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Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. have shown in vitro antioxidant, anti-inflammatory and antitumor properties. The aim of this work was to evaluate the therapeutic properties of a hydroethanolic extract obtained from T. platyphyllos in HPV16-transgenic mice. The animals were divided into eight groups according to their sex and phenotype. Four groups of female: HPV+ exposed to linden (HPV linden; n = 6), HPV+ (HPV water; n = 4), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 4) and four groups of male: HPV+ exposed to linden (HPV linden; n = 5), HPV+ (HPV water; n = 5), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 7). The linden (Tilia platyphyllos Scop.) extract was orally administered at a dose of 4.5 mg/10 mL per animal (dissolved in water) and changed daily for 33 days. The hydroethanolic extract of T. platyphyllos consisted of protocatechuic acid and (-)-epicatechin as the most abundant phenolic acid and flavonoid, respectively, and was found to be stable during the studied period. In two male groups a significant positive weight gain was observed but without association with the linden extract. Histological, biochemical, and oxidative stress analyses for the evaluation of kidney and liver damage support the hypothesis that the linden extract is safe and well-tolerated under the present experimental conditions. Skin histopathology does not demonstrate the chemopreventive effect of the linden extract against HPV16-induced lesions. The linden extract has revealed a favourable toxicological profile; however, additional studies are required to determine the chemopreventive potential of the linden extract. This journal is This work was supported by the project IBERPHENOL, project number 0377_IBERPHENOL_6_E; Interact R&D project, operation number NORTE-01-0145-FEDER-000017, National Funds by FCT – Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020 (CITAB), and project UIDB/ CVT/00772/2020 (CECAV) and the post-graduation grant SFRH/ BD/136747/2018 and 2020.04789.BD; the authors are also grateful to FCT, Portugal and FEDER under programme PT2020 for financial support to CIMO (UIDB/00690/2020) and L. Barros acknowledges the national funding by FCT, P. I., through the institutional scientific employment program-contract. The authors would like to thank Cantinho das Aromáticas organic farmers from Vila Nova de Gaia (Portugal) for providing the samples. This work was financially supported by: Base Funding - UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE - funded by national funds through the FCT/MCTES (PIDDAC). info:eu-repo/semantics/publishedVersion

The toxicological knowledge of mancozeb (MZ)-containing commercial formulations on non-target species is scarce and limited. Therefore, the objective of this work was to represent a realistic application scenario by evaluating the toxicity of environmental relevant and higher concentrations of a commercial formulation of MZ using zebrafish embryos. Following determination of the 96-h LC50 value, the embryos at the blastula stage (~ 2 h post-fertilisation, hpf) were exposed to 0.5, 5, and 50 μg L−1 of the active ingredient (~ 40× lower than the 96-h LC50). During the exposure period (96 h), lethal, sublethal, and teratogenic parameters, as well as behaviour analysis, at 120 hpf, were assayed. Biochemical parameters such as oxidative stress–linked enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)), reactive oxygen species (ROS) levels, and glutathione levels (GSH and GSSG), as well as the activity of degradation (glutathione S-transferase (GST) and carboxylesterase (CarE)), neurotransmission (acetylcholinesterase (AChE)), and anaerobic respiration (lactate dehydrogenase (LDH))–related enzymes, were analysed at the end of the exposure period. Exposed embryos showed a marked decrease in the hatching rate and many malformations (cardiac and yolk sac oedema and spinal torsions), with a higher prevalence at the highest concentration. A dose-dependent decreased locomotor activity and a response to an aversive stimulus, as well as a light-dark transition decline, were observed at environmental relevant concentrations. Furthermore, the activities of SOD and GR increased while the activity of GST, AChE, and MDA contents decreased. Taken together, the involvement of mancozeb metabolites and the generation of ROS are suggested as responsible for the developmental phenotypes. While further studies are needed to fully support the hypothesis presented, the potential cumulative effects of mancozeb-containing formulations and its metabolites could represent an environmental risk which should not be disregarded.

Nasopharyngeal myiasis in red deer has never been studied in Portugal. For this reason, from December 2015 to February 2016 a study was derived on hunted red deer in Idanha-a-Nova county to evaluate the Diptera larvae presence. During the initial examination on the spot, the larvae was analysed at the nasopharynx. When present, larvae were collected for further species identification. The infestation prevalence was 50.6 ± 7.61% (CI 95%), and the mean parasitism intensity was 11.38 larvae per affected host. Two larvae species were found

Obesity, a rising concern in the Eastern world, encompasses several co-morbidities, namely non-alcoholic fatty liver disease (NAFLD). Potential natural-based interventions to decrease the burden of obesity complications are being investigated. Many of the edible parts of plants are not sold for consumption and end up as massive waste, losing nutritional potential. In fact, a sizeable amount of waste is generated within the different steps of the food supply chain, representing a massive loss of both plant material and natural resources. A good example is Brassica by-products (BBPs). The objective of this work was to investigate the effect of three different extracts from broccoli (Brassica oleracea var italica) by-products in an in vitro model of free fatty acid (FFA)-induced lipotoxicity using human hepatoma HepG2 cells. Broccoli leaf, stalk, and inflorescence extracts induced a dose-dependent decrease in the cell viability of HepG2 cells. However, the maximal non-lethal concentrations of leaves, stalks, and inflorescences (10 μg/mL) did not compromise mitochondrial function or neutral lipid accumulation in HepG2 cells. The extracts significantly decreased FFA-induced lipid accumulation in HepG2 cells either in a co-incubation or pre-incubation strategy. The broccoli extracts’ capacity to prevent the FFA-induced decrease in catalase activity in HepG2 may explain the observed effects.

Glyphosate-based herbicides (GBH) are the most used herbicides in the world, carrying potentially adverse consequences to the environment and non-target species due to their massive and inadequate use. This study aimed to evaluate the effects of acute exposure to a commercial formulation of glyphosate, Roundup® Flex (RF), at environmentally relevant and higher concentrations in zebrafish larvae through the assessment of the inflammatory, oxidative stress and cell death response. Transgenic Tg(mpxGFP)i114 and wild-type (WT) zebrafish larvae (72 h post-fertilisation) were exposed to 1, 5, and 10 µg mL−1 of RF (based on the active ingredient concentration) for 4 h 30 min. A concentration of 2.5 µg mL−1 CuSO4 was used as a positive control. Copper sulphate exposure showed effectiveness in enhancing the inflammatory profile by increasing the number of neutrophils, nitric oxide (NO) levels, reactive oxygen species (ROS), and cell death. None of the RF concentrations tested showed changes in the number of neutrophils and NO. However, the concentration of 10 µg a.i. mL−1 was able to induce an increase in ROS levels and cell death. The activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), the biotransformation activity, the levels of reduced (GSH) and oxidised (GSSG) glutathione, lipid peroxidation (LPO), lactate dehydrogenase (LDH), and acetylcholinesterase (AChE) were similar among groups. Overall, the evidence may suggest toxicological effects are dependent on the concentration of RF, although at concentrations that are not routinely detected in the environment. Additional studies are needed to better understand the underlying molecular mechanisms of this formulation.

Na sequência do crescente peso que a cultura tem vindo a assumir nas economias dos países mais desenvolvidos, a arte contemporânea africana é entendida como um potencial fator de desenvolvimento da indústria do turismo em África e, especificamente, em Moçambique. A comercialização a que a arte está ou passará a estar sujeita não representa, no contexto desta discussão, qualquer perigo de empobrecimento estético, desde que as políticas públicas incentivem, por um lado, a produção artística com os meios e as condições necessárias à garantia de qualidade e, por outro, providenciem informação adequada aos potenciais compradores., Este trabalho é financiado por fundos nacionais através da FCT – Fundação para a Ciência e a Tecnologia, I.P., no âmbito do projeto UIDB/00736/2020. É também apoiado no âmbito da “Knowledge for Development Initiative”, pela Rede Aga Khan para o Desenvolvimento e pela FCT - Fundação para a Ciência e Tecnologia, IP (n.º 333162622) no contexto do projeto Memories, cultures and identities: how the past weights on the present-day intercultural relations in Mozambique and Portugal?

The use of herbicides with glyphosate as an active ingredient, the so-called glyphosate-based herbicides (GBH), has increased dramatically in recent years currently being the most widely used in the world. Therefore, glyphosate residues have been detected in water and soils near the application sites. Recent studies indicate that GBH may cause adverse effects on vertebrates although these have been attributed to the presence of adjuvants in the commercial formulations rather than to the sole compound. Accordingly, the objective of this work was to investigate the lethal and sub-lethal developmental effects, neurotoxic potential and oxidative stress responses of zebrafish embryos to Roundup® Ultramax (RU) exposure. Embryos were exposed during 72 h to 0, 2, 5, 8.5 μg a.i. mL−1 of RU. Increased mortality was observed in embryos exposed to concentrations above 8.5 μg a.i. mL−1 as well as increased number of malformations. Decreased heart rate and hatchability were also observed. By contrast, exposure to concentrations that do not evoke teratogenic outcomes induced a dose-dependent decrease of heart rate although not inducing significant developmental changes. However, histological changes were not observed in the larvae exposed to these concentrations. Moreover, the generation of reactive oxygen species, the antioxidant enzymes activities (SOD and CAT), the GST biotransformation activity, the glutathione levels (GSH and GSSG), the oxidative damage (MDA) and the acetylcholinesterase and lactate dehydrogenase were similar among groups following exposure. Overall, available evidence suggests a dose-dependent toxicological effect of this formulation at concentrations that are not routinely detected in the environment. However, additional studies should be performed to better understand the underlying molecular mechanisms in favor of this formulation.

Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. have shown in vitro antioxidant, anti-inflammatory and antitumor properties. The aim of this work was to evaluate the therapeutic properties of a hydroethanolic extract obtained from T. platyphyllos in HPV16-transgenic mice. The animals were divided into eight groups according to their sex and phenotype. Four groups of female: HPV+ exposed to linden (HPV linden; n = 6), HPV+ (HPV water; n = 4), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 4) and four groups of male: HPV+ exposed to linden (HPV linden; n = 5), HPV+ (HPV water; n = 5), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 7). The linden (Tilia platyphyllos Scop.) extract was orally administered at a dose of 4.5 mg/10 mL per animal (dissolved in water) and changed daily for 33 days. The hydroethanolic extract of T. platyphyllos consisted of protocatechuic acid and (-)-epicatechin as the most abundant phenolic acid and flavonoid, respectively, and was found to be stable during the studied period. In two male groups a significant positive weight gain was observed but without association with the linden extract. Histological, biochemical, and oxidative stress analyses for the evaluation of kidney and liver damage support the hypothesis that the linden extract is safe and well-tolerated under the present experimental conditions. Skin histopathology does not demonstrate the chemopreventive effect of the linden extract against HPV16-induced lesions. The linden extract has revealed a favourable toxicological profile; however, additional studies are required to determine the chemopreventive potential of the linden extract.

Previous embryonic fish data have shown caffeine to induce potential teratogenic and long-term neurodevelopmental outcomes through oxidative stress-mediated apoptosis. In this context, antioxidants may have the potential to counteract the caffeine-induced effects. Therefore, the present study aimed to investigate the potential protective role of 24-epibrassinolide (24-EPI), a natural brassinosteroid with proven antioxidant properties, against caffeine-induced teratogenic effects during early zebrafish development. Embryos (~2 h post-fertilization - hpf) were exposed to 0.5 mM caffeine, co-exposed to 24-EPI (0.01, 0.1 and 1 μM) and to 24-EPI alone (1 μM) for 96 h. During exposure, lethal and sublethal developmental parameters were evaluated. At the end of the exposure, biochemical evaluations were made, and 24 h after, different behavioural paradigms were assessed. An increased number of animals showing oedema and malformations were observed after caffeine exposure, while these were reduced after co-exposure to 24-EPI concentration, namely the tail curvature. The results showed oxidative stress and related parameters similar among treatments. Yet, caffeine exposure resulted in locomotor deficits (decreased speed and distance) and disrupted anxiety-like and avoidance responses. The co-exposure to caffeine and to the highest 24-EPI concentrations resulted in less pronounced behavioural deficits. Overall, there was an absence of effects in the embryo/larvae exposed solely to 24-EPI, while caffeine caused developmental and neurotoxic effects. Although further studies are needed, the results showed promising protective effects of the highest 24-EPI concentration tested against the toxicity induced by caffeine in zebrafish.

Prostate cancer (PCa) is one of the most common cancers in men, with a huge impact on their health. The use of Castanea sativa Mill. flowers (CFs) in beverages has been reported, through ancestral claims, as having health benefits. In vitro research has evidenced the properties of CFs, such as antitumor and antioxidant activities. This study aimed to evaluate the effects of CF extract in an animal model of PCa. Forty male Wistar Unilever rats were randomly assigned to four groups: control, induced, control + CF, and induced + CF groups. Animals from the induced groups were exposed to a multistep protocol for PCa induction. The CF extract, rich in trigalloyl-HHDP-glucoside and obtained via decoction, was administered to the CF groups in drinking water (3 mg per animal per day) for 49 weeks. Animals were sacrificed at 61 weeks of age. Regarding the effects of CFs on dorsolateral prostate tumorigenesis, no significant differences were observed between the induced and induced + CF groups. However, animals exposed to the CF extract showed fewer inflammation areas on the dorsolateral prostate lobe than those not exposed to CF. Moreover, the CF extract alleviated the hepatic oxidative stress associated with the multistep protocol, resulting in lower levels of lipid peroxidation. These results suggest that CF extract has antioxidant and anti-inflammatory properties. This journal is. This work was supported by European Investment Funds by FEDER/COMPETE/POCI - Operational Competitiveness and Internationalization and National Funds by FCT - Portuguese Foundation for Science and Technology, under the projects UIDB/04033/2020 (CITAB), UIDB/00690/2020 (CIMO), UIDB/50006/2020 (LAQV), UIDB/CVT/00772/2020 (CECAV), and UIDP/00616/2020 (CQ-VR), the project RUNawayPCa (POCI-01-0145- FEDER-016728 and PTDC/DTP-DES/6077/2014), and PhD fellowship SFRH/BD/136747/2018. L. Barros also acknowledges national funding by FCT, P.I., through the institutional scientific employment program-contract for her contract. The Interreg Program received financial support from the Project IBERPHENOL, Project Number 0377_IBERPHENOL_6_E, cofinanced by the European Regional Development Fund (ERDF) through POCTEP 2014-2020. info:eu-repo/semantics/publishedVersion

The improper use of synthetic fungicides has raised public concerns related to environmental pollution and animal health. Over the years, plant-derived antifungals have been investigated as safer alternatives, although little scientific evidence of its neurodevelopmental effects exist. The main objective of this study was to explore the effects of three alternative natural extracts (Equisetum arvense, Mimosa tenuiflora, Thymol) with antifungal properties during the early development of zebrafish by evaluating different teratogenic, oxidative stress and behavioural outcomes. Following the determination of the 96 h-LC50, exposure to sublethal concentrations showed the safety profile of both E. arvense and M. tenuiflora. However, following 96-h exposure to Thymol, increased lethality, pericardial oedema, yolk and eye deformations, and decreased body length were observed. The reduced and oxidized glutathione (GSH:GSSG) ratio was increased, and the glutathione-s-transferase activity in the group exposed to the highest Thymol concentration. Overall, these results support a more reducing environment associated with possible effects at the cellular proliferation level. In addition, the disruption of behavioural states (fear- and anxiety-like disorders) were noted, pointing to alterations in the c-Jun N-terminal kinase developmental signalling pathway, although further studies are required to explore this rationale. Notwithstanding, the results provide direct evidence of the teratogenic effects of Thymol, which might have consequences for non-target species.

Azoxystrobin is a broad-spectrum strobilurin fungicide for use on a wide range of crops available to end-users as formulated products. Due to its extensive application, it has been detected in aquatic ecosystems, raising concerns about its environmental impact, which is still poorly explored. The objective of this work was to study the effects of a commercial formulation of azoxystrobin in the zebrafish embryo model. Sublethal and lethal effects were monitored during the exposure period from 2 h post fertilisation (hpf) to 96 hpf after exposure to azoxystrobin concentrations (1, 10 and 100 µg L-1). The responses of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR)) as well as detoxifying enzymes (glutathione-s-transferase (GST) and carboxylesterase (CarE)) were evaluated at 96 hpf. Similarly, glutathione levels (reduced (GSH) and oxidised (GSSG) glutathione), neurotransmission (acetylcholinesterase (AChE)) and anaerobic respiration (lactate dehydrogenase (LDH)) -related enzymes were assayed. At 120 hpf, larvae from each group were used for behaviour analysis. Results from this study showed concentration-dependent teratogenic effects, particularly by increasing the number of malformations (yolk and eye), with a higher prevalence at the highest concentration. However, it was found that the lowest concentration induced a high generation of reactive oxygen species (ROS) and increased activity of SOD, GST, and CarE. In addition, GR and GSSG levels were decreased by the lowest concentration, suggesting an adaptive response to oxidative stress, which is also supported by the increased AChE activity and absence of behavioural changes. These findings advance the knowledge of the azoxystrobin developmental and environmental impacts, which may impose ecotoxicological risks to non-target species. The authors would like to thank Prof. Dr. Fernando Nunes for the experimental assistance in the chromatographic procedures. This work was financially supported by European Investment Funds by FEDER/ COMPETE/POCI– Operational Competitiveness and Internationalization Programme, under the project POCI-01-0145-FEDER-006958 and National Funds by FCT - “Fundação para a Ciência e a Tecnologia”, under the project UIBD/04033/2020 and under the PhD grant SFRH/ BD/144904/2019.

After describing and discussing the conditions of artistic production in peripheral contexts, the course of the Angolan visual arts from the end of the colonial period to the present time is analysed, a period when these enjoy a relative international projection. This projection is the result of a double sustainability: on the one hand, the material conditions for creation and artistic production and, on the other hand, the sustainability or maintenance of an aesthetic pattern rooted in the tradition and history of the country. Depois de se descrever e discutir as condições de produção artística em contextos periféricos, analisa-se o percurso das artes plásticas angolanas desde finais do período colonial até à atualidade, momento em que as mesmas desfrutam de uma relativa projeção internacional. Essa projeção é o resultado de uma dupla sustentabilidade: por um lado, as condições materiais de criação e produção artística e, por outro, a sustentabilidade ou manutenção de um padrão estético enraizado na tradição e na história do país.

The use of herbicides with glyphosate as an active ingredient (a.i.) has increased dramatically in recent years, with its residues often being found in either soil or water. Nevertheless, concerns have arisen about its harmful side effects for both ecosystems and wildlife health. Therefore, the objective of this work was to assess the effects of a commercial formulation of glyphosate (RoundUp® UltraMax), at environmentally relevant concentrations on zebrafish embryos through a set of behavioural patterns. Zebrafish embryos were exposed to 0, 1, 2 and 5 μg a.i. mL−1 concentrations of the glyphosate formulation for 72 h (from 2.5 to 75 h post-fertilization (hpf)). After exposure, larvae were washed and allowed to develop until 144 hpf. At this point, the larvae behaviour was evaluated using a battery of tests to assess the general exploratory motility, escape-like responses, anxiety-related behaviours and social interactions. In addition, cortisol levels were assessed. No significant changes were observed relative to the exploratory behaviour in the standard open field. The anxiety-related behaviours were similar among groups, and no social interference was observed following exposure to these glyphosate concentrations. Likewise, cortisol levels remained similar among treatments. Still, the larvae exposed to 5 μg a.i. mL−1 did not react to the presence of an aversive stimulus, supporting glyphosate-induced changes in the sensory-motor coordination during development. In general, these results indicate a possible neurotoxic effect of this glyphosate-based formulation that should be further evaluated. In addition, the results obtained could impose a risk for wildlife sensitive species that should not be neglected.

The production of chestnut (Castanea sativa Miller) is mostly concentrated in Europe. Chestnut is recognized by its high content of antioxidants and phytosterols. This work aimed to evaluate the effects of dietary chestnut consumption over physiological variables of FVB/n mice. Eighteen FVB/n male 7-month-old mice were randomly divided into three experimental groups (n = 6): 1 (control group) fed a standard diet, 2 fed a diet supplemented with 0.55% (w/w) chestnut, and 3 supplemented with 1.1% (w/w) chestnut. Body weight, water, and food intake were recorded weekly. Following 35 days of supplementation, the mice were sacrificed for the collection of biological samples. Chestnut supplementation at 1.1% reduced abdominal adipose tissue. Lower serum cholesterol was also observed in animals supplemented with chestnut. There were no significant differences concerning the incidence of histological lesions nor in biochemical markers of hepatic damage and oxidative stress. These results suggest that chestnut supplementation may contribute to regulate adipose tissue deposition.

Objective To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringer's lactate (RL) and hydroxyethyl starch (HES) 130/0.4, on histological lesions of the small intestinal mucosa in anesthetized pigs subjected to severe acute bleeding. Design Prospective experimental study. Setting University teaching hospital. Animals Twenty-eight healthy Large White pigs, 3 months of age. Interventions Pigs were subjected to severe acute bleeding (30 mL/kg) under total intravenous anesthesia with propofol and remifentanil. Pigs were randomly allocated to 3 groups: Group 1 (n = 11) received RL solution (25 mL/kg) after bleeding; Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg) after bleeding; and Group 3 (n = 6) volume replacement nor induced bleeding. Pigs were euthanized and the small intestine was harvested for histopathological analysis. Measurements and Main Results The small intestine was histologically evaluated and the presence of the following lesions were characterized: edema, congestion, hyperemia, hemorrhage, inflammatory infiltration, cellular degeneration, necrosis, and epithelial detachment. Mucosal loss percentage (%ML) and crypt:interstitium ratio (C:I) were also assessed. In the duodenum, jejunum, and ileum, and the entire small intestine, the %ML was significantly higher in Group 1, than in Groups 2 and 3. Hyperemia in the small intestine was significantly higher in pigs resuscitated with HES 130/0.4 compared to pigs resuscitated with RL. Conclusions and Clinical Relevance In a setting of controlled hemorrhage, resuscitation with HES 130/0.4 was associated with a lower percentage of mucosal loss on the small intestine, compared with resuscitation with RL solution. Our study also suggests that the duodenum may be more sensitive to hypovolemia induced by severe hemorrhage.

A ação de vender, trocar e comprar é uma dinâmica que acontece há milhares de anos, o comércio de produtos, bens e serviços faz parte do dia a dia das pessoas e neste sentido o atacado distribuidor busca as melhores alternativas para fazer o produto chegar aos consumidores com um nível de serviço adequado, de maneira segura e lucrativa para a empresa vendedora e de forma acessível, confiável e que satisfaça as necessidades dos clientes. O setor atacadista distribuidor é, no geral, um negócio de baixa lucratividade, sendo assim, a frugalidade nas gestões dos custos indesejáveis de estoque é ainda mais importante para a saúde das empresas desse setor. O objetivo desse trabalho é mensurar o impacto dos custos de oportunidade dos Itens com Giro Insatisfatório (IGI) e com vendas perdidas (Lost Sales) na rentabilidade de um Atacado Distribuidor e quais as possíveis causas do IGI e Lost Sales sob a perspectiva ótica dos compradores e gerentes de compras, tendo como referência os conceitos de custo de oportunidade relacionado a estoque, sendo que para o IGI será utilizado para mensuração o custo médio ponderado de capital (WACC) e para o Lost Sales será utilizado como racional de rentabilidade a margem de contribuição perdida pela venda não efetivada, e usando para tal uma abordagem quantitativa com objetivos descritivos e, como procedimentos técnicos, um estudo de caso em um Atacado Distribuidor. A presente dissertação é dividida em duas perspectivas principais de análise, a primeira relacionada ao IGI e a segunda direcionada para Lost Sales. Após avaliação dos custos de oportunidade (Co), verificou-se que, nos anos de 2014, 2015 e 2016, o Co total foi de R$ 154,8 milhões, cerca de 78% do lucro operacional do Atacado Distribuidor no acumulado dos 3 anos, sendo que desse montante o Co do IGI corresponde a algo em torno de R$ 71,6 milhões, que equivale a cerca de 36% do lucro operacional e suas principais causas estão relacionadas com queda de preço no mercado e compras de oportunidade, e o Co do Lost Sales ao valor de R$ 83,1 milhões, correspondente a cerca de 42% do lucro operacional e suas principais causas estão relacionadas com falta de produto na indústria, produtos em renegociação de custo e assuntos relacionados a transporte. Com base no diagnostico desta dissertação, foi criado um simulador como objetivo de mitigar uma das principais causas relacionadas ao Co as compras de oportunidades. Para estudos futuros, sugerese a utilização de outros períodos, atacados e segmentos de negócios para análise. The act of selling, trading and buying is a dynamic that has been going on for thousands of years. The commerce of products, goods, and services is part of people's day-to-day. Based on what has been said the wholesale distributor seeks the best alternatives to make the product reach customers with an adequate level of service, in a safe and profitable way for the company that is selling and in an accessible and reliable way, to satisfy the customer's needs. The wholesale sector is in general a low-profit business, therefore, the frugality in managing undesirable inventory costs, is even more important for the health of companies in this sector. The goal of this work is to measure the impact of opportunity costs on Unsatisfactory Product Turnover and Lost Sales on the profitability of a Wholesale Distributor and what are the possible causes of Unsatisfactory Product Turnover and Lost Sales from the perspective of purchasers and purchasing managers taking reference on the concepts of inventory's related opportunity cost. For the Unsatisfactory Turnover will be used as measurement, the weighted average cost of capital (WACC). For the Lost Sales will be used as rational of profitability the contribution’s margin made by the non-effected sale, using a quantitative approach for descriptive purposes. As technical procedures, will be used a study case in a Wholesale Distributor. This dissertation is divided into two main analysis perspectives; the first related to Unsatisfactory Product Turnover and the second one directed at Lost Sales. After evaluating the opportunity's costs it has been noted that in the years of 2014, 2015 and 2016, the total opportunity's costs was around R$ 154.8 million, approximately 78% of 3 years accumulated operating income in the Wholesale Distributor. Which of this amount the Unsatisfactory Product Turnover corresponds to something around R$ 71.6 million, equivalent to 36% of the operating profit. Its main causes are related to the decrease in market prices and opportunity purchases, and the Lost Sale's opportunity's cost R$ 83.1 million corresponds to approximately 42% of operating profit and its main causes are related to the lack of products in the industry, products in cost's renegotiation, and subjects related to transportation. Based on this dissertation’s diagnosis a simulator has been created in order to mitigate one of the main causes related to opportunity’s costs and opportunity’s purchases. For future references it strongly advised to use other periods, wholesalers, and business segments for analysis. Dissertação (Mestrado)

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16−/− without treatment, group II: treated HPV16−/−, group III: HPV16+/− without treatment and group IV: treated HPV16+/−). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wildtype animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers. This work was supported by: Integrative Research in Environment, Agro-Chains and Technology no. NORTE-01- 0145-FEDER-000017, in its line of research entitled ISAC, cofinanced by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020). European Investment Funds by FEDER/COMPETE/ POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. This study was also funded by Liga Portuguesa Contra o Cancro, by the Research Center of the Portuguese Institute of Oncology of Porto (CI-IPOP 37-2016), by project POCI-01-0145- FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE), project POCI-01-0145-FEDER-006958 and UID/AGR/04033/2013, funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT – Fundação para a Ciência e a Tecnologia; Rui M. Gil da Costa was funded by grant number SFRH/BPD/85462/2012 from FCT, funded by the Portuguese Government and the Social European Fund. The authors are also grateful to FCT, Portugal and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/ 00690/2013), and to the Interreg España-Portugal for financial support through the project 0377_Iberphenol_6_E. info:eu-repo/semantics/publishedVersion