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1. Methods for the Assessment of Multisensory Processing: Behavioral and Neuropsychological Approaches

Author

Valeriani, M, de Tommaso, M, Manzone, D, Nava, E, Bolognini, N, Manzone D. M., Nava E., Bolognini N., Valeriani, M, de Tommaso, M, Manzone, D, Nava, E, Bolognini, N, Manzone D. M., Nava E., and Bolognini N.

Abstract

Since birth, we learn about the perceptual and social world through our senses. Learning to appropriately bind multisensory information is key to effectively interact with our surroundings. In this chapter, we will review the behavioral, computational, and neurophysiological methods used to assess multisensory processing in healthy adult individuals. In the first part, we will provide an overview of fundamental principles governing the activity of multisensory neurons in the animal brain since these principles still provide an influential framework for the investigation of multisensory processing in humans too. In the second part, we will present a series of behavioral paradigms that have been adopted in the past 20 years to assess multisensory processing, particularly focusing on the difference between paradigms assessing multisensory integration and paradigms assessing crossmodal interactions, in which stimulation of one sensory system affects the experience in a different sense, typically leading to illusory percepts. The last part will provide a critical overview of electrophysiological and neuroimaging approaches to measure multisensory interactions in the human brain.

Published
2024

3. Morphogenic effect of common solvent in the self-assembly behavior of amphiphilic PEO-b-PLA

Author

Simonutti, R, Bertani, D, Marotta, R, Ferrario, S, Manzone, D, Mauri, M, Gregori, M, Orlando, A, Masserini, M, Simonutti, R., Bertani, D., Marotta, R., Ferrario, S., Manzone, D., Mauri, M., Gregori, M., Orlando, A., Masserini, M., Simonutti, R, Bertani, D, Marotta, R, Ferrario, S, Manzone, D, Mauri, M, Gregori, M, Orlando, A, Masserini, M, Simonutti, R., Bertani, D., Marotta, R., Ferrario, S., Manzone, D., Mauri, M., Gregori, M., Orlando, A., and Masserini, M.

Abstract

The formation of block copolymer nanoparticles is commonly obtained by switching solvent quality from good solvent for both blocks to a selective solvent for one block. The effect of the selective solvent on particle dimension, shape and inner structure has been analyzed in detail, instead less attention has been focused on the role of the common solvent. Poly(ethylene oxide)-block-poly(lactic acid) (PEO-b-PLA) is widely used for the preparation of nanometric drug delivery systems and the control of the particle morphology has relevant effects on bioactivity. In this work we investigate the effect of using different common solvents (acetone, dioxane, tetrahydrofuran, dimethylformamide) on the self-assembly behavior of narrowly dispersed PEO-b-PLA copolymers, synthesized by metal free ring-opening polymerization, with large variation of molecular weight of the hydrophobic block (from 65 to 1300 lactic units). Dynamic light scattering (DLS) and cryo-electron microscopy (cryo-EM) analyses of PEO-b-PLA nanoparticles reveal that their size and shape are strongly dependent on the hydrogen bonding ability of the common solvent used in the self-assembly process. As consequence of these variations, also the cytoxicity of the nanoparticles is affected.

Published
2021

6. Autoassemblaggio di copolimeri a blocchi anfifilici da buoni solventi: verso una mappa morfologica predittiva per la scelta del sistema di trasporto dei farmaci

Author

Manzone, D, SIMONUTTI, ROBERTO, MANZONE, DANIELA MADDALENA, Manzone, D, SIMONUTTI, ROBERTO, and MANZONE, DANIELA MADDALENA

Abstract

Polymeric nanoparticles (NPs) are very promising “smart carriers” for the future of nanomedicine. The main advantages of polymeric NPs manufactured by self-assembly are: high control of shape and size, high stability and significant increase of the solubility of poorly soluble drugs. Particle morphology can condition cytotoxicity, circulation time in blood, release of drug and removal of NPs from the body and thus improve the therapeutic efficacy. In turn, assembly can be guided by the choice of the environment. In this work, a protocol was developed for the synthesis and characterization of self-assembled polymeric NPs. We selected amphiphilic block copolymers of polyethylene oxide (PEO) and polylactic acid (PLA), two polymers already approved by the US Food and Drugs Administration (FDA) for medical use. The synthesis of the poly (lactic acid block) on a block of poly (ethylene oxide) has been carried out, by means of ROP (Ring Opening Polymerization) using a completely metal-free synthesis, catalyzed by 1,5-diazabiciclo[5.4.0]undec-5-ene (DBU), in order to avoid any problems of poor biocompatibility or allergenicity. The compositional characterization was carried out by solution Nuclear Magnetic Resonance (NMR) and calorimetric properties have been studied by Differential Scanning Calorimetry (DSC). After polymerizing a great variety of PLA chains of different length (PEO113-b-PLAx- with x ranging from 30 to 1359), nanoparticles were assembled from different organic solvents: dimethylformamide (DMF), acetone, tetrahydrofuran (THF) and dioxane, using the technique of nanoprecipitation. NPs were then purified by dialysis and analyzed by Dynamic Light Scattering (DLS), obtaining for each sample a mean hydrodynamic diameter value and a value of dispersion diameters. Particle diameter ranged from 40 to 800 nm, with many of the polymers presenting different values as a function of the starting solvent. A plot of all samples in terms of the DLS variables displayed sever

Published
2017

10. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: Patterns and differences

Author

Cavalca, V, Tremoli, E, Porro, B, Veglia, F, Myasoedova, V, Squellerio, I, Manzone, D, Zanobini, M, Trezzi, M, Di Minno, M, Werba, J, Tedesco, C, Alamanni, F, Parolari, A, Parolari, A., MANZONE, DANIELA MADDALENA, Cavalca, V, Tremoli, E, Porro, B, Veglia, F, Myasoedova, V, Squellerio, I, Manzone, D, Zanobini, M, Trezzi, M, Di Minno, M, Werba, J, Tedesco, C, Alamanni, F, Parolari, A, Parolari, A., and MANZONE, DANIELA MADDALENA

Abstract

OBJECTIVES: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve reg

Published
2013

12. Morphogenic effect of common solvent in the self-assembly behavior of amphiphilic PEO-b-PLA

Author

A. Orlando, D. Manzone, Michele Mauri, M. Masserini, S. Ferrario, D. Bertani, Roberto Marotta, Maria Gregori, Roberto Simonutti, Simonutti, R, Bertani, D, Marotta, R, Ferrario, S, Manzone, D, Mauri, M, Gregori, M, Orlando, A, and Masserini, M

Subjects
Morphology, Polymers and Plastics, Block copolymer, Organic Chemistry, technology, industry, and agriculture, Nanoparticle, macromolecular substances, 02 engineering and technology, Self assembly, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, Solvent, chemistry.chemical_compound, Dynamic light scattering, Chemical engineering, Polymerization, chemistry, Amphiphile, Materials Chemistry, Copolymer, Dimethylformamide, 0210 nano-technology, Tetrahydrofuran
Abstract

The formation of block copolymer nanoparticles is commonly obtained by switching solvent quality from good solvent for both blocks to a selective solvent for one block. The effect of the selective solvent on particle dimension, shape and inner structure has been analyzed in detail, instead less attention has been focused on the role of the common solvent. Poly(ethylene oxide)-block-poly(lactic acid) (PEO-b-PLA) is widely used for the preparation of nanometric drug delivery systems and the control of the particle morphology has relevant effects on bioactivity. In this work we investigate the effect of using different common solvents (acetone, dioxane, tetrahydrofuran, dimethylformamide) on the self-assembly behavior of narrowly dispersed PEO-b-PLA copolymers, synthesized by metal free ring-opening polymerization, with large variation of molecular weight of the hydrophobic block (from 65 to 1300 lactic units). Dynamic light scattering (DLS) and cryo-electron microscopy (cryo-EM) analyses of PEO-b-PLA nanoparticles reveal that their size and shape are strongly dependent on the hydrogen bonding ability of the common solvent used in the self-assembly process. As consequence of these variations, also the cytoxicity of the nanoparticles is affected.

Published
2021

13. Autoassemblaggio di copolimeri a blocchi anfifilici da buoni solventi: verso una mappa morfologica predittiva per la scelta del sistema di trasporto dei farmaci

Author

MANZONE, DANIELA MADDALENA, Manzone, D, and SIMONUTTI, ROBERTO

Subjects
Self-Assembly, Copolymer, Solvent, Map, CHIM/04 - CHIMICA INDUSTRIALE, nanomedicine
Abstract

Polymeric nanoparticles (NPs) are very promising “smart carriers” for the future of nanomedicine. The main advantages of polymeric NPs manufactured by self-assembly are: high control of shape and size, high stability and significant increase of the solubility of poorly soluble drugs. Particle morphology can condition cytotoxicity, circulation time in blood, release of drug and removal of NPs from the body and thus improve the therapeutic efficacy. In turn, assembly can be guided by the choice of the environment. In this work, a protocol was developed for the synthesis and characterization of self-assembled polymeric NPs. We selected amphiphilic block copolymers of polyethylene oxide (PEO) and polylactic acid (PLA), two polymers already approved by the US Food and Drugs Administration (FDA) for medical use. The synthesis of the poly (lactic acid block) on a block of poly (ethylene oxide) has been carried out, by means of ROP (Ring Opening Polymerization) using a completely metal-free synthesis, catalyzed by 1,5-diazabiciclo[5.4.0]undec-5-ene (DBU), in order to avoid any problems of poor biocompatibility or allergenicity. The compositional characterization was carried out by solution Nuclear Magnetic Resonance (NMR) and calorimetric properties have been studied by Differential Scanning Calorimetry (DSC). After polymerizing a great variety of PLA chains of different length (PEO113-b-PLAx- with x ranging from 30 to 1359), nanoparticles were assembled from different organic solvents: dimethylformamide (DMF), acetone, tetrahydrofuran (THF) and dioxane, using the technique of nanoprecipitation. NPs were then purified by dialysis and analyzed by Dynamic Light Scattering (DLS), obtaining for each sample a mean hydrodynamic diameter value and a value of dispersion diameters. Particle diameter ranged from 40 to 800 nm, with many of the polymers presenting different values as a function of the starting solvent. A plot of all samples in terms of the DLS variables displayed several clusters, ideally associated to different morphologies. To verify the corresponding shapes, and then transform the plot into a morphological map that is able to guide the selection of the most promising nanocarriers for medical applications, Cryogenic Trasmission Electron Microscopy (cryo-TEM) investigation was necessary. Specificly we mapped the region of simple micelles (low diameter, low PDI) the region of polymersomes was mapped as well. The cytotoxicity tests were performed on all samples and only the largest nanoparticles reduced cell viability. Additional experiments of uptake and release of drugs were carried out, also through ad hoc assemblies in solvent mixtures that optimize the solubility of the drugs without affecting the morphology of “nanocarriers”.

Published
2017

14. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: Patterns and differences

Author

Marco Zanobini, Benedetta Porro, Francesco Alamanni, Matteo Trezzi, Alessandro Parolari, Elena Tremoli, Viviana Cavalca, Fabrizio Veglia, José Pablo Werba, Veronika A. Myasoedova, Matteo Nicola Dario Di Minno, Daniela Manzone, Calogero C. Tedesco, Isabella Squellerio, Cavalca, V, Tremoli, E, Porro, B, Veglia, F, Myasoedova, V, Squellerio, I, Manzone, D, Zanobini, M, Trezzi, M, Di Minno, M, Werba, J, Tedesco, C, Alamanni, F, Parolari, A, Cavalca, Viviana, Tremoli, Elena, Porro, Benedetta, Veglia, Fabrizio, Myasoedova, Veronika, Squellerio, Isabella, Manzone, Daniela, Zanobini, Marco, Trezzi, Matteo, DI MINNO, Matteo, Werba, José Pablo, Tedesco, Calogero, Alamanni, Francesco, and Parolari, Alessandro

Subjects
Aortic valve, Male, medicine.medical_treatment, Coronary Artery Disease, Antioxidants, Coronary artery bypass surgery, chemistry.chemical_compound, Aortic valve replacement, Principal Component Analysi, Prospective Studies, Coronary Artery Bypass, Heart Valve Prosthesis Implantation, Principal Component Analysis, Calcinosis, Mitral Valve Insufficiency, Middle Aged, medicine.anatomical_structure, Bypass surgery, Aortic valve stenosis, Aortic Valve, Cardiology, Calcinosi, Linear Model, Female, Antioxidant, Mitral valve regurgitation, Case-Control Studie, Cardiology and Cardiovascular Medicine, Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Aortic valve stenosi, Nitric Oxide, Internal medicine, medicine, Humans, Aged, Mitral valve repair, Chi-Square Distribution, business.industry, Coronary Artery Bypa, Oxidative Stre, Aortic Valve Stenosis, Original Articles, Biomarker, medicine.disease, Oxidative Stress, Prospective Studie, chemistry, Case-Control Studies, Biological Marker, Linear Models, Surgery, Asymmetric dimethylarginine, business, Biomarkers
Abstract

OBJECTIVES: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve regurgitation show more pronounced perturbations in these pathways. The clinical implications of these findings need to be investigated. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Published
2013

15. Ipsilateral eye contributions to online visuomotor control of right upper-limb movements.

Author

Loria T, Manzone D, Crainic V, and Tremblay L

Abstract

A limb's initial position is often biased to the right of the midline during activities of daily living. Given this specific initial limb position, visual cues of the limb become first available to the ipsilateral eye relative to the contralateral eye. The current study investigated online control of the dominant limb as a function of having visual cues available to the ipsilateral or contralateral eye, in relation to the initial start position of the limb. Participants began each trial with their right limb on a home position to the left or right of the midline. After movement onset, a brief visual sample was provided to the ipsilateral or contralateral eye. On one third of the trials, an imperceptible 3 cm target jump was introduced. If visual information from the eye ipsilateral to the limb is preferentially used to control ongoing movements of the dominant limb, corrections for the target jump should be observed when movements began from the right of the body's midline and vision was available to the ipsilateral eye. As expected, limb trajectory corrections for the target jump were only observed when participants started from the right home position and visual information was provided to the ipsilateral eye. We purport that such visuomotor asymmetry specialization emerges via neurophysiological developments, which may arise from naturalistic and probabilistic limb trajectory asymmetries., Competing Interests: Declaration of Competing Interest The authors have no financial interest or benefit that may arise from the direct application of this research., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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16. I Spy With My Dominant Eye.

Author

Manzone D, Loria T, and Tremblay L

Subjects
Female, Hand physiology, Humans, Male, Psychomotor Performance, Young Adult, Functional Laterality physiology, Movement physiology, Vision, Binocular physiology, Vision, Monocular physiology
Abstract

The authors investigated how visual information from the nondominant and dominant eyes are utilized to control ongoing dominant hand movements. Across 2 experiments, participants performed upper-limb pointing movements to a stationary target or an imperceptibly shifted target under monocular-dominant, monocular-nondominant, and binocular viewing conditions. Under monocular-dominant viewing conditions, participants exhibited better endpoint precision and accuracy. On target jump trials, participants spent more time after peak limb velocity and significantly altered their trajectories toward the new target location only when visual information from the dominant eye was available. Overall, the results suggest that the online visuomotor control processes that typically take place under binocular viewing conditions are significantly influenced by input from the dominant eye.

Published
2018
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17. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: patterns and differences.

Author

Cavalca V, Tremoli E, Porro B, Veglia F, Myasoedova V, Squellerio I, Manzone D, Zanobini M, Trezzi M, Di Minno MN, Werba JP, Tedesco C, Alamanni F, and Parolari A

Subjects
Aged, Antioxidants metabolism, Aortic Valve metabolism, Aortic Valve surgery, Aortic Valve Stenosis diagnosis, Aortic Valve Stenosis metabolism, Biomarkers blood, Biomarkers urine, Calcinosis diagnosis, Calcinosis metabolism, Case-Control Studies, Chi-Square Distribution, Coronary Artery Disease diagnosis, Coronary Artery Disease metabolism, Female, Humans, Linear Models, Male, Middle Aged, Mitral Valve Insufficiency diagnosis, Mitral Valve Insufficiency metabolism, Principal Component Analysis, Prospective Studies, Aortic Valve pathology, Aortic Valve Stenosis surgery, Calcinosis surgery, Coronary Artery Bypass, Coronary Artery Disease surgery, Heart Valve Prosthesis Implantation, Mitral Valve Insufficiency surgery, Nitric Oxide metabolism, Oxidative Stress
Abstract

Objectives: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency., Methods: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis., Results: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis., Conclusions: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve regurgitation show more pronounced perturbations in these pathways. The clinical implications of these findings need to be investigated.

Published
2013
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18. Falsely negative Doppler examinations in testicular torsion.

Author

Nasrallah PF, Manzone D, and King LR

Subjects
Adolescent, Child, Humans, Male, Rheology, False Negative Reactions, Spermatic Cord Torsion diagnosis, Ultrasonography
Abstract

Use of the Doppler ultrasonic flowmeter to assess testicular perfusion has potentially precise application in the evaluation of acute scrotal swelling. Recent reports suggest an almost infallible degree of accuracy in differentiating testicular torsion, with reduced or absent blood flow, from inflammatory processes, with accompanying increased vascular perfusion. This report of 4 falsely negative Doppler examinations confirmed by surgical exploration warns against relying on this as a single test in the diagnosis of testicular torsion. Only thorough clinical assessment of each patient and exploration in doubtful cases will assure maximum testicular salvage.

Published
1977
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