Rene policistico autosomico dominante: dalla patogenesi alla terapia

Autosomal Dominant Polycystic Kidney (ADPKD) is the most common genetically determined kidney disease of Mendelian inheritance. It has a variable prevalence, depending on the case series, from 1:1,000 to 1:2,500, and represents the fourth cause of renal failure in the world. It is part of the so-called ciliopathies and is mainly caused by the mutation of two genes: PKD1, located on chromosome 16p and the PKD2 gene, located on chromosome 4q and coding for Polycystin-2 (PC2); although two other disease-causing genes have recently been identified: DNAJB11 and GANAB. These two proteins consist, respectively, of a calcium channel and a transmembrane receptor, and they play a decisive role in regulating cell proliferation, division and differentiation, apoptosis and autophagy. The molecular mechanisms underlying the genesis of the cysts are multiple and for this reason not yet completely understood and although several of them have been the subject of preclinical and clinical studies aimed at evaluating the efficacy of therapies that could continue to interfere in a specific way, to date, only tolvaptan and octreotide-LAR (the latter only in Italy) have been approved for the treatment of renal disease secondaryto ADPKD. Here, we therefore recapitulate the different pathogenetic pathways in ADPKD and the possible therapeutic treatments

Flood propagation modelling with the Local Inertia Approximation: theoretical and numerical analysis of its physical limitations

Attention of the researchers has increased towards a simplification of the complete Shallow water Equations called the Local Inertia Approximation (LInA), which is obtained by neglecting the advection term in the momentum conservation equation. In the present paper it is demonstrated that a shock is always developed at moving wetting-drying frontiers, and this justifies the study of the Riemann problem on even and uneven beds. In particular, the general exact solution for the Riemann problem on horizontal frictionless bed is given, together with the exact solution of the non-breaking wave propagating on horizontal bed with friction, while some example solution is given for the Riemann problem on discontinuous bed. From this analysis, it follows that drying of the wet bed is forbidden in the LInA model, and that there are initial conditions for which the Riemann problem has no solution on smoothly varying bed. In addition, propagation of the flood on discontinuous sloping bed is impossible if the bed drops height have the same order of magnitude of the moving-frontier shock height. Finally, it is found that the conservation of the mechanical energy is violated. It is evident that all these findings pose a severe limit to the application of the model. The numerical analysis has proven that LInA numerical models may produce numerical solutions, which are unreliable because of mere algorithmic nature, also in the case that the LInA mathematical solutions do not exist. The applicability limits of the LInA model are discouragingly severe, even if the bed elevation varies continuously. More important, the non-existence of the LInA solution in the case of discontinuous topography and the non-existence of receding fronts radically question the viability of the LInA model in realistic cases. It is evident that classic SWE models should be preferred in the majority of the practical applications

Measurement of Sea Waves

Sea waves constitute a natural phenomenon with a great impact on human activities, and their monitoring is essential for meteorology, coastal safety, navigation, and renewable energy from the sea. Therefore, the main measurement techniques for their monitoring are here reviewed, including buoys, satellite observation, coastal radars, shipboard observation, and microseism analysis. For each technique, the measurement principle is briefly recalled, the degree of development is outlined, and trends are prospected. The complementarity of such techniques is also highlighted, and the need for further integration in local and global networks is stressed

Therapeutic apheresis in peripheral and retinal circulatory disorders

In microcirculation disorders, the therapeutic apheresis seems to have two different effects. The first, achieved after only a few sessions, is acute, consisting of drastic reduction of blood viscosity and obtained with the use of low-density lipoprotein (LDL) apheresis, rheopheresis, or fibrinogen apheresis. The second effect is long term, or chronic, and needs to be evaluated after a long course of treatment. The mechanisms underlying the chronic effect are still objects of debate and take into account the pleiotropic effects of apheresis. However, it is likely that the acute effect of apheresis mainly influences the functional components of the vascular damage, and so the derived rheological benefit might last only for a short period. The chronic effect, on the contrary, by acting on the morphological alterations of the vascular walls, requires the apheresis treatment to be prolonged for a longer period or even cycles of treatment to be programmed

A New Orbiting Deployable System for Small Satellite Observations for Ecology and Earth Observation

In this paper, we present several study cases focused on marine, oceanographic, and atmospheric environments, which would greatly benefit from the use of a deployable system for small satellite observations. As opposed to the large standard ones, small satellites have become an effective and affordable alternative access to space, owing to their lower costs, innovative design and technology, and higher revisiting times, when launched in a constellation configuration. One of the biggest challenges is created by the small satellite instrumentation working in the visible (VIS), infrared (IR), and microwave (MW) spectral ranges, for which the resolution of the acquired data depends on the physical dimension of the telescope and the antenna collecting the signal. In this respect, a deployable payload, fitting the limited size and mass imposed by the small satellite architecture, once unfolded in space, can reach performances similar to those of larger satellites. In this study, we show how ecology and Earth Observations can benefit from data acquired by small satellites, and how they can be further improved thanks to deployable payloads. We focus on DORA—Deployable Optics for Remote sensing Applications—in the VIS to TIR spectral range, and on a planned application in the MW spectral range, and we carry out a radiometric analysis to verify its performances for Earth Observation studies

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Preliminary aerothermal design of axial compressors

This dissertation documents a compressor preliminary design study conducted by the author in fulfilment of his MSc thesis requirements. The compressor is intended for a new development engine within the 20Klbf thrust category, planned to be used on a short-haul aircraft, namely the ERJ-190. A market research suggests that there exists a definite opportunity for a commercially profitable engine within this thrust class. Furthermore, the proposed new engine is projected to outperform current production engines on critical issues such as fuel efficiency and operability. By and large, the objectives of this work have been achieved and a compressor design and layout is suggested, which matched or exceeded all the initial requirements. The quality of the results from this study are thought to be of sufficient detail to allow a further, more detailed development study to resolve some subtle pending issues. It is expected that, some compressor stages may have to be altered slightly during detailed design to augment their performance and ease of manufacture and assembly. Throughout this study, the importance of the compressor design figure of merits, pertaining to a short haul engine, has been outlined and their interaction on the design process is well documented. Furthermore, some rather unorthodox objectives such as compressor performance retention and reliability have been discussed. The author approached these subjects in an innovative way due to the limited non-proprietary knowledge available on these issues, especially considering their implications within preliminary design. Furthermore, the author developed and tested a new preliminary turbomachinery design code, named Turbodev, which can be used as an aid in future compressor design endeveours. Turbodev can handle most types of compressor layouts and generates an overall aerodynamic assessment of the turbomachinery performance. In conclusion; this documentation and the associated literature review aim to provide the reader with an overview of the work done and yield a better understanding of the decisions that face any design bureau when developing a new or modified engine component.The research work disclosed in this publication is partially funded by the Strategic Educational Pathways Scholarship Scheme (Malta). The scholarship is part-financed by the European Union – European Social Fund under Programme II – Cohesion Policy 2007-2013

Insufficienza renale gestione della uremia e della terapia sostitutiva

Replacement therapy implemented by renal transplantation is preferable to dialysis treatment and also in uremic population with ADPKD. In preparation for the transplant nephrectomy is a procedure associated with morbidity and mortality in patient with ADPKD, it should be performed on the basis of stringent clinical indications. When the kidney transplant is not possible, peritoneal dialysis in appropriate patients is not contraindicated with comparable results to the extracorporeal dialytic treatment. The therapeutic targets in substitution treatment with respect to pressure levels, lipids, hemoglobin, anticoagulation regime are comparable to the non ADPKD uremic population