Spontaneous intracranial hypotension : two steroid-responsive cases

Purpose: Spontaneous intracranial hypotension (SIH) is characterised by orthostatic headache, low cerebrospinal fluid pressure and diffuse pachymeningeal enhancement after intravenous gadolinium contrast administration. Magnetic resonance imaging (MRI) often plays a crucial role for correct diagnosis. Case description: We described two similar cases of SIH, whose clinical and imaging features are typical for this pathology. At MRI brain scan, both patients showed diffuse and intense pachymeningeal enhancement and moderate venous distension and epidural vein engorgement. The two patients were treated with bed rest and oral steroid therapy, with complete and long-lasting symptomatic relief. Conclusions: Orthostatic nature of headache is the most indicative clinical feature suggesting SIH; contrast-enhanced MRI provides definite imaging diagnostic findings. Conservative treatment coupled to steroid therapy is often sufficient to obtain complete disappearance of symptoms

Supporting ECO-innovation in SMEs by TRIZ Eco-guidelines

An Eco-Design methodology based on two abridged Life Cycle Assessment tools (eVerdEE [1] developed by ENEA [2] and the French Standard NF 01-005) plus TRIZ [3] Eco-guidelines is presented. This method is one of the outputs of the European project REMake [4] (started September 2009 ended December 2012), which had the goal of developing and testing new approaches for eco-innovation, recycling and material consumption for manufacturing small and medium sized enterprises (SMEs). The number of SMEs involved in the project has been around 250, in six countries. The proposed method consists of a preliminary scanning of a given product or process in order to disclose all the material involved and the energy flows, and to assess their environmental impact by means of a simplified Life Cycle Assessment (LCA) approach and the related indexes. The "hot spots" of the product or process are then identified by adding a brand new index called "IFR (Ideal Final Result) index", conceived from the TRIZ "Ideal System" concept [5], to classical LCA criteria. Once the hot points are identified, a set of over 300 TRIZ based eco-design guidelines [6,7] are selectively introduced to develop design variants to the given system with the aim of providing a lower global environmental impact. An in-depth explanation about ECO guideline implementation is given, together with a case study concerning a manufacturer of machine tools

Venice as a short-term city. Between global trends and local lock-ins

This paper examines the ongoing transition of Venice towards a short-term city, posited as an urban form which accommodates the dwelling practices of temporary populations as tourists, at the expenses of a stable resident population. This shift is approached through the conceptual framework of resilience, which is also explored in its political and discursive dimensions. At the base of the emergence of a short-term city, we analyse the redistributive impacts of short-term rentals mediated by digital platforms and their influence on the housing market, but also the related entrenchments of a local policy agenda supporting the resilience of the industry itself above that of the city as a living organism. After illustrating the development of the hospitality sector in the city fabric over the last four decades and presenting the historical challenges that Venice has been facing in regard to its capacity to retain a stable population, we seek to unravel the debate on ‘the future of Venice’, which confronts local and global agents defending a ‘conservationist’ approach for Venice as an ineluctably tourist city, with social actors who claim for the defence of residence – and therefore for a ban on STR – as a necessary condition for a socially resilient alternative

Hepatitis C virus related cirrhosis decreased as indication to liver transplantation since the introduction of direct-acting antivirals: A single-center study

AIM: To evaluate waiting list (WL) registration and liver transplantation (LT) rates in patients with hepatitis C virus (HCV)-related cirrhosis since the introduction of direct-acting antivirals (DAAs). METHODS: All adult patients with cirrhosis listed for LT at Padua University Hospital between 2006-2017 were retrospectively collected using a prospectively-updated database; patients with HCV-related cirrhosis were divided by indication for LT [dec-HCV vs HCV/ hepatocellular carcinoma (HCC)] and into two interval times (2006-2013 and 2014-2017) according to the introduction of DAAs. For each patient, indications to LT, severity of liver dysfunction and the outcome in the WL were assessed and compared between the two different time periods. For patients receiving DAA-based regimens, the achievement of viral eradication and the outcome were also evaluated. RESULTS: One thousand one hundred and ninty-four [male (M)/female (F): 925/269] patients were included. Considering the whole cohort, HCV-related cirrhosis was the main etiology at the time of WL registration (490/1194 patients, 41%). HCV-related cirrhosis significantly decreased as indication to WL registration after DAA introduction (from 43.3% in 2006-2013 to 37.2% in 2014-2017, P = 0.05), especially amongst dec-HCV (from 24.2% in 2006-2013 to 15.9% in 2014-2017, P = 0.007). Even HCV remained the most common indication to LT over time (289/666, 43.4%), there was a trend towards a decrease after DAAs introduction (from 46.3% in 2006-2013 to 39% in 2014-2017, P = 0.06). HCV patients (M/F: 43/11, mean age: 57.7 \ub1 8 years) who achieved viral eradication in the WL had better transplant-free survival (log-rank test P = 0.02) and delisting rate (P = 0.002) than untreated HCV patients. CONCLUSION: Introduction of DAAs significantly reduced WL registrations for HCV related cirrhosis, especially in the setting of decompensated cirrhosis

STUDY OF THE MECHANISMS OF DRUG PASSAGE THROUGH BIOLOGICAL BARRIERS AIMED TO OPTIMIZE BIOAVAILABILITY AND/OR BLOOD-BRAIN BARRIER PERMEATION

Phospholipophilicity, i.e. the affinity of a drug for phospholipids, is one of the key features modulating pharmacokinetics. It would be desirable to assess it in the early stages of pharmaceutical drug development. The fastest method to achieve phospholipophilicity measures is liquid chromatography performed on stationary phases functionalized with phospholipid analogues, so called Immobilized Artificial Membrane (IAM). The logarithms of the chromatographic retention coefficients of drugs, measured or extrapolated to 100% aqueous phase on such stationary phases (log kwIAM), are often used to surrogate drug membrane passage data measured in vivo or in situ. Indeed, the research group I worked with proposed a novel method to unravel the total drug/phospholipid interaction forces in a lipophilic/hydrophobic component, mainly described by the n-octanol/water lipophilicity, possibly acting as a “driving force” in membrane barrier passage, and a polar/electrostatic one, possibly acting instead as a “trapping force”. The latter is parameterized by ∆log kwIAM, a novel physico-chemical parameter proposed by the research team I worked with. It is the difference between phospholipophilicity values determined by IAM-HPLC (log kwIAM) and the values expected on the basis of n-octanol/water lipophilicity of the neutral forms of the analytes (log PN). The rationale of this parameter arises from the fact that log kwIAM values of structurally non-related neutral compounds having polar surface area (PSA) equal to zero relate unambiguously with n-octanol lipophilicity values by highly significant direct linear relationships (r2 0.96) in a log P range 1.15-4.80; in contrast, such relationships are no longer observed for analytes having PSA greater than 0 and, in larger extent, for ionizable analytes. In fact, for instance, poorly and medially lipophilic bases, ionized at the experimental conditions, show an IAM chromatographic retention higher than that of neutral isolipophilic compounds. Such peculiar behavior was referred to the occurrence of an extra interaction component, mainly of electrostatic nature, actually taking place in drug-phospholipid interaction. ∆log kwIAM was found as a suitable descriptor of the drug/biomembrane polar/electrostatic interaction component. This component was demonstrated as related by highly significant inverse linear relationships to Blood-Brain Barrier (BBB) penetration data (log BB). For the BBB passage of acidic compounds, it was necessary to magnify the electrostatic interaction component by calculating it taking into account log D7.4 rather than log PN so yielding ∆’log kwIAM values. In this Ph.D. thesis, a study has been performed for (a) the elucidation of the molecular mechanisms actually involved in drug/biomembrane interactions (b) verifying the soundness of ∆log kwIAM in predicting different data of passive drug uptake either measured in vivo or in vitro (c) the improvement of the throughput of the technique so as to offer to the pharmaceutical companies an high-throughput screening method to evaluate new drug candidates. The relationships between data of BBB penetration (log BB) and ∆log kwIAM reported in recent works were based on a limited dataset (n= 21). As a consequence, the first part of the present research was focused on validating the proposed model on an enlarged dataset. Therefore, further 21 analytes, whose log BB values were known and taken from a single bibliographic source, were taken into account and their chromatographic retention coefficients were determined on two different stationary phases, i.e. IAM.PC.MG and IAM.PC.DD2. A good relationship between log BB and log PN values could be observed after the exclusion of two data points (chlorambucil and domperidone), but fairly good and highly significant inverse linear relationships were observed between log BB and ∆log kwIAM.MG (r2 = 0.681) and ∆log kwIAM.DD2 (r2 = 0.825), respectively, for the all the analytes. The results from our previous work were then assembled with the newly determined values in a single doubled dataset (n = 42) to verify the model proposed; again remarkably significant linear inverse relationships were achieved when plotting log BB values vs either ∆log kwIAM.MG (r2 = 0.738) or ∆log kwIAM.DD2 (r2 = 0.826), with only two points (haloperidol and chlorpromazine) behaving as outliers. Subsequently, starting from the observation according to which membrane passive diffusion of analytes has been suggested to be a universal process, regardless the different composition or function of the biological barrier involved, possible relationships between delta values and intestinal absorption data as measured by the in situ LOC-I-GUT perfusion technique were for the first time investigated. For this second part of this research activity, 15 structurally unrelated analytes, known to be passively absorbed at intestinal level, were taken into account and their IAM chromatographic retention coefficients were determined. Although moderate linear direct relationships between intestinal absorption data and log P values were found, again much more significant relationships were obtained by plotting intestinal absorption data vs ∆log kwIAM.MG (r2 = 0.803) and ∆log kwIAM.DD2 (r2 = 0.784). However, these results, albeit really encouraging, were based on a limited dataset. However, this model had to be validated by taking into account a larger number of biological data, and this opportunity was provided by permeation data achieved on cultured cells model, such as Caco-2 and MDCK cultured cells. Indeed, Caco-2 and MDCK permeation assays, for the morphological similarity of cellular monolayers employed to the intestinal epithelium, are claimed as mirroring rather closely drug intestinal absorption. However, in such assays the in vitro apparent permeability values, log Papp, i.e. the crude permeation data, can be separated into four contributions i) aqueous boundary layer (represented by the accessible intestinal surface area - PABL), ii) filter-determined permeability related to the polycarbonate porous support of the cultured cells (Pf), transcellular permeability (PC), and paracellular permeability (Ppara). The role played by these contributions markedly differs between in vitro and in vivo systems. Therefore, the investigation was carried out employing two datasets: the first one consisting of 38 compounds whose crude Caco-2 permeation data, log Papp, were reported in the literature; the second one consisting of 47 compounds whose Caco-2/MDCK permeation data were corrected to express the sole transcellular intrinsic permeability of the drugs, log P0Caco-2/MDCK. As to the the first dataset, log Papp values were found as related to the apparent lipophilicity of the analytes measured at pH 7.4 (log D7.4) by a parabolic trend, and reasonable relationships between log Papp and delta values were only visible selecting the analytes heavier than 300 Da. Indeed, for these compounds, the occurrence of paracellular passage mechanisms can be reasonably excluded. On the other hand, when taking into account the second dataset, highly significant inverse linear relationships between log P0Caco-2/MDCK and ∆log kwIAM.MG (r2 = 0.765) and ∆log kwIAM.DD2 (r2 = 0.806) were achieved. Indeed, log P0Caco-2/MDCK express the sole transcellular intrinsic permeability. The last part of this Ph.D. project was devoted to the improvement of throughput technique so as to appeal pharmaceutical companies, too. The first strategy applied was the development and validation of partial-least-squares (PLS) based statistic models, starting from molecular descriptors calculated in silico aimed at predicting phospholipophilicity data measured on IAM stationary phases. This led to the development of two mathematical models able to predict phospholipophilicity as measured on IAM.PC.MG and IAM.PC.DD2, with an accuracy of 75% and 79%, respectively. These results allow a rapid and reliable in silico prediction of delta log kwIAM values suitable for accurate estimates of the intestinal absorption/BBB entering potential of new leads or hypothetical molecules. In parallel, the conditions of the analytical methods were optimized to gain experimental values in a reasonably short time. The coupling of the LC system to an Electrospray Ionization Source (ESI) – Time of Flight (TOF) mass spectrometer detector allowed to analyze the compounds of interest simultaneously in mixtures of up to 10 compounds at the same time thanks to the higher selectivity of m/z ratio. This approach resulted in the development of an MS analytical method 100 times faster than the one traditionally employed in this sort of determinations

PLASTIC MATERIALS IN EUROPEAN AGRICULTURE: ACTUAL USE AND PERSPECTIVES

The world consumption of plastics in agriculture amounts yearly to 6.5 million tons. In addition to conventional polymers used in agriculture for greenhouses and mulches such as PE, PVC, EVA, photo-selective and luminescent polymers have been used, in order to improve the quality of crops. For the same reason plastic nets are used mainly in countries with tropical and Mediterranean climates. For an environmentally friendly agricultural activity, an alternative strategy can be represented by bio-based agricultural raw materials. For low environmental impact applications, biodegradable materials for agricultural films are nowadays produced. An overview of the main methods for the disposal and recycling of plastic materials are presented with the results of mechanical and radiometric tests on recycled plastics. The strategies to reduce the burden of plastics in agriculture are: a correct procedure for the collection, disposal and recycling of post-consumption plastics; the increase of lifetime duration and performance; and the introduction and promotion of bio-based materials

Multi-scale analysis on soil improved by alkali activated fly ashes

The development of soil treatment techniques using alkali-activated binders is a relevant issue since the increasing interest into the use of new binders as an alternative solution for geotechnical engineering applications, such as soil improvement. Alkali activated binders are formed by alkaline activation of an aluminosilicate source, containing precursor materials like fly ash, silica fume, steel sludge, which chemically react with an alkaline solution (i.e. sodium hydroxide, sodium silicate) forming a three-dimensional aluminosilicate gel with cementitious properties (Duxon et al. 2007, Provis and van Deventer 2014, Davidovits 1991, Xu and van Deventer 2000, Shi et al. 2006). Recycling of waste materials such as by-product from industrial process to synthesize a new binder favors a closed loop of material use, which minimizes the generation of waste and reduces the costs of production. Alkali activated binders represent a viable sustainable alternative to the use of ordinary binders for soil improvement (Vitale et al. 2017a; Vitale et al. 2017b). In the present study, an insight into the mechanical improvement induced by alkali-activated binders based on the activation of two different type of fly ashes on a clayey soil has been presented. An experimental multiscale analysis on chemo-physical evolution of the systems and its influence on microstructural features of treated soil has been developed highlighting the link between alkaline activation processes and macroscopic evolution of soil properties. Mechanical tests have been performed and interpreted taking into account the chemo-physical evolution of alkali activated fly ashes. Effects of binder content and curing time have been also considered. Addition of alkali-activated binders increases shear strength of the treated samples since the very short term. A reduction of compressibility and an increase of yield stress of treated samples have been also detected, whose extent depends on the curing time and on the binder content. Macroscopic behaviour of treated soil has been linked to the experimental evidences at microscale. Mineralogical and fabric changes induced by alkali-activated binders have been monitored over time by means of X ray diffraction (XRD), thermogravimetric analysis, 29Si NMR spectroscopy and Mercury Intrusion Porosimetry (MIP). Test results showed a high reactivity of alkali activated fly ashes as alumino-silicate source promoting precipitation of new mineralogical phase forming chains and networks with cementitious properties, responsible of the mechanical improvement of the treated soil. The efficiency of treatment has been also highlighted by comparing the mechanical performance induced by alkali-activated binder with the one promoted by ordinary Portland cement. Duxon P., Fernàndez-Jiménez A., Provis J.L., Lukey G.C., Palomo A., van Deventer J.S.J (2007). Geopolymer Technology: The Current State of the Art. Journal of Materials Science 42, 9, 2917-2933. Provis J.L., van Deventer J.S.J (2014). eds. Alkali Activated Materials. Vol.13. RILEM State of the Art Reports. Dordrecht: Springer Netherlands. Davidovits J. (1991). Geopolymers: inorganic polymeric new materials. J Therm Anal, 37,1633-1656. Xu H., van Deventer J.S.J. (2000). The geopolymerisation of alumina-silicate minerals. Int J Miner Process, 59, 247-266. Shi C., Krivenko P.V., Roy D.M. (2006). Alkali-activated Cements and Concretes. Abington, UK, Taylor and Francis. Vitale E., Coudert E., Deneele D., Paris M., Russo G. (2017a). Multiscale analysis on a kaolin improved by an alkali-activated binder. Proceedings of the 2nd Symposium on Coupled Phenomena in Environmental Geotechnics (CPEG2), Leeds, UK. Vitale E., Russo G., Dell’Agli G., Ferone C., Bartolomeo C. (2017b). Mechanical behaviour of soil improved by alkali activated binders. Environments, 4, 80, doi:10.3390/environments4040080

Lessening stress and anxiety-related behaviors by means of AI-driven drones for aromatherapy

Stress and anxiety are part of the human mental process which is often unavoidably yield by circumstances and situations such as waiting for a flight at the airport gate, hanging around before an exam,or while in an hospital waiting room. In this work we devise a decision system for a robotic aroma diffusion device designed to lessen stress and anxiety-related behaviors. The robot is intended as designed for deployments in closed environments that resembles the aspect and structure of a waiting room with different chairs where people sit and wait. The robot can be remotely driven by means of an artificial intelligence based on Radial Basis Function Neural Networks classifiers. The latter is responsible to recognize when stress or anxiety levels are arising so that the diffusion of specific aromas could relax the bystanders. We make use of thermal images to infer the level of stress by means of an ad hoc feature extraction approach. The system is prone to future improvements such as the refinement of the classification process also by means of ac-curate psychometric studies that could be based on standardized tests or derivatives

Liver transplantation for viral hepatitis in 2015

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release

First hypothesis for optimized monitoring strategy through ambient vibrations in historic buildings

Dynamic identification strategies and, in particular, Operational Modal Analysis (OMA) approaches demonstrated to be a significant source of information about the condition of an investigated building, as well as, repeated data acquisitions and processing methods, developed in the field of Structural Health Monitoring (SHM), have been successfully used to track the evolution of this condition over time. Nonetheless, planning a cost-effective ambient vibration monitoring campaign is still an open challenge as several uncertainties must be considered to ensure a beneficial trade-off between number of sensors or set-ups and quality of the information collected. This is particularly important when dealing with historical masonry buildings. The present work discusses the preliminary results of a project, currently under development, whose aim is the definition of optimised protocols for data acquisition and processing for built cultural heritage dynamic identification and monitoring, with specific focus on the Venetian palace typology.FCT - Fundação para a Ciência e a Tecnologia(UIDB/04029/2020