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AimTo uncover sex-related microvascular abnormalities that underlie the early presentation of reduced perfusion in leg skeletal muscle in a type II rat model of diabetic cardiomyopathy.Methods and ResultsDiabetes was induced using a non-obese, diet-based, low-dose streptozotocin model in adult female (18 diabetic, 9 control) and male rats (29 diabetic, 11 control). Time-course monitoring over 12 months following diabetes induction was performed using echocardiography, treadmill exercise, photoacoustic imaging, flow-mediated dilation (FMD), histopathology, and immunohistochemistry. Diabetic rats maintained normal weights. Hypertension appeared late in both diabetic males (7 months) and females (10 months), while only diabetic males had elevated cholesterol (7 months). On echocardiography, all diabetic animals maintained normal ejection fraction and exhibited diastolic dysfunction, mild systolic dysfunction, and a slightly enlarged left ventricle. Exercise tolerance declined progressively and early in males (4 months), later in females (8 months); FMD showed lower baseline femoral arterial flow but unchanged reactivity in both sexes (5 months); and photoacoustic imaging showed lower tissue oxygen saturation in the legs of diabetic males (4 months) and diabetic females (10 months). Myocardial perfusion was normal in both sexes. Histopathology at the final timepoint of Month 10 (males) and Month 12 (females) revealed that myocardial microvasculature was normal in both vessel density and structure, thus explaining normal perfusion on imaging. However, leg muscle microvasculature exhibited perivascular smooth muscle thickening around small arterioles in diabetic females and around large arterioles in diabetic males, explaining the depressed readings on photoacoustic and FMD. Histology also confirmed the absence of commonly reported HFpEF markers, including microvessel rarefaction, myocardial fibrosis, and left ventricular hypertrophy.ConclusionExercise intolerance manifesting early in the progression of diabetic cardiomyopathy can be attributed to decreased perfusion to the leg skeletal muscle due to perivascular smooth muscle thickening around small arterioles in females and large arterioles in males. This microvascular abnormality was absent in the myocardium, where perfusion levels remained normal throughout the study. We conclude that although skeletal muscle microvascular dysfunction of the vasculature presents at different levels depending on sex, it consistently presents early in both sexes prior to overt cardiac changes such as rarefaction, fibrosis, or hypertrophy.

Brain arteriovenous malformations (AVMs) are a disorder wherein abnormal, enlarged blood vessels connect arteries directly to veins, without an intervening capillary bed. AVMs are one of the leading causes of hemorrhagic stroke in children and young adults. Most human sporadic brain AVMs are associated with genetic activating mutations in the KRAS gene. Our goal was to develop an in vitro model that would allow for simultaneous morphological and functional phenotypic data capture in real time during AVM disease progression. By generating human endothelial cells harboring a clinically relevant mutation found in most human patients (activating mutations within the small GTPase KRAS) and seeding them in a dynamic microfluidic cell culture system that enables vessel formation and perfusion, we demonstrate that vessels formed by KRAS4A(G12V) mutant endothelial cells (ECs) were significantly wider and more leaky than vascular beds formed by wild-type ECs, recapitulating key structural and functional hallmarks of human AVM pathogenesis. Immunofluorescence staining revealed a breakdown of adherens junctions in mutant KRAS vessels, leading to increased vascular permeability, a hallmark of hemorrhagic stroke. Finally, pharmacological blockade of MEK kinase activity, but not PI3K inhibition, improved endothelial barrier function (decreased permeability) without affecting vessel diameter. Collectively, our studies describe the creation of human KRAS-dependent AVM-like vessels in vitro in a self-assembling microvessel platform that is amenable to phenotypic observation and drug delivery.

Due to the fierce competition between tourism destinations; the continuous changes in today’s world, impacting directly on tourism; and the importance of this sector, economically, for several countries worldwide, it is crucial to provide a clear identity and a perceivable personality for each destination. Thus, to clear any confusions regarding positioning. Therefore, The brand personality of a tourism destination, through online and offline content analysis, would be a way to find the gap between operators’ positioning of a destination and the one applied by destination’s marketers. In this study, the Aaker (1997)’s model, of Brand Personality Scale (BPS), has been modified and applied to a tourism destination. The findings conclude clear disparities between Governmental and operators’ positioning of the selected country, most of which are accepted as part of ‘a supplementing positioning strategy’, and few may be considered as errors. Thus, this article presents insights to tourism professionals and responsible bodies on the way to fill the gaps through a supplementing strategy.

Relatório (Estágio curricular) - Universidade Federal de Santa Catarina. Centro de Comunicação e Expressão. Departamento de Expressão Gráfica. Design. Prof. Luciano Patrício Souza de Castro

In the last decade, research studies have increased on the development of delivery systems for polyphenols, for protection, improvement of stability and increase of their bioavailability. Rosmarinic acid is a polyphenol with described bioactivities, such as antioxidant, anti-mutagenic, anti-bacterial and anti-viral capabilities. Thus, the aim of this research work was to produce stable solid lipid nanoparticles (SLN) using carnauba wax as lipidic matrix, for delivery of rosmarinic acid, to be further incorporated into food matrices. Hence, different concentrations of wax (0.5, 1 and 1.5%, w/v) and percentages of surfactant (1, 2 and 3%, v/v) were tested. Physical properties, surface morphology and association efficiencies were studied at time of production and after 28 day at refrigerated storage. Thermal properties and the nature of the chemical interactions between the lipids waxes and rosmarinic acid were also evaluated. The particles showed range size between 35-927 nm and zeta potentials of ca. -38 to 40, showing high stability, with no risk of aggregation due to electric repulsion of SLN. High association efficiencies % (ca. 99%) were obtained. FTIR analyses proved the association of rosmarinic acid and lipidic matrix. The low lipid and high surfactant concentrations leads to small SLN. The surfactant, polysorbate 80 decreases the interfacial tension in the SLN surfaces, preventing aggregation, leading to the development of small particles. These properties were maintained throughout the 28 day of refrigerated storage, and no rosmarinic acid was released by the particles during refrigeration, indicating good compatibility between rosmarinic acid and the waxy core of SLN. The optimum range values to obtain the desirable features for incorporation in a functional food suggest formulations containing 1.0 and 1.5% (w/v) of lipid and 2% (v/v) of surfactant. This journal is © The Royal Society of Chemistry 2015.

Additional file 1. Validated questionnaire used for assessing adverse food reactions in Portuguese adults.

O Turismo tem -se destacado como um setor com enorme potencial à escala nacional e mundial, tendo um papel proeminente como instrumento de competitividade e impulsionador de desenvolvimento regional. Muitos são os estudos sobre esta temática, no entanto ainda são deficitários aqueles que são centrados na validação empírica de modelos de competitividade de um destino turístico. A presente investigação propõe- -se contribuir para o preenchimento deste gap, cujo objetivo baseia -se na avaliação da competitividade da área regional de turismo do Algarve, mediante a identificação dos fatores de competitividade de turismo nesta região. A metodologia adotada na investigação exigiu a aplicação de dados primários, onde foi usado um questionário aplicado às empresas com as atividades características da conta satélite da Organização Mundial do Turismo. Com recurso a modelos de equações estruturais, os resultados demonstram a existência de várias relações significativas entre os recursos, a oferta e a gestão do destino turístico, como fatores essenciais para a competitividade da área regional em estudo. Tourism has emerged as an industry with enormous potential for national and global scale, taking a prominent role as an instrument of competitiveness and regional development booster. There are many studies on this subject, however are still deficient those who are focused on empirical validation of a tourist destination competitiveness models. This research intends to contribute to filling this gap, the purpose of which is based on the evaluation of the competitiveness of the regional area of the Algarve tourism, by identifying the tourism competitiveness factors in this region. The methodology used in the research required the application of primary data, where it was used a questionnaire to the companies with the satellite account of characteristics activities of the World Tourism Organization. Using structural equation models, the results show that there are several significant relationships between resources, supply and destination management as key factors for the competitiveness of the regional study area.

Chronic kidney disease (CKD) is a progressive disease that is characterized by the occurrence of an irreversible lesion of the nephrons that consequently causes changes in kidney function. It is defined as the most common renal disease in felines. This progressive disease is characterized by the loss of structure and function of one and both kidneys and is a major cause of morbidity and mortality in cats, with prevalence proportional to the age of the animal, affecting approximately 30-50% of geriatric cats. The etiology of this pathological condition is multifactorial and may be attributed to congenital conditions, glomerulopathies or acquired systemic conditions. In clinical practice, CKD is often diagnosed when the animal is already at an advanced stage of disease, which causes therapeutic limitations and may lead to a worse prognosis. CKD staging is performed according to the International Society of Renal Interest (IRIS) recommendations to facilitate appropriate treatment and better monitor the patient. This classification is based on measurement of serum creatinine, proteinuria and systemic blood pressure. In 2015, a new biomarker, Symmetric Dimethylarginine (SDMA) was implemented by the IRIS, for early detection of CKD. The aim of this paper was to conduct a literature review on the current knowledge of renal biomarkers in feline, which may have the potential to be used for early identification of CKD. Current biomarkers have been classified into three subgroups, glomerular function markers, proximal tubular function markers and renal inflammation markers. The identification of new biomarkers for CKD in felines is crucial and aims to be a usefull diagnostic tool with the objective of a better monitoring of cats affected by this condition. Its introduction into clinical practice may contribute to improve current approaches to diagnosis and therapy in veterinary nephrology. However, in order to understand the true value of these markers in CKD approach, further research in veterinary medicine are needed, as the goal of early detection is to increase longevity and improve the prognosis of cats with this condition.