Increased frequency of the autism broader phenotype in mothers transmitting etiological CNVs to sons affected by Autism Spectrum Disorder (ASD)

Introduction: Autism Spectrum Disorder (ASD) is a frequent and complex neurodevelopmental disorder, characterized by impairments in social communication and repetitive behaviors and with a high male to female ratio: ~4:1. Genetic factors, including rare Copy Number Variants (CNVs), have a substantial impact in ASD risk 1, and are associated with specific phenotypic manifestations 2. Recent studies reported that rare inherited CNVs are enriched in mothers of ASD children compared with mothers of controls and are preferentially transmitted from mothers to ASD children suggesting a sex bias in CNV transmission; further, the imbalanced transmission of small pathogenic CNVs from unaffected mothers to their sons with ASD has been described 3, 4. An increased prevalence of autism - like personality traits is found in unaffected relatives of ASD children, suggesting a genetic liability of a broader autism phenotype (BAP) 5. The BAP in parents of autistic children can be assessed by the Social Responsiveness Scale (SRS) 6 and Broad Autism Phenotype Questionnaire (BAPQ) 7 reports . The SRS is 65 - item questionnaire to identify sub - clinical social impairments and interpersonal behaviour in individuals . The BAPQ is a 36 - item questionnaire measures social aloofness, rigid personality, and pragmatic language deficits in both parents and children.

Avaliação do potencial cancerigénico de microcistinas (cianotoxinas)

Tese de doutoramento em Farmácia (Toxicologia), apresentada à Faculdade de Farmácia da Universidade de Lisboa, 2009.

A denúncia de situações de Violência na população portuguesa com 60 ou mais anos

Atualmente a violência contra as pessoas idosas é uma problemática reconhecida em Portugal. Têm sido desenvolvidos estudos (ABUEL e AVOW), nos últimos anos, sobre a sua extensão e natureza, mas permanecem lacunas na literatura, nomeadamente ao nível da procura de ajuda e denúncia por parte das vítimas. É, contudo, consensual que a maior parte das pessoas idosas não denuncia ou procura ajuda quando vivencia uma situação de violência em contexto familiar. No âmbito do estudo de prevalência a nível nacional de violência contra as pessoas idosas em contexto familiar - “Envelhecimento e violência” – apresentam-se alguns dados relativos à denúncia por parte de pessoas com 60+ anos vítimas de violência. O estudo recolheu, através de um inquérito telefónico, dados sobre experiências de violência em contexto familiar a partir de uma amostra aleatória de 1123 indivíduos com 60+ anos a residir em Portugal. Apenas um terço (35%) das vítimas de violência em Portugal denunciou ou apresentou queixa sobre a situação de violência que viveu. Das vítimas que procuraram uma instituição ou serviço, a maioria dirigiu-se a uma força de segurança, como a GNR e a PSP (20%), seguindo-se a rede informal (7%). Dos motivos evocados, pelas pessoas com 60+ anos vítimas de violência, para não denunciarem ou procurarem ajuda, considerar o incidente como irrelevante (38.1%) foi um dos principais, seguindo-se a importância da família e os laços afetivos com o agressor (10.5%). Com menor frequência as vítimas indicaram o medo (de represálias ou de agravar a situação), bem como o medo que ninguém acreditasse (5.9%) e a falta de informação relativa a quem recorrer (5.1%). Estes resultados sugerem que esta problemática permanece ainda como um tabu, com a maior parte das vítimas a vivenciarem em silêncio a violência. As barreiras internas, que se referem ao sistema de crenças da vítima e à dinâmica relacional da vítima com o perpetrador, aparentam ser mais determinantes que as barreiras externas, como serão as dificuldades no acesso e utilização de serviços e respostas sociais.

Combined exposure to multiple mycotoxins in food: are we ready for risk assessment and risk management?

It is nowadays recognized that the risk of human co-exposure to multiple mycotoxins is real. In the last years, a number of studies have approached the issue of co-exposure and the best way to develop a more precise and realistic assessment. Likewise, the growing concern about the combined effects of mycotoxins and their potential impact on human health has been reflected by the increasing number of toxicological studies on the combined toxicity of these compounds. Nevertheless, risk assessment of these toxins, still follows the conventional paradigm of single exposure and single effects, incorporating only the possibility of additivity but not taking into account the complex dynamics associated to interactions between different mycotoxins or between mycotoxins and other food contaminants. Considering that risk assessment is intimately related to the establishment of regulatory guidelines, once the risk assessment is completed, an effort to reduce or manage the risk should be followed to protect public health. Risk assessment of combined human exposure to multiple mycotoxins thus poses several challenges to scientists, risk assessors and risk managers and opens new avenues for research. This presentation aims to give an overview of the different challenges posed by the likelihood of human co-exposure to mycotoxins and the possibility of interactive effects occurring after absorption, towards knowledge generation to support a more accurate human risk assessment and risk management. For this purpose, a physiologically-based framework that includes knowledge on the bioaccessibility, toxicokinetics and toxicodynamics of multiple toxins is proposed. Regarding exposure assessment, the need of harmonized food consumption data, availability of multianalyte methods for mycotoxin quantification, management of left-censored data and use of probabilistic models will be highlight, in order to develop a more precise and realistic exposure assessment. On the other hand, the application of predictive mathematical models to estimate mycotoxins’ combined effects from in vitro toxicity studies will be also discussed. Results from a recent Portuguese project aimed at exploring the toxic effects of mixtures of mycotoxins in infant foods and their potential health impact will be presented as a case study, illustrating the different aspects of risk assessment highlighted in this presentation. Further studies on hazard and exposure assessment of multiple mycotoxins, using harmonized approaches and methodologies, will be crucial towards an improvement in data quality and contributing to holistic risk assessment and risk management strategies for multiple mycotoxins in foodstuffs.

The third dimension: new developments in cell culture models for colorectal research

Cellular models are important tools in various research areas related to colorectal biology and associated diseases. Herein, we review the most widely used cell lines and the different techniques to grow them, either as cell monolayer, polarized two-dimensional epithelia on membrane filters, or as three-dimensional spheres in scaffoldfree or matrix-supported culture conditions. Moreover, recent developments, such as gut-on-chip devices or the ex vivo growth of biopsy-derived organoids, are also discussed. We provide an overview on the potential applications but also on the limitations for each of these techniques, while evaluating their contribution to provide more reliable cellular models for research, diagnostic testing, or pharmacological validation related to colon physiology and pathophysiology.