953 resultados para INTERMITTENT HYPOXIA


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Vegetative propagation of lavender offers several advantages over sexual propagation, among them crop homogeneity and yield of higher quality essential oil. However, Lavandula species have been propagated mostly by seeds and are said to be recalcitrant to rooting when propagated by cuttings. During cutting propagation, one of the important variables that influence the rooting capacity of cuttings is the leaf retention. The objective of this work was to evaluate the influence of leaf retention on rooting of L. dentata cuttings. Apical cuttings of L. dentata of 10 cm in length, keeping approximately 1/3, 1/2 or 2/3 of their leaves were planted in commercial substrate Plantmax HT® under intermittent mist. After two months, averages of root number, length of the longest root, root fresh and dry weights, and the survival percentage were evaluated. Root length and fresh weight were statistically greater with 2/3 of leaf retention and when fewer leaves were kept on the cuttings, lower means of root dry weight was observed. Under the conditions applied in this study, greater leaf retention was better for rooting of L. dentata cuttings.

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Background: Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as “Warburg effect”. Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. Results: The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. Conclusions: This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

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As porfirias são um grupo de oito doenças metabólicas raras, em resultado de uma deficiência enzimática em cada uma das oito enzimas envolvidas na biossíntese do grupo heme. São doenças maioritariamente hereditárias, mas podem também ser adquiridas aquando da exposição a certos fatores ambientais e/ou patológicos. Estes fatores externos, denominados de porfirinogénicos também têm um papel preponderante no diagnóstico das porfirias, uma vez que mimetizam os sintomas clínicos de um ataque agudo de porfiria, contribuindo para subestimar esta doença, levando a um atraso no diagnóstico e diminuído o sucesso do prognóstico. Os ataques agudos de porfiria, nomeadamente na porfiria aguda intermitente, porfiria variegata, coproporfiria hereditária, e deficiência da desidratase do ácido delta-aminolevulínico, apesar de serem doenças multissistémicas, têm em comum como apresentação clínica, a dor abdominal aguda. A pesquisa de porfobilinogénio (PBG) na urina, através da realização do teste de Hoesch, é uma forma rápida e fácil de excluir a suspeita clínica de porfiria. Pretendemos com este trabalho, alertar para a necessidade de um diagnóstico laboratorial atempado, que pela sua simplicidade poderá descartar ou confirmar se a dor abdominal aguda, tão frequente nas urgências hospitalares, será ou não uma manifestação clínica de um ataque agudo de porfiria. Este estudo contribuirá não só para aumentar o nosso conhecimento acerca destas doenças, como também permitirá uma melhor compreensão dos mecanismos de patogenicidade das porfirias, o qual ainda permanece pouco conhecido.

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New K/Ar dating and geochemical analyses have been carried out on the WNW-ESE elongated oceanic island of S. Jorge to reconstruct the volcanic evolution of a linear ridge developed close to the Azores triple junction. We show that S. Jorge sub-aerial construction encompasses the last 1.3 Myr, a time interval far much longer than previously reported. The early development of the ridge involved a sub-aerial building phase exposed in the southeast end of the island and now constrained between 1.32 +/- 0.02 and 1.21 +/- 0.02 Ma. Basic lavas from this older stage are alkaline and enriched in incompatible elements, reflecting partial melting of an enriched mantle source. At least three differentiation cycles from alkaline basalts to mugearites are documented within this stage. The successive episodes of magma rising, storage and evolution suggest an intermittent reopening of the magma feeding system, possibly due to recurrent tensional or trans-tensional tectonic events. Present data show a gap in sub-aerial volcanism before a second main ongoing building phase starting at about 750 ka. Sub-aerial construction of the S. Jorge ridge migrated progressively towards the west, but involved several overlapping volcanic episodes constrained along the main WNW-ESE structural axis of the island. Malic magmas erupted during the second phase have been also generated by partial melting of an enriched mantle source. Trace element data suggest, however, variable and lower degrees of partial melting of a shallower mantle domain, which is interpreted as an increasing control of lithospheric deformation on the genesis and extraction of primitive melts during the last 750 kyr. The multi-stage development of the S. Jorge volcanic ridge over the last 1.3 Myr has most likely been greatly influenced by regional tectonics, controlled by deformation along the diffuse boundary between the Nubian and the Eurasian plates, and the increasing effect of sea-floor spreading at the Mid-Atlantic Ridge.

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O tecido adiposo é um órgão endócrino dinâmico, secretando factores importantes na regulação do metabolismo, fluxo vascular sanguíneo e linfático, e função imunológica, entre outros. Em caso de acumulação de tecido adiposo por ingestão de uma dieta gorda, ou por disfunção metabólica, os adipócitos podem desencadear uma reacção inflamatória por falha na drenagem linfática, acumulando-se mediadores inflamatórios, os quais potenciam a propagação da reacção. Assim, questiona-se uma potencial associação entre o aumento de tecido adiposo na obesidade, hipóxia adipocitária e estimulação da linfangiogénese. Além disso, a expressão de adipocinas varia de acordo com a distribuição do tecido adiposo (subcutâneo, TAS e visceral, TAV). Deste modo, pretende-se com este estudo contribuir para o aumento do conhecimento sobre os complexos mecanismos moleculares subjacentes à linfangiogénese. Ensaios com ratinhos da estirpe C57Bl/6J (modelo de obesidade) e BALB/c (modelo de asma e obesidade), divididos em grupos submetidos a dieta normal e dieta rica em gordura. Avaliação semi-quantitativa da expressão tecidular de LYVE-1 (marcador da linfangiogénese) por imunohistoquímica em material embebido em parafina, no TAS e TAV, e cromatografia líquida de ultra-performance acoplada de espectrometria de massa (UPLC-MS) para análise da expressão plasmática de ceramida e esfingosina-1-fosfato (S1P). No modelo de obesidade observou- -se diminuição do número de vasos linfáticos e expressão de LYVE-1 ao longo do tempo no TAV, e aumento de ambos os parâmetros e hipertrofia adipocitária no TAS. As concentrações de ceramida e S1P corroboram a existência de um processo inflamatório nos ratinhos em estudo, ainda que numa fase muito inicial. No modelo de asma e obesidade, após 17 semanas de tratamento, observou-se incremento da linfangiogénese no TAV, mas não no TAS. A resposta inflamatória avaliada através dos diferentes parâmetros permite afirmar que num estadio inicial de obesidade a proliferação linfática poderá estar a ser retardada pela hipertrofia adipocitária. A libertação de adipocinas será observada apenas numa fase posterior, desencadeando todo o processo inflamatório que incrementará a proliferação linfática. Adicionalmente, é possível sugerir que a maior pressão à qual o TAV se encontra sujeito não favorece a proliferação linfática, pelo menos num estadio incial.

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In this paper, a stochastic programming approach is proposed for trading wind energy in a market environment under uncertainty. Uncertainty in the energy market prices is the main cause of high volatility of profits achieved by power producers. The volatile and intermittent nature of wind energy represents another source of uncertainty. Hence, each uncertain parameter is modeled by scenarios, where each scenario represents a plausible realization of the uncertain parameters with an associated occurrence probability. Also, an appropriate risk measurement is considered. The proposed approach is applied on a realistic case study, based on a wind farm in Portugal. Finally, conclusions are duly drawn. (C) 2011 Elsevier Ltd. All rights reserved.

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The use of distributed energy resources, based on natural intermittent power sources, like wind generation, in power systems imposes the development of new adequate operation management and control methodologies. A short-term Energy Resource Management (ERM) methodology performed in two phases is proposed in this paper. The first one addresses the day-ahead ERM scheduling and the second one deals with the five-minute ahead ERM scheduling. The ERM scheduling is a complex optimization problem due to the high quantity of variables and constraints. In this paper the main goal is to minimize the operation costs from the point of view of a virtual power player that manages the network and the existing resources. The optimization problem is solved by a deterministic mixedinteger non-linear programming approach. A case study considering a distribution network with 33 bus, 66 distributed generation, 32 loads with demand response contracts and 7 storage units and 1000 electric vehicles has been implemented in a simulator developed in the field of the presented work, in order to validate the proposed short-term ERM methodology considering the dynamic power system behavior.

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The introduction of new distributed energy resources, based on natural intermittent power sources, in power systems imposes the development of new adequate operation management and control methods. This paper proposes a short-term Energy Resource Management (ERM) methodology performed in two phases. The first one addresses the hour-ahead ERM scheduling and the second one deals with the five-minute ahead ERM scheduling. Both phases consider the day-ahead resource scheduling solution. The ERM scheduling is formulated as an optimization problem that aims to minimize the operation costs from the point of view of a virtual power player that manages the network and the existing resources. The optimization problem is solved by a deterministic mixed-integer non-linear programming approach and by a heuristic approach based on genetic algorithms. A case study considering a distribution network with 33 bus, 66 distributed generation, 32 loads with demand response contracts and 7 storage units has been implemented in a PSCADbased simulator developed in the field of the presented work, in order to validate the proposed short-term ERM methodology considering the dynamic power system behavior.

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The large penetration of intermittent resources, such as solar and wind generation, involves the use of storage systems in order to improve power system operation. Electric Vehicles (EVs) with gridable capability (V2G) can operate as a means for storing energy. This paper proposes an algorithm to be included in a SCADA (Supervisory Control and Data Acquisition) system, which performs an intelligent management of three types of consumers: domestic, commercial and industrial, that includes the joint management of loads and the charge/discharge of EVs batteries. The proposed methodology has been implemented in a SCADA system developed by the authors of this paper – the SCADA House Intelligent Management (SHIM). Any event in the system, such as a Demand Response (DR) event, triggers the use of an optimization algorithm that performs the optimal energy resources scheduling (including loads and EVs), taking into account the priorities of each load defined by the installation users. A case study considering a specific consumer with several loads and EVs is presented in this paper.

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Introdução – A negligência no controlo da dor é um problema amplamente reconhecido em Portugal. Desde 2001 têm sido realizadas inúmeras iniciativas para melhorar a prática de cuidados nesta área. Desenvolveram-se ações de sensibilização e formação dos profissionais de saúde, publicaram-se orientações técnicas e guias de boas práticas e realizaram-se os primeiros estudos para se fazer um diagnóstico da situação. Objetivos – O objetivo deste trabalho foi o de caracterizar os cuidados prestados na avaliação e no controlo da dor nas crianças até aos 18 anos internadas em serviços hospitalares em Portugal e analisar a evolução feita nos cuidados entre os anos de 2002 e 2012. Metodologia – Estudo descritivo, transversal, de consulta retrospetiva seriada de registos intermitentes efetuados no processo clínico em relação a um período de 24 horas. O recrutamento da amostra foi aleatório e incluiu todos os processos clínicos de crianças até aos 18 anos internados em serviços de quatro hospitais Portugueses entre agosto e dezembro de 2011. Resultados – A prevalência de dor reduziu de forma significativa entre 2002 e 2012. As crianças livres de dor subiram de 37% para 75%. O registo da avaliação da intensidade da dor e a colheita de informação sobre a história de dor passou a ser uma prática comum na maioria dos casos (53% e 64%, respetivamente), embora ainda direcionada para o modelo de cuidados biomédico. A prevalência das intervenções farmacológicas não se alterou (43% versus 42%), mas a implementação de estratégias não-farmacológicas baixou significativamente (72% versus 15%). Conclusões – As ações de sensibilização/formação realizadas no âmbito das políticas implementadas nestes últimos dez anos na área da avaliação e controlo da dor pediátrica geraram evidentes ganhos na qualidade de cuidados prestados, pelo que o investimento na formação deve continuar. No entanto, deve ser dada prioridade à formação para a aplicação de estratégias de intervenção não-farmacológicas e ao desenvolvimento de mais investigação que suporte as práticas.

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Asthma is a chronic inflammatory disorder of the respiratory airways affecting people of all ages, and constitutes a serious public health problem worldwide (6). Such a chronic inflammation is invariably associated with injury and repair of the bronchial epithelium known as remodelling (11). Inflammation, remodelling, and altered neural control of the airways are responsible for both recurrent exacerbations of asthma and increasingly permanent airflow obstruction (11, 29, 34). Excessive airway narrowing is caused by altered smooth muscle behaviour, in close interaction with swelling of the airway walls, parenchyma retractile forces, and enhanced intraluminal secretions (29, 38). All these functional and structural changes are associated with the characteristic symptoms of asthma – cough, chest tightness, and wheezing –and have a significant impact on patients’ daily lives, on their families and also on society (1, 24, 29). Recent epidemiological studies show an increase in the prevalence of asthma, mainly in industrial countries (12, 25, 37). The reasons for this increase may depend on host factors (e.g., genetic disposition) or on environmental factors like air pollution or contact with allergens (6, 22, 29). Physical exercise is probably the most common trigger for brief episodes of symptoms, and is assumed to induce airflow limitations in most asthmatic children and young adults (16, 24, 29, 33). Exercise-induced asthma (EIA) is defined as an intermittent narrowing of the airways, generally associated with respiratory symptoms (chest tightness, cough, wheezing and dyspnoea), occurring after 3 to 10 minutes of vigorous exercise with a maximal severity during 5 to 15 minutes after the end of the exercise (9, 14, 16, 24, 33). The definitive diagnosis of EIA is confirmed by the measurement of pre- and post-exercise expiratory flows documenting either a 15% fall in the forced expiratory volume in 1 second (FEV1), or a ≥15 to 20% fall in peak expiratory flow (PEF) (9, 24, 29). Some types of physical exercise have been associated with the occurrence of bronchial symptoms and asthma (5, 15, 17). For instance, demanding activities such as basketball or soccer could cause more severe attacks than less vigorous ones such as baseball or jogging (33). The mechanisms of exercise-induced airflow limitations seem to be related to changes in the respiratory mucosa induced by hyperventilation (9, 29). The heat loss from the airways during exercise, and possibly its post-exercise rewarming may contribute to the exercise-induced bronchoconstriction (EIB) (27). Additionally, the concomitant dehydration from the respiratory mucosa during exercise leads to an increased interstitial osmolarity, which may also contribute to bronchoconstriction (4, 36). So, the risk of EIB in asthmatically predisposed subjects seems to be higher with greater ventilation rates and the cooler and drier the inspired air is (23). The incidence of EIA in physically demanding coldweather sports like competitive figure skating and ice hockey has been found to occur in up to 30 to 35% of the participants (32). In contrast, swimming is often recommended to asthmatic individuals, because it improves the functionality of respiratory muscles and, moreover, it seems to have a concomitant beneficial effect on the prevalence of asthma exacerbations (14, 26), supporting the idea that the risk of EIB would be smaller in warm and humid environments. This topic, however, remains controversial since the chlorified water of swimming pools has been suspected as a potential trigger factor for some asthmatic patients (7, 8, 20, 21). In fact, the higher asthma incidence observed in industrialised countries has recently been linked to the exposition to chloride (7, 8, 30). Although clinical and epidemiological data suggest an influence of humidity and temperature of the inspired air on the bronchial response of asthmatic subjects during exercise, some of those studies did not accurately control the intensity of the exercise (2, 13), raising speculation of whether the experienced exercise overload was comparable for all subjects. Additionally, most of the studies did not include a control group (2, 10, 19, 39), which may lead to doubts about whether asthma per se has conditioned the observed results. Moreover, since the main targeted age group of these studies has been adults (10, 19, 39), any extrapolation to childhood/adolescence might be questionable regarding the different lung maturation. Considering the higher incidence of asthma in youngsters (30) and the fact that only the works of Amirav and coworkers (2, 3) have focused on this age group, a scarcity of scientific data can be identified. Additionally, since the main environmental trigger factors, i.e., temperature and humidity, were tested separately (10, 28, 39) it would be useful to analyse these two variables simultaneously because of their synergic effect on water and heat loss by the airways (31, 33). It also appears important to estimate the airway responsiveness to exercise within moderate environmental ranges of temperature and humidity, trying to avoid extreme temperatures and humidity conditions used by others (2, 3). So, the aim of this study was to analyse the influence of moderate changes in air temperature and humidity simultaneously on the acute ventilatory response to exercise in asthmatic children. To overcome the above referred to methodological limitations, we used a 15 minute progressive exercise trial on a cycle ergometer at 3 different workload intensities, and we collected data related to heart rate, respiratory quotient, minute ventilation and oxygen uptake in order to ensure that physiological exercise repercussions were the same in both environments. The tests were done in a “normal” climatic environment (in a gymnasium) and in a hot and humid environment (swimming pool); for the latter, direct chloride exposition was avoided.

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Mestrado em Engenharia Electrotécnica – Sistemas Eléctricos de Energia

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Mestrado em Engenharia Electrotécnica – Sistemas Eléctricos de Energia

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Bladder cancer is a common urologic cancer and the majority has origin in the urothelium. Patients with intermediate and high risk of recurrence/progression bladder cancer are treated with intravesical instillation with Bacillus Calmette-Guérin, however, approximately 30% of patients do not respond to treatment. At the moment, there are no accepted biomarkers do predict treatment outcome and an early identification of patients better served by alternative therapeutics. The treatment initiates a cascade of cytokines responsible by recruiting macrophages to the tumor site that have been shown to influence treatment outcome. Effective BCG therapy needs precise activation of the Th1 immune pathway associated with M1 polarized macrophages. However, tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype, either immunosuppressive or angiogenic, that interfere in different ways with the BCG induced antitumor immune response. The M2 macrophage is influenced by different microenvironments in the stroma and the tumor. In particular, the degree of hypoxia in the tumors is responsible by the recruitment and differentiation of macrophages into the M2 angiogenic phenotype, suggested to be associated with the response to treatment. Nevertheless, neither the macrophage phenotypes present nor the influence of localization and hypoxia have been addressed in previous studies. Therefore, this work devoted to study the influence of TAMs, in particular of the M2 phenotype taking into account their localization (stroma or tumor) and the degree of hypoxia in the tumor (low or high) in BCG treatment outcome. The study included 99 bladder cancer patients treated with BCG. Tumors resected prior to treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. Tumor hypoxia was evaluated based on HIF-1α expression. As a main finding it was observed that a high predominance of CD163+ macrophage counts in the stroma of tumors under low hypoxia was associated with BCG immunotherapy failure, possibly due to its immunosuppressive phenotype. This study further reinforces the importance the tumor microenvironment in the modulation of BCG responses.

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OBJECTIVE: Bacillus Calmette-Guérin (BCG) immunotherapy is the gold standard treatment for superficial bladder tumors with intermediate/high risk of recurrence or progression. However, approximately 30% of patients fail to respond to the treatment. Effective BCG therapy needs precise activation of the type 1 helper cells immune pathway. Tumor-associated macrophages (TAMs) often assume an immunoregulatory M2 phenotype and may directly interfere with the BCG-induced antitumor immune response. Thus, we aim to clarify the influence of TAMs, in particular of the M2 phenotype in stroma and tumor areas, in BCG treatment outcome. PATIENTS AND METHODS: The study included 99 patients with bladder cancer treated with BCG. Tumors resected before treatment were evaluated using immunohistochemistry for CD68 and CD163 antigens, which identify a lineage macrophage marker and a M2-polarized specific cell surface receptor, respectively. CD68+ and CD163+ macrophages were evaluated within the stroma and tumor areas, and high density of infiltrating cells spots were selected for counting. Hypoxia, an event known to modulate macrophage phenotype, was also assessed through hypoxia induced factor (HIF)-1α expression. RESULTS: Patients in whom BCG failed had high stroma-predominant CD163+ macrophage counts (high stroma but low tumor CD163+ macrophages counts) when compared with the ones with a successful treatment (71% vs. 47%, P = 0.017). Furthermore, patients presenting this phenotype showed decreased recurrence-free survival (log rank, P = 0.008) and a clear 2-fold increased risk of BCG treatment failure was observed in univariate analysis (hazard ratio = 2.343; 95% CI: 1.197-4.587; P = 0.013). Even when adjusted for potential confounders, such as age and therapeutic scheme, multivariate analysis revealed 2.6-fold increased risk of recurrence (hazard ratio = 2.627; 95% CI: 1.340-5.150; P = 0.005). High stroma-predominant CD163+ macrophage counts were also associated with low expression of HIF-1α in tumor areas, whereas high counts of CD163+ in the tumor presented high expression of HIF-1α in tumor nests. CONCLUSIONS: TAMs evaluation using CD163 is a good indicator of BCG treatment failure. Moreover, elevated infiltration of CD163+ macrophages, predominantly in stroma areas but not in the tumor, may be a useful indicator of BCG treatment outcome, possibly owing to its immunosuppressive phenotype.