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Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50–69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.

The purpose of this paper is to raise important issues in engineering education in the face of contemporary challenges and demands through the voices of different stakeholders in engineering curricula and in the practice of professional engineering. Several challenges and future perspectives are based on important skills, like soft skills, which are required by employers and include communication, decision-making, problem-solving, leadership and emotional intelligence, as well as the ability to work with people of different backgrounds and apply technical knowledge. A qualitative data analysis of interviews with students, alumni, teachers and employers revealed the demand for more balanced qualified curricula for higher education institutions in the field of engineering. This includes the promotion of collaborative learning spaces, authentic learning experiences based on engaging students in real situations, project-based learning, industrial visits, guest lectures and problem-solving methodologies that are perceived by these stakeholders as essential in the construction of a curriculum, in line with the specific technical competences of each area.

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-β-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.

Abstract Background The growing necessity of providing better education, notably through the development of Adaptive Learning Systems (ALSs), leveraged the study of several psychological constructs to accurately characterize learners. A concept extensively studied in education is engagement, a multidimensional construct encompassing behavioral expression and motivational backgrounds. This metric can be used to not only guide certain pedagogic methodologies, but also to endow systems with the right tutoring techniques. As such, this article aims to inspire improved teaching styles and automatic learning systems, by experimentally verifying the influence of in-class behaviors in students’ engagement. Results Over 16 math lessons, the occurrence of students’ and instructors’ behaviors, alongside students’ engagement estimates, were recorded using the COPUS observation protocol. After behavior-profiling the classes deploying such lessons, significant linear models were computed to relate the frequency of the students’ or instructors’ behaviors with the students’ engagement at different in-class periods. The models revealed a positive relation of students’ initial individual thinking and later group activity participation with their collective engagement, as well as a positive engagement relation with the later application of instructor’s strategies such as giving feedback and moving through class, guiding on-going work. Conclusions The results suggest the benefit of applying a workshop-like learning process, providing more individual explanations and feedback at the beginning of an interaction, leaving collective feedback and students’ guidance of on-going work for later on. Based on the relations suggested by our models, several guidelines for developing ALSs are proposed, and a practical illustrative example is formulated.

Este trabalho apresenta os resultados laboratoriais de um solo argiloso ligado com cimento, utilizando um cimento Portland, CEM IV/A 32,5 R, adicionado nas percentagens de 8 % e 12 % em relação à massa seca do solo. Foram realizados ensaios de compressão não confinada, em provetes compactados num molde Proctor com um teor em água ótimo (owc), para diferentes tempos de cura até 90 dias. Os resultados mostram que o uso de cimento permite um aumento na resistência à compressão de 30% até 7 dias de cura e apenas um aumento de 6% dos 7 aos 90 dias de cura, para os dois teores em cimento estudados. São propostas correlações entre a resistência à compressão não confinada, Rc e a percentagem de cimento e o tempo de cura, bem como para o módulo de deformabilidade secante, E30, permitindo prever, a longo prazo, o comportamento dessas misturas, conhecendo as propriedades de compactação e resistência do solo utilizado.

Como não podia deixar de ser, as transformações no mundo do trabalho estão associadas à evolução das técnicas e das tecnologias que agora ocorrem a uma velocidade bem superior àquela em que no passado essas transformações decorreram. Que o mundo se transforma e que o mercado de trabalho também se transforma, todos sabemos, mas o que temos é de garantir que essas mudanças se façam num quadro de regras e valores de respeito pelas pessoas e pela dignidade do trabalho, isto é, dentro do quadro de princípios que associamos ao conceito de trabalho digno. Deste modo, o que aqui se quer dizer é que estamos confrontados com uma realidade de mudança permanente, porque, como o Poeta já nos lembrava, os tempos são feitos sempre de mudanças, tomando sempre novas qualidades. Essas mudanças integram novos saberes e novas competências, o que determina novas responsabilidades para a sociedade em termos de definição de novos enquadramentos que viabilizem a adaptação permanente que todos temos de fazer, no quadro daquilo que se designa por aprendizagem ao longo da vida. Finalmente, importa sublinhar que estas mudanças, para serem ricas e enriquecedoras, requerem também ambientes de diálogo e de participação.

The Interview Simulation for Police Officers (ISPO) is a serious game developed to train police officers in communication competencies related to the interview of victims, witnesses and suspects. It was developed by Gameware Europe in collaboration with the Portuguese Police (Policia Judiciaria) within the RAGE project. The ISPO serious game was created using the modern methodologies and practices that are used in real-life police interviews. The focus of the game is on the training of communication competencies regarding gathering information from both victims and offenders. In order to evaluate the training effectiveness of the game, we conducted a study with 194 participants where general subjective learning effectiveness, using the Perceived Competence subscale of the IMI questionnaire, and domain-specific subjective learning effectiveness using the Police Interview Competency Inventory (PICI) were measured. Overall, ISPO improved the self-perceived competence of its players. Additionally, participants changed their opinion about the attitude to conduct a successful interview. Participants’ level of importance attributed to being dominant diminished and the level of importance attributed to being more benevolent and communicative during police interviews increased. Effects were stronger in inexperienced users leading us to believe that the game is an added value for use in a police officer school.

Objetivo: investigar a prevalência da Síndrome de Burnout entre universitários da área da saúde e a sua associação com variáveis sociodemográficas e acadêmicas. Método: estudo transversal, realizado com 231 universitários da área da saúde entre os meses de setembro e outubro de 2020. Aplicou-se o Maslach Burnout Inventory/ Student Survey para avaliar a Síndrome de Burnout e associou-se um questionário para levantamento das variáveis sociodemográficas e acadêmicas. A associação entre variáveis categóricas foi avaliada por meio dos testes Qui-quadrado e Exato de Fisher. Considerou-se nível de significância de 5%. Resultados: a prevalência da Síndrome de Burnout foi de 31,2%. A variável curso apresentou significância estatística (p

Non-melanoma carcinoma has high incidence rates and has two most common subtypes: basal cell carcinoma and squamous cell carcinoma. This type of carcinoma is usually not fatal; however, it can destroy sensory organs such as the nose, ears, and lips. The treatment of these injuries using non-invasive methods is thus strongly recommended. Some treatments for non-melanoma carcinoma are already well defined, such as surgery, cryosurgery, curettage and electrode section, and radiotherapy; however, these conventional treatments cause inflammation and scarring. In the non-surgical treatment of non-melanoma carcinoma, the topical administration of chemotherapeutic drugs contributes for an effective treatment with reduced side effects. However, the penetration of anticancer drugs in the deeper layers of the skin is required. Lipid delivery systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers) have been developed to overcome epidermal barrier of the skin and to allow the drugs to reach tumor cells. These lipid nanoparticles contribute to control the release profile of the loaded chemotherapeutic drugs, maintaining their stability and increasing death of tumor cells. In this review, the characteristics of non-melanoma carcinoma will be discussed, describing the main existing treatments, together with the contribution of lipid delivery systems as an innovative approach to increase the effectiveness of topical therapies for non-melanoma carcinomas.

In recent years, cocoa and dark chocolate have attracted the interest of consumers not only for their sensory characteristics but also for their nutritional properties and positive impact on health. The baobab is a fruit of African origin with a sour and slightly sweet flavour, widely consumed by local communities due to its unique nutritional features. The aim of this work was to evaluate the impact of the concentration of baobab flour in the development of functional dark chocolate, including physical, chemical, nutritional and sensory evaluations. The results presented a positive correlation between the incorporation of baobab flour and the antioxidant activity (up to 2297 mmol TE/100 g), vitamin C content (up to 49.7 mg/100 g), calcium (up to 1052 mg/kg), potassium (up to 10,175 mg/kg), phosphorus (up to 795.9 mg/kg), chlorine (up to 235.4 mg/kg) and sulphur (up to 1158 mg/kg). The sensory evaluation of dark chocolate with 3% baobab presented the highest evaluation on the parameters “texture” and “overall flavour”, while the parameter “overall flavour” presented the lowest evaluation on chocolate with 9% baobab. No influence was observed on fatty acid profile, protein, fat and hardness.

In this article, we seek to present the synthesis of the global ethanol market in the United States (US) and Brazil by using caloric equivalence to empirically characterize the elasticity of supply and demand. We also seek to evaluate the relationship between world ethanol production and prices of agricultural commodities (wheat, rice, corn, soybeans and sugar) from 1981 to 2016 using climate-induced yield shocks as instrumental variables. The main results for the world market indicate that the production and demand for ethanol respond elastically to changes in commodity prices. The world ethanol production has no significant relationship with food prices. However, evaluation of the ethanol market and its interaction with the agricultural commodities market confirms the hypothesis that Brazilian ethanol is weakly related to the price of food.

Serpa is a protected designation of origin (PDO) cheese produced with raw ewes’ milk and coagulated with Cynara cardunculus. Legislation does not allow for milk pasteurization and starter culture inoculation. Although natural Serpa’s rich microbiota allows for the development of a unique organoleptic profile, it also suggests high heterogeneity. This raises issues in the final sensory and safety properties, leading to several losses in the sector. A possible solution to overcoming these issues is the development of an autochthonous starter culture. In the present work, some Serpa cheese Lactic acid bacteria (LAB)-isolated microorganisms, previously selected based on their safety, technological and protective performance, were tested in laboratory-scale cheeses. Their acidification, proteolysis (protein and peptide profile, nitrogen fractions, free amino acids (FAA)), and volatiles generation (volatile fatty acids (VFA) and esters) potential was investigated. Significant differences were found in all parameters analyzed, showing a considerable strain effect. Successive statistical analyses were performed to compare cheese models and Serpa PDO cheese. The strains L. plantarum PL1 and PL2 and the PL1 and L. paracasei PC mix were selected as the most promising, resulting in a closer lipolytic and proteolytic profile of Serpa PDO cheese. In future work, these inocula will be produced at a pilot scale and tested at the cheese level to validate their application.

Introdução: A riqueza de conteúdos que os Jogos Desportivos Coletivos encerram, permite que estejam vincadamente presentes na vida das crianças e jovens, na medida em que representam uma forma privilegiada do seu desenvolvimento físico e desportivo. Objetivos: O presente estudo pretende aferir a perceção dos treinadores da Associação de Andebol de Viseu acerca da importância dos jogos condicionados e reduzidos, frequência de utilização, variantes utilizadas e motivo de utilização, no treino do Andebol. Métodos: O grupo de estudo foi composto por 35 treinadores, com efetiva participação em processo de treino e competição. Os instrumentos de pesquisa utilizados foram entrevistas individuais semiestruturadas, organizadas a partir de um conjunto de questões fundamentadas nas três dimensões de análise indicadas. Resultados: Os jogos reduzidos e condicionados permitem desenvolver a tomada de decisão, adequando-a ao modelo de jogo da equipa, assim como possibilitam desenvolver e transferir um conjunto de princípios necessários ao desempenho em competição. Conclusão: Os jogos reduzidos e condicionados devem ser geridos de forma diversificada e dependentes do objetivo final do treinador, pois condições de tarefa específicas (duração, número de jogadores, modificação das regras) promovem diferentes respostas em termos de carga física, técnica, tática e de tomada de decisão aplicada, emergindo daí a necessidade em periodizar adequadamente o processo de treino.

This study examines the association between firms’ environmental, social, and governance (ESG) performance and the cost of capital for the largest European firms listed on the STOXX Euro 600 in a large panel from 2002 to 2018. We find that ESG is priced by both debt and equity markets, although in different directions. While better ESG performance is associated with a lower cost of equity, the relationship is positive regarding the cost of debt. We also account for industry idiosyncrasies. The relationship with the cost of equity is penalized for firms lagging in ESG performance compared with industry peers, and the industry median corporate sustainability performance score is around optimal to balance the cost of equity and cost of debt. We also find that ESG is not influential in shaping firms’ cost of capital in periods of financial and sovereign crises. Overall, in the same research setting, we find that the channels of firms’ cost of capital composition behave differently in response to changes in sustainability performance.

Infilled frames are usually modelled in the context of global building analysis using simplified procedures without considering the aspects resulting from the interaction between the panel and the frame. Other aspects, such as adequate design of the floor beams and the beam-columns’ joints, and control of potential sliding shear failure of the columns, that significantly affect the structural response, are also typically not accounted for. In the present work it is intended to look over the literature to evaluate the state of the art regarding the lessons learn from recent earthquakes, the evolution of the structural codes considering the infill masonry panels, and how this influences the evolution of the numerical models and the experimental works to overcome the existent gaps.

The baobab tree (Adansonia digitata L.) is found widely in the forests and savannas of sub-Saharan Africa. The baobab fruit has a sour and slightly sweet taste and is widely consumed by the natives, thus containing a high nutritional value and providing a source of income for rural people. This study aimed to compare the nutritional composition of baobab fruit pulp from different localities in the Namibe province (Angola). Twenty samples of baobab pulp were collected in markets of the four municipalities of Namibe. The results obtained showed that there is some geographic location dependence on nutritional and functional composition. The municipality of Camucuio showed samples with higher fibre content (56.62 g/100 g) and vitamin C (288.9 mg/100 g). Samples from the Virei municipality stood out for their antioxidant activity (1936 mmol TE/100 g), high K content (42.4 mg/g) and higher values of protein (2.42 g/100 g). The samples collected in the municipality of Bibala stood out for their high contents of carbohydrates (28.1 g/100 g), total phenolic compounds (972 mg GAE/100 g) and Ca (3.80 mg/g). Despite the differences in origin, the high nutritional value of baobab fruit has the potential to improve the diet of thousands of people in Africa qualitatively.

Serpa is a protected designation of origin cheese produced with a vegetable coagulant (Cynara cardunculus L.) and raw ovine milk. Despite the unique sensory profile of raw milk cheeses, numerous parameters influence their sensory properties and safety. To protect the Serpa cheese quality and contribute to unifying their distinctive features, some rheologic and physicochemical parameters of cheeses from four PDO producers, in distinct seasons and with different sensory scores, were monitored. The results suggested a high chemical diversity and variation according to the dairy, month and season, which corroborates the significant heterogeneity. However, a higher incidence of some compounds was found: a group of free amino acids (Glu, Ala, Leu, Val and Phe), lactic and acetic acids, some volatile fatty acids (e.g., iC4, iC5, C6 and C12) and esters (e.g., ethyl butanoate, decanoate and dodecanoate). Through the successive statistical analysis, 13 variables were selected as chemical markers of Serpa cheese specificity: C3, C4, iC5, C12, Tyr, Trp, Ile, 2-undecanone, ethyl isovalerate, moisture content on a fat-free basis, the nitrogen-fractions (maturation index and non-protein and total nitrogen ratio) and G’ 1 Hz. These sensory markers’ identification will be essential to guide the selection and development of an autochthonous starter culture to improve cheese quality and safety issues and maintain some of the Serpa authenticity.

O objetivo do estudo foi refletir sobre o contexto da implantação da Escola Normal Rural Dom Joaquim Silvério de Souza, no distrito de Conselheiro Mata, município de Diamantina, seu funcionamento e a formação das normalistas para o meio rural. Foi realizada uma pesquisa nas bibliotecas da Universidade Federal de Minas Gerais e da Universidade Federal dos Vales do Jequitinhonha e Mucuri, sendo encontradas duas dissertações e duas teses, que foram a base da presente análise. Esta análise pontuou os acontecimentos políticos que estimularam a reestruturação da educação rural, como também a forma como as normalistas eram preparadas para a atuação no meio rural. Foram abordadas questões relativas à renovação teórica e instrumental na formação do professor primário para o meio rural, identificação e compreensão das relações entre práticas tradicionais e práticas escolares de saúde das populações rurais e a investigação das práticas de escrita por meio da análise dos diários produzidos na escola. Esses estudos são de grande valia para os educadores, pois a forma de abordagem das disciplinas faz aparecer particularidades educacionais e sociais de cada época, que podem tentar acobertar as diferenças e diversidades como também incutir pensamentos de acordo com os interesses da política vigente.

The aim of this study was to evaluate the impact of high-pressure processing (HPP) on the long-term storage of chocolate fillings at room temperature, compared with conventional storage at lower temperatures. Dark chocolate fillings were treated at different pressure levels, holding times and stored at 20 °C for 12 months. Unprocessed batches were stored at 4 °C and at −12 °C. Moisture, water activity (aw), pH, colour, G′1Hz and indigenous microflora were measured at 2, 4, 6, 8, 10 and 12 months of storage. Results showed that 600 MPa/20 min processing was the most effective controlling mesophilic group, presenting 3.8 log cfu/g after 12 months of storage, and inactivating moulds and yeasts after HPP treatment. Colour was affected by storage, including a reduction in the L* parameter in all conditions to final values between 37.8 and 39.3, while the a* parameter increased during storage time at −12 °C and 4 °C to final values of around 12, and parameter b* decreased at storage temperature 20 °C to 5.3. Storage time affected the rheological behaviour of HPP-treated samples, increasing G′1Hz from the 2nd to 12th month of storage time to the final values between 1603 kPa and 2139 kPa. Moisture, aw and pH were not affected by HPP treatment nor storage time.

N/a.

O estudo testa as potencialidades oferecidas pelas plataformas de metadados abertos na monitorização do estado do Acesso Aberto (AA), caracterizando parte da produção científica do ISCTE-IUL entre 2014 e 2018 no que se refere a dimensões selecionadas. Possibilita igualmente o levantamento das dificuldades e/ou limitações de interoperabilidade entre diferentes sistemas de informação científica.

In food industry, vegetable oils are commonly used as functional ingredients. Cold pressed oils containing fatty acids show a variety of chemical properties, which are mainly dependent on the saturation of fatty acids. In this study, we have analyzed meadowfoam seed oil (MSO), obtained from seeds of Limnanthes alba, and extra virgin olive oil (EVO). Firstly, the fatty acids composition, denoted as Cox value, was determined for the oils that are considered as the most stable. The Cox value for MSO reached 0.032, while that for EVO was 1.780. We have also determined the content of fatty acids in both of the oils using gas chromatography, while the use of mid-infrared (MIR) and near-infrared (NIR) spectroscopy allowed us to assign bands corresponding to the vibrations present in the tested functional groups. Significant differences in the shape and intensity of some bands were observed due to different content of unsaturated fatty acids. Vibrational spectroscopy methods confirmed the presence of long chain fatty acids in MSO.

O portão quinhentista em ferro forjado e policromado que integra a capela de São Nicolau no Claustro da Sé de Lamego, apresentava-se em mau estado de conservação, com instabilidade química e física, destacamento generalizado da policromia, corrosão activa do ferro, perda de material, desajuste do eixo de rotação das portas, apresentava ainda elementos estruturais soltos da alvenaria. Após avaliação e análise preliminar, definiu-se a metodologia de intervenção, optando-se pelo trabalho in situ com desmontagens parciais. Os objectivos principais da intervenção foram: conservar a policromia sobre um suporte de ferro; reposicionar a grade de ferro, de modo a conferir-lhe estabilidade e correcta articulação das portas; refazer as áreas em falta com resina Rezosurf 816; testar a utilização da imagem multi-espectral com o sistema XpeCAM X01. Os resultados obtidos foram satisfatórios conseguindo-se preservar as policromias, dando ao conjunto estabilidade física e química, melhorando o seu funcionamento, aspecto e leitura.

Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, specific strategies to overcome this barrier are needed. Liposomes are nanometric-sized delivery systems composed of phospholipids, which are key components of cell membranes, making liposomes well tolerated and devoid of toxicity. As their lipid compositions are similar to those of the skin, liposomes are used as topical, dermal, and transdermal delivery systems. However, permeation of the first generation of liposomes through the skin posed some limitations; thus, a second generation of liposomes has emerged, overcoming permeability problems. Various mechanisms of permeation/penetration of elastic/ultra-deformable liposomes into the skin have been proposed; however, debate continues on their extent/mechanisms of permeation/penetration. In vivo bioavailability of an API administered in the form of ultra-deformable liposomes is similar to the bioavailability achieved when the same API is administered in the form of a solution by subcutaneous or epi-cutaneous injection, which demonstrates their applicability in transdermal drug delivery.

Traditional ewe’s cheese producers face certain challenges caused by fluctuating environmental parameters inside the ripening room, which lead to lack of homogeneity in the final product. The present research discusses the application of computer fluid dynamics for simulating the distribution of environmental parameters, predicting the airflow pattern, and identifying critical areas where such parameters could cause reduced cheese quality. A new monitoring system was developed including presence sensors, temperature and humidity dataloggers, pneumatic actuators, microcontrollers, and microcomputers connected remotely for control, data visualization, and processing. The validation of the computer simulation and monitoring system was made with a batch of 40 ewe’s cheeses distributed in three different zones inside a prototype ripening room and ripened for 35 days. At 35 days, a physical, chemical, and microbiological characterization of cheeses was made for evaluation of the influence of environmental conditions on cheese quality. The comparison between simulated and local measurements showed close agreement, especially concerning air velocity inside the stacks of cheese. The results of Pearson’s correlation analysis and PCA concluded that temperature affected the appearance of the rind, hardness, number and area occupied by holes. Humidity affected aw and mFeret. Air velocity affected pH and the circularity of gas holes.

Nanoencapsulation via spray cooling (also known as spray chilling and spray congealing) has been used with the aim to improve the functionality, solubility, and protection of drugs; as well as to reduce hygroscopicity; to modify taste and odor to enable oral administration; and many times to achieve a controlled release profile. It is a relatively simple technology, it does not require the use of low-cost solvents (mostly associated to toxicological risk), and it can be applied for lipid raw materials as excipients of oral pharmaceutical formulations. The objective of this work was to revise and discuss the advances of spray cooling technology, with a greater emphasis on the development of lipid micro/nanoparticles to the load of active pharmaceutical ingredients for oral administration.

X-ray microcomputed tomography has been gaining relevance in the field of cellular materials to characterize materials and analyse their microstructure. So, here, it was used together with finite element modelling to develop numerical models to estimate the effective properties (Young’s modulus) of aluminium alloy foams and evaluate the effects of processing on the results. A manual global thresholding technique using the mass as a quality indicator was used. The models were reconstructed (Marching Cubes 33), then simplified and analysed in terms of mass and shape maintenance (Hausdorff distance algorithm) and face quality. Two simplification procedures were evaluated, with and without small structural imperfections, to evaluate the impact of the procedures on the results. Results demonstrate that the developed procedures are good at minimizing changes in mass and shape of the geometries while providing good face quality, i.e., face aspect ratio. The models are also shown to be able to predict the effective properties of metallic foams in accordance with the findings of other researchers. In addition, the process of obtaining the models and the presence of small structural imperfections were shown to have a great impact on the results.

The need for effective and safe therapies for cancer is growing as aging is modifying its epidemiology. Cold atmospheric plasma (CAP) has gained attention as a potential anti-tumor therapy. CAP is a gas with enough energy to ionize a significant fraction of its constituent particles, forming equal numbers of positive ions and electrons. Timely-resolved output voltage measurement, emission spectroscopy, and quantification of reactive species (RS) in plasma-activated media (PAM) were performed to characterize the physical and chemical properties of plasma. To assess the cytotoxicity of cold atmospheric plasma in human tumors, different cell lines were cultured, plated, and exposed to CAP, followed by MTT and SRB colorimetric assays 24 h later. Human fibroblasts, phenotypically normal cells, were processed similarly. Plasma cytotoxicity was higher in cells of breast cancer, urinary bladder cancer, osteosarcoma, lung cancer, melanoma, and endometrial cancer. Cytotoxicity was time-dependent and possibly related to the increased production of hydrogen peroxide in the exposed medium. Sixty seconds of CAP exposure renders selective effects, preserving the viability of fibroblast cells. These results point to the importance of conducting further studies of the therapy with plasma.

The variability and heterogeneity found in Évora cheeses, Protected Designation of Origin (PDO), can affect consumers’ choices. Assessing the ripening conditions and their effect can be helpful. To study the effect of ripening duration in Évora cheese PDO, sensory and chemical analyses were performed in cheese samples subjected to 30, 60, and 120 days of ripening under controlled conditions (temperature 14 to 15 °C and humidity 65 to 70%). Sensory analysis was conducted with a homogenous panel previously familiarized with the product after a short training period, and chemical analyses including pH, moisture, NaCl content, aw, and salt-in-moisture were determined. Panelists were able to distinguish the differences in the organoleptic characteristics of the three cheese stages, and chemical determinations showed significant differences between stages. Interrater agreement was higher in the sensory evaluation of cheeses with a longer maturation period. As expected, cheeses in the 120 days ripening period presented lower pH, moisture, and water activity and had higher salt-in-moisture content. This stage received the highest scores in hardness and color of the crust, intensity, pungency of the aroma, intensity of taste and piquancy, and firmness and granular characteristics of texture. Overall acceptance of cheese samples was positive, regardless of the ripening stage, which probably reflects both the homogeneity of taster profiles and the previous knowledge of this particular product. The degree of ripeness influences the physical, chemical, and sensory characteristics but does not affect the acceptance of this product by the consumer.

Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulations—nanopharmaceutics—have been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of poorly water-soluble drugs, the pharmacokinetic and pharmacodynamic profiles of known drugs but also of new biomolecules, to modify the release profile of loaded compounds, or to decrease the risk of toxicity by providing site-specific delivery reducing the systemic distribution and thus adverse side effects. To succeed with the development of a nanopharmaceutical formulation, it is first necessary to analyze the type of drug which is to be encapsulated, select the type matrix to load it (e.g., polymers, lipids, polysaccharides, proteins, metals), followed by the production procedure. Together these elements have to be compatible with the administration route. To be launched onto the market, the selected production method has to be scaled-up, and quality assurance implemented for the product to reach clinical trials, during which in vivo performance is evaluated. Regulatory issues concerning nanopharmaceutics still require expertise for harmonizing legislation and a clear understanding of clinically compliant production methods. The first part of this study addressing “Nanopharmaceutics: Part I—Clinical trials legislation and Good Manufacturing Practices (GMP) of nanotherapeutics in the EU” has been published in Pharmaceutics. This second part complements the study with the discussion about the production scales and clinically compliant production methods of nanopharmaceutics.

The latest advances in pharmaceutical technology are leading to the development of cutting edged approaches to produce what is now known as the “Holy Grail” of medicine—nanopharmaceutics. Over the latest decade, the pharmaceutical industry has made important contributions to the scale up of these new products. To ensure their quality, efficacy, and safety for human use, clinical trials are mandatory. Yet, regulation regarding nanopharmaceuticals is still limited with a set of guidelines being recently released with respect to compliance with quality and safety. For the coming years, updates on regulatory issues about nanopharmaceuticals and their use in clinical settings are expected. The use of nanopharmaceuticals in clinical trials depends on the approval of the production methods and assurance of the quality of the final product by implementation and verification of the good manufacturing practices (GMP). This review addresses the available legislation on nanopharmaceuticals within the European Union (EU), the GMP that should be followed for their production, and the current challenges encountered in clinical trials of these new formulations. The singular properties of nanopharmaceuticals over their bulk counterparts are associated with their size, matrix composition, and surface properties. To understand their relevance, four main clinical trial guidelines, namely, for intravenous iron-based nanopharmaceuticals, liposomal-based nanopharmaceuticals, block copolymer micelle-based nanopharmaceuticals, and related to surface coating requirements, are described here.

The eye presents extensive perspectives and challenges for drug delivery, mainly because of the extraordinary capacity, intrinsic to this path, for drugs to permeate into the main circulatory system and also for the restrictions of the ocular barriers. Depending on the target segment of the eye, anterior or posterior, the specifications are different. The ocular route experienced in the last decades a lot of progresses related with the development of new drugs, improved formulations, specific-designed delivery and even new routes to administer a drug. Concomitantly, new categories of materials were developed and adapted to encapsulate drugs. With such advances, a multiplicity of parameters became possible to be optimized as the increase in bioavailability and decreased toxic effects of medicines. Also, the formulations were capable to easily adhere to specific tissues, increase the duration of the therapeutic effect and even target the delivery of the treatment. The ascending of new delivery systems for ocular targeting is a current focus, mainly because of the capacity to extend the normal time during which the drug exerts its therapeutic effect and, so, supplying the patients with a product which gives them fewer side effects, fewer number of applications and even more effective outcomes to their pathologies, surpassing the traditionally-used eye drops. Depending on the systems, some are capable of increasing the duration of the drug action as gels, emulsions, prodrugs, liposomes, and ocular inserts with hydrophilic properties, improving the absorption by the cornea. In parallel, other devices use as a strategy the capacity to sustain the release of the carried drugs by means of erodible and non-erodible matrices. This review discusses the different types of advanced formulations used for ocular delivery of therapeutics presenting the most recent patents according to the clinical applications.

The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas’s disease, is attributed to a set of biological and ecological factors associated with the socioeconomic context of developing countries and with a significant burden to health care systems. Both Leishmaniasis and Chagas’s disease are caused by different protozoa and develop diverse symptoms, which depend on the specific species infecting man. Currently available drugs to treat these disorders have limited therapeutic outcomes, frequently due to microorganisms’ drug resistance. In recent years, significant efforts have been made towards the development of innovative drug delivery systems aiming to improve bioavailability and pharmacokinetic profiles of classical drug therapy. This paper discusses the key facts of Leishmaniasis and Chagas’s disease, the currently available pharmacological therapies and the new drug delivery systems for conventional drugs.

Nanoemulsions are pharmaceutical formulations composed of particles within a nanometer range. They possess the capacity to encapsulate drugs that are poorly water soluble due to their hydrophobic core nature. Additionally, they are also composed of safe gradient excipients, which makes them a stable and safe option to deliver drugs. Cancer therapy has been an issue for several decades. Drugs developed to treat this disease are not always successful or end up failing, mainly due to low solubility, multidrug resistance (MDR), and unspecific toxicity. Nanoemulsions might be the solution to achieve efficient and safe tumor treatment. These formulations not only solve water-solubility problems but also provide specific targeting to cancer cells and might even be designed to overcome MDR. Nanoemulsions can be modified using ligands of different natures to target components present in tumor cells surface or to escape MDR mechanisms. Multifunctional nanoemulsions are being studied by a wide variety of researchers in different research areas mainly for the treatment of different types of cancer. All of these studies demonstrate that nanoemulsions are efficiently taken by the tumoral cells, reduce tumor growth, eliminate toxicity to healthy cells, and decrease migration of cancer cells to other organs.

The aim of this study was to determine how abiotic factors drive the phytoplankton community in a water supply reservoir within short sampling intervals. Samples were collected at the subsurface (0.1 m) and bottom of limnetic (8 m) and littoral (2 m) zones in both the dry and rainy seasons. The following abiotic variables were analyzed: water temperature, dissolved oxygen, electrical conductivity, total dissolved solids, turbidity, pH, total nitrogen, nitrite, nitrate, total phosphorus, total dissolved phosphorus and orthophosphate. Phytoplankton biomass was determined from biovolume values. The role abiotic variables play in the dynamics of phytoplankton species was determined by means of Canonical Correspondence Analysis. Algae biomass ranged from 1.17×10(4) to 9.21×10(4) µg.L-1; cyanobacteria had biomass values ranging from 1.07×10(4) to 8.21×10(4) µg.L-1. High availability of phosphorous, nitrogen limitation, alkaline pH and thermal stability all favored cyanobacteria blooms, particularly during the dry season. Temperature, pH, total phosphorous and turbidity were key factors in characterizing the phytoplankton community between sampling times and stations. Of the species studied, Cylindrospermopsis raciborskii populations were dominant in the phytoplankton in both the dry and rainy seasons. We conclude that the phytoplankton was strongly influenced by abiotic variables, particularly in relation to seasonal distribution patterns.O objetivo deste estudo foi detectar a influência dos fatores abióticos sobre a comunidade fitoplanctônica em um reservatório de abastecimento, em curtos intervalos amostrais. As amostras foram coletadas na subsuperfície (0,1 m) e fundo das regiões pelágica (8 m) e litorânea (2 m), durante dois períodos sazonais, estações seca e chuvosa. As variáveis abióticas analisadas foram: temperatura da água, oxigênio dissolvido, condutividade elétrica, sólidos totais dissolvidos, turbidez, pH, nitrogênio total, nitrito, nitrato, fósforo total, fósforo total dissolvido e ortofosfato. A biomassa fitoplanctônica foi determinada a partir de valores de biovolume. A influência das variáveis abióticas na dinâmica das espécies fitoplanctônicas foi determinada através da Análise de Correspondência Canônica. A biomassa algal variou de 1,17×10(4) a 9,21×10(4) µg.L-1, sendo que as cianobactérias apresentaram valores de biomassa entre 1,07×10(4) e 8,21×10(4) µg.L-1. A mais alta disponibilidade de fósforo, limitação de nitrogênio, pH alcalino e estabilidade térmica favoreceram florações de cianobactérias, especialmente durante o período seco. As diferenças entre os horários e as estações amostrais na distribuição da comunidade fitoplanctônica foram determinadas pelos valores de temperatura, pH, fósforo total e turbidez. As associações fitoplanctônicas que mais se destacaram foram do grupo funcional Sn, formado por Cylindrospermopsis raciborskii, que predominou no sistema em ambos períodos sazonais. Concluiu-se que o fitoplâncton apresentou uma forte influência das variáveis abióticas especialmente no estabelecimento de padrões sazonais de distribuição.

The aim of this study was to characterize phytoplankton associations, as well as discuss controlling factors determining algal dominance in a eutrophic tropical reservoir, Mundaú, Pernambuco, Brazil. Water samples were collected during the dry period (January/2005) and the rainy period (June/2005). The samples were collected from both limnetic and littoral regions, and the phytoplankton assemblages identified from current literature after preservation in formaldehyde 4%. At the same time as sampling was done, in situ measurements of water temperature, transparency, dissolved oxygen, and pH were also taken. Total phosphorus, total nitrogen concentration and the Trophic State Index were subsequently determined in the laboratory. Phytoplankton density (ind. L-1) was estimated using an inverted Zeiss microscope. Grouping of the phytoplankton associations was carried out using the Reynolds phytosociological classification. During the dry period, reservoir water showed low dissolved oxygen concentrations, alkaline pH and was relatively turbid compared to the situation during the rainy season. Reservoir water is limited by nitrogen during both seasonal periods. The Trophic State Index is classified as determining eutrophic conditions. Phytoplankton was represented by 70 infrageneric taxa grouped in 16 functional associations, with the majority typical of eutrophic systems. This fact is supported by quantitative analysis, which shows the dominance of S associations comprising exclusively R-strategist cyanobacteria.O objetivo deste estudo foi caracterizar as associações fitoplanctônicas, bem como discutir os fatores controladores determinantes da dominância algal em um reservatório eutrófico, Mundaú, Pernambuco, Brasil. As amostras foram coletadas durante dois períodos sazonais, seco (janeiro/2005) e chuvoso (junho/2005). As amostras foram coletadas nas regiões limnética e litorânea, seguidas pela identificação através de literatura específica, e preservadas com formol a 4%. No mesmo momento das coletas dos dados bióticos, alguns parâmetros abióticos como temperatura e transparência da água, oxigênio dissolvido, pH foram obtidos e, em laboratório, foram determinados o fósforo total, nitrogênio total e o Índice de Estado trófico. Os agrupamentos das associações fitoplanctônicas foram feitos a partir da classificação fitossociológica de Reynolds. O reservatório esteve limitado por nitrogênio em ambos os períodos sazonais. No período seco, este sistema apresentou água pouco oxigenada, pH alcalino e relativa turbidez quando comparado com o período chuvoso. O fitoplâncton foi representado por 70 táxons infragenéricos agrupados em 16 associações, sendo a maioria, típica de ecossistemas eutróficos. Este fato é corroborado pela análise quantitativa, os quais evidenciam a dominância de associações S, constituídas exclusivamente por cianobactérias R- estrategistas.

The importance of the superficial external pudendal artery in cases of lower limb obstructive arteriopathies has been established, and a perfect knowledge of its anatomy is desirable for the creation of successful flaps involving it. However, little information is available on the morphometry of this artery. PURPOSE: In this study, we conducted a quantitative investigation of the superficial external pudendal artery as the basis for skin grafts. METHOD: Twenty-five right and left sides of the inguinal region of male cadavers were dissected. After retracting the skin at the inguinal region, the femoral vessels and the sapheno-femoral junction were exposed. The following aspects were then analyzed: 1) the presence of the superficial external pudendal artery, 2) the place of origin of the superficial external pudendal artery and the common trunk, 3) the duplication of the superficial external pudendal artery, 4) the distance from the superficial external pudendal artery or the common trunk to the inguinal ligament, and 5) the diameter of the superficial external pudendal artery. RESULTS: The results were the following: 1) superficial external pudendal arteries were found in 46 of 50 sides (92%); 2) they originated from the femoral artery in 45 cases and from the deep femoral artery in only 1 case; 3) the arteries were found duplicated in 21 cases (46%), as a common trunk in 11 cases (24%), and as a single artery in 14 cases (30%); 4) the distance from the superficial external pudendal artery to the inguinal ligament ranged from 0.8 cm to 8.5 cm; from the common trunk, it ranged from 3.5 cm to 6.7 cm; 5) the diameter of the superficial external pudendal artery ranged from 1.2 mm to 3.8 mm; and 6) the diameter of the common trunk ranged from 1.35 mm to 5.15 mm. CONCLUSION: The results show that the superficial external pudendal artery generally originates from the femoral artery. It was found as a common trunk, duplicated, or as a single artery. There was a great variability in both the diameter of the artery and the distance from the artery to the inguinal ligament. Most of the data showed no significant differences between the right and the left sides.A importância do conhecimento da anatomia da artéria pudenda superficial externa está bem estabelecida e um conhecimento adequado de sua anatomia é desejável para a criação bem sucedida de flaps. Entretanto, são escassos os trabalhos morfométricos sobre esta artéria. OBJETIVO. No presente estudo, foi feita uma análise quantitativa da artéria pudenda superficial externa, como base para enxertos de pele. MÉTODO. Foram dissecadas 25 regiões inguinais direitas e 25 esquerdas de cadáveres do sexo masculino. Após rebater a pele da região inguinal, os vasos femorais, a junção safeno-femoral e a artéria pudenda superficial externa foram expostas. Os seguintes aspectos foram então analisados: 1. Presença da artéria pudenda superficial externa; 2. Local de origem da artéria pudenda superficial externa ou do tronco comum; 3. Duplicação da artéria pudenda superficial externa; 4. Distância da artéria pudenda superficial externa ou do tronco comum ao ligamento inguinal; 5. Diâmetro da artéria pudenda superficial externa. RESULTADOS. Os resultados mostraram que: 1. A artéria pudenda superficial externa foi encontrada em 46 dos 50 lados dissecados (92%); 2. A artéria teve origem na artéria femoral em 45 casos; em um único caso teve origem na artéria femoral profunda; 3. A artéria foi encontrada duplicada, em 21 casos (46%), formando um tronco comum, que depois se bifurcava, em 11 casos (24%) e como uma artéria única 14 vezes (30%); 4. A distância da artéria ao ligamento inguinal variou de 0,8 cm a 8,5 cm; quando sob a forma de tronco comum, esta distância variou de 3,5 cm a 6,7 cm; 5. O diâmetro da artéria pudenda superficial externa variou de 1,36 mm a 5,15 mm. CONCLUSÕES. Os resultados mostram que a artéria pudenda superficial externa origina-se, na grande maioria dos casos, da artéria femoral. Foi encontrada como um tronco comum, duplicada ou como uma artéria única. O diâmetro da artéria mostrou grande variabilidade assim como a distância da artéria ao ligamento inguinal. A maioria dos dados não mostrou diferença significante entre os lados direito e esquerdo.

Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and (7)Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT.

The external dependency of many industries and the corresponding low value added generated in production, combined with a relatively weak export potential, create high external deficits and growing debt to GDP ratios in several open economies. In this paper we propose an empirical method to assess the evolution of these vulnerabilities, based on a new treatment of interindustry production multipliers. The (gross) output growth potential given by the column sums of the Leontief inverse matrix (backward linkage indicators) results from three terms: interindustry consumptions, value added and imported inputs. After a convenient arrangement of these terms, the evolution of backward linkage indicators can be used to detect structural changes, particularly quantifying a (net) growth effect (more value-added generation) and an external dependency effect (more imported inputs), and to classify the productive sectors accordingly. An application to the Portuguese Economy is made, using input-output tables for the years 1980, 1995 and 2005. This method can also be useful as a simple, but suggestive, device to compare the evolution of two or more economies, along their development processes in time.

Emprego do parasiticida Mebendazole no tratamento de parasitoses intestinais, experimentado em portadores de dermatoses diversas. Resultado da pesqusa ifeita em 100 pacientes, num período de 12 meses, na cidade de Londrina.

Quando se analisa o número de arguidos e condenados por crime de incêndio e se cruza com os registos desse crime feitos pelas autoridades, mesmo tendo em conta a falta de informação e a sua reduzida qualidade, verifica-se a existência de alguns problemas no respeitante à investigação das causas e à investigação criminal conducente à constituição dos referidos arguidos.

Emprego do parasiticida Mebendazole no tratamento de parasitoses intestinais, experimentado em portadores de dermatoses diversas. Resultado da pesqusa ifeita em 100 pacientes, num período de 12 meses, na cidade de Londrina.

O presente artigo tem como objectivo a descrição dos principais critérios de concepção e execução considerados na definição de soluções de contenção e recalçamento, projectadas e executadas no âmbito da obra do Centro Empresarial Palácio Sotto Mayor, a qual teve lugar em Lisboa. Destaca-se em particular a análise do comportamento do Palácio durante os trabalhos de escavação. Os principais objectivos da intervenção prenderam-se com a execução de uma escavação em formações miocénicas para a construção de oito pisos enterrados e com o recalçamento do edifício do Palácio, localizado no interior do recinto de escavação.