A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.

Are cognitive interventions for multiple sclerosis effective and feasible?

Purpose: Fifty percent of patients with Multiple Sclerosis (MS) are estimated to have cognitive impairments leading to considerable decline in productivity and quality of life. Cognitive intervention has been considered to complement pharmacological treatments. However, a lack of agreement concerning the efficacy of cognitive interventions in MS still exists. A systematic review and meta-analysis was conducted to assess the effects of cognitive interventions in MS. Methods: To overcome limitations of previous meta-analyses, several databases were searched only for Randomized Clinical Trials (RCTs) with low risk of bias. Results: Five studies (total of 139 participants) met our eligibility criteria. Although good completion and adherence rates were evident, we found no evidence of intervention effects on cognition or mood in post-intervention or follow-up assessments. Conclusions: This is the first meta-analysis assessing the effects of cognitive intervention in MS including only RCTs with comparable conditions. Research regarding efficacy, cost-effectiveness and feasibility is still in its infancy. Caution is advised when interpreting these results due to the small number of RCTs meeting the inclusion criteria. Considering the costs of disease, good completion and adherence rates of this approach, further research is warranted. Recommendations concerning improved research practices in the field are presented as well.

Cheese whey: a cost-effective alternative for hyaluronic acid production by Streptococcus zooepidemicus

This study focuses on the optimization of cheese whey formulated media for the production of hyaluronic acid HA by Streptococcus zooepidemicus. Culture media containing whey (W; 2.1 g/L) or whey hydrolysate (WH; 2.4 g/L) gave the highest HA productions. Both W and WH produced high yields on protein consumed, suggesting cheese whey is a good nitrogen source for S. zooepidemicus production of HA. Polysaccharide concentrations of 4.0 g/L and 3.2 g/L were produced in W and WH in a further scale-up to 5 L bioreactors, confirming the suitability of the low-cost nitrogen source. Cheese whey culture media provided high molecular weight (> 3000 kDa) HA products. This study revealed replacing the commercial peptone by the low-cost alternative could reduce HA production costs by up to a 70%compared to synthetic media.

Natural fibers for soil reinforcement

The reinforcement of soil is defined as an effective and reliable technique to improve strength and stability. For this propose, the use of natural fibers has been commonly. Over the past years, a series of studies have been performed in order to investigate the influence of randomly oriented fibers, especially for compressible clayey soils. However, less attention has been given to the reinforcing of sandy materials, as well as the use of oriented fibers meshes in order to improve mechanical behaviour. The main aim of this study is to identify the influence that different percentages of fibers, as well as the use of meshes of oriented fibers, has on soil mechanical behaviour. For this purpose, unconfined compression tests with local strain measurements were performed on a silty sand reinforced with Sisal fibers and a comparative study between randomly oriented and 0° and 90° fibers is presented.

Sinistralidade rodoviária e o marketing relacional: perspetivas de soluções mais eficazes no seu combate em Portugal

Dissertação de mestrado em Marketing e Estratégia

Enquadramento para a compreensão dos impactos do Open Government Data

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

Self-evaluated burden in adults with attention-deficit hyperactivity disorder (ADHD): a pilot study

OBJECTIVES: To investigate feasibility and easiness of administration of a brief and simple instrument addressing impairment associated with adult attention deficit hyperactivity disorder (ADHD) and if ADHD subtypes were correlated to specific profiles of self-reported impairment. METHODS: Thirty-five adults (19 men and 16 women; mean age of 31.74 years) diagnosed with ADHD according to DSM-IV with a semi-structured interview (K-SADS PL) were asked to fill out a Likert scale covering six different functional areas (academic, professional, marital, familiar, social and daily activities). Clinicians questioned patients about their understanding of the questionnaire and investigated their answers in more details to check consistency of their answers. RESULTS: No patient reported difficulties in understanding the questionnaire. Further questioning of patients' answers confirmed their choices in the six areas. Academic burden had the highest average score in the whole sample, followed by professional burden. Social area had the lowest average score in this sample.

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Development of folate-targeted liposomes for rheumatoid arthritis therapy

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Is psychodynamic psychotherapy an effective intervention for individuals at ultra-high risk (UHR) of psychosis?: a case report

OBJECTIVE: To report a case and to discuss the use of psychodynamic psychotherapy (PD-P) to treat individuals at ultra-high risk (UHR) of psychosis. METHODS: An individual at UHR was followed up for 24 months. The baseline evaluation included a psychiatric interview, the Structured Interview for Prodromal Symptoms (SIPS), the Scale of Prodromal Symptoms (SOPS), and neuropsychological assessment. He underwent weekly sessions of PD-P for 12 months and was followed up for 12 months after the end of PD-P. The evaluations were at baseline, after 6-, 12-, and 24-month follow-up. No medication was prescribed during the 24-month follow-up. RESULTS: The prodromal symptoms remitted. The initial total score on the SIPS/SOPS was 37 points. After the first 12 months of PD-P, there was a reduction to 12 points on the SIPS/SOPS score, which stabilized in the 24-month follow-up. There was also a slight improvement in his performance on the neuropsychological evaluations. CONCLUSION: This case report suggests that PD-P can reduce prodromal symptoms; nevertheless, a better understanding of the specificity and efficacy of PD-P as an option of treatment for UHR individuals is needed.

Development of Janus hydrogel microcapsules as novel biomaterials-stem cells construct for 3D co-culture applications

Co-cultures of two or more cell types and biodegradable biomaterials of natural origin have been successfully combined to recreate tissue microenvironments. Segregated co-cultures are preferred over conventional mixed ones in order to better control the degree of homotypic and heterotypic interactions. Hydrogel-based systems in particular, have gained much attention to mimic tissue-specific microenvironments and they can be microengineered by innovative bottom-up approaches such as microfluidics. In this study, we developed bi-compartmentalized (Janus) hydrogel microcapsules of methacrylated hyaluronic acid (MeHA)/methacrylated-chitosan (MeCht) blended with marine-origin collagen by droplet-based microfluidics co-flow. Human adipose stem cells (hASCs) and microvascular endothelial cells (hMVECs) were co-encapsulated to create platforms of study relevant for vascularized bone tissue engineering. A specially designed Janus-droplet generator chip was used to fabricate the microcapsules (<250â μm units) and Janus-gradient co-cultures of hASCs: hMVECs were generated in various ratios (90:10; 75:25; 50:50; 25:75; 10:90), through an automated microfluidic flow controller (Elveflow microfluidics system). Such monodisperse 3D co-culture systems were optimized regarding cell number and culture media specific for concomitant maintenance of both phenotypes to establish effective cell-cell (homotypic and heterotypic) and cell-materials interactions. Cellular parameters such as viability, matrix deposition, mineralization and hMVECs re-organization in tube-like structures, were enhanced by blending MeHA/MeCht with marine-origin collagen and increasing hASCs: hMVECs co-culture gradient had significant impact on it. Such Janus hybrid hydrogel microcapsules can be used as a platform to investigate biomaterials interactions with distinct combined cell populations.

Spawning habitat selection by Octopus vulgaris: new insights for a more effective management of this resource

The selection of spawning habitat of a population of Octopus vulgaris that is subject to a small-scale exploitation was studied in the Cíes Islands within the National Park of the Atlantic Islands of Galicia (NW Spain). The technique used was visual censuses by scuba diving. We conducted 93 visual censuses from April 2012 to April 2014. The total swept area was 123.69 ha. Habitat features (season, depth, zone, bottom temperature, swept area, bottom substrate type, and creels fishing impact) were evaluated as predictors of the presence/absence of spawning dens using GAM models. O. vulgaris has a noteworthy preference for spawning in areas with hard bottom substrate and moderate depth (approximately 20 m). The higher density of spawning dens (1.08ha−1) was found in a surveyed area of 50.14ha located in the northeastern part of the northern Cíes Island. We propose to protect the area comprised from Punta Escodelo to Punta Ferreiro between 5 and 30 m depth. This area has a surface of 158 ha equivalent to 5.98% of the total marine area of the Cíes islands. The strengths and weaknesses of a management strategy based on the protection of the species’ spawning habitat are discussed.

Glucose addiction in cancer therapy : advances and drawbacks

Glucose addiction in cancer therapy: advances and drawbacks.

Compatibilidade do contrato de concessão comercial com as regras de defesa da concorrência

Dissertação de mestrado em Direito dos Contratos e da Empresa

Mediação Penal Juvenil: um novo paradigma de resposta à delinquência

Dissertação de mestrado em Direito Judiciário (Direitos Processuais e Organização Judiciária)