%) biallelic and 9 (11.4%) monoallelic MYH germline mutation carriers were identified. Among patients with a family history compatible with autosomal recessive inheritance (n=45), 1 (10.0%) out of 10 classical polyposis and 6 (17.1%) out of 35 attenuated polyposis patients carried biallelic MYH alterations, 2 of which represent novel gene variants (p.R171Q and p.R231H). Colorectal cancer was significantly (p<0.007) more frequent in biallelic mutation carriers (71.4%) compared with that of monoallelic and MYH mutation-negative polyposis patients (0 and 13.8%, respectively). On the basis of our findings and earlier reports, MYH mutation screening should be considered if all of the following criteria are fulfilled: (i) presence of classical or attenuated polyposis coli, (ii) absence of a pathogenic APC mutation, and (iii) a family history compatible with an autosomal recessive mode of inheritance.


Assuntos
Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/genética , DNA Glicosilases/genética , Genes APC , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Adulto , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Reparo do DNA , Feminino , Humanos , Padrões de Herança , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Suíça
4.
Gastroenterology ; 128(5): 1160-71, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15887099

RESUMO

BACKGROUND & AIMS: Germline mutations in the DNA mismatch repair (MMR) genes MSH2, MSH6, or MLH1 predispose to colorectal cancer (CRC) with an autosomal dominant inheritance pattern. The protein encoded by PMS2 is also essential for MMR; however, alterations in this gene have been documented only in extremely rare cases. We addressed this unexpected finding by analyzing a large series of CRCs. METHODS: Expression of MSH2, MSH6, MLH1, and PMS2 was studied by immunohistochemistry in 1048 unselected, consecutive CRCs. Where absence of MMR proteins was detected, microsatellite instability and cytosine methylation of the respective gene promoter were analyzed. The DNA of patients presenting with PMS2-deficient cancers was examined for germline and somatic alterations in the PMS2 gene. RESULTS: An aberrant pattern of MMR protein expression was detected in 13.2% of CRCs. Loss of expression of MSH2, MSH6, or MLH1 was found in 1.4%, 0.5%, and 9.8%, respectively. PMS2 deficiency accompanied by microsatellite instability was found in 16 cases (1.5%) with a weak family history of cancer. The PMS2 promoter was not hypermethylated in these cases. Despite interference of the PMS2 pseudogenes, we identified several heterozygous germline mutations in the PMS2 gene. CONCLUSIONS: PMS2 defects account for a small but significant proportion of CRCs and for a substantial fraction of tumors with microsatellite instability. However, the penetrance of heterozygous germline mutations in PMS2 is considerably lower than that of mutations in other MMR genes. The possible underlying causes of this unorthodox inheritance pattern are discussed.


Assuntos
Adenoma/genética , Adenoma/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte , Metilação de DNA , Feminino , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Imuno-Histoquímica , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fenótipo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo
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