Diabetes and Ischemic Stroke: An Old and New Relationship an Overview of the Close Interaction between These Diseases

Diabetes mellitus is a comprehensive expression to identify a condition of chronic hyperglycemia whose causes derive from different metabolic disorders characterized by altered insulin secretion or faulty insulin effect on its targets or often both mechanisms. Diabetes and atherosclerosis are, from the point of view of cardio- and cerebrovascular risk, two complementary diseases. Beyond shared aspects such as inflammation and oxidative stress, there are multiple molecular mechanisms by which they feed off each other: chronic hyperglycemia and advanced glycosylation end-products (AGE) promote ‘accelerated atherosclerosis’ through the induction of endothelial damage and cellular dysfunction. These diseases impact the vascular system and, therefore, the risk of developing cardio- and cerebrovascular events is now evident, but the observation of this significant correlation has its roots in past decades. Cerebrovascular complications make diabetic patients 2–6 times more susceptible to a stroke event and this risk is magnified in younger individuals and in patients with hypertension and complications in other vascular beds. In addition, when patients with diabetes and hyperglycemia experience an acute ischemic stroke, they are more likely to die or be severely disabled and less likely to benefit from the one FDA-approved therapy, intravenous tissue plasminogen activator. Experimental stroke models have revealed that chronic hyperglycemia leads to deficits in cerebrovascular structure and function that may explain some of the clinical observations. Increased edema, neovascularization, and protease expression as well as altered vascular reactivity and tone may be involved and point to potential therapeutic targets. Further study is needed to fully understand this complex disease state and the breadth of its manifestation in the cerebrovasculature.     

Senescent CD4+CD28− T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4⁺ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28⁻ Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4⁺CD28⁻ T lymphocytes in periodontitis.     

Pathogenetic Mechanisms of Hypertension–Brain-Induced Complications: Focus on Molecular Mediators

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.     

Physicochemical and Theoretical Characterization of a New Small Non-Metal Schiff Base with a Differential Antimicrobial Effect against Gram-Positive Bacteria

Searching for adequate and effective compounds displaying antimicrobial activities, especially against Gram-positive bacteria, is an important research area due to the high hospitalization and mortality rates of these bacterial infections in both the human and veterinary fields. In this work, we explored (E)-4-amino-3-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino) benzoic acid (SB-1, harboring an intramolecular hydrogen bond) and (E)-2-((4-nitrobenzilidene)amino)aniline (SB-2), two Schiff bases derivatives. Results demonstrated that SB-1 showed an antibacterial activity determined by the minimal inhibitory concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus (Gram-positive bacteria involved in human and animal diseases such as skin infections, pneumonia, diarrheal syndrome, and urinary tract infections, among others), which was similar to that shown by the classical antibiotic chloramphenicol. By contrast, this compound showed no effect against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica). Furthermore, we provide a comprehensive physicochemical and theoretical characterization of SB-1 (as well as several analyses for SB-2), including elemental analysis, ESMS, ¹H and ¹³C NMR (assigned by 1D and 2D techniques), DEPT, UV-Vis, FTIR, and cyclic voltammetry. We also performed a computational study through the DFT theory level, including geometry optimization, TD-DFT, NBO, and global and local reactivity analyses.     

Innovation regional planning and latent dimensions: the case of the Algarve region

Regional innovation systems (RSI) concept is an important theoretical framework to analyse regional profiles of regions when trying to understand Innovation but it has also been used by practioners to design and implement policies. This study hopes to contribute to the understanding of the Algarve RSI, a peripheral Portuguese region in the National and European framework, where an economic growth is supported by Tourism, which leaves it out of the group of poorest regions when the GDPpc indicator is taken in account. The regional profile, the comparison with the other European regions and the characterisation of RSI following developed typologies are discussed in this paper. Through the analysis of 175 regions of the EU 15 the study seeks to find the dimensions underlying the innovative phenomena and to create homogeneous groups of regions that display similar profiles. Factorial Analysis was used to reduce the dimension of data from a barrage of regional indicators such as: Critical Mass of Territories, Economic Performance, Level of Wealth, Employment Market, Sectoral Structure of the Economy, Age Group Structure, Education and Training, Technological Employment, R&D and Patents. Having determined the four main factors with significant results (Technological Innovation, Human Capital, Economic Structure and Availability of the Employment Market) what followed was a hierarchical analysis of Clusters, resulting in five groupings of regions: Disadvantaged Regions, Average Regions, Central Regions, Large Economic Centres and Innovating Regions. A synthesis of the recent Regional Innovation Strategies for the Algarve is presented including previous experiences (Ettirse and INOVAlgarve) and the Algarve’s Regional Innovation Plan, which will try to create a pathway for regional development supported by knowledge-based activities for a more diversified regional economy.     

A contribution to the interpretation of polymer viscoelasticity in DMTA testing

Some ideas relevant to the prevailing viscoelasticity interpretations of dynamic mechanical thermal analysis (DMTA) experiments are presented. The main aspect is the inclusion of kinetic energy and inertia as variables, seeing the relaxing mass constantly increasing during strain, assigning inertial variation and not viscosity to energy dissipation. The equations developed make it possible to obtain the values of important viscoelastic properties, under in any experimental condition, with the data taken from previous experiments.     

Colloidal Processing of Zirconium Diboride Ultra‐High Temperature Ceramics

Colloidal processing of the Ultra‐High Temperature Ceramic (UHTC) zirconium diboride (ZrB₂) to develop near?net‐shaping techniques has been investigated. The use of the colloidal processing technique produces higher particle packing that ultimately enables achieving greater densification at lower temperatures and pressures, even pressureless sintering. ZrB₂ suspension formulations have been optimized in terms of rheological behavior. Suspensions were shaped into green bodies (63% relative density) using slip casting. The densification was carried out at 1900°C, 2000°C, and 2100°C, using both hot pressing at 40 MPa and pressureless sintering. The colloidally processed materials were compared with materials prepared by a conventional dry processing route (cold pressed at 50 MPa) and subjected to the same densification procedures. Sintered densities for samples produced by the colloidal route are higher than produced by the dry route (up to 99.5% relative density by hot pressing), even when pressureless sintering is performed (more than 90% relative density). The promising results are considered as a starting point for the fabrication of complex‐shaped components that can be densified at lower sintering temperatures without pressure.     

Scalable approach to uncertainty quantification and robust design of interconnected dynamical systems

Development of robust dynamical systems and networks such as autonomous aircraft systems capable of accomplishing complex missions faces challenges due to the dynamically evolving uncertainties coming from model uncertainties, necessity to operate in a hostile cluttered urban environment, and the distributed and dynamic nature of the communication and computation resources. Model-based robust design is difficult because of the complexity of the hybrid dynamic models including continuous vehicle dynamics, the discrete models of computations and communications, and the size of the problem. We will overview recent advances in methodology and tools to model, analyze, and design robust autonomous aerospace systems operating in uncertain environment, with stress on efficient uncertainty quantification and robust design using the case studies of the mission including model-based target tracking and search, and trajectory planning in uncertain urban environment. To show that the methodology is generally applicable to uncertain dynamical systems, we will also show examples of application of the new methods to efficient uncertainty quantification of energy usage in buildings, and stability assessment of interconnected power networks.     

Emission inventory: An urban public policy instrument and benchmark

Global concern with climate change has led to the development of a variety of solutions to monitor and reduce emissions on both local and global scales. Under the United Nations Framework Convention on Climate Change (UNFCCC), both developed and emerging countries have assumed responsibility for developing and updating national inventories of greenhouse gas emissions from anthropic sources. This creates opportunities and incentives for cities to carry out their own local inventories and, thereby, develop air quality management plans including both essential key players and stakeholders at the local level. The aim of this paper is to discuss the role of local inventories as an urban public policy instrument and how this type of local instrument may bring advantages countrywide in enhancing the global position of a country. Local inventories have been carried out in many cities of the world and the main advantage of this is that it allows an overview of emissions produced by different municipal activities, thereby, helps decision makers in the elaboration of efficient air quality management plans. In that way, measures aimed at the reduction of fossil fuel consumption to lower local atmospheric pollution levels can also, in some ways, reduce GHG emissions.