Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
1.
Genes Chromosomes Cancer ; 62(12): 710-720, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37436117

RESUMEN

Prostate cancer (PrCa) is one of the three most frequent and deadliest cancers worldwide. The discovery of PARP inhibitors for the treatment of tumors with deleterious variants in homologous recombination repair (HRR) genes has placed PrCa on the roadmap of precision medicine. However, the overall contribution of HRR genes to the 10%-20% of carcinomas arising in men with early-onset/familial PrCa has not been fully clarified. We used targeted next-generation sequencing (T-NGS) covering eight HRR genes (ATM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, and RAD51C) and an analysis pipeline querying both small and large genomic variations to clarify their global and relative contribution to hereditary PrCa predisposition in a series of 462 early-onset/familial PrCa cases. Deleterious variants were found in 3.9% of the patients, with CHEK2 and ATM being the most frequently mutated genes (38.9% and 22.2% of the carriers, respectively), followed by PALB2 and NBN (11.1% of the carriers, each), and finally by BRCA2, RAD51C, and BRIP1 (5.6% of the carriers, each). Using the same NGS data, exonic rearrangements were found in two patients, one pathogenic in BRCA2 and one of unknown significance in BRCA1. These results contribute to clarify the genetic heterogeneity that underlies PrCa predisposition in the early-onset and familial disease, respectively.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Neoplasias de la Próstata , Masculino , Humanos , Reparación del ADN por Recombinación/genética , Predisposición Genética a la Enfermedad , Genotipo , Neoplasias de la Próstata/genética , Mutación de Línea Germinal , Recombinación Homóloga
2.
Br J Cancer ; 128(6): 1077-1085, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36564567

RESUMEN

BACKGROUND: Prostate cancer (PrCa) is one of the most hereditable human cancers, however, only a small fraction of patients has been shown to carry deleterious variants in known cancer predisposition genes. METHODS: Whole-exome sequencing was performed in multiple affected members of 45 PrCa families to select the best candidate genes behind part of the PrCa missing hereditability. Recurrently mutated genes were prioritised, and further investigated by targeted next-generation sequencing in the whole early-onset and/or familial PrCa series of 462 patients. RESULTS: PRUNE2 stood out from our analysis when also considering the available data on its association with PrCa development. Ten germline pathogenic/likely pathogenic variants in the PRUNE2 gene were identified in 13 patients. The most frequent variant was found in three unrelated patients and identical-by-descent analysis revealed that the haplotype associated with the variant is shared by all the variant carriers, supporting the existence of a common ancestor. DISCUSSION: This is the first report of pathogenic/likely pathogenic germline variants in PRUNE2 in PrCa patients, namely in those with early-onset/familial disease. Importantly, PRUNE2 was the most frequently mutated gene in the whole series, with a deleterious germline variant identified in 2.8% of the patients, representing a novel prostate cancer predisposition gene.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias de la Próstata , Humanos , Masculino , Secuenciación del Exoma , Mutación de Línea Germinal , Neoplasias de la Próstata/genética , Factores de Transcripción/genética
3.
Opt Express ; 30(2): 2230-2246, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35209368

RESUMEN

In this work we demonstrate the fabrication and characterization of a temperature insensitive, two-dimensional curvature sensor using a resin based Fabry-Pérot interferometer, constructed using a multicore fiber (MCF). The fabrication simplicity makes this fiber device very attractive compared to the already reported technologies. Furthermore, the sensitivity reached (>400 pm/m-1), 7 times higher than the one reported for fiber Bragg gratings written on a similar MCF. The reconstruction of the amplitude and curvature has been performed for, showing errors lower than 4%. A numerical study has also been developed, allowing us to understand the sensor response at different fiber sensor geometries.

4.
Genes Chromosomes Cancer ; 55(12): 954-961, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27401275

RESUMEN

Truncating activating mutations in the last exon of PPM1D have been described in patients with breast, ovarian, colorectal and non-small cell lung cancer, but recent data indicate that they may be associated with previous chemotherapy. In this study we evaluated the prevalence of PPM1D mutations in white blood cells (WBC) of 462 patients with early-onset and/or familial/hereditary prostate cancer (PrCa) by sequencing the coding region of exon 6. Two truncating mutations were found in two patients (0.4%), both treated with androgen-ablation therapy but no chemotherapy prior to blood collection. Next generation sequencing analysis showed that the truncating variants were present in 21.4% and 32.4% of the reads, indicating that they were in mosaic in WBC, something that was confirmed by its absence in a different tissue from one of these patients. Additionally, nine patients (1.95%) were found to harbor non-synonymous germline mutations, with three patients sharing the same missense variant, c.1607G > A, p.Arg536Lys. This variant was predicted to be deleterious by different in silico tools and was not found in the 293 male control subjects tested. Large cohorts and/or functional evaluation are needed to clarify the nature of the truncating mosaic mutations in PrCa patients treated with and without androgen-ablation therapy and to evaluate the contribution of the recurrent missense variant to the risk of developing PrCa. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Carcinoma Basocelular/genética , Predisposición Genética a la Enfermedad , Mutación/genética , Neoplasias de la Próstata/genética , Proteína Fosfatasa 2C/genética , Adenocarcinoma/patología , Edad de Inicio , Carcinoma Basocelular/patología , Estudios de Casos y Controles , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/patología
7.
Front Pediatr ; 9: 755484, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34858905

RESUMEN

The implementation of managed protocols contributes to a systematized approach to the patient and continuous evaluation of results, focusing on improving clinical practice, early diagnosis, treatment, and outcomes. Advantages to the adoption of a pediatric sepsis recognition and treatment protocol include: a reduction in time to start fluid and antibiotic administration, decreased kidney dysfunction and organ dysfunction, reduction in length of stay, and even a decrease on mortality. Barriers are: absence of a written protocol, parental knowledge, early diagnosis by healthcare professionals, venous access, availability of antimicrobials and vasoactive drugs, conditions of work, engagement of healthcare professionals. There are challenges in low-middle-income countries (LMIC). The causes of sepsis and resources differ from high-income countries. Viral agent such as dengue, malaria are common in LMIC and initial approach differ from bacterial infections. Some authors found increased or no impact in mortality or increased length of stay associated with the implementation of the SCC sepsis bundle which reinforces the importance of adapting it to most frequent diseases, disposable resources, and characteristics of healthcare professionals. Conclusions: (1) be simple; (2) be precise; (3) education; (5) improve communication; (5) work as a team; (6) share and celebrate results.

8.
Rev Port Cardiol (Engl Ed) ; 40(6): 409-419, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34274081

RESUMEN

INTRODUCTION AND OBJECTIVES: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease-related costs. METHODS: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real-world data from primary care, the 2014 National Health Interview Survey, and expert opinion. RESULTS: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%). CONCLUSIONS: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.


Asunto(s)
Aterosclerosis , Costo de Enfermedad , Aterosclerosis/epidemiología , Gastos en Salud , Hospitalización , Humanos , Portugal/epidemiología
9.
Eur Urol Oncol ; 4(4): 570-579, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33436325

RESUMEN

BACKGROUND: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes. OBJECTIVE: To precisely estimate the contribution of germline ATM mutations to PrCa risk. DESIGN, SETTING, AND PARTICIPANTS: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated. RESULTS AND LIMITATIONS: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (pdifference = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7). CONCLUSIONS: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families. PATIENT SUMMARY: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias de la Próstata , Proteínas de la Ataxia Telangiectasia Mutada/genética , Mutación de Línea Germinal , Humanos , Masculino , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética
10.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-33158149

RESUMEN

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

11.
Agora (Rio J.) ; 26: e280609, 2023.
Artículo en Portugués | LILACS, Index Psi (psicología) | ID: biblio-1527671

RESUMEN

RESUMO: O objeto central deste artigo, fundamentado na psicanálise, é a problemática da exclusão social. Trata-se de mostrar a importância desse saber em uma reflexão dedicada a situações de precariedade social. Um de seus eixos principais concerne à dimensão de pertencimento, própria ao laço social, tendo em vista, em particular, vividos subjetivos marcados por significativas falhas quanto a essa dimensão. A questão da colonialidade é um operador de relevo neste trabalho, visando ao aprofundamento da relação exclusão/pertencimento. A noção de desamparo e sua modalidade extrema, o desalento, têm grande relevância neste estudo, o qual se ancora na articulação entre subjetividade e universo sócio-cultural.


ABSTRACT: From social exclusion to discouragement: a "decolonial" look. The central object of this article, based on psychoanalysis, is the issue of social exclusion. It is about showing the importance of this knowledge in a reflection dedicated to situations of social precariousness. One of its main axes concerns the dimension of belonging, specific to the social bond, taking into account, in particular, subjective experiences marked by significant flaws in this dimension. The issue of coloniality is a relevant operator in this work, aiming to deepen the relationship of exclusion/belonging. The notion of helplessness and its extreme modality, discouragement, has great relevance in this study, which is anchored in the articulation between subjectivity and the socio-cultural universe.


Asunto(s)
Aislamiento Social , Colonialismo , Tristeza
12.
Medicina (Ribeirao Preto, Online) ; 56(3)nov. 2023. tab, ilus
Artículo en Inglés | LILACS | ID: biblio-1551212

RESUMEN

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored pre- and post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal's method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, show-ing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation (AU).


Introdução e objetivos: Durante a pandemia COVID-19 o acompanhamento de doentes medicados com antagonistas da vitamina K (AVKs) pode ter sido afetado. Este estudo pretende comparar a forma como estes doentes foram monitorizados antes e depois da pandemia COVID-19 e compreender o impacto da consulta não presencial no seu seguimento. Métodos: Estudo de coorte retrospetivo num Centro de Saúde em Portugal. O estudo incluiu doentes tratados com AVKs e seguidos no Centro de Saúde para monitorização do International Normalized Ratio(INR) entre março de 2019 e março de 2021. Dados recolhidos: sexo, idade, tipo de AVK; INR; data da avaliação do INR, tipo de consulta (presencial ou por telefone/e-mail). Foi utilizado o método de interpolação linear de Rosendaal para calcular o tempo em intervalo terapêutico (TTR) pré- e pós-COVID-19. Foi definido um bom controle se valores de TTR ≥ 70%. Resultados: Foram incluídos 44 doentes. A média de TTR no período pré-COVID-19 foi de 64,55% (95% IC: 58,10 - 71,00%). A média pós-COVID-19 foi ligeiramente superior (+ 2,26%), 66,81% (95% IC: 59,66 - 73,97%), mas a diferença não foi estatisticamente significativa (p = 0,576). A utilização da consulta não presencial não contribuiu para o agravamento do TTR no período pós-pandemia, não mostrando um seguimento inferior ao do período pré-pandemia em que todos os contatos foram presenciais [IC (95%) -0,397 - 0,196 para um intervalo de referência -0,489 - 0,693]. Conclusões: O valor de TTR em ambos os períodos foi semelhante e inferior ao valor definido para hipocoagulação eficaz. A utilização da consulta não presencial no período pós-COVID-19 não parece ter influenciado a qualidade da hipocoagulação (AU).


Asunto(s)
Humanos , Masculino , Femenino , Warfarina , COVID-19 , Anticoagulantes
13.
Psicol. teor. prát ; 24(2): 13977, 14.06.2022.
Artículo en Inglés | LILACS | ID: biblio-1434963

RESUMEN

Neste artigo, é analisada a questão do impacto psicológico produzido pela coronavirus disease 2019 (Covid-19) tendo em vista sua incidência num contexto de exclusão e precariedade social. Trata-se de experiências subjetivas de ruptura de laços sociais e simbólicos que são relativas a diferentes planos de pertencimento coletivo: econômico, político, racial e cultural. Os modos de enfrentamento e a própria ameaça que a pandemia representa são reveladores da sociedade atual considerando-se, particularmente, a singularidade de suas diferentes camadas. A partir de um referencial psicanalítico, com ênfase na articulação subjetividade/laço social, é explorada a ideia de que o fenômeno da Covid-19 produz efeitos de aprofundamento de processos de exclusão, já existentes na cena social contemporânea, com consequências nefastas para o psiquismo de sujeitos cuja existência é marcada pela invisibilidade social. Diante de uma crescente situação de desproteção, acirrada pela crise econômica, política e sanitária, o sujeito luta diariamente pela sobrevivência física, o que pode resultar em uma traumática situação de urgência subjetiva


In this article, we analyze the issue of the psychological impact of the coronavirus disease 2019 (Covid-19) in view of its incidence in a context of exclusion and social precariousness. We refer to subjective experiences of rupture of social and symbolic bonds that are related to different forms of belonging: economic, political, racial, and cultural. The threat that the pandemic represents and the ways of coping with it reveal central aspects of society nowadays, considering the singularity of its different layers. From a psychoanalytical point of view, stressing the articulation of subjectivity/social bond, we study the idea that the phenomenon of Covid-19 intensifies the processes of exclusion, already present in the contemporary social scene, with nefarious consequences for the psyche of subjects whose existence is marked by social invisibility. In the context of a situation of social insecurity, exacerbated by unprecedented economic, political, and health crisis, individuals face a daily struggle for survival, which can result in a traumatic experience of subjective urgency


En este artículo, analizamos el tema del impacto psicológico de la coronavirus disease 2019 (Covid-19) en vista de su incidencia en un contexto de exclusión y precariedad social. Se trata de experiencias subjetivas de ruptura de vínculos sociales y simbólicos que se relacionan con diferentes planes de pertenencia colectiva: económico, político, racial y cultural. Las formas de enfrentamiento y la propia amenaza que representa la pandemia revelan la sociedad actual, teniendo especialmente en cuenta la singularidad de sus diferentes estratos. Desde un punto de vista psicoanalítico, destacando la articulación subjetividad/vinculo social, exploramos la idea de que el fenómeno de Covid-19 produce efectos de profundización de los procesos de exclusión, ya existentes en la escena social contemporánea, con consecuencias nefastas para la psique de sujetos cuya existencia está marcada por la invisibilidad social. Ante una situación creciente de desprotección, agravada por la crisis económica, política y sanitaria, el sujeto enfrenta una lucha diaria por la supervivencia, lo que puede resultar en una experiencia traumática de urgencia subjetiva.


Asunto(s)
Humanos , Masculino , Femenino , Aislamiento Social , COVID-19 , Sociedades , Relaciones Interpersonales
14.
Artículo en Portugués | LILACS | ID: biblio-1426314

RESUMEN

O artigo desenvolve a hipótese de que haveria no discurso freudiano sobre a criatividade artística a presença de uma postura estética subentendida no próprio encontro de Freud com as obras de arte de seu tempo. O argumento expõe alguns dados históricos sobre o panorama artístico da época; algumas referências do arquivo epistolar do autor; e um recorte da metapsicologia. Sugerimos que o trilho da estética possibilitou a emergência do emblemático texto O estranho, em 1919, que antecede a formalização da segunda tópica. O artigo consiste numa adaptação da primeira parte de uma tese que versa sobre o aspecto estranho e regressivo da criação artística ­ inscrito, portanto, numa dimensão além do princípio do prazer ­ de modo que o discurso que articula a arte ao sonho, o devaneio e a brincadeira é aqui apresentado como base, portanto, de uma estranheza esteticamente marcada na obra freudiana.


Asunto(s)
Arte , Psicoanálisis , Estética
15.
Pediatr Crit Care Med ; 7(5): 423-7, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16885787

RESUMEN

OBJECTIVE: To verify the frequency of discrepancies between clinical diagnoses and autopsy findings in patients from a pediatric intensive care unit and to look for predictive factors of the discrepancies. DESIGN: Prospective evaluation performed between September 1996 and December 1998. SETTING: Eight-bed pediatric intensive care unit of a university hospital. PATIENTS: One hundred and two autopsies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Disagreements between autopsy and antemortem diagnoses were classified as proposed by Goldman. Patient age, presence of underlying disease, and length of stay were studied as possible predictive factors for diagnosis discrepancies. During the 28 months of study there were 779 admissions to the pediatric intensive care unit; the death rate was 26% and the autopsy rate was 55%. One hundred and two of 114 (89.5%) autopsies were evaluated. The median age of the patients was 21 months, and 85% of them had a previous underlying disease. One third of patients died before 24 hrs of admission to the pediatric intensive care unit. The autopsy revealed unexpected findings in 73 study patients (72%), 33 of which were related to "major diagnoses" (Goldman's classes I or II), either causes of death or main underlying disease. In 12 patients (12%), the correct diagnosis, if known before death, might have led to a change in the patient's therapy or outcome (class I). Unexpected findings in this group included viral or fungal infection and pulmonary embolism. None of the possible predictive factors that we studied showed significant statistical association between clinical and autopsy discrepant diagnoses in the univariate analysis. CONCLUSIONS: Although diagnoses of both cause of death and underlying disease were accurate in most cases before death, some autopsies revealed findings that would have changed intensive care unit therapy. Nonbacterial infections and pulmonary thromboembolism should always be considered when managing critically ill patients with underlying disease. Autopsy examinations continue to provide important information, especially in the pediatric intensive care unit setting, despite the advances in diagnostic technology.


Asunto(s)
Autopsia , Causas de Muerte , Errores Diagnósticos , Hallazgos Incidentales , Unidades de Cuidado Intensivo Pediátrico , Adolescente , Brasil , Niño , Preescolar , Femenino , Predicción , Humanos , Lactante , Infecciones/diagnóstico , Masculino , Estudios Prospectivos , Embolia Pulmonar/diagnóstico
16.
Oncoscience ; 3(9-10): 288-296, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28050579

RESUMEN

The recurrent germline mutation HOXB13 p.(Gly84Glu) (G84E) has recently been identified as a risk factor for prostate cancer. In a recent study, we have performed full sequencing of the HOXB13 gene in 462 Portuguese prostate cancer patients with early-onset and/or familial/hereditary disease, and identified two novel missense mutations, p.(Ala128Asp) (A128D) and p.(Phe240Leu) (F240L), that were predicted to be damaging to protein function. In the present work we aimed to investigate the potential oncogenic role of these mutations, comparing to that of the recurrent G84E mutation and wild-type HOXB13. We induced site-directed mutagenesis in a HOXB13 expression vector and established in vitro cell models of prostate carcinogenesis with stable overexpression of either the wild-type or the mutated HOXB13 variants. By performing in vitro assays we observed that, while the wild-type promotes proliferation, also observed with the F240L variant along with a decrease in apoptosis, the A128D mutation decreases apoptosis and promotes anchorage independent growth. No phenotypic impact was observed for the G84E mutation in the cell line model used. Our data show that specific HOXB13 mutations are involved in the acquisition of different cancer-associated capabilities and further support an oncogenic role for HOXB13 in prostate carcinogenesis.

17.
Rev. latinoam. psicopatol. fundam ; 24(4): 682-705, out.-dez. 2021.
Artículo en Portugués | LILACS-Express | LILACS, Index Psi (psicología) | ID: biblio-1361065

RESUMEN

Baseando-nos nas análises genealógica e epistemológica propostas por Foucault e Lantéri-Laura, nosso objetivo principal é discernir quais são as principais linhas discursivas que constituíram o saber em torno da perversão, produzindo um sujeito dito perverso. Emerge de maneira fundamental dessa leitura como a ideia de transgressão de limites acompanha a história dos perversos: seja o limite moral imposto pela autoridade divina, seja o limite jurídico determinado pela lei penal, seja o limite do normal definido pela medicina, a perversão sempre aponta para o excesso transgressor. Tais leituras constituem o solo epistemológico sobre o qual Freud se apoia na concepção de uma metapsicologia cujo eixo central é a sexualidade. O discurso freudiano subverte o estatuto da perversão ao afirmá-la como dimensão inescapável da sexualidade e da constituição da subjetividade humana.


Based on the genealogical and epistemological analyzes proposed by Foucault and Lanteri-Laura, we aim to discern which are the main discursive lines that constituted the knowledge around perversion, producing a so-called perverse subject. It emerges in a fundamental way from this reading how the idea of transgression of limits accompanies the history of the perverse: whether the moral limit imposed by divine authority, whether the legal limit determined by criminal law, or the normal limit defined by medicine, perversion always points towards the transgressive excess. Such readings constitute the epistemological ground on which Freud relies to develop the conception of a metapsychology whose central axis is sexuality. The Freudian discourse subverts the status of perversion by affrming it as an inescapable dimension of sexuality and of the constitution of human subjectivity.


Sur la base des analyses généalogique et épistémologique proposées par Foucault et Lanteri-Laura, notre objectif principal est de discerner quelles sont les principales lignes discursives qui constituaient les connaissances autour de la perversion, produisant un sujet dit pervers. Il ressort de manière fondamentale de cette lecture comment l'idée de transgression des limites accompagne l'histoire du pervers : soit la limite morale imposée par l'autorité divine, soit la limite légale déterminée par le droit pénal, ou la limite normale définie par la médecine, la perversion pointe toujours dans la direction de l'excès transgressif. Ces lectures constituent le terrain épistémologique sur lequel Freud s'appuie pour la conception d'une métapsychologie dont l'axe central est la sexualité. Le discours freudien subvertit le statut de perversion en l'affrmant comme une dimension incontournable de la sexualité et de la constitution de la subjectivité humaine.


Basado en los análisis genealógico y epistemológico propuestos por Foucault y por Lanteri-Laura, nuestro principal objetivo es discernir cuáles son las principales líneas discursivas que constituyeron el conocimiento en materia de perversión, produciendo un sujeto denominado perverso. De esta lectura surge de manera fundamental la idea de que la transgresión de los límites acompaña la historia de lo perverso: ya sea el límite moral impuesto por la autoridad divina, el límite legal determinado por el derecho penal o el límite normal definido por la medicina, la perversión siempre señala el exceso transgresor. Tales lecturas constituyen el fundamento epistemológico en el que Freud se basa para la concepción de una metapsicología cuyo eje central es la sexualidad. El discurso freudiano trastorna el estatuto de la perversión al afirmarla como una dimensión ineludible de la sexualidad y de la constitución de la subjetividad humana.

18.
Fam Cancer ; 15(1): 111-21, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26289772

RESUMEN

Prostate cancer (PrCa) is one of the most common cancers diagnosed worldwide and 5-10 % of all cases are estimated to be associated with inherited predisposition. Even though there is strong evidence that the genetic component is significant in PrCa, the genetic etiology of familial and early-onset disease is largely unknown. Although it has been suggested that men from families with hereditary breast/ovarian cancer (HBOC) and, more recently, with Lynch syndrome may have an increased risk for PrCa, the contribution of these syndromes to PrCa predisposition in families ascertained for early-onset and/or familial PrCa, independently of the presence of other cancers in the family, is uncertain. To quantify the contribution of genes associated with HBOC and Lynch syndromes to PrCa predisposition, we have tested for germline mutations 460 early-onset and/or familial PrCa patients. All patients were screened for the six mutations that are particularly common in Portugal and 38 of them were selected for complete sequencing of BRCA1/2 and/or MLH1, MSH2 and MSH6. Two patients were found to harbor the same MSH2 mutation and a third patient carried a Portuguese BRCA2 founder mutation. None of the alterations were identified in 288 control subjects. Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161) and Lynch syndrome (n = 124) families previously diagnosed at our department, and found five other BRCA2 mutation carriers and two additional MSH2 mutation carriers. The clinicopathological characteristics of mutation carriers are in concordance with earlier data suggesting an aggressive PrCa phenotype and support the hypothesis that mutation carriers might benefit from targeted screening according to the gene mutated in the germline.


Asunto(s)
Reparación de la Incompatibilidad de ADN/genética , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad/genética , Neoplasias de la Próstata/genética , Adulto , Edad de Inicio , Análisis Mutacional de ADN , Genotipo , Mutación de Línea Germinal , Humanos , Masculino , Persona de Mediana Edad
19.
Estilos clín ; 26(1): 44-57, jan.-abr. 2021.
Artículo en Portugués | LILACS, Index Psi (psicología) | ID: biblio-1286415

RESUMEN

Com base em um projeto de intervenção social clínica, fundamentado na psicanálise e dirigido ao atendimento de professores do ensino básico da rede municipal do Rio de Janeiro, são analisados neste artigo aspectos envolvidos em sua experiência subjetiva. É priorizada a questão de sua relação com a esfera do trabalho, tendo como foco central as ressonâncias psíquicas do confronto sofrido por eles com a situação da pandemia da Covid-19. Trata-se de abordar seu impacto na rotina das atividades de trabalho desses sujeitos, na área da Educação, já marcadas pela precariedade social, fonte de vulnerabilidade psíquica. O isolamento social imposto pela pandemia, aliado a outras consequências, evidenciou, e mesmo acentuou esse quadro, objeto de especial atenção na proposta clínica, cujas linhas mestras são brevemente trazidas no texto.


Basado en un proyecto de intervención social clínica, apoyado en la psicoanálisis y dirigido a la asistencia a profesores de la enseñanza de la red municipal en Rio de Janeiro, analizamos aspectos envueltos en su experiencia subjetiva. La cuestión de su relación con la esfera del trabajo es priorizada, habiendo como foco central las resonancias psíquicas del confronto que ellos sufren con la situación de la pandemia de Covid-19. Es cuestión de abordar su impacto en la rutina de las actividades de trabajo de esos sujetos, en el área de la Educación, ya marcadas por la precariedad social, fuente de vulnerabilidad psíquica. El aislamiento social impuesto por la pandemia ha evidenciado tal cuadro, objeto de atención en la propuesta clínica, cuyas líneas maestras están brevemente expuestas en el texto.


Based on a project of social clinical intervention, founded on psychoanalysis and addressed to the assistance of teachers of basic education in the local network in Rio de Janeiro, we examine in this article some features involved in their subjective experience. The issue of their relation to the sphere of work is prioritized, having as a central focus the psychic resonances of the confrontation they endured in the situation of Covid-19 pandemic. It's a matter of approaching its impact on the routine of work of these individuals in the area of education, already marked by social precariousness, source of psychic vulnerability.The social isolation imposed by the pandemic highlighted and even reinforced such picture, object of attention in the clinical proposition whose guidelines are briefly developed in the text.


En tenant comme base un projet d'intervention social clinique, en ayant comme fondement la psychanalyse, projet consacré au soin de professeurs de l'enseignement assuré par le reseau municipal de Rio de Janeiro, dans cet article des aspects liés à leur expérience subjective seront analysés. La question de leur relation avec le champs du travail sera privilegiée dont l'axe central sont les ressonances psychiques de la confrontation de ces sujets avec la pandémie du Covid 19. Il s'agit d'aborder son impact sur leur quotidien de travail, dans le champs de l'Education, déjà marqué par la precarité social, source de vulnérabilité psychique. L'isolement social, imposé par la pandémie a evidentié et a aussi acentué ce cadre, objet d'attention dans la proposition clinique dont les grandes lignes sont syntétiquementpresentées dans ce texte.


Asunto(s)
Humanos , Psicoanálisis , Maestros/psicología , Intervención Psicosocial , COVID-19 , Carga de Trabajo , Educación a Distancia , Distrés Psicológico
20.
Tempo psicanál ; 52(1): 111-132, jan.-jun. 2020.
Artículo en Portugués | LILACS-Express | LILACS, Index Psi (psicología) | ID: biblio-1150207

RESUMEN

Na adicção sexual, a realização do ato sexual se impõe ao sujeito de modo compulsivo. A sexualidade perde grande parte de seu potencial fantasístico, passando a servir como motor de uma busca desmedida e destrutiva de prazer que não comporta a possibilidade de vínculo libidinal com o outro. Este artigo, fundamentado no saber psicanalítico, tem por objetivo explorar o papel do complexo de Édipo nas determinações da situação clínica em questão, aspecto teórico de fundamental importância para a compreensão dos impasses que entravam a relação do sex-addict com seus parceiros e com sua própria sexualidade. A problemática edípica não se reduz à clássica descrição freudiana do complexo de Édipo, mas abarca uma série de condições e circunstâncias que precedem o ingresso do infante nessa etapa, sendo a construção da cena primitiva o fator decisivo que viabilizará ou não a entrada do sujeito num efetivo sistema de triangulação. Dedicaremos, portanto, particular atenção à vertente originária do Édipo, a qual tem na construção da cena primitiva o seu núcleo essencial. Esse eixo de trabalho nos conduzirá, por fim, a refletir sobre a adicção sexual em suas manifestações mais radicais e extremas, nas quais a crescente adesão a situações de risco por parte do sex-addict se torna paradigmática de uma busca sem limites e perigosa que, em seu sentido mais profundo, revela determinadas contingências de uma tumultuada história relacional.


In sexual addiction, the performance of the sexual act imposes itself on the subject compulsively. Sexuality loses much of its potential of fantasy, starting to serve as the engine of an excessive and destructive search for pleasure that does not include the possibility of libidinal bond with the other. This article, based on psychoanalytical knowledge, aims at exploring the role of the Oedipus complex in the determinations of the clinical situation in question, a theoretical aspect of fundamental importance for understanding the impasses that interfere with the sex addict relationship with his/her partners and with his/her own sexuality. The oedipal problem is not reduced to the classic Freudian description of the Oedipus complex, but it encompasses a series of conditions and circumstances that precede the infant's entry into this stage, the construction of the primal scene being the decisive factor that will enable or not the entrance of the subject into an effective triangulation system. We will therefore devote particular attention to the original aspect of the Oedipus, which has its essential nucleus in the construction of the primal scene. This axis of work will ultimately lead us to reflect on sexual addiction in its most radical and extreme manifestations, where the increasing adherence to risky situations by the sex addict becomes paradigmatic of a limitless and dangerous search that, in its deepest sense, reveals certain contingencies of a tumultuous relational history.


En la adicción sexual, la realización del acto sexual se impone al sujeto de modo compulsivo. La sexualidad pierde gran parte de su potencial fantasístico, pasando a servir como motor de una búsqueda desmedida y destructiva de placer que no comporta la posibilidad de vínculo libidinal con el otro. Este artículo, fundamentado en el saber psicoanalítico, tiene por objetivo explorar el papel del complejo de Edipo en las determinaciones de la situación clínica en cuestión, aspecto teórico de fundamental importancia para la comprensión de los impasses que entraban la relación del sex-addict con sus parejas y con su pareja propia sexualidad. La problemática edípica no se reduce a la clásica descripción freudiana del complejo de Edipo, pero abarca una serie de condiciones y circunstancias que preceden al ingreso del infante en esa etapa, siendo la construcción de la escena primitiva el factor decisivo que viabilizará o no la entrada del sujeto en un efectivo sistema de triangulación. Dedicaremos, por lo tanto, particular atención a la vertiente originaria del Edipo, la cual tiene en la construcción de la escena primitiva su núcleo esencial. Este eje de trabajo nos conducirá, por fin, a reflexionar sobre la adicción sexual en sus manifestaciones más radicales y extremas, donde la creciente adhesión a situaciones de riesgo por parte del sex-addict se vuelve paradigmática de una búsqueda sin límites y peligrosa que, en su sentido más profundo, revela ciertas contingencias de una tumultuosa historia relacional.

SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda