Publications by authors named "Vincenzo Montano"

11 Publications

  • Page 1 of 1

3D Printing of a Self-Healing Thermoplastic Polyurethane through FDM: From Polymer Slab to Mechanical Assessment.

Polymers (Basel) 2021 Jan 19;13(2). Epub 2021 Jan 19.

Novel Aerospace Materials Group, Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, 2629 HS Delft, The Netherlands.

The use of self-healing (SH) polymers to make 3D-printed polymeric parts offers the potential to increase the quality of 3D-printed parts and to increase their durability and damage tolerance due to their (on-demand) dynamic nature. Nevertheless, 3D-printing of such dynamic polymers is not a straightforward process due to their polymer architecture and rheological complexity and the limited quantities produced at lab-scale. This limits the exploration of the full potential of self-healing polymers. In this paper, we present the complete process for fused deposition modelling of a room temperature self-healing polyurethane. Starting from the synthesis and polymer slab manufacturing, we processed the polymer into a continuous filament and 3D printed parts. For the characterization of the 3D printed parts, we used a compression cut test, which proved useful when limited amount of material is available. The test was able to quasi-quantitatively assess both bulk and 3D printed samples and their self-healing behavior. The mechanical and healing behavior of the 3D printed self-healing polyurethane was highly similar to that of the bulk SH polymer. This indicates that the self-healing property of the polymer was retained even after multiple processing steps and printing. Compared to a commercial 3D-printing thermoplastic polyurethane, the self-healing polymer displayed a smaller mechanical dependency on the printing conditions with the added value of healing cuts at room temperature.
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http://dx.doi.org/10.3390/polym13020305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835810PMC
January 2021

Therapeutical Management and Drug Safety in Mitochondrial Diseases-Update 2020.

J Clin Med 2020 Dec 29;10(1). Epub 2020 Dec 29.

Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, 56126 Pisa, Italy.

Mitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the absence of a specific disease-modifying therapy. Management of patients with MDs is based on different therapeutical strategies, particularly the early treatment of organ-specific complications and the avoidance of catabolic stressors or toxic medication. In this review, we discuss the therapeutic management of MDs, supported by a revision of the literature, and provide an overview of the drugs that should be either avoided or carefully used both for the specific treatment of MDs and for the management of comorbidities these subjects may manifest. We finally discuss the latest therapies approved for the management of MDs and some ongoing clinical trials.
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http://dx.doi.org/10.3390/jcm10010094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794679PMC
December 2020

Primary mitochondrial myopathy: Clinical features and outcome measures in 118 cases from Italy.

Neurol Genet 2020 Dec 20;6(6):e519. Epub 2020 Oct 20.

Department of Clinical and Experimental Medicine (V.M., F.G., G.S., M.M.), Neurological Clinic, University of Pisa, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (V.C., M.L.V.), UOC Clinica Neurologica, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM) (V.C., M.L.V.), University of Bologna, Italy; Dino Ferrari Centre (G.P.C.), Department of Pathophysiology and Transplantation (DEPT), University of Milan, Italy; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (G.P.C., M.M.), Neuromuscular and Rare Disease Unit; Unit of Neurology (M.F.), ASST "Spedali Civili" and University of Brescia, Italy; UO Medical Genetics and Neurogenetics (C.L., S.M.), Fondazione IRCCS Istituto Neurologico C.Besta, Milan, Italy; Neuromuscular Unit (M.T., S.B.), Department of Neurosciences, University of Torino, Italy; Department of Clinical and Experimental Medicine (O.M., A.T., G.T.), UOC Neurologia e Malattie Neuromuscolari, University of Messina, Italy; UOC Neurofisiopatologia Fondazione Policlinico Universitario A. Gemelli IRCCS (S.S., G.P.), Roma, Italy; Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore (S.S., G.P.), Roma, Italy; Department of Neurosciences (P.T.), Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, Italy; Neurorehabilitation Unit (A.M.), Department of Neurosciences, University Hospital of Verona, Italy; Neuromuscular Unit (S.B.), Department of Neurosciences, University of Torino, Italy.

Objective: To determine whether a set of functional tests, clinical scales, patient-reported questionnaires, and specific biomarkers can be considered reliable outcome measures in patients with primary mitochondrial myopathy (PMM), we analyzed a cohort of Italian patients.

Methods: Baseline data were collected from 118 patients with PMM, followed by centers of the Italian network for mitochondrial diseases. We used the 6-Minute Walk Test (6MWT), Timed Up-and-Go Test (x3) (3TUG), Five-Times Sit-To-Stand Test (5XSST), Timed Water Swallow Test (TWST), and Test of Masticating and Swallowing Solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional Pain Inventory as patient-reported outcome measures; and FGF21, GDF15, lactate, and creatine kinase (CK) as biomarkers.

Results: A total of 118 PMM cases were included. Functional outcome measures (6MWT, 3TUG, 5XSST, TWST, and TOMASS) and biomarkers significantly differed from healthy reference values and controls. Moreover, functional measures correlated with patients' perceived fatigue and pain severity. Patients with either mitochondrial or nuclear DNA point mutations performed worse in functional measures than patients harboring single deletion, even if the latter had an earlier age at onset but similar disease duration. Both the biomarkers FGF21 and GDF15 were significantly higher in the patients compared with a matched control population; however, there was no relation with severity of disease.

Conclusions: We characterized a large cohort of PMM by evaluating baseline mitochondrial biomarkers and functional scales that represent potential outcome measures to monitor the efficacy of treatment in clinical trials; these outcome measures will be further reinvestigated longitudinally to define the natural history of PMM.
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http://dx.doi.org/10.1212/NXG.0000000000000519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670572PMC
December 2020

Linking interfacial work of deformation from deconvoluted macro-rheological spectrum to early stage healing in selected polyurethanes.

Phys Chem Chem Phys 2020 Oct;22(38):21750-21760

Novel Aerospace Materials group, Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, 2629 HS, Delft, The Netherlands.

The use of rheology and terminal flow relaxation times to predict healing behavior at long healing times is by now quite well accepted. In this work we go one step further and explore the use of macro-rheology (in particular the stored work of deformation) to predict the early stage interfacial healing properties (fracture resistance) of a set of self-healing polyurethanes. The interfacial healing is measured by single edge notch fracture experiments, using short healing times and a low healing temperature to exclude the effect of long range molecular motion on mechanical properties restoration. The systems based on aromatic diisocyanates show high fracture resistance after healing, while very limited restoration of the mechanical properties is observed for aliphatic and cycloaliphatic based polyurethanes. Linear sweep rheology and time-temperature-superposition allow obtaining the macro-rheological master curve and the mechanical relaxation spectra (H(t)). The application of a recently established deconvolution protocol to the H(t) gives the characteristic relaxation times and stored works of deformation associated to individual dynamic processes such as segmental motion, reversible bonds, and terminal flow. It is found that the calculated stored works of deformation related to the reversible bond relaxation reproduce the trend observed by fracture resistance at healed interfaces and reveal a qualitative correspondence between reversible bonds work of deformation and interfacial healing fracture resistance. Moreover, the method seems to point to the existence of a threshold interfacial work of deformation below which no efficient load transfer can be observed.
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http://dx.doi.org/10.1039/d0cp03776aDOI Listing
October 2020

Fibroblast growth factor 21 and grow differentiation factor 15 are sensitive biomarkers of mitochondrial diseases due to mitochondrial transfer-RNA mutations and mitochondrial DNA deletions.

Neurol Sci 2020 Dec 6;41(12):3653-3662. Epub 2020 Jun 6.

UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy.

Background: Diagnosis of mitochondrial diseases (MDs) is challenging, since they are multisystemic disorders, characterized by a heterogeneous symptomatology. Recently, an increase in serum levels of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) has been found in the majority of patients with MDs compared with healthy controls. On the other hand, the finding of low FGF21 and GDF15 levels in some patients with MDs suggests that different types of respiratory chain defects may lead to different profiles of these two proteins.

Objective: In this study, we aimed to validate the diagnostic reliability of FGF21 and GDF15 assays in MDs and to evaluate a possible correlation between serum levels of the two biomarkers with genotype of MD patients. Serum FGF21 and GDF15 levels were measured by a quantitative ELISA.

Results: Our results showed increased serum FGF21 and GDF15 levels in MD patients; however, GDF15 measurement seems to be more sensitive and specific for screening tests for MD than FGF21. Moreover, we showed a positive correlation with both FGF21 and GDF15 levels and the number of COX-negative fibers.

Conclusion: Finally, we also demonstrated that the increase of FGF21 and GDF15 was related to MDs caused by mitochondrial translation defects, and multiple and single mtDNA deletions, but not to MDs due to mutations in the respiratory chain subunits.
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http://dx.doi.org/10.1007/s10072-020-04422-5DOI Listing
December 2020

Controlling Healing and Toughness in Polyurethanes by Branch-Mediated Tube Dilation.

Macromolecules 2019 Nov 17;52(21):8067-8078. Epub 2019 Oct 17.

Novel Aerospace Materials group, Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, 2629 HS, Delft, The Netherlands.

In this work, we propose the use of regular branching of polyurethanes as a way to regulate chain dynamics and govern crystallization in highly dense hydrogen-bonded systems. As a result, robust and healable polyurethanes can be obtained. To this end, we synthesized a range of aliphatic propane diol derivatives with alkyl branches ranging from butyl (C4) to octadecanyl (C18). The series of brush polyurethanes was synthesized by polyaddition of the diols and hexamethylene diisocyanate. Polyurethanes with very short (C < 4) and very long (C = 18) brush lengths did not lead to any significant healing due to crystallization. An intermediate amorphous regime appears for polymers with middle branch lengths (C = 4 to 8) showing a fine control of material toughness. For these systems, the side chain length regulates tube dilation, and significant macroscopic healing of cut samples was observed and studied in detail using melt rheology and tensile testing. Despite the high healing degrees observed immediately after repair, it was found that samples with medium to long length brushes lost their interfacial strength at the healed site after being heated to the healing temperature for some time after the optimal time to reach full healing. Dedicated testing suggests that annealed samples, while keeping initial tackiness, are not able to completely heal the cut interface. We attribute such behavior to annealing-induced interfacial crystallization promoted by the aliphatic branches. Interestingly, no such loss of healing due to annealing was observed for samples synthesized with C4 and C7 diols, which is identified as the optimal healing regime. These results point at the positive effect of branching on healing, provided that a critical chain length is not surpassed, as well as the need to study healing behavior long after the optimal healing times.
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http://dx.doi.org/10.1021/acs.macromol.9b01554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854654PMC
November 2019

A deconvolution protocol of the mechanical relaxation spectrum to identify and quantify individual polymer feature contributions to self-healing.

Phys Chem Chem Phys 2019 May;21(19):10171-10184

Novel Aerospace Materials Group, Faculty of Aerospace Engineering, Delft University of Technology, Kluyverweg 1, Delft, 2629 HS, The Netherlands.

Starting from experimental macro-rheological data, we develop a fitting protocol that succeeded in the separation of the overlapping relaxation phenomena in the dissipative regime for a set of intrinsic healing polymers healing most effectively near their glass transition temperature Tg. To allow for a proper deconvolution, the rheological master curves are converted to a relaxation spectrum (H(τ)) and this is fitted using an optimized mechanical model, e.g. the Maxwell-Weichert model. The deconvolution of overlapping segmental mobility and reversible interactions is successfully demonstrated for a set of polyimide and polyamide polymers containing none, one and two reversible dynamic features near-Tg. Through the fitting parameters, the relaxation timescale of each feature and their apparent process enthalpies are obtained. The quantitative data obtained using the fitting protocol are then compared to macroscopic healing results. As a result, a clear correspondence between the energy stored by the system to accomplish reversible (e.g. H-bonds, π-π) and chain interdiffusion relaxation transitions and the healing efficiency of such polymers are obtained. The implementation of this protocol allows for a clearer identification of the relevant mechanisms in self-healing polymers and paves the way for the development of more efficiently healable polymeric systems.
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http://dx.doi.org/10.1039/c9cp00417cDOI Listing
May 2019

Mitochondrial m.3243A > G mutation and carotid artery dissection.

Mol Genet Metab Rep 2016 Dec 1;9:12-4. Epub 2016 Sep 1.

Unit of Molecular Neurogenetics, The Foundation "Carlo Besta" Institute of Neurology - IRCCS Milan, Italy.

The common m.3243A > G mutation of the mitochondrial DNA tRNALeu (UUR) gene is a maternally inherited mutation causing a wide spectrum of neurological and multisystemic disorders, including MELAS, characterized by recurrent cerebral infarction from young age. Vascular pathology in mitochondrial diseases has been described for small vessels, while large vessels involvement in mitochondrial diseases is considered rare. Here we report two female patients harboring the m.3243A > G mutation, in whom the diagnosis of mitochondrial disease was made after acute dissection of the internal carotid arteries. Our cases expand the clinical spectrum of this mutation, and support the idea of large vessels vasculopathy due to impaired mitochondrial function in the vessel wall that may lead to arterial wall weakness. Thus, stroke in mitochondrial diseases could also be related to large vessels disease, but further studies are strongly needed. Moreover, mitochondrial aetiology should be kept in mind in patients with large vessel dissection, especially in those with additional mitochondrial red flags.
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http://dx.doi.org/10.1016/j.ymgmr.2016.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021764PMC
December 2016

Acute encephalopathy of the temporal lobes leading to m.3243A>G. When MELAS is not always MELAS.

Mitochondrion 2016 Sep 21;30:148-50. Epub 2016 Jul 21.

Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy. Electronic address:

MELAS syndrome (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a rare genetic condition whose differential diagnosis is often posed with juvenile stroke, but more rarely even with inflammatory/infectious encephalitis, causing diagnostic challenges. Here we report the case of a young man harbouring the m.3243A>G MELAS mutation presenting an acute onset mimicking the clinical and neuroimaging features of infective encephalitis.
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http://dx.doi.org/10.1016/j.mito.2016.07.008DOI Listing
September 2016

Genetics of ischaemic stroke in young adults.

BBA Clin 2015 Jun 29;3:96-106. Epub 2014 Dec 29.

Department of Experimental and Clinical Medicine, Neurological Clinic, University of Pisa, 56126 Pisa PI, Italy.

Background: Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach.

Scope Of Review: Here we review the single-gene causes of ischemic stroke, bringing the reader from the candidate gene method toward the exciting new horizons of genetic technology.

Major Conclusions: The aetiological diagnosis of ischemic stroke in young adults is more complex than in the elderly. The identification of a genetic cause is important to provide appropriate counseling and to start a correct therapy, when available. The advent of GWAS technology, such as for other complex pathological conditions, has contributed enormously to the understanding of many of these genetic bases. For success large, well phenotyped case cohorts are required, and international collaborations are essential.

General Significance: This review focuses on the main causes of genetically-based ischemic stroke in young adults, often classified as indeterminate, investigating also the recent findings of the GWAS, in order to improve diagnostic and therapeutic management.
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http://dx.doi.org/10.1016/j.bbacli.2014.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661509PMC
June 2015

Cerebral sinus venous thrombosis: clinical and pathogenetic perspectives from Tuscany.

Blood Coagul Fibrinolysis 2015 Jul;26(5):505-8

Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Italy.

Cerebral sinus venous thrombosis (CSVT) is a rare condition representing the 0.5-1% of all stroke cases which can have serious consequences. Early diagnosis and complete screening for acquired or inherited risk factors is crucial for decreasing morbidity and mortality. We have investigated clinical and aetiological factors in an Italian cohort of 43 patients with cerebral sinus venous thrombosis. Common presentation complaints were headache (81.4%), focal signs (20.9%), vomiting (11.6%) and seizures (6.9%). Acquired or inherited conditions were observed in more than 80% of cases. The commonest aetiological factors were contraceptives (74.1% of women), congenital thrombophilia (34.9%), infections and dysthyroidism (16.3%), hyperhomocysteinemia (9.3%), migraine (11.6%), cranial trauma (9.3%) and chronic myeloproliferative diseases (11.6%). Outcome was favourable in more than 80% of patients. Early diagnosis and anticoagulant treatment may decrease mortality and/or morbidity rates related with CVST in these patients. Thrombophilic abnormalities, either inherited or acquired, are worthy to be widely investigated.
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http://dx.doi.org/10.1097/MBC.0000000000000262DOI Listing
July 2015