Metodi di machine learning per la valutazione del dolore tramite l'elaborazione di segnali fisiologici

Tra i sintomi provati dai pazienti con sclerosi multipla (SM), malattia cronica del sistema nervoso centrale, il dolore risulta essere uno di quelli che maggiormente influenza la qualità della vita e il benessere, anche psicologico, del paziente. Nella pratica clinica, il dolore viene valutato sulla base di una stima soggettiva da parte del paziente, utilizzando principalmente scale e questionari. Tali strumenti presentano diversi limiti, in quanto possono essere influenzati da aspetti emotivi e amministrati solo da pazienti in grado di comunicare verbalmente il proprio stato. Dal momento che l’esperienza dolorosa innesca meccanismi che portano alla modifica di alcune funzioni fisiologiche, negli ultimi anni la ricerca scientifica si è mossa verso lo sviluppo di metodi di valutazione del dolore basati sull’elaborazione di segnali fisiologici. Tali approcci danno la possibilità di avere una stima oggettiva del dolore esperito, che prescinde dalla comunicazione verbale. Nel presente lavoro di tesi è stata condotta un’analisi esplorativa su segnali registrati mediante sensori indossabili su pazienti con SM in relazione al dolore esperito. Da ogni segnale (PPG, EDA, temperatura superficiale e segnale accelerometrico) sono state ricavate diverse feature, su cui è stata condotta un’analisi qualitativa per valutare eventuali pattern al variare dell’intensità e del tipo di dolore esperito (nocicettivo vs neuropatico). Le stesse features sono state poi utilizzate per addestrare degli algoritmi di machine learning per la classificazione binaria in “dolore lieve” e “dolore moderato”. Dall’analisi qualitativa sono emersi andamenti concordi in base al tipo di dolore, con le features dell’EDA maggiormente sensibili all’intensità del dolore. Applicando diverse strategie per la fase di features selection e di addestramento, gli algoritmi di ML presentano in generale valori di sensibilità superiori a quelli di specificità, con valori di accuratezza fra il 55% e il 75%

Bridging thermodynamics and metrology in non-equilibrium Quantum Thermometry

Single-qubit thermometry presents the simplest tool to measure the temperature of thermal baths with reduced invasivity. At thermal equilibrium, the temperature uncertainty is linked to the heat capacity of the qubit, however the best precision is achieved outside equilibrium condition. Here, we discuss a way to generalize this relation in a non-equilibrium regime, taking into account purely quantum effects such as coherence. We support our findings with an experimental photonic simulation.Comment: 7 pages, 4 figure

The effects of general anaesthesia on heart rate variability during abdominal surgery

We aimed to realized a pilot study that investigated heart rate variability (HRV) during anesthesia to study of alterations in the autonomous function and study the effects of anesthetic drugs with a not invasive test. We studied 15 subjects of both sexes (9 women and 6 men) with a mean age of 53.6 ± 14.3 years. ECG signal recording, lasting 5 minutes each, in three times: First time, the    registration before anaesthesia. The second was performed after anaesthesia induction and after 5 minutes after the start of maintenance. The third measurement was  performed 24 hours after surgery. The mean heart rate did not show significant alterations during anesthesia and after 24 hours of surgery compared with baseline. On the contrary, the indices of heart rate variability in the frequency domain showed significant variations during general anesthesia. In fact there was a significant decrease in LF, expressed in normalized units and at the same time a significant increase in HF, always expressed in normalized units. It follows that the LF / HF ratio has been significantly reduced during the period of anesthesia. All indices are nearly returned to baseline after 24 hours of surgery. The analysis of anesthetic effects on HRV may provide a more valuable noninvasive tool for investigating alterations in autonomic function. Anesthetics used in general anesthesia suppress the autonomic nervous system and contribute to the safety of general anesthesia not only because suppress the excessive sympathetic activity caused by the operation but also because suppress parasympathetic reactions. The attenuation of sympathetic activity during general anesthesia is usually assessed by measuring changes in blood pressure or heart rate. In all cases, because of these antagonistic effects, evaluation becomes problematic when parasympathetic activity is simultaneously depressed. Keywords: HRV; heart rate variability; general anaesthesia; autonomic nervous system

Cardiovascular Risk Evaluation through Heart Rate Variability (HRV) Analysis in Patients with Psoriasis before and after 12 Weeks of Etanercept Therapy: A Preliminary Prospective Study

Background The association between psoriasis and cardiovascular diseases is suggested by epidemiological studies. The sub-inflammatory systemic state that characterizes both psoriasis and atherosclerosis has been proposed as the link between these conditions; it cannot, however, explain the increased incidence of sudden cardiac death reported in young patients with severe psoriasis without common cardiovascular risk factors. In a previous study we reported higher levels of autonomic dysregulation in psoriatic patients, concluding that the prevalence of the sympathetic arm over the para-sympathetic one could increase cardiovascular risk. Objectives To assess the influence of etanercept, an anti-TNFα agent, on the autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. Methods Five-minute ECG recordings were collected at rest conditions before and after 12 weeks of therapy with etanercept in 19 young psoriatic patients without cardiovascular risk factors. The Cardiolab CE pocket PC ECG system was used for linear methods of heart rate variability (HRV) analysis. Results No significant change in HRV analysis parameters was apparent after 12 weeks of etanercept therapy. Conclusion Our data suggest that treatment with etanercept in patients with moderate-to-severe psoriasis doesn\u27t affect cardiovascular autonomic regulation, and subsequently the cardiovascular risk.</p

Expression Of Mir-34a In T-cells Infected By Human T-lymphotropic Virus 1

Human T-lymphotropic virus 1 (HTLV-1) immortalizes T-cells and is the causative agent of adult T-cell leukemia/lymphoma (ATLL). HTLV-1 replication and transformation are governed by multiple interactions between viral regulatory proteins and host cell factors that remain to be fully elucidated. The present study investigated the impact of HTLV-1 infection on the expression of miR-34a, a microRNA whose expression is downregulated in many types of cancer. Results of RT-PCR assays showed that five out of six HTLV-1-positive cell lines expressed higher levels of miR-34a compared to normal PBMC or purified CD4+ T-cells. ATLL cell line ED, which did not express miR-34a, showed methylation of the miR-34a promoter. Newly infected PBMC and samples from 10 ATLL patients also showed a prominent increase in miR-34a expression compared to PBMC controls. The primary miR-34a transcript expressed in infected cell line C91PL contained binding motifs for NF-kappa B and p53. Pharmacological inhibition of NF-kappa B with Bay 11-7082 indicated that this pathway contributes to sustain miR-34a levels in infected cells. Treatment of infected cell lines with the p53 activator nutlin-3a resulted in a further increase in miR-34a levels, thus confirming it as a transcriptional target of p53. Nutlin-3a-treated cells showed downregulation of known miR-34a targets including the deacetylase SIRT1, which was accompanied by increased acetylation of p53, a substrate of SIRT1. Transfection of C91PL cells with a miR-34a mimic also led to downregulation of mRNA targets including SIRT1 as well as the pro-apoptotic factor BAX. Unlike nutlin-3a, the miR-34a mimic did not cause cell cycle arrest or reduce cell viability. On the other hand, sequestration of miR-34a with a sponge construct resulted in an increase in death of C91PL cells. These findings provide evidence for a functional role for miR-34a in fine-tuning the expression of target genes that influence the turnover of HTLV-1-infected cells

Sustained Exendin-4 Secretion through Gene Therapy Targeting Salivary Glands in Two Different Rodent Models of Obesity/Type 2 Diabetes.

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile

Could persistent organic pollutants affect future generations of sea turtles by maternal transfer? First results for Caretta caretta nests along the North-Western coast of Italy

Since 2013, loggerhead sea turtle (Caretta caretta, Linnaeus 1758) nesting has been observed further north along the Italian coast, reaching the Tuscan coast (NW Mediterranean Sea). The four nesting events that occurred in Tuscany in the summer of 2019 spurred the scientific community to monitor these occurrences more carefully, following them from egg deposition to hatching. This provided an opportunity to collect samples for conducting multidisciplinary investigations, including the toxicological investigations of the biological material collected from the four nests. The aim of this study was to conduct an initial assessment of persistent organic pollutants in the eggs laid in Tuscany, aiming to establish a baseline on this topic for subsequent nesting events that have occurred until today. Organochlorine compounds (OCs), specifically polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its metabolites, and hexachlorobenzene (HCB), were analyzed and detected in unhatched eggs, embryos, and chorio-allantoic membranes (CAMs). OCs were detected in all samples, with PCBs &gt; DDTs ≫ HCB. A significant spatial variation in pollutant levels and profiles among sea turtle nesting locations was found. Embryos showed higher levels of contamination than egg contents regardless of the developmental stages. Depth of the laying chamber and egg mass were not significant factors in OC bioaccumulation. For the first time in the Mediterranean Sea, this study assessed the role of CAM in the transfer of contaminants to the embryo. Overall, the OC levels found were lower compared to the results from other studies conducted worldwide on loggerhead sea turtle biological material. This was the first assessment of nest biological material for the North-Western coast of Italy

Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL).1,2 Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases, and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt utilizes a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivating domains of ERG, but inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia, in which DUX4 deregulation results in loss-of-function of ERG, either by deletion or induction of expression of an isoform that is a dominant negative inhibitor of wild type ERG function