Validation of a test for the physical performance evaluation of elderly and diseased subjects

In questo lavoro di tesi è stato validato un test sottomassimale per la valutazione funzionale di soggetti con prestazioni fisiche limitate (anziani e pazienti con malattie cardiovascolari), anche inseriti in programmi riabilitativi. Il "test of performance" (TOP) è di facile esecuzione, rappresenta un'alternativa al "test cardiopolmonare", molto più complesso, e prevede lo sviluppo di strumentazione e algoritmi di valutazione specifici. Nella modalità più semplice viene registrato il solo segnale elettrocardiografico (ECG) durante una prova da sforzo a basso carico, eseguita secondo un protocollo che prevede la suddivisione del test in due fasi. Nella prima fase si svolge il "tilt test" in cui il paziente passa dal clinostatismo all'ortostatismo, per valutare la funzionalità del sistema nervoso autonomo. Nella seconda fase il paziente esegue il test da sforzo sul cicloergometro a due carichi di lavoro diversi, inizialmente un carico lieve e poi uno moderato. Il test è basato sull'analisi delle modalità di adeguamento elettrocardiografico ai diversi livelli di sforzo e nella fase di recupero. Il segnale acquisito durante il tilt test è analizzato utilizzando metodi che quantificano la variabilità della frequenza cardiaca (HRV), che permette di valutare il bilanciamento tra l'attività del sistema vagale e del sistema simpatico. L'analisi HRV viene eseguita nel dominio del tempo, e nel dominio della frequenza. Il segnale elettrocardiografico rilevato durante la successiva fase a carico crescente, viene analizzato valutando le modalità di adeguamento della frequenza cardiaca sia per i cambiamenti sia per le stabilizzazioni. Particolare attenzione viene data all'analisi della fase adattativa al diverso carico e alla fase di recupero dopo lo sforzo. Da queste analisi, mediate confronto tra diverse classi di pazienti, si ritiene di potere ottenere parametri quantitativi di efficienza funzionale

Analisi e confronto di sequenze di DNA mediante modelli Markoviani

Lo scopo di questa tesi è quello di evidenziare, attraverso varie analisi statistiche ed applicazione di modelli stocastici, il comportamento strutturale e funzionale dei dinucleotidi che compongono le sequenze di DNA di diversi organismi. Gli organismi che abbiamo scelto di prendere in considerazione sono l'uomo, il topo e l'Escherichia coli. Questa scelta non è stata casuale, ma oculata, al fine di mettere in risalto alcune differenze tra organismi eucarioti, quali l'uomo e il topo, ed organismi procarioti come il batterio E.coli. Nella prima parte del nostro studio, abbiamo computato le distanze che intercorrono tra occorrenze successive dello stesso dinucleotide lungo la sequenza, usando un metodo di non sovrapposizione, ed abbiamo iterato il calcolo per tutti i 16 dinucleotidi. Dopodiché ci siamo preoccupati di graficare le distribuzioni di distanza dei 16 dinucleotidi per l'E.Coli, il topo e l'uomo; gli istogrammi evidenziano un comportamento anomalo della distribuzione di CG che accomuna gli organismi eucarioti e di cui, invece, è esente l'organismo procariote esaminato. Questo dato statistico trova una spiegazione nei processi biologici di metilazione che possono innescarsi sul dinucleotide CG nelle sequenze eucariotiche. In seguito, per determinare quanto ciascuna delle 16 distribuzioni si discosti dalle altre abbiamo usato la divergenza di Jensen-Shannon. Per quantificare le differenze sostanziali tra le distribuzioni di CG dei 3 organismi considerati abbiamo deciso di verificare quale fosse il miglior fit per tali curve tra un esponenziale ed una power-law. L'esponenziale rappresenta un buon fit per le code delle distribuzioni di CG del topo e dell'uomo; ciò rivela la presenza di una lunghezza caratteristica per entrambi gli organismi. Nella seconda parte dello studio, i risultati vengono confrontati con modelli markoviani: sequenze random generate con catene di Markov di ordine zero (basate sulle frequenze relative dei nucleotidi) e uno (basate sulle probabilità di transizione tra diversi nucleotidi). Quest'ultima riproduce abbastanza fedelmente la sequenza biologica di partenza, per cui abbiamo scelto di utilizzare la catena Markov del 1° ordine per altre analisi statistiche riguardanti le distribuzioni dei nucleotidi, dinucleotidi, ed anche dei trinucleotidi con particolare interesse per quelli in cui è contenuto CG, in modo da verificare se l'anomalia si ripercuote anche in essi. Riteniamo pertanto che metodi basati su questo approccio potrebbero essere sfruttati per confermare le peculiarità biologiche e per migliorare l'individuazione delle aree di interesse, come le isole CpG, ed eventualmente promotori e Lamina Associated Domains (LAD), nel genoma di diversi organismi

Cortical thickness of primary visual cortex correlates with motion deficits in periventricular leukomalacia

Abstract Impairments of visual motion perception and, in particular, of flow motion have been consistently observed in premature and very low birth weight subjects during infancy. Flow motion information is analyzed at various cortical levels along the dorsal pathways, with information mainly provided by primary and early visual cortex (V1, V2 and V3). We investigated the cortical stage of the visual processing that underlies these motion impairments, measuring Grey Matter Volume and Cortical Thickness in 13 children with Periventricular Leukomalacia (PVL). The cortical thickness, but not the grey matter volume of area V1, correlates negatively with motion coherence sensitivity, indicating that the thinner the cortex, the better the performance among the patients. However, we did not find any such association with either the thickness or volume of area MT, MST and areas of the IPS, suggesting damage at the level of primary visual cortex or along the optic radiation

Light-triggered control of Glucocerebrosidase inhibitors: towards photoswitchable pharmacological Chaperones

Piperidine-based photoswitchable derivatives have been developed as putative pharmacological chaperones for glucocerebrosidase (GCase), the defective enzyme in Gaucher disease (GD). The structure-activity study revealed that both the iminosugar and the light-sensitive azobenzene are essential features to exert inhibitory activity towards human GCase and a system with the correct inhibition trend (IC50 of the light-activated form lower than IC50 of the dark form) was identified. Kinetic analyses showed that all compounds are non-competitive inhibitors (mixed or pure) of GCase and the enzyme allosteric site involved in the interaction was identified by means of MD simulations. A moderate activity enhancement of mutant GCase assessed in GD patients' fibroblasts (ex vivo experiments) carrying the most common mutation was recorded. This promising observation paves the way for further studies to improve the benefit of the light-to-dark thermal conversion for chaperoning activity

Using Cone Beam Computed Tomography for radiological assessment beyond dento-maxillofacial imaging: a review of the clinical applications in other anatomical districts

Background: Cone Beam Computed Tomography (CBCT) represents the optimal imaging solution for the evaluation of the maxillofacial and dental area when quantitative geometric and volumetric accuracy is necessary (e.g., in implantology and orthodontics). Moreover, in recent years, this technique has given excellent results for the imaging of lower and upper extremities. Therefore, significant interest has been increased in using CBCT to investigate larger and non-traditional anatomical districts. Objective: The purpose of this work is to review the scientific literature in Pubmed and Scopus on CBCT application beyond head districts by paying attention to image quality and radiological doses. Method: The search for keywords was conducted in Pubmed and Scopus databases with no back-date restriction. Papers on applications of CBCT to head were excluded from the present work. From each considered paper, parameters related to image quality and radiological dose were extracted. An overall qualitative evaluation of the results extracted from each issue was done by comparing the conclusive remarks of each author regarding doses and image quality. PRISMA statements were followed during this process. Results: The review retrieved 97 issues from 83 extracted papers; 46 issues presented a comparison between CBCT and Multi-Detector Computed Tomography (MDCT), and 51 reviewed only CBCT. The radiological doses given to the patient with CBCT were considered acceptable in 91% of cases, and the final image quality was found in 99%. Conclusion: CBCT represents a promising technology not only for imaging of the head and upper and lower extremities but for all the orthopedic districts. Moreover, the application of CBCT derived from C-arms (without the possibility of a 360 ° rotation range) during invasive investigations demonstrates the feasibility of this technique for non-standard anatomical areas, from soft tissues to vascular beds, despite the limits due to the incomplete rotation of the tube

Inversion of perceived direction of motion caused by spatial undersampling in two children with periventricular leukomalacia

We report here two cases of two young diplegic patients with cystic periventricular leukomalacia who systematically, and with high sensitivity, perceive translational motion of a random-dot display in the opposite direction. The apparent inversion was specific for translation motion: Rotation and expansion motion were perceived correctly, with normal sensitivity. It was also specific for random-dot patterns, not occurring with gratings. For the one patient that we were able to test extensively, contrast sensitivity for static stimuli was normal, but was very low for direction discrimination at high spatial frequencies and all temporal frequencies. His optokinetic nystagmus movements were normal but he was unable to track a single translating target, indicating a perceptual origin of the tracking deficit. The severe deficit for motion perception was also evident in the seminatural situation of a driving simulation video game. The perceptual deficit for translational motion was reinforced by functional magnetic resonance imaging studies. Translational motion elicited no response in the MT complex, although it did produce a strong response in many visual areas when contrasted with blank stimuli. However, radial and rotational motion produced a normal pattern of activation in a subregion of the MT complex. These data reinforce the existent evidence for independent cortical processing for translational, and circular or radial flow motion, and further suggest that the two systems have different vulnerability and plasticity to prenatal damage. They also highlight the complexity of visual motion perception, and how the delicate balance of neural activity can lead to paradoxical effects such as consistent misperception of the direction of motion. We advance a possible explanation of a reduced spatial sampling of the motion stimuli and report a simple model that simulates well the experimental results

Outcome Prediction for SARS-CoV-2 Patients Using Machine Learning Modeling of Clinical, Radiological, and Radiomic Features Derived from Chest CT Images

Featured Application The present study demonstrates that semi-automatic segmentation enables the identification of regions of interest affected by SARS-CoV-2 infection for the extraction of prognostic features from chest CT scans without suffering from the inter-operator variability typical of segmentation, hence offering a valuable and informative second opinion. Machine Learning methods allow identification of the prognostic features potentially reusable for the early detection and management of other similar diseases. (1) Background: Chest Computed Tomography (CT) has been proposed as a non-invasive method for confirming the diagnosis of SARS-CoV-2 patients using radiomic features (RFs) and baseline clinical data. The performance of Machine Learning (ML) methods using RFs derived from semi-automatically segmented lungs in chest CT images was investigated regarding the ability to predict the mortality of SARS-CoV-2 patients. (2) Methods: A total of 179 RFs extracted from 436 chest CT images of SARS-CoV-2 patients, and 8 clinical and 6 radiological variables, were used to train and evaluate three ML methods (Least Absolute Shrinkage and Selection Operator [LASSO] regularized regression, Random Forest Classifier [RFC], and the Fully connected Neural Network [FcNN]) for their ability to predict mortality using the Area Under the Curve (AUC) of Receiver Operator characteristic (ROC) Curves. These three groups of variables were used separately and together as input for constructing and comparing the final performance of ML models. (3) Results: All the ML models using only RFs achieved an informative level regarding predictive ability, outperforming radiological assessment, without however reaching the performance obtained with ML based on clinical variables. The LASSO regularized regression and the FcNN performed equally, both being superior to the RFC. (4) Conclusions: Radiomic features based on semi-automatically segmented CT images and ML approaches can aid in identifying patients with a high risk of mortality, allowing a fast, objective, and generalizable method for improving prognostic assessment by providing a second expert opinion that outperforms human evaluation

Continuing evidence that COVID-19 has influenced syphilis epidemiology in Rome

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Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on NCT 05200715