L???adeguamento del patrimonio infrastrutturale esistente

Il nostro Paese ha un'orografia complessa ed è caratterizzato da un sistema insediativo composto per lo più da città di medie dimensioni, da paesi e da borghi, formatosi in un territorio prealpino, appenninico, e comunque collinare come nelle Isole maggiori, tutti accomunati dalla presenza di emergenze storico-ambientali, testimonianza di una storia plurisecolare. A questo dato territoriale, corrisponde un patrimonio stradale costituito, solo nella misura del 4% (circa 7.000 km), da strade a carreggiate separate, assimilabili al tipo autostradale, e quindi prevalentemente composto da strade a carreggiata unica, appartenenti a differenti Enti ed Amministrazioni, spesso inadeguate in termini di sicurezza della circolazione

The Multi-Method Tool ‘PAST’ for Evaluating Cultural Routes in Historical Cities: Evidence from Cagliari, Italy

Thematic paths are a central aspect of urban policies for cultural heritage valorization. In fact, thematic paths are central spatial features for structuring the image of a historical landscape. Hence, this study proposes the cultural paths assessment tool (PAST) as a methodological framework for individuating a network of routes connecting cultural heritage components and for assessing their usefulness. Usefulness is herein defined as the potential of a street network to support the meaningful experience of a historical urban landscape. PAST combines space syntax techniques, a geographic information system, and a qualitative analysis within a multi-criteria analysis framework for addressing four aspects of connecting cultural heritage components, including: i) the individuation of relevant assets; ii) the identification of the sub-network of most central street segments; iii) the definition of the street network of thematic routes; iv) the assessment of the usefulness of thematic paths, according to the criteria of usability, imageability, and accessibility. The proposed methodology, applied to the historical district of Marina in the city of Cagliari in Italy, supports planning and design processes in two ways: 1) by identifying street segments and squares comprising a network of thematic routes; 2) by individuating high-leverage interventions for improving the usefulness of thematic routes. Consequently, the proposed study addresses the need to establish methodologies and analytic tools that support decision making processes for conserving, managing, and valorizing historic urban landscapes

Urea-containing topical formulations

Urea is a well-known moisturiser and keratolytic topical agent. As it is widely used in dermatology, several formulations at different concentrations have been marketed: lotions, creams, foams, ointments, gels and lacquers. Availability of different vehicles and concentration may vary in different countries, but in general products at low, medium and high urea concentration are accessible worldwide. The proper formulation should be chosen according to the disorder to treat, its severity, body areas involved and patients' preference

Smart city governance and children’s agency: an assessment of the green infrastructure impact on children’s activities in Cagliari (Italy) with the tool “Opportunities for Children in Urban Spaces (OCUS)"

The increases in urbanization, pollution, resource depletion, and climate change underline the need for urban planning policies that incorporate blue–green infrastructure (BGI) and ecosystem services. This paper proposes a framework for assessing BGI’s effect on children’s outdoor activities. This effect, called meaningful usefulness, is a central issue due to the influence of experiences with nature on children’s development and the global trend of concentration of children in urban areas. Based on the concept of affordance, the methodology formalizes meaningful usefulness in terms of an index of usefulness of individual settings (IUIS) and a synthetic index of usefulness of BGI in a specific area (ISGI). These are determined via an audit protocol, Opportunities for Children in Urban Spaces (OCUS), which incorporates a set of indicators measuring micro-scale properties of individual places and contextual macro-scale factors. The methodology is applied to BGI components in Cagliari, Sardinia, Italy, which was selected for its superior density of urban green spaces. The application of the OCUS tool confirms its usefulness for investigating functional affordances incorporated into the trans-scalar structures of BGIs. The analytic protocol further contributes to the implementation of urban planning strategies within the smart city paradigm

Expression of Tight Junction and Drug Efflux Transporter Proteins in an in vitro Model of Human Blood–Brain Barrier

Interendothelial cell tight junctions (TJs) proteins contribute to maintain the structural and functional integrity of the blood–brain barrier (BBB) and several efflux transporters regulate transport of compounds across BBB. A unique double compartment-model of the BBB, consisting of cerebral endothelial cells isolated from cryopreserved human glial tumors, alone and in the presence of human astroglial cells derived from the same tissue preparation was established. Endothelial cell viability and transendothelial electrical resistance (TEER) were measured in this model and three representative TJ proteins – occludin (OCLN), zonula occludens-1 (ZO-1) and claudin-5 (CLN-5) – as well as several drug efflux transporters – P-glycoprotein (P-gp), multidrug resistance protein-1 and 2 (MRP-1 and MRP-2), organic anion-transporting polypeptide-1 and 3 (oatp1 and oatp3) were analyzed at both the protein and gene transcript level. Functional activity of P-gp and MRP-1 was also assessed. Endothelial cell viability as well as TEER significantly increased in the presence of glial cells. A significant increase of expression of OCLN, ZO-1, and CLN-5 proteins as well as of several drug transporter proteins except oatp3 and MRP-1, was also found in the presence of glial cells. All the gene transcripts protein analyzed were found to be significantly increased in the presence of glial cells. A suitable functional activity of P-gp and MRP-1 was also found. These results demonstrate that this brain endothelium culture system mimics a physiologically relevant situation and may therefore provide a new tool for studying the effects of biological fluids such as serum and cerebrospinal fluid from patients with neurological disorders underlying a BBB alteration in disease pathogenesis

Orexin A-Mediated Modulation of Reproductive Activities in Testis of Normal and Cryptorchid Dogs: Possible Model for Studying Relationships Between Energy Metabolism and Reproductive Control

Orexin A (OxA) is a neuropeptide produced in the lateral hypothalamus that performs pleiotropic functions in different tissues, including involvement in energy homeostasis and reproductive neuroendocrine functions. The role of OxA is particularly important given the well-studied relationships between physiological mechanisms controlling energy balance and reproduction. The enzyme P450 aromatase (ARO) helps convert androgens to estrogens and has roles in steroidogenesis, spermatogenesis, and energy metabolism in several organs. The goal of this study was thus to investigate the role of OxA in ARO activity and the effects of this regulation on reproductive homeostasis in male gonads from healthy and cryptorchid dogs. The cryptorchidism is a specific condition characterized by altered reproductive and metabolic activities, the latter of which emerge from impaired glycolysis. OxA helps to stimulate testosterone (T) synthesis in the dog testis. We aimed to investigate OxA-mediated modulation of 17β-estradiol (17β-E) synthesis, ARO expression and metabolic indicators in testis of normal and cryptorchid dogs. Our results indicate putative effects of OxA on estrogen biosynthesis and ARO activity based on western blotting analysis and immunohistochemistry for ARO detection and in vitro tests. OxA triggered decrease in estrogen production and ARO activity inhibition; reduced ARO activity thus prevented the conversion of T to estrogens and increasing OxA-mediated synthesis of T. Furthermore, we characterized some metabolic and oxidative modulations in normal and cryptorchid dog's testis. The steroidogenic regulation by OxA and its modulation of ARO activity led us to hypothesize that OxA is a potential therapeutic target in pathological conditions associated with steroidogenic alterations and OxA possible involvement in metabolic processes in the male gonad

Anti-diabetic combination therapy with pioglitazone or glimepiride added to metformin on the AGE-RAGE axis: a randomized prospective study

Introduction: The ratio between advanced glycation end products (AGEs) and soluble form of receptor (s-RAGE) has been proposed as a risk marker for renal and cardiovascular diseases. The aim of this study was to evaluate in the diabetes condition the influence of two different oral anti-diabetic treatments on the AGE/ s-RAGE ratio, during a 5-year observation period. Methods: Seventy-three patients with type 2 diabetes mellitus were randomly assigned to a drug therapy with pioglitazone or glimepiride, combined to metformin. Each subject was evaluated at baseline and after 5 years of treatment. Results: In both groups s-RAGE levels did not significantly vary, while the levels of AGE and AGE/s-RAGE were both significantly reduced, basal compared to 5-year values. Within pioglitazone group, as well within glimepiride group, significant variations (D, as difference between 5 years of treatment minus basal) were observed for AGE (D= ˗21.1±13.4 μg/ml, P<0.001 for pioglitazone; D= ˗14.4±11.4 μg/ml, P<0.001 for glimepiride) and in AGE/s-RAGE (D= -0.037±0.022 μg/pg, P<0.001 for pioglitazone; D= -0.024±0.020μg/pg, P<0.001 for glimepiride), suggesting an average decrease of the parameters by more than 50% in both treatments. Pioglitazone was more effective than glimepiride in reducing AGE/s- RAGE ratio after 5 years of therapy. Conclusion: These data can help to explain the benefits of oral anti-diabetic therapy in relation to the reduction of cardiovascular risk, as suggested by variations in AGE/s-RAGE ratio as biochemical marker of endothelial function; in particular, treatment with pioglitazone seems to offer greater long-term benefit on AGE-RAGE axis

Palmitoylethanolamide modulates high-fat diet-shaped gut function and microbiota composition in obese mice

Introduction/Background & aims: Emerging data indicate a pivotal role for gut microbiota in the progression of obesity. Indeed, in the gut, high-fat diet (HFD) intake induces the loss of barrier integrity, causing the transfer of detrimental factors (i.e. lipopolysaccharide, LPS) into the systemic circulation, leading to metabolic dysfunctions and an overall state of low-grade inflammation, called “met- ainflammation” [1]. The metabolic and anti-inflammatory activities of palmitoylethanolamide (PEA), an endogenous lipid mediator, prompt us to evaluate its capability to improve intestinal homeostasis and shape gut microbiota composition altered in HFD-fed obese mice. Method/Summary of work: Male C57Bl/6 J mice received standard diet (STD) or HFD (n = 10 each group). After 12 weeks, a subgroup of HFD mice was treated with PEA (30 μg/kg/die per os) for 7 weeks. Body weight was monitored during the treatment and fat mass was evaluated at the end of experimental time. Systemic parameters and intestinal function were examined using ELISA assay, and Real-Time PCR analysis, respectively. Faecal microbiota was studied by per- forming 16S rDNA amplicon sequencing and linear discriminant analy- sis in order to obtain the operational taxonomic units (OTUs) defining the bacterial communities