The neural basis of fatigue in multiple sclerosis: A multimodal MRI approach

BACKGROUND: Fatigue is a frequent disabling symptom in multiple sclerosis (MS), but its pathophysiology remains incompletely understood. This study aimed to explore the underlying neural basis of fatigue in patients with MS. METHODS: We enrolled 60 consecutive patients with MS and 60 healthy controls (HC) matched on age, sex, and education. Fatigue was assessed using the Portuguese version of the Modified Fatigue Impact Scale (MFIS). All participants underwent 3T brain MRI (conventional and diffusion tensor imaging [DTI] sequences). White matter (WM) focal lesions were identified and T1/T2 lesion volumes were computed. Tract-based spatial statistics were applied for voxel-wise analysis of DTI metrics fractional anisotropy and mean diffusivity (MD) on normal-appearing WM (NAWM). Using Freesurfer software, total and regional volumes of cortical and subcortical gray matter (GM) were calculated. RESULTS: Compared to HC, patients with MS scored significantly higher on MFIS (33.8 ± 19.7 vs 16.5 ± 15.1, p < 0.001). MFIS scores were not significantly correlated with T1/T2 lesion volumes, total GM volume, or any regional volume of cortical and subcortical GM. Significant correlations were found between global scores of MFIS and MD increase of the NAWM skeleton, including corona radiata, internal capsule, external capsule, corticospinal tract, cingulum, corpus callosum, fornix, superior longitudinal fasciculus, superior fronto-occipital fasciculus, sagittal stratum, posterior thalamic radiation, cerebral peduncle, and uncinate fasciculus. CONCLUSIONS: In this study, fatigue was associated with widespread NAWM damage but not with lesion load or GM atrophy. Functional disconnection, caused by diffuse microstructural WM damage, might be the main neural basis of fatigue in MS.info:eu-repo/semantics/publishedVersio

Effects of serine proteases inhibitors in bovine sperm cryopreservation.

Proceedings of the 30th Annual Meeting of the Brazilian Embryo Technology Society (SBTE); Foz do Iguaçu, PR, Brazil, August 25th to 27th, 2016, and 32nd Meeting of the European Embryo Transfer Association (AETE); Barcelona, Spain, September 9th and 10th, 2016

Uncovering the Cyanobacterial Chemical Diversity: The Search for Novel Anticancer Compounds

This article belongs to the Proceedings of The 7th Iberian Congress on Cyanotoxins/3rd Iberoamerican Congress on Cyanotoxins[Abstract] Cancer has a tremendous negative socio-economic impact on our society. Thus, the discovery of new and more effective anticancer drugs is of utmost importance. To address this societal challenge, the main goal of the CYANCAN project was the discovery of anticancer compounds from cyanobacteria. These photosynthetic bacteria are considered among the most promising groups capable of producing metabolites with pharmaceutical applications. A valuable and underexplored natural resource that can underpin the discovery of promising compounds can be found in the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) at CIIMAR (Interdisciplinary Centre of Marine and Environmental Research), comprising more than 700 different cyanobacterial strains. Herein, we present the recent advances implemented for finding robust anticancer lead compounds from LEGE-CC cyanobacteria. For this purpose, we developed a natural product library. Sixty cyanobacterial strains, representative of LEGE-CC biodiversity, were chromatographed to yield 480 fractions that were tested for their cytotoxic activity against 2D and 3D models of human colon carcinoma (HCT 116). The conjugation of monolayer assays and 3D cancer spheroids led to the selection of 11 active fractions, of which the chemical space was studied using an untargeted metabolomics approach. The putative annotation and identification of several compounds led to the selection of two marine strains for compound isolation: Leptothoe sp. and Lusitaniella coriacea. The isolation of the compounds was guided through bioactivity assays and mass spectrometry. These molecules were purified from the crudes by employing several chromatography methods, and the chemical structures were determined by means of NMR (nuclear magnetic resonance) and MS/MS (tandem mass spectrometry) experiments. Thus, a novel macrolide-type compound was isolated from Leptothoe sp., which presented a highly cytotoxic activity against our cancer cell models. Its effects on cancer vascularization and metastasis were studied using the zebrafish model. Moreover, from L. coriacea, five unprecedented salicyl-capped thiazol(in)e NRPs-PKs (nonribosomal peptides-polyketides) compounds were isolated. These compounds showed the potential to act as reversers of P-glycoprotein efflux activity.CIIMAR strategic funds UIDB/04423/2020 and UIDP/04423/2020; CYANCAN PTDC/MED-QUI/30944/2017, co-financed by NORTE 2020, Portugal 2020, and the European Union through the ERDF. EMERTOX: EU Horizon 2020 R&I programme under the Marie Skłodowska-Curie grant agreement No 778,069. Ribeiro, T: FCT grant SFRH/BD/139131/2018. Castelo-Branco, R: FCT grant SFRH/BD/136367/2018Centro Interdisciplinar de Investigação Marinha e Ambiental (Porto); UIDB/04423/2020Portugal. Fundação para a Ciência e a Tecnologia; PTDC/MED-QUI/30944/2017Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/139131/2018Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/136367/201

Misturas asfálticas inteligentes: mito ou realidade?

A finalidade geral dos pavimentos rodoviários consiste na capacidade de resistir ao tráfego rodoviário e as ações meteorológicas, garantindo condições de rolamento seguras e confortáveis, com o menor dispêndio possível de recursos e danos sobre o meio ambiente. Um pavimento rodoviário é considerado inteligente quando possui funcionalidades adicionais ou capacidade de reagir a um estímulo externo. Estas aptidões podem ser incorporadas através da utilização de diversos materiais, por exemplo: nano/micropartículas (semicondutores e microcápsulas), materiais de mudança de fase, corantes e fibras. Dentre as novas capacidades, é possível destacar: fotocatálise, superhidrofobicidade, autolimpeza, degelo/anti-gelo, autorreparação, termocromismo e armazenamento de energia térmica latente. Algumas destas novas aptidões resultam da implementação de técnicas como: modificação de ligante asfáltico, revestimento por pulverização, espalhamento e incorporação volumétrica de componentes. Este trabalho revê as novas capacidades conferidas às misturas asfálticas, expõe informações sobre métodos de funcionalização, ensaios, materiais empregados e resultados e fornece recomendações para trabalhos futuros.The purpose of road pavements is to withstand road traffic and weather loads, while ensuring safe and comfortable driving conditions with the least possible expenditure of resources and damage to the environment. A road pavement is considered smart when it has additional abilities or capacity to react to an external stimulus. These abilities can be incorporated through various materials: nano/microparticles (semiconductors and microcapsules), phase change materials, dyes, and fibers. Among the new abilities added to asphalt mixtures are photocatalysis, superhydrophobicity, self-cleaning, de-icing/anti-icing, self-healing, thermochromism, and latent heat thermal energy storage. Some of these new capabilities result from different techniques, such as asphalt binder modification, spray coating, spreading, and volume incorporation of components. The present work reviews the new abilities conferred to asphalt mixtures, exposes the information about functionalization methods, tests, materials used and results, and provides recommendations for future work.Este trabalho foi apoiado pela Fundação para a Ciência e a Tecnologia (FCT) no âmbito dos projetos do Financiamento Estratégico UIDB/04650/2020, do projecto MicroCoolPav EXPL/EQU-EQU/1110/2021, e do projecto NanoAir PTDC/FISMAC/6606/2020. Os autores também agradecem pelo financiamento dos projetos MLC-0191-00144.01.00/22 (Edital Mulheres na Ciência Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico Funcap) e Processo 404978/2021-5, Chamada CNPq/MCTI/FNDCT Nº 18/2021 - Faixa B - Grupos Consolidados Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq)

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