Il VDS di Gerhard Rohlfs da visitare: una prima proposta per il vocabolario in 3-D

The Rohlfs’ VDS is known as a masterpiece among dialectal dictionaries, but it’s nevertheless true that a renovation of the opera seems to be necessary today. This research tries to renew Rohlfs’ opera, without distorting its substance, by the creation of two new versions of the vocabulary: a papery and a virtual one. The virtual version of VDS is realized with the use of ICT (Information and Communication Technologies). Thanks to the precious help of two designers, Chiara Destino and Daniele Rolli, the gamification is applied to the dialectal lexicon, that become tridimensional, alive and vivid. The project will transform the consultation of pages in a virtual journey among the words. The new papery version will see a different structure in the definition: a longer and deeper explanation will be completed with a photo, that will be very usefull for the youngest public. This is only the begin of a project that can be continued

Intravenously administered gene therapy for neuronopathic Gaucher disease

Gaucher disease is a lysosomal storage disorder caused by mutations in the GBA1 gene encoding the enzyme glucocerebrosidase (GCase). Deficiency of GCase causes the accumulation of its substrate glucosylceramide in both visceral organs and the brain. Enzyme replacement therapy is successfully used to ameliorate the visceral pathology, however there is no treatment available for the lethal neurodegeneration. This research focuses on Gaucher disease type II, the most acute neuronopathic form, in which the neuropathology results in death during early infancy. The aim of this project is to intravenously administer adeno-associated viral vector (AAV) based gene therapy to a GCase-deficient mouse model of acute neuronopathic Gaucher disease and assess improvement in lifespan, behaviour, brain and visceral pathology. The untreated Gba1 knock-out mice die 12-14 days after birth following severe neurodegeneration. The AAV vector carrying the functional human GBA1 gene under control of a ubiquitous promoter was intravenously administered to neonatal knock-out mice, with treated animals showing a significant increase in their lifespan (p=0.0081). Since the animals did not develop any evident pathological symptoms, they were sacrificed at 55 days of age for a short-term study. The neuropathology was ameliorated and several of the most affected areas of the brain were partially rescued. The analysis of liver, spleen, lung and heart tissues revealed promising improvements in the visceral pathology. A consequent long-term study was performed on 180-day-old treated mice, with the aim to compare intravenous and intracranial administration of the viral vector. In order to enhance the therapeutic effects of the treatment and improve gene expression in the central nervous system, a novel construct where the GBA1 gene is controlled by a neuron-specific promoter was administered to neonatal knock-out mice. The severe neurodegeneration was further rescued and the life span of treated animals increased. Together, these encouraging results demonstrate that gene therapy could provide an effective treatment for the neuronopathic form of Gaucher disease, for which therapeutic needs are currently unmet

Sinus rhythm restoration with electrical cardioversion: acute effect of shock configuration and subsequent modifications in peripheral flow and sleep.

Atrial fibrillation (AF) is a widespread arrhythmia, associated with higher risk of stroke, sleep disorders and dementia. In some conditions, electrical cardioversion (ECV) represents the best choice for rhythm control. Nowadays, there is a growing interest in developing new devices for screening and monitoring of AF patients. We aimed to improve acute efficacy of ECV procedure and to explore the feasibility of the use of new wearable devices for monitoring in candidates to AF ECV. We compared antero-apical pads vs antero-posterior patches approach for AF ECV, and we elaborated a decision algorithm to improve acute efficacy. After, we evaluated the feasibility of the use of new wearable devices for monitoring of candidates to AF ECV. In particular, we analysed the effect of AF ECV on heart rate variability and vascular age parameters derived from PPG signals registered with Empatica (CE 1876/MDD 93/42/EEC), and on EEG pattern registered with Neurosteer (Israel). From December 2005 to September 2019, 492 patients were enrolled. We evaluated acute efficacy of the two approaches for AF ECV and we elaborated a decision algorithm based on body surface area, weight, and height. The decision algorithm improved first shock efficacy (93.2% vs. 87.2%, p=0.025). From 1st November 2021 to 1st April 2022, 24 patients were enrolled in PPEEG-AF pilot study. Considering vascular age parameters, a significant reduction in TPR and a wave was observed (p<0.001). Considering sleep patterns, a tendency to higher coherence was observed in registrations acquired during AF, or considering signals registered for each patient independently from AF. The new decision algorithm improved acute efficacy and reduced costs associated with adhesive patches. Significant modifications were observed on vascular age parameters measured before and after ECV, and a possible AF effect on sleep pattern was noticed. More data are necessary to confirm these preliminary results

Wrist Photoplethysmography Signal Quality Assessment for Reliable Heart Rate Estimate and Morphological Analysis

Photoplethysmographic (PPG) signals are mainly employed for heart rate estimation but are also fascinating candidates in the search for cardiovascular biomarkers. However, their high susceptibility to motion artifacts can lower their morphological quality and, hence, affect the reliability of the extracted information. Low reliability is particularly relevant when signals are recorded in a real-world context, during daily life activities. We aim to develop two classifiers to identify PPG pulses suitable for heart rate estimation (Basic-quality classifier) and morphological analysis (High-quality classifier). We collected wrist PPG data from 31 participants over a 24 h period. We defined four activity ranges based on accelerometer data and randomly selected an equal number of PPG pulses from each range to train and test the classifiers. Independent raters labeled the pulses into three quality levels. Nineteen features, including nine novel features, were extracted from PPG pulses and accelerometer signals. We conducted ten-fold cross-validation on the training set (70%) to optimize hyperparameters of five machine learning algorithms and a neural network, and the remaining 30% was used to test the algorithms. Performances were evaluated using the full features and a reduced set, obtained downstream of feature selection methods. Best performances for both Basic- and High-quality classifiers were achieved using a Support Vector Machine (Acc: 0.96 and 0.97, respectively). Both classifiers outperformed comparable state-of-the-art classifiers. Implementing automatic signal quality assessment methods is essential to improve the reliability of PPG parameters and broaden their applicability in a real-world context

Cardiac resynchronization therapy in persistent left superior vena cava: Can you do it two-leads-only?

Cardiac resynchronization therapy in persistent left superior vena cava: Can you do it two-leads-only

Controlled assembly of metal colloids on dye-doped silica particles to tune the photophysical properties of organic molecules

The use of plasmonic nanomaterials is a challenging strategy to control radiation and radiation-induced processes at a nanometric scale. The localized surface plasmons of metal nanoparticles have been shown to affect the efficiency of a variety of radiative and non-radiative processes occurring in organic molecules. In this contribution, we present an overview of the results obtained through an original approach based on the hierarchical assembly of plasmonic gold colloids on silica templates, covalently doped with organic dyes. The detailed morphological characterization demonstrates the disposition of gold colloids on silica achieved through the tight control of the synthetic conditions. The studies carried out while gradually increasing the concentration of gold nanoparticles allow the detailed investigation of the effects of the progressive addition of plasmonic particles on the photophysical behaviour of organic molecules. In particular, the fluorescence behaviour of three dyes with different spectral properties, namely fluorescein, rhodamine B and 9-aminoacridine, are investigated in the presence of increasing concentrations of gold nanoparticles. In order to fix the distance between the dye and the gold nanoparticles, the dyes are anchored to silica nanoparticles, and the metal colloids are chemically adsorbed on the silica surface. The steady state and time-resolved data are analysed to evaluate the impact of plasmonic nanoparticles on the radiative and non-radiative processes of the dyes; the data provide evidence that the modulation of the fluorescence intensity (enhancement or quenching) can be achieved by changing the concentration of gold colloids. The plasmonic nanostructures can be employed to favour one deactivation process over the others. For example, we demonstrate that the photoinduced formation of reactive oxygen species (ROS) can be enhanced upon the plasmonic engineering of a photosensitizing agent (Protoporphyrin IX, PpIX). The Vis-excitation of silica-PpIX samples in the presence of gold nanoparticles results in a faster and more efficient photoinduced formation of ROS species either in solution or in a hydrogel. The ROS efficiency data and the fluorescence behaviour of PpIX in the presence of gold colloids suggest that the enhancement of the excitation field occurs through a plasmonic effect. For the application of the assembled hybrid materials, further advantages come from the development of photosensitizer-containing hydrogel films that are able to efficiently produce ROS upon visible excitation. Our preliminary results are herein reported and discussed

Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective

Mitochondrial diseases (MDs) are a group of severe genetic disorders caused by mutations in the nuclear or mitochondrial genome encoding proteins involved in the oxidative phosphorylation (OXPHOS) system. MDs have a wide range of symptoms, ranging from organ-specific to multisystemic dysfunctions, with different clinical outcomes. The lack of natural history information, the limits of currently available preclinical models, and the wide range of phenotypic presentations seen in MD patients have all hampered the development of effective therapies. The growing number of pre-clinical and clinical trials over the last decade has shown that gene therapy is a viable precision medicine option for treating MD. However, several obstacles must be overcome, including vector design, targeted tissue tropism and efficient delivery, transgene expression, and immunotoxicity. This manuscript offers a comprehensive overview of the state of the art of gene therapy in MD, addressing the main challenges, the most feasible solutions, and the future perspectives of the field

Microfluidic production of nanogels as alternative triple transfection reagents for the manufacture of adeno-associated virus vectors

Adeno-associated viral vectors (AAVs) have proved a mainstay in gene therapy, owing to their remarkable transduction efficiency and safety profile. Their production, however, remains challenging in terms of yield, the cost-effectiveness of manufacturing procedures and large-scale production. In this work, we present nanogels produced by microfluidics as a novel alternative to standard transfection reagents such as polyethylenimine-MAX (PEI-MAX) for the production of AAV vectors with comparable yields. Nanogels were formed at pDNA weight ratios of 1 : 1 : 2 and 1 : 1 : 3, of pAAV cis-plasmid, pDG9 capsid trans-plasmid and pHGTI helper plasmid respectively, where vector yields at a small scale showed no significant difference to those of PEI-MAX. Weight ratios of 1 : 1 : 2 showed overall higher titers than 1 : 1 : 3, where nanogels with nitrogen/phosphate ratios of 5 and 10 produced yields of ≈8.8 × 10^{8} vg mL^{-1} and ≈8.1 × 10^{8} vg mL^{-1} respectively compared to ≈1.1 × 10^{9} vg mL^{-1} for PEI-MAX. In larger scale production, optimised nanogels produced AAV at a titer of ≈7.4 × 10^{11} vg mL^{-1}, showing no statistical difference from that of PEI-MAX at ≈1.2 × 10^{12} vg mL^{-1}, indicating that equivalent titers can be achieved with easy-to-implement microfluidic technology at comparably lower costs than traditional reagents

The impact of particle radiotherapy on the functioning of cardiac implantable electronic devices: a systematic review of in vitro and in vivo studies according to PICO criteria

The number of oncological patients who may benefit from proton beam radiotherapy (PBT) or carbon ion radiotherapy (CIRT), overall referred to as particle radiotherapy (RT), is expected to strongly increase in the next future, as well as the number of cardiological patients requiring cardiac implantable electronic devices (CIEDs). The management of patients with a CIED requiring particle RT deserves peculiar attention compared to those undergoing conventional photon beam RT, mostly due to the potential generation of secondary neutrons by particle beams interactions. Current consensus documents recommend managing these patients as being at intermediate/high risk of RT-induced device malfunctioning regardless of the dose on the CIED and the beam delivery method used, despite the last one significantly affects secondary neutrons generation (very limited neutrons production with active scanning as opposed to the passive scattering technique). The key issues for the current review were expressed in four questions according to the Population, Intervention, Control, Outcome criteria. Three in vitro and five in vivo studies were included. Based on the available data, PBT and CIRT with active scanning have a limited potential to interfere with CIED that has only emerged from in vitro study so far, while a significant potential for neutron-related, not severe, CIED malfunctions (resets) was consistently reported in both clinical and in vitro studies with passive scattering

Risk factors for gram-negative bacterial infection of cardiovascular implantable electronic devices: Multicentre observational study (CarDINe Study)

Background: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. Methods: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. Results: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). Conclusions: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group