Le Dislipidemie Genetiche. Il Progetto LIPIGEN

Le Dislipidemie genetiche rappresentano un gruppo di patologie dell\u2019Adulto e pediatriche che interessano nel nostro paese un numero considerevole di individui. Alcune di esse come le Ipercolesterolemie determinano un elevatissimo rischio cardiovascolare. Altre si associano a presentazioni cliniche polimorfe, specie in et\ue0 pediatrica. Una proporzione rilevante di pazienti non viene diagnosticato e per la stragrande maggioranza di soggetti affetti da una di queste forme la diagnosi genetico-molecolare non \ue8 sempre disponibile. Allo scopo di risolvere tali criticit\ue0, la SISA si \ue8 fatta promotore del progetto LIPIGEN, un network strutturato per la gestione clinica e di laboratorio delle Dislipidemie Genetiche

Evaluating the impact of intracortical microstimulation on distant cortical brain regions for neuroprosthetic applications

Enhancing functional motor recovery after localized brain injury is a widely recognized priority in healthcare as disorders of the nervous system that cause motor impairment, such as stroke, are among the most common causes of adult-onset disability. Restoring physiological function in a dysfunctional brain to improve quality of life is a primary challenge in scientific and clinical research and could be driven by innovative therapeutic approaches. Recently, techniques using brain stimulation methodologies have been employed to promote post-injury neuroplasticity for the restitution of motor function. One type of closed-loop stimulation, i.e., activity-dependent stimulation (ADS), has been shown to modify existing functional connectivity within either healthy or injured cerebral cortices and used to increase behavioral recovery following cortical injury. The aim of this PhD thesis is to characterize the electrophysiological correlates of such behavioral recovery in both healthy and injured cortical networks using in vivo animal models. We tested the ability of two different intracortical micro-stimulation protocols, i.e., ADS and its randomized open-loop version (RS), to potentiate cortico-cortical connections between two distant cortical locations in both anaesthetized and awake behaving rats. Thus, this dissertation has the following three main goals: 1) to investigate the ability of ADS to induce changes in intra-cortical activity in healthy anesthetized rats, 2) to characterize the electrophysiological signs of brain injury and evaluate the capability of ADS to promote electrophysiological changes in the damaged network, and 3) to investigate the long-term effects of stimulation by repeating the treatment for 21 consecutive days in healthy awake behaving animals. The results of this study indicate that closed-loop activity-dependent stimulation induced greater changes than open-loop random stimulation, further strengthening the idea that Hebbian-inspired protocols might potentiate cortico-cortical connections between distant brain areas. The implications of these results have the potential to lead to novel treatments for various neurological diseases and disorders and inspire new neurorehabilitation therapies

Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum.

Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5th percentile of the distribution in the population. HBL are defined as primary or secondary according to the underlying causes. Primary monogenic HBL are caused by mutations in several known genes (APOB, PCSK9, MTP, SARA2) or mutations in genes not yet identified. Familial hypobetalipoproteinemia (FHBL) is the most frequent monogenic form of HBL with a dominant mode of inheritance. It may be due to loss-of-function mutations in APOB or, less frequently, in PCSK9 genes. The rare recessive forms of primary monogenic HBL are represented by abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) due to mutations in MTP and SARA2 genes, respectively. The clinical phenotype of heterozygous FHBL is usually mild, being frequently characterized by fatty liver. The clinical phenotype of homozygous FHBL, ABL, and CMRD is usually severe being characterized by intestinal lipid malabsorption and fat-soluble vitamin deficiency. Secondary HBL are due to several nongenetic factors such as diet, drugs, and disease-related conditions. The aim of this review is to discuss the biochemistry, genetics, and clinical spectrum of HBL and to provide a clinical and laboratory diagnostic algorithm

Infinitely many weak solutions for a mixed boundary value system with (p_1,…,p_m)-Laplacian

The aim of this paper is to prove the existence of infinitely many weak solutions for a mixed boundary value system with (p_1,\cdots,p_m)-Laplacian. The approach is based on variational methods

Synthesis of H2 in dirty ice mantles by fast ion energy loss: New experimental results increase the relevance of this mechanism

Recent experimental results support the importance of H2 production in molecular clouds by cosmic ray bombardment of the mantles of grains. The formation of molecules different from those originally present in the irradiated layer can be explained by the production of molecular fragments induced by the release of energy if the impinging fast particle. One way of considering the process is in terms of a transiently hot cylinder, initially about 50 A in diameter, that exists around the track of an individual fast ion. Since ice has a relatively low thermal conductivity, energy lost by the ion in the ice layers remains confined around the track for time long enough to be thermalized. The hot cylinder increases in diameter and decreases in temperature on a time scale of 10(exp -11) to 10(exp -10) sec. Molecular fragments that are formed in this high temperature region acquire enough mobility to recombine with different partners, forming new molecules. A Monte Carlo simulation of the interaction between cosmic rays and grain mantles, at various depths in the core of a spherical molecular cloud, was performed. The simulation was continued until 40,000 ions had hit each grain of the type and size chosen. During the performed experiments thin icy films made of H2O and CD4 mixed in the gas phase and deposited on a cold finger at 9 K were irradiated with 1.5 MeV helium beams. Among synthesized molecules were found H2, HD, and D2

Clinical experience of lomitapide therapy in patients with homozygous familial hypercholesterolaemia

The microsomal triglyceride transfer protein (MTP) inhibitor lomitapide is a licenced adjunct to a low-fat diet and other lipid-lowering medication, with or without low-density lipoprotein apheresis, for the treatment of adults with homozygous familial hypercholesterolaemia (HoFH). In a recently published phase 3 study, patients with HoFH received lomitapide in addition to maximally tolerated lipid-lowering therapy. Treatment with lomitapide resulted in a mean approximate 50% reduction in LDL-C levels after 26 weeks compared with baseline levels (p < 0.0001). This decrease in LDL-C was maintained at Weeks 56 and 78 (44% [p < 0.0001] and 38% [p = 0.0001], respectively). This paper offers clinical perspectives based on selected case histories of patients participating in the phase 3 lomitapide study. These cases provide illustrative examples of the efficacy of lomitapide, with or without apheresis, and show that the effective management of adverse effects can enable patients to remain on effective treatment

An Iconic Framework for Learning the Art of Programming

The integration of programming teachings, in all levels of education, highlights the need to acquire the art of programming for each individual student through versatile tools based on specific cognitive methods. Diversified linguistic metaphors have to be adopted by the developing frame, in order to highlight the qualities of each student. Therefore, a framework, oriented to learning the art of programming, must foster polychrome constructs representations, a number of data structures and an intuitive interfaces in order to make easier to understand the evolution of the algorithm that have to be developed. The following contribution will present a theoretical formalization of a framework for teaching and learning the art of programming and therefore its development will propose as a graph-based execution and iconic modular interfaces on the methodologies to be developed