Sviluppo di un tomografo multi-energy per lo studio pre-clinico di nuove metodiche diagnostiche finalizzate al riconoscimento precoce della patologia tumorale

A new multi-energy CT for small animals is being developed at the Physics Department of the University of Bologna, Italy. The system makes use of a set of quasi-monochromatic X-ray beams, with energy tunable in a range from 26 KeV to 72 KeV. These beams are produced by Bragg diffraction on a Highly Oriented Pyrolytic Graphite crystal. With quasi-monochromatic sources it is possible to perform multi-energy investigation in a more effective way, as compared with conventional X-ray tubes. Multi-energy techniques allow extracting physical information from the materials, such as effective atomic number, mass-thickness, density, that can be used to distinguish and quantitatively characterize the irradiated tissues. The aim of the system is the investigation and the development of new pre-clinic methods for the early detection of the tumors in small animals. An innovative technique, the Triple-Energy Radiography with Contrast Medium (TER), has been successfully implemented on our system. TER consist in combining a set of three quasi-monochromatic images of an object, in order to obtain a corresponding set of three single-tissue images, which are the mass-thickness map of three reference materials. TER can be applied to the quantitative mass-thickness-map reconstruction of a contrast medium, because it is able to remove completely the signal due to other tissues (i.e. the structural background noise). The technique is very sensitive to the contrast medium and is insensitive to the superposition of different materials. The method is a good candidate to the early detection of the tumor angiogenesis in mice. In this work we describe the tomographic system, with a particular focus on the quasi-monochromatic source. Moreover the TER method is presented with some preliminary results about small animal imaging

Conduction and Gating Properties of the TRAAK Channel from Molecular Dynamics Simulations with Different Force Fields

In recent years, the K2P family of potassium channels has been the subject of intense research activity. Owing to the complex function and regulation of this family of ion channels, it is common practice to complement experimental findings with the atomistic description provided by computational approaches such as molecular dynamics (MD) simulations, especially, in light of the unprecedented timescales accessible at present. However, despite recent substantial improvements, the accuracy of MD simulations is still undermined by the intrinsic limitations of force fields. Here, we systematically assessed the performance of the most popular force fields employed to study ion channels at timescales that are orders of magnitude greater than the ones accessible when these energy functions were first developed. Using 32 μs of trajectories, we investigated the dynamics of a member of the K2P ion channel family, the TRAAK channel, using two established force fields in simulations of biological systems: AMBER and CHARMM. We found that while results are comparable on the nanosecond timescales, significant inconsistencies arise at microsecond timescales.</p

Conduction and Gating Properties of the TRAAK Channel from Molecular Dynamics Simulations with Different Force Fields

In recent years, the K2P family of potassium channels has been the subject of intense research activity. Owing to the complex function and regulation of this family of ion channels, it is common practice to complement experimental findings with the atomistic description provided by computational approaches such as molecular dynamics (MD) simulations, especially, in light of the unprecedented timescales accessible at present. However, despite recent substantial improvements, the accuracy of MD simulations is still undermined by the intrinsic limitations of force fields. Here, we systematically assessed the performance of the most popular force fields employed to study ion channels at timescales that are orders of magnitude greater than the ones accessible when these energy functions were first developed. Using 32 μs of trajectories, we investigated the dynamics of a member of the K2P ion channel family, the TRAAK channel, using two established force fields in simulations of biological systems: AMBER and CHARMM. We found that while results are comparable on the nanosecond timescales, significant inconsistencies arise at microsecond timescales.</p

Sviluppo di una micro CT con sorgente Quasi-Monocromatica Multi-Energy per lo studio in vivo della crescita e della metastasi tumorale

Un innovativo micro scanner CT per piccolo animali – basato su di una sorgente che genera una coppia di fasci X Quasi-Monocromatici paralleli con diverse energie selezionabili – è in corso di installazione e caratterizzazione al Dipartimento di Fisica dell’Università di Bologna. Lo scopo della ricerca è quello di effettuare l’imaging radiologico in vivo del tessuto tumorale e/o dei pattern di neo-angiogenesi in una fase diagnostica precoce realizzando la separazione del tessuto patologico da quello sano per mezzo della tecnica multi-energy che consiste nell’utilizzo di due o più fasci di raggi X quasi-monocromatici in sostituzione dell’unico fascio policromatico utilizzato nella radiologia convenzionale. Lo strumento consentirà inoltre lo studio, sui topi, della crescita tumorale e della formazione delle metastasi per differenti tipologie di tumore. Per la diagnosi precoce del tumore è essenziale essere in grado di rivelare i cambiamenti tissutali precancerosi, come la neo-angiogenesi. Si tratta di un meccanismo che si verifica in una fase iniziale dello sviluppo della patologia ed è dovuto alla produzione di molecole che stimolano la creazione di nuovi vasi sanguigni per alimentare la crescita delle cellule cancerose. Come dimostrato in precedenti studi di fattibilità [1], un sistema di imaging basato su due fasci di raggi X quasi-monocromatici di differenti energie fornisce maggiore sensibilità nella rivelazione di basse concentrazioni di mezzo di contrasto iodato rispetto ai tradizionali apparati RX con fascio policromatico. La K-edge dual energy radiology è una tecnologia potenzialmente in grado di rivelare il processo di neo-angiogenesi tumorale in uno stadio precoce quando la strumentazione convenzionale non dispone di sufficiente sensibilità. Inoltre, la possibilità di selezionare le energie dei fasci quasi-monocromatici consente l’applicazione della Multi-Energy Quasi-MonochromaticRadiology: selezionando opportunamente le energie è possibile esaltare le differenze fra i coefficienti di attenuazione lineare del tessuto patologico rispetto a quello sano aumentando il contrasto della patologia. Infatti, la tecnica multi-energy consente di ricostruire il numero atomico efficace e persino la composizione chimica del tessuto irradiato. Tuttavia, per ottenere questo risultato, si dovrebbero conoscere le bande di energia in cui l’assorbimento dei raggi X da parte del tessuto tumorale eventualmente differisce significativamente da quello dei tessuti sani. Per questo motivo è stata iniziata una sistematica caratterizzazione radiologica di molti tipi di tessuti sani e neoplastici, murini e umani allo scopo di costituire un catalogo delle finestre di energia in cui sarà possibile applicare la metodica multi-energy

Supporting CPS Modeling Through a New Method for Solving Complex Non-holomorphic Equations

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Unbalance of intestinal microbiota in atopic children

BACKGROUND: Playing a strategic role in the host immune function, the intestinal microbiota has been recently hypothesized to be involved in the etiology of atopy. In order to investigate the gastrointestinal microbial ecology of atopic disease, here we performed a pilot comparative molecular analysis of the faecal microbiota in atopic children and healthy controls. RESULTS: Nineteen atopic children and 12 healthy controls aged 4–14 years were enrolled. Stools were collected and the faecal microbiota was characterized by means of the already developed phylogenetic microarray platform, HTF-Microbi.Array, and quantitative PCR. The intestinal microbiota of atopic children showed a significant depletion in members of the Clostridium cluster IV, Faecalibacterium prausnitzii, Akkermansia muciniphila and a corresponding increase of the relative abundance of Enterobacteriaceae. CONCLUSION: Depleted in key immunomodulatory symbionts, the atopy-associated microbiota can represent an inflammogenic microbial consortium which can contribute to the severity of the disease. Our data open the way to the therapeutic manipulation of the intestinal microbiota in the treatment of atopy by means of pharmaceutical probiotics

Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders

The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset

Development of a digital research assistant for the management of patients\u2019 enrollment in oncology clinical trials within a research hospital

Clinical trials in cancer treatment are imperative in enhancing patients\u2019 survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients\u2019 accrual in clinical trials. We developed a specific platform, called \u201cDigital Research Assistant\u201d (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients\u2019 records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients\u2019 records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient\u2019s data and clinical trial\u2019s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis