Physical, Mechanical, and Biological Properties of PMMA-Based Composite Bone Cement Containing Silver-Doped Bioactive and Antibacterial Glass Particles with Different Particles Sizes

Abstract: In the present work, antibacterial composite bone cement was designed by introducing a bioactive and antibacterial glass into a commercial formulation. The effect of glass particles’ addition on the curing parameters of the polymeric matrix was evaluated; moreover, the influence of the glass particle size on the glass dispersion, compressive and bending strength, bioactivity, and antibacterial effect was estimated. The results evidence a delay in the polymerization kinetics of the composite cement, which nevertheless complies with the requirements of the ISO standard. Morphological characterization provides evidence of good dispersion of the glass in the polymeric matrix and its exposition on the cement surface. The different glass grain sizes do not affect the composites’ bioactivity and compressive strength, while a slight reduction in bending strength was observed for samples containing glass powders with greater dimensions. The size of the glass particles also appears to have an effect on the antibacterial properties, since the composites containing larger glass particles do not produce an inhibition halo towards the S. aureus strain. The obtained results demonstrate that, by carefully tailoring the glass amount and size, a multifunctional device for artificial joint fixing, temporary prostheses, or spinal surgery can be obtained

Computational Structural Biology of S-nitrosylation of Cancer Targets

Nitric oxide (NO) plays an essential role in redox signaling in normal and pathological cellular conditions. In particular, it is well known to react in vivo with cysteines by the so-called S-nitrosylation reaction. S-nitrosylation is a selective and reversible post-translational modification that exerts a myriad of different effects, such as the modulation of protein conformation, activity, stability, and biological interaction networks. We have appreciated, over the last years, the role of S-nitrosylation in normal and disease conditions. In this context, structural and computational studies can help to dissect the complex and multifaceted role of this redox post-translational modification. In this review article, we summarized the current state-of-the-art on the mechanism of S-nitrosylation, along with the structural and computational studies that have helped to unveil its effects and biological roles. We also discussed the need to move new steps forward especially in the direction of employing computational structural biology to address the molecular and atomistic details of S-nitrosylation. Indeed, this redox modification has been so far an underappreciated redox post-translational modification by the computational biochemistry community. In our review, we primarily focus on S-nitrosylated proteins that are attractive cancer targets due to the emerging relevance of this redox modification in a cancer setting

Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants

Background and purpose: there are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. Methods: we applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. Results: according to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. Conclusions: the 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients

WOOD-UP

The fundamental vision of the WOOD-UP project was to develop existing wood gasification plants in South Tyrol towards a polygenerative use in order to be able to produce not only energy but also high-quality charcoal (biochar) for the improvement of soil fertility and for climate protection. The project, funded by the European Regional Development Fund ERDF 2014–2020, was implemented by the Free University of Bolzano together with the Laimburg Research Centre. Based on the life cycle analysis (LCA) or scenario analysis of the entire production chain of wood gasification, strengths and weaknesses of the existing systems were identified with regard to their impact on the environment. Thanks to the results obtained, a number of suggestions for improvement could be formulated.; Il miglioramento verso un assetto poligenerativo degli attuali impianti altoatesini di gassificazione della biomassa legnosa, dove oltre all’energia si possa produrre biochar di qualità da impiegare in agricoltura come ammendante con effetti positivi sulla fertilità dei suoli e sulla mitigazione dei cambiamenti climatici è la visione che ha sostenuto il progetto WOOD-UP. Il progetto, finanziato con fondi FESR 2014-2020, ha visto la collaborazione tra la Libera Università di Bolzano e il Centro di Sperimentazione Laimburg. L’analisi del ciclo di vita e di scenario dell’intera filiera di gassificazione ha evidenziato elementi di forza e di debolezza dell’attuale filiera in termini di impatti ambientali e ha permesso di avanzare proposte di miglioramento sulla base dei risultati ottenuti dalla sperimentazione. ; Grundlegende Vision des Projektes WOOD-UP war die Entwicklung der bestehenden Holzvergasungsanlagen in Südtirol hin zu einer polygenerativen Nutzung, um neben Energie auch hochwertige Holzkohle (Biochar) zur Verbesserung der Bodenfruchtbarkeit und zum Klimaschutz erzeugen zu können. Das mit Mitteln aus dem Europäischen Fonds für regionale Entwicklung EFRE 2014–2020 finanzierte Projekt wurde von der Freien Universität Bozen gemeinsam mit dem Versuchszentrum Laimburg umgesetzt. Anhand der Lebenszyklusanalyse (LCA) bzw. der Szenarioanalyse der gesamten Produktionskette der Holzvergasung wurden Stärken und Schwächen der bestehenden Systeme hinsichtlich ihrer Auswirkungen auf die Umwelt aufgezeigt. Dank der erzielten Versuchsergebnisse konnte eine Reihe von Verbesserungsvorschlägen formuliert werden

STUDIO DELLE AREE VISIVE IN PAZIENTI CON NEUROFIBROMATOSI DI TIPO 1 E GLIOMA DELLE VIE OTTICHE MEDIANTE RISONANZA MAGNETICA FUNZIONALE

Neurofibromatosis 1 (NF1) is an autosomal dominant condition characterized by neuro-cutaneous involvement and a predisposition to tumour development. The most common NF1-associated central nervous system tumour is optic pathway glioma (OPG), affecting about 15% of NF1 patients and characterized by an unpredictable evolution with no clear prognostic factors identified so far. Resting-state fMRI has recently emerged as a powerful tool for functional brain analysis, allowing the examination of brain functional networks. The aim of our study was to analyze through resting-state fMRI the possible functional modifications of the visual network in patients affected by NF1 and OPG. We enrolled 57 patients with NF1 (31 females and 16 males; mean age at brain MRI scan 13.31 ± 6.07). Of them 35 presented OPG: in 15 (42.8%) patients it involved only the optic nerves, in 20 (57.2%) also the chiasmatic area; of the latter, 5 (25%) patients also the posterior optic pathways. Eleven (19.3%) of our patients with NF1 presented altered visual acuity. All of them underwent resting-state brain fMRI to analyze the visual network. Nineteen subjects non-affected by NF1 were used as controls Our data revealed a reduced connectivity in patients with NF1 and OPG limited to the optic nerves in the medial visual network in the area of paramedian cuneus bilaterally in the occipital lobe. No other significant difference were found in visual network connectivity between patients with larger OPG vs control or between patients with altered visual acuity vs. control. In our study we analyzed the impact of OPG on the visual network in patients with NF1; we expected to find more significant abnormalities in patients affected with OPG involving largely the optic pathways, yet we detected a significant reduction of the network connectivity only in patients with OPG limited in the optic nerves. These findings may be secondary to the relatively small number of patients enrolled and to the indolent evolution of the OPG in our cohort of subjects. A follow-up study with a larger number of enrolled patients may help us clarify the possible predictive role of visual network connectivity in the OPG prognosis.La Neurofibromatosi di tipo 1 (NF1), è una malattia neurocutanea monogenica caratterizzata dalla predisposizione allo sviluppo di tumori del sistema nervoso, sia benigni che maligni. Il glioma delle vie ottiche (OPG) è il tumore più comune in questi pazienti, con una prevalenza del 15% e un’evoluzione spesso imprevedibile; a tutt’oggi non sono stati individuati sicuri fattori prognostici. L’obbiettivo del nostro studio è stato l’indagine tramite Risonanza Magnetica funzionale (fMRI) dell’impatto di OPG sulle reti neurali visive dei pazienti con NF1. Sono stati selezionati 46 pazienti affetti da NF1 seguiti presso il nostro Dipartimento e 11 pazienti affetti da NF1 seguiti presso l’Ospedale Pediatrico di Genova (31 femmine e 16 maschi; età media alla fMRI 13.31 ± 6.07); 19 soggetti sani sono stati arruolati come controlli. I soggetti stati tutti sottoposti a Risonanza Magnetica con acquisizione di sequenze per lo studio funzionale e a valutazione oculistica con particolare attenzione all’acuità visiva. Dei pazienti con NF1 35 presentavano OPG: in 15 (42.8%) coinvolgeva solo i nervi ottici, in 20 (57.2%) anche il chiasma e le vie retro-chiasmatiche; tra questi, in 5 (25%) casi erano coinvolti anche i tratti posteriori. Undici (19.3%) dei pazienti con NF1 presentavano acuità visiva alterata. E’ stata confrontata con fMRI la connettività della rete neurale visiva in pazienti con NF1 e OPG con diversa estensione e nei controlli. Si è rilevata una riduzione della connettività della rete neurale visiva statisticamente significativa tra i pazienti con NF1 e glioma delle vie ottiche limitato ai nervi ottici e controlli, nell’area corrispondente al cuneo paramediano bilaterale. Non sono emerse differenze significative tra gli altri gruppi. La mancanza di chiari fattori prognostici noti per quanto riguarda l’OPG ci ha spinto a valutare le differenze funzionali delle reti neurali visive in pazienti affetti. I risultati ottenuti dimostrano inaspettatamente una differente connettività solo in coloro affetti da OPG limitato ai nervi ottici; uno studio di follow-up, effettuato su una popolazione di numerosità maggiore ci potrà aiutare a chiarire questi dati

STUDIO DELLE AREE VISIVE IN PAZIENTI CON NEUROFIBROMATOSI DI TIPO 1 E GLIOMA DELLE VIE OTTICHE MEDIANTE RISONANZA MAGNETICA FUNZIONALE

Neurofibromatosis 1 (NF1) is an autosomal dominant condition characterized by neuro-cutaneous involvement and a predisposition to tumour development. The most common NF1-associated central nervous system tumour is optic pathway glioma (OPG), affecting about 15% of NF1 patients and characterized by an unpredictable evolution with no clear prognostic factors identified so far. Resting-state fMRI has recently emerged as a powerful tool for functional brain analysis, allowing the examination of brain functional networks. The aim of our study was to analyze through resting-state fMRI the possible functional modifications of the visual network in patients affected by NF1 and OPG. We enrolled 57 patients with NF1 (31 females and 16 males; mean age at brain MRI scan 13.31 ± 6.07). Of them 35 presented OPG: in 15 (42.8%) patients it involved only the optic nerves, in 20 (57.2%) also the chiasmatic area; of the latter, 5 (25%) patients also the posterior optic pathways. Eleven (19.3%) of our patients with NF1 presented altered visual acuity. All of them underwent resting-state brain fMRI to analyze the visual network. Nineteen subjects non-affected by NF1 were used as controls Our data revealed a reduced connectivity in patients with NF1 and OPG limited to the optic nerves in the medial visual network in the area of paramedian cuneus bilaterally in the occipital lobe. No other significant difference were found in visual network connectivity between patients with larger OPG vs control or between patients with altered visual acuity vs. control. In our study we analyzed the impact of OPG on the visual network in patients with NF1; we expected to find more significant abnormalities in patients affected with OPG involving largely the optic pathways, yet we detected a significant reduction of the network connectivity only in patients with OPG limited in the optic nerves. These findings may be secondary to the relatively small number of patients enrolled and to the indolent evolution of the OPG in our cohort of subjects. A follow-up study with a larger number of enrolled patients may help us clarify the possible predictive role of visual network connectivity in the OPG prognosis.La Neurofibromatosi di tipo 1 (NF1), è una malattia neurocutanea monogenica caratterizzata dalla predisposizione allo sviluppo di tumori del sistema nervoso, sia benigni che maligni. Il glioma delle vie ottiche (OPG) è il tumore più comune in questi pazienti, con una prevalenza del 15% e un’evoluzione spesso imprevedibile; a tutt’oggi non sono stati individuati sicuri fattori prognostici. L’obbiettivo del nostro studio è stato l’indagine tramite Risonanza Magnetica funzionale (fMRI) dell’impatto di OPG sulle reti neurali visive dei pazienti con NF1. Sono stati selezionati 46 pazienti affetti da NF1 seguiti presso il nostro Dipartimento e 11 pazienti affetti da NF1 seguiti presso l’Ospedale Pediatrico di Genova (31 femmine e 16 maschi; età media alla fMRI 13.31 ± 6.07); 19 soggetti sani sono stati arruolati come controlli. I soggetti stati tutti sottoposti a Risonanza Magnetica con acquisizione di sequenze per lo studio funzionale e a valutazione oculistica con particolare attenzione all’acuità visiva. Dei pazienti con NF1 35 presentavano OPG: in 15 (42.8%) coinvolgeva solo i nervi ottici, in 20 (57.2%) anche il chiasma e le vie retro-chiasmatiche; tra questi, in 5 (25%) casi erano coinvolti anche i tratti posteriori. Undici (19.3%) dei pazienti con NF1 presentavano acuità visiva alterata. E’ stata confrontata con fMRI la connettività della rete neurale visiva in pazienti con NF1 e OPG con diversa estensione e nei controlli. Si è rilevata una riduzione della connettività della rete neurale visiva statisticamente significativa tra i pazienti con NF1 e glioma delle vie ottiche limitato ai nervi ottici e controlli, nell’area corrispondente al cuneo paramediano bilaterale. Non sono emerse differenze significative tra gli altri gruppi. La mancanza di chiari fattori prognostici noti per quanto riguarda l’OPG ci ha spinto a valutare le differenze funzionali delle reti neurali visive in pazienti affetti. I risultati ottenuti dimostrano inaspettatamente una differente connettività solo in coloro affetti da OPG limitato ai nervi ottici; uno studio di follow-up, effettuato su una popolazione di numerosità maggiore ci potrà aiutare a chiarire questi dati

Biological network analysis with the Core&Peel method

Genes are organized in functional modules (or pathways), thus their action and their dysregulation in diseases may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method is used to detect disease modules in a co-expression network of genes. We first validate Core&Peel for the general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma, and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner, and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Finally, we apply Core&Peel and other methods to explore the transcriptional response of human cells to SARS-CoV-2 infection, finding supporting evidence for drug repositioning efforts at a pre-clinical level. Computational drug repositioning aims at ranking and selecting existing drugs for novel diseases or novel use in old diseases. In silico drug screening has the potential for speeding up considerably the shortlisting of promising candidates in response to outbreaks of diseases such as COVID-19 for which no satisfactory cure has yet been found. We describe DrugMerge as a methodology for preclinical computational drug repositioning based on merging multiple drug rankings obtained with an ensemble of disease active subnetworks. DrugMerge uses differential transcriptomic data on drugs and diseases in the context of a large gene co-expression network. Experiments with four benchmark diseases demonstrate that our method detects in first position drugs in clinical use for the specified disease, in all four cases. Application of DrugMerge to COVID-19 found rankings with many drugs currently in clinical trials for COVID-19 in top positions, thus showing that DrugMerge can mimic human expert judgment. Apoptosis and autophagy play essential roles in cellular homeostasis, and their deregulation can lead to cancer. These two pathways are interconnected by several molecular nodes of crosstalk, enabling their regulation. The finding of new molecules acting in the crosstalk is an important step for a more complete understanding of the regulation of autophagy and apoptosis, which is essential for the rational design of successful anticancer therapeutics. To predict new proteins acting in the crosstalk, we apply the Core&Peel method to a protein-protein interaction network to firstly predict complexes involved in apoptosis and autophagy. Core&Peel can predict complexes that have some proteins in common with each other, and this feature enables us to select proteins that are shared between the apoptosis-complexes and autophagy-complexes. These candidate proteins are presumably involved in both pathways since they belong to apoptosis-complex and autophagy-complex. In the end, we obtained 54 candidate proteins that include two short linear motifs that are crucial in mediating autophagic and apoptotic processes, and they are annotated in the main apoptosis and autophagy pathways

Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method

Genes are organized in functional modules (or pathways), thus their action and their dysregulation in diseases may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method is used to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma, and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner, and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover, for the two cancer datasets, Core&Peel detects further eight relevant pathways not discovered by the other methods used in the comparative analysis. Finally, we apply Core&Peel and other methods to explore the transcriptional response of human cells to SARS-CoV-2 infection, finding supporting evidence for drug repositioning efforts at a pre-clinical level