The Nf2 Tumor Suppressor, Merlin, Functions in Rac-Dependent Signaling

Mutations in the neurofibromatosis type II (NF2) tumor suppressor predispose humans and mice to tumor development. The study of Nf2+/- mice has demonstrated an additional effect of Nf2 loss on tumor metastasis. The NF2-encoded protein, merlin, belongs to the ERM (ezrin, radixin, and moesin) family of cytoskeleton:membrane linkers. However, the molecular basis for the tumor- and metastasis- suppressing activity of merlin is unknown. We have now placed merlin in a signaling pathway downstream of the small GTPase Rac. Expression of activated Rac induces phosphorylation and decreased association of merlin with the cytoskeleton. Furthermore, merlin overexpression inhibits Rac-induced signaling in a phosphorylation-dependent manner. Finally, Nf2-/- cells exhibit characteristics of cells expressing activated alleles of Rac. These studies provide insight into the normal cellular function of merlin and how Nf2 mutation contributes to tumor initiation and progression

Abordagens Diagnósticas e Terapêuticas nos Transtornos de Personalidade: Uma Revisão da Literatura

This article provides a literature review on Personality Disorders (PD), focusing on diagnostic and therapeutic approaches. The analysis spans studies from the last ten years, highlighting the transition to a dimensional approach in diagnostic criteria and the diversity of effective therapeutic strategies, including cognitive-behavioral and dialectical-behavioral therapies. The clinical complexity of PDs, the frequent presence of comorbidities, and therapeutic challenges are discussed. Future perspectives in PD research are explored, emphasizing the need for innovative therapeutic strategies and an enhanced understanding of neurobiological foundations. The review aims to contribute to more holistic clinical practices and inform future research in the field.O presente artigo oferece uma revisão da literatura sobre Transtornos de Personalidade (TP), enfocando abordagens diagnósticas e terapêuticas. A análise abrange estudos dos últimos dez anos, destacando a transição para uma abordagem dimensional nos critérios diagnósticos e a diversidade de estratégias terapêuticas efetivas, incluindo terapias cognitivo-comportamentais e dialecticocomportamentais. A complexidade clínica dos TP, a presença frequente de comorbidades e os desafios terapêuticos são discutidos. Perspectivas futuras na pesquisa sobre TP são exploradas, enfatizando a necessidade de estratégias terapêuticas inovadoras e uma compreensão aprimorada das bases neurobiológicas. A revisão busca contribuir para práticas clínicas mais holísticas e informar futuras investigações no campo

Caminhos para o Diagnóstico Precoce: Biomarcadores Neurogenéticos na Doença de Alzheimer.

This paper proposes a literature review on neurogenetic biomarkers in Alzheimer's disease (AD), highlighting their fundamental role in early diagnosis and understanding of the disease's pathogenesis. The analysis covers the identification of specific genetic variants, such as those in the TOMM40 gene, and polymorphisms identified through genome-wide association studies (GWAS). Additionally, the differential expression of genes associated with AD in early stages offers a unique opportunity for more effective therapeutic interventions. Despite advances, challenges such as external validation and genetic variability are crucial. The neurogenetic approach represents progress in understanding the genetic heterogeneity in AD, providing a foundation for future research. The abstract highlights the promising implications of neurogenetic biomarkers and emphasizes the importance of ethical and social awareness.Este trabalho propõe uma revisão de literatura sobre biomarcadores neurogenéticos na doença de Alzheimer (DA), destacando seu papel fundamental no diagnóstico precoce e na compreensão da patogênese da doença. A análise abrange a identificação de variantes genéticas específicas, como aquelas no gene TOMM40, e polimorfismos identificados por meio de estudos de associação genômica ampla (GWAS). Além disso, a expressão diferencial de genes associados à DA em estágios iniciais oferece uma oportunidade única para intervenções terapêuticas mais eficazes. Apesar dos avanços, desafios como a validação externa e a variabilidade genética são cruciais. A abordagem neurogenética representa um avanço na compreensão da heterogeneidade genética na DA, fornecendo uma base para pesquisas futuras. O resumo destaca as implicações promissoras dos biomarcadores neurogenéticos e destaca a importância da conscientização ética e social

Abordagens para Prevenção Secundária do Tromboembolismo Pulmonar (TEP): Uma Revisão de Literatura

This literature review aims to investigate contemporary strategies for the secondary prevention of Pulmonary Embolism (PE). The research encompassed recent studies, focusing on anticoagulation, including novel oral anticoagulants, surgical interventions, and advanced diagnostic methods. Emphasizing the importance of personalized treatment considering individual factors, the review underscores the need for additional studies to validate conclusions and inform more robust clinical guidelines. This review contributes to an in-depth understanding of secondary prevention strategies for PE, highlighting the integrated and personalized approach as crucial for optimizing clinical outcomes and reducing PE recurrence.Esta revisão de literatura explora estratégias contemporâneas para a prevenção secundária do Tromboembolismo Pulmonar (TEP). A pesquisa abrangeu estudos recentes, enfocando anticoagulação, incluindo novos anticoagulantes orais, intervenções cirúrgicas, e métodos de diagnóstico avançados. Destaca-se a importância da personalização do tratamento, considerando fatores individuais, enquanto ressalta a necessidade de estudos adicionais para validar conclusões e informar diretrizes clínicas mais sólidas. Esta revisão contribui para uma compreensão aprofundada das estratégias de prevenção secundária do TEP, enfatizando a abordagem integrada e personalizada como crucial para otimizar desfechos clínicos e reduzir recorrências do TEP

Why the Derivation of Nutrient Reference Values Should be Harmonized and How It Can be Accomplished

The adoption of a panel of Nutrient Reference Values (NRVs) in place of a single recommended intake allowed for assessment of nutritional adequacy and safe upper intake levels for nutrients on a population level and for individuals. The Average Requirement (AR) and Tolerable Upper Intake Level (UL) comprise 2 core NRVs needed to obtain accurate, comparable estimates of population-level nutrient intakes, which are necessary to plan and evaluate nutrition support programs globally. Harmonizing the derivation of NRVs, particularly the AR and UL, is essential to ensure inclusion of all countries, whether high-, middle-, or low-income, in the process and to improve access for all users to the tools and data needed to carry it out. The NRV process today is more rigorous and transparent than the first derivation of DRIs because of adoption of systematic reviews and bias assessment methodologies, updated food and nutrient databases, data on cultural and context-specific dietary patterns, and better metabolic markers of nutritional status. A proposed framework for the derivation of NRVs builds on available methodologies to support the NRV process; however, this is not sufficient to achieve harmonization of the process. Fundamental to moving forward toward harmonization is removing existing barriers, including limited access to resources and databases and variance in terminology used to identify specific NRVs; adoption of more rigorous and transparent methodologies, including chronic disease endpoints, in the review process; and creating a central repository for easily accessible evidence. Chief among the barriers to harmonization is a willingness of global bodies to support an agreed-upon approach to the derivation process. Improving access to tools and data resources and providing guidance and support to encourage their adoption are critical to achieving harmonization of the NRV process. The factorial approach for calculating a nutrient requirement is described as the sum of total endogenous nutrient loss (endogenous fecal, urinary, integumental, seminal, menstrual) divided by its bioavailability or fractional absorption