A avaliação da comunicação da criança com perturbação do espetro do autismo: perspetiva de pais e de profissionais

Dissertação de mestrado em Educação Especial (área de especialização Intervenção Precoce)

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

The role of social cognition and motor imagery in gesture processing: a patients' study

Dissertação de mestrado integrado em Psicologia

Paving the way for predictive diagnostics and personalized treatment of invasive aspergillosis

Invasive aspergillosis (IA) is a life-threatening fungal disease commonly diagnosed among individuals with immunological deficits, namely hematological patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation. Vaccines are not available, and despite the improved diagnosis and antifungal therapy, the treatment of IA is associated with a poor outcome. Importantly, the risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and microbiological exposure. Recent insights into antifungal immunity have further highlighted the complexity of host-fungus interactions and the multiple pathogen-sensing systems activated to control infection. How to decode this information into clinical practice remains however, a challenging issue in medical mycology. Here, we address recent advances in our understanding of the host-fungus interaction and discuss the application of this knowledge in potential strategies with the aim of moving toward personalized diagnostics and treatment (theranostics) in immunocompromised patients. Ultimately, the integration of individual traits into a clinically applicable process to predict the risk and progression of disease, and the efficacy of antifungal prophylaxis and therapy, holds the promise of a pioneering innovation benefiting patients at risk of IA.

Assessing the application of polypropylene multifilament yarns in brain phantoms

The currently available clinical imaging methods do not provide highly detailed information about location and severity of axonal injury or the expected recovery time of patients with traumatic brain injury [1]. High-Definition Fiber Tractography (HDFT) is a novel imaging modality that allows visualizing and quantifying, directly, the degree of axons damage, predicting functional deficits due to traumatic axonal injury and loss of cortical projections. This imaging modality is based on diffusion technology [2]. The inexistence of a phantom able to mimic properly the human brain hinders the possibility of testing, calibrating and validating these medical imaging techniques. Most research done in this area fails in key points, such as the size limit reproduced of the brain fibers and the quick and easy reproducibility of phantoms [3]. For that reason, it is necessary to develop similar structures matching the micron scale of axon tubes. Flexible textiles can play an important role since they allow producing controlled packing densities and crossing structures that match closely the human crossing patterns of the brain. To build a brain phantom, several parameters must be taken into account in what concerns to the materials selection, like hydrophobicity, density and fiber diameter, since these factors influence directly the values of fractional anisotropy. Fiber cross-section shape is other important parameter. Earlier studies showed that synthetic fibrous materials are a good choice for building a brain phantom [4]. The present work is integrated in a broader project that aims to develop a brain phantom made by fibrous materials to validate and calibrate HDFT. Due to the similarity between thousands of hollow multifilaments in a fibrous arrangement, like a yarn, and the axons, low twist polypropylene multifilament yarns were selected for this development. In this sense, extruded hollow filaments were analysed in scanning electron microscope to characterize their main dimensions and shape. In order to approximate the dimensional scale to human axons, five types of polypropylene yarns with different linear density (denier) were used, aiming to understand the effect of linear density on the filament inner and outer areas. Moreover, in order to achieve the required dimensions, the polypropylene filaments cross-section was diminished in a drawing stage of a filament extrusion line. Subsequently, tensile tests were performed to characterize the mechanical behaviour of hollow filaments and to evaluate the differences between stretched and non-stretched filaments. In general, an increase of the linear density causes the increase in the size of the filament cross section. With the increase of structure orientation of filaments, induced by stretching, breaking tenacity increases and elongation at break decreases. The production of hollow fibers, with the required characteristics, is one of the key steps to create a brain phantom that properly mimics the human brain that may be used for the validation and calibration of HDFT, an imaging approach that is expected to contribute significantly to the areas of brain related research.

Cognitive rehabilitation in a visual variant of Alzheimer's disease

Alzheimer's disease (AD) is commonly associated with marked memory deficits; however, nonamnestic variants have been consistently described as well. Posterior cortical atrophy (PCA) is a progressive degenerative condition in which posterior regions of the brain are predominantly affected, therefore resulting in a pattern of distinctive and marked visuospatial symptoms, such as apraxia, alexia, and spatial neglect. Despite the growing number of studies on cognitive and neural bases of the visual variant of AD, intervention studies remain relatively sparse. Current pharmacological treatments offer modest efficacy. Also, there is a scarcity of complementary nonpharmacological interventions with only two previous studies of PCA. Here we describe a highly educated 57-year-old patient diagnosed with a visual variant of AD who participated in a cognitive intervention program (comprising reality orientation, cognitive stimulation, and cognitive training exercises). Neuropsychological assessment was performed across moments (baseline, postintervention, follow-up) and consisted mainly of verbal and visual memory. Baseline neuropsychological assessment showed deficits in perceptive and visual-constructive abilities, learning and memory, and temporal orientation. After neuropsychological rehabilitation, we observed small improvements in the patient's cognitive functioning, namely in verbal memory, attention, and psychomotor abilities. This study shows evidence of small beneficial effects of cognitive intervention in PCA and is the first report of this approach with a highly educated patient in a moderate stage of the disease. Controlled studies are needed to assess the potential efficacy of cognition-focused approaches in these patients, and, if relevant, to grant their availability as a complementary therapy to pharmacological treatment and visual aids.

Volumetric alterations in the nucleus accumbens and caudate nucleus in bulimia nervosa: a structural magnetic resonance imaging study

Bulimia nervosa (BN) is an eating disorder characterized by recurrent episodes of binge eating and inappropriate compensatory behaviors (such as purging, fasting, or excessive exercise) to prevent weight gain. BN has been associated with deficits in inhibitory control processes. The basal ganglia specifically, the nucleus accumbens (NAc) and the caudate nucleus (CN) are part of the frontostriatal circuits involved in inhibitory control. The main goal of this study was to investigate the presence of morphological alterations in the NAc and the CN in a sample of patients diagnosed with BN.

Characterization of the oculomotor alterations in inicial phase of Multiple Sclerosis

Dissertação de mestrado em Advanced Optometry

A search for t(t)over-bar resonances using lepton-plus-jets events in proton-proton collisions at root s=8 TeV with the ATLAS detector

A search for new particles that decay into top quark pairs is reported. The search is performed with the ATLAS experiment at the LHC using an integrated luminosity of 20.3 fb−1 of proton-proton collision data collected at a centre-of-mass energy of s√=8 TeV. The lepton-plus-jets final state is used, where the top pair decays to W+bW−b¯¯, with one W boson decaying leptonically and the other hadronically. The invariant mass spectrum of top quark pairs is examined for local excesses or deficits that are inconsistent with the Standard Model predictions. No evidence for a top quark pair resonance is found, and 95% confidence-level limits on the production rate are determined for massive states in benchmark models. The upper limits on the cross-section times branching ratio of a narrow Z′ boson decaying to top pairs range from 4.2 pb to 0.03 pb for resonance masses from 0.4 TeV to 3.0 TeV. A narrow leptophobic topcolour Z′ boson with mass below 1.8 TeV is excluded. Upper limits are set on the cross-section times branching ratio for a broad colour-octet resonance with Γ/m = 15% decaying to tt¯. These range from 4.8 pb to 0.03 pb for masses from 0.4 TeV to 3.0 TeV. A Kaluza-Klein excitation of the gluon in a Randall-Sundrum model is excluded for masses below 2.2 TeV.

Neurocognitive profile and cognitive intervention in Alzheimer's disease

Tese de Doutoramento em Psicologia (Especialidade de Psicologia Clínica)

Stress-triggered synaptic malfunction: a gate along the path from depressionto dementia

Tese de Doutoramento em Ciências da Saúde.

Consciência do déficit na doença de Alzheimer: diferenças entre os domínios cognitivo e funcional

OBJETIVOS: Revisar sistematicamente desenhos de estudo, instrumentos de avaliação e fatores relacionados ao comprometimento dos domínios cognitivo e funcional da consciência do déficit em pessoas com doença de Alzheimer (DA). MÉTODO: Pesquisa nas bases de dados PubMed e ISI de estudos sobre consciência do déficit na DA publicados entre 2008 e 2013. As palavras-chave utilizadas foram: "dementia", "Alzheimer", "awareness", "awareness of memory" e "awareness of functioning", "deficits", "cognition". RESULTADOS: Os 10 artigos selecionados utilizaram os conceitos "falta de consciência do déficit", "anosognosia", "insight", "falta de consciência das dificuldades cognitivas" e "consciência limitada das deficiências". A etiologia do comprometimento da consciência do déficit foi relacionada a fatores biológicos como gravidade clínica da doença, associações neuroanatômicas, alterações neuropsiquiátricas e fatores psicológicos e sociais. O desenho de estudo mais utilizado foi o corte transversal. No domínio cognitivo, a memória e as funções executivas foram as duas principais funções investigadas. No domínio funcional, foram encontradas associações com a disfunção executiva, declínio da interação social, depressão e a influência do desempenho ocupacional. CONCLUSÕES: As distintas hipóteses etiológicas, a operacionalização variável do conceito e a falta de instrumentos de avaliação padronizados impossibilitam a obtenção de resultados homogêneos. Essas dificuldades comprometem a compreensão e a investigação dos domínios cognitivo e funcional.

Normal aging and decision-making: a systematic review of the literature of the last 10 years

Objective Conduct a systematic review to investigate whether healthy elderly have deficits in the decision-making process when compared to the young. Methods We performed a systematic search on SciELO, Lilacs, PsycINFO, Scopus and PubMed database with keywords decision making and aging (according to the description of Mesh terms) at least 10 years. Results We found nine studies from different countries, who investigated 441 young and 377 elderly. All studies used the IOWA Gambling Task as a way of benchmarking the process of decision making. The analysis showed that 78% of the articles did not have significant differences between groups. However, 100% of the studies that assessed learning did find relevant differences. Furthermore, studies that observed the behavior of individuals in the face of losses and gains, 60% of articles showed that the elderly has more disadvantageous choices throughout the task. Conclusion: The consulted literature showed no consensus on the existence of differences in performance of the decision-making process between old and young, but it is observed that the elderly has deficits in learning and a tendency to fewer advantageous choices.

Virtual reality in assessment and treatment of schizophrenia: a systematic review

Objective To conduct a systematic review about the use of virtual reality (VR) for evaluation, treatment and/or rehabilitation of patients with schizophrenia, focused on: areas, fields and objectives; methodological issues; features of the VR used; viability and efficiency of this resource. Methods Searches were performed about schizophrenia and virtual reality in PsycINFO, Academic Search Complete, MEDLINE Complete, CINAHL with Full Text, Web of Science and Business Source Premier databases, using the following keywords: [“schizophrenia”] AND [“virtual reality” OR “serious game”] AND [“treatment” OR “therapy” OR “rehabilitation”]. The search was carried out between November 2013 and June 2014 without using any search limiters. Results A total of 101 papers were identified, and after the application of exclusion criteria, 33 papers remained. The studies analysed focused on the use of VR for the evaluation of cognitive, social, perceptual and sensory skills, and the vast majority were experimental studies, with virtual reality specifically created for them. All the reviewed papers point towards a reliable and safe use of VR for evaluating and treating cognitive and social deficits in patients with schizophrenia, with different results in terms of generalisation, motivation, assertiveness and task participation rate. Some problems were highlighted, such as its high cost and a constant need for software maintenance. Conclusion The studies show that using the virtual reality may streamline traditional evaluation/rehabilitation programmes, allowing to enhance the results achieved, both in the cognitive and in the social field, helping for the legitimisation of this population’s psycho-social inclusion.

Redefining the MED13L syndrome

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.