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Driving is a common activity with a significant impact on the quality of life since enables independence and fosters social activities. Nevertheless, driving is a rather complex task that requires different skills, such as physical abilities, proper judgement, risks perception / evaluation. Both these physical and cognitive abilities can be impaired after Multiple Sclerosis (MS) and can additionally be affected by the individual emotional state and disease progression. Driving simulators can be a good solution to assess and train driving skills of people with MS, but there are currently few studies focused on MS and driving ability. Moreover, they mostly aim at understanding driving performance impairments, mostly during monotonous highway drives. Here, we describe the framework of a new personalized driving simulator ADRIS 2.0, and the results of a first test on a group of unimpaired young adults and of a pilot test with three MS and sex and age-matched control subjects. Subjects trained with ADRIS 2.0 for a session of 30 minutes, driving through scenarios with different levels of difficulties. The system resulted easy to use and able to provide a realistic driving experience for all three groups of subjects. It also provided quantitative metrics that described MS drivers slower and prone to commit more infractions and collisions than control subjects. Thus, the developed simulator resulted well tolerated by all users, capable of detecting differences between control and MS subjects and its potential could be further exploited into the design of a personalized training of MS people.

Vol. 3, n. 1, 2021 Special Issue: Mannese, E., Presentazione, P. 1 ; Violante, L., La politica come pedagogia, P. 3 ; Buttafuoco, P., Ancora un bicchiere di cicuta, P. 9 ; Caligiuri, M., Per una pedagogia della nazione. Politica ed educazione in Italia nel XXI secolo, P. 14 ; Carboni, C., Il knowledge gap e come contrastarlo , P. 28 ; Ceruti, M. - Bellusci, F., Governare ed educare al tempo della complessit��, P. 37 ; Colosimo, M.L., L���improvviso fiume del vivere, P. 43 ; Dipasquale, G., Edipo, il potente impaurito. Una ipotesi di messinscena, P. 46 ; Elia, G., L���educazione alla politica come esercizio di cittadinanza e fiducia nel futuro, P. 61 ; Ferrari, F., Paideia e Polis nella Repubblica di Platone, P. 69 ; Impagliazzo, M., Le scuole della pace: un modello di educazione alla democrazia e alla pace, P. 83 ; Leganza, G., Leonardo Sciascia e Leonardo Sinisgalli, P. 91 ; Lombardi, M.G., Pedagogia e Politica tra neoliberalismo e responsabilit�� educative, P. 99 ; Ricci, S., L���educazione alla democrazia e l���esercizio del soft power, P. 103 ; Salmeri, S., Pensare criticamente e educare alla democrazia, P. 111 ; Sirignano, F.M., La crisi delle democrazie europee e l���esigenza di una pedagogia politica, P. 122 ; Interviste di Emiliana Mannese a Marco Damilano, Maria Grazia Riva, Massimiliano Fiorucci, Vincenzo Loia, P. 134 ; Balzano, V., Democrazia, educazione e dignit��: la centralit�� della persona nel rinnovato rapporto tra pedagogia e politica, P. 152 ; Cagol, M., Per una pedagogia etica e politica della complessit��, P. 163 ; Castaldi, M.C., Libert��, cura e generativit��: le parole comuni della relazione pedagogia-politica, P. 171 ; Della Piana, B., Costruire Spazi di Apprendimento Inclusivi per Pensare Collettivamente: Lo sviluppo di Risorse Umane Culturalmente Intelligenti, P. 181 ; Donato, D. - Garc��a de Fez, S., La escuela del siglo XXI: una oportunidad para cogenerar la educaci��n como bien com��n, P. 192 ; Giordano, M., Ripensare il rapporto dialettico tra Pedagogia e Politica al tempo della complessit��, P. 202 ; Rubin, A., Pedagogia e politica: prospettive di ricerca, P. 211.

Prep1 is a homeodomain transcription factor which has an important role in hindbrain development. Prep1 expression is also kept in adult mouse brain and in particular within the olfactory bulbs. Moreover, many Prep1 neurons co-localize with Calbindin-positive periglomerular interneurons in olfactory glomerular layer. However, Prep1 function in this brain region is still unknown. In this study, we show that Prep1 hypomorphic heterozygous (Prep1i/+) mice express low levels of protein and feature a 30% reduction of olfactory bulb area, compared to WT mice. In addition, Prep1i/+ mice olfactory bulb histological analysis indicated a 20% lower cytochrome C oxidase activity within the glomerular layer, accompanied by a reduced number of periglomerular interneurons, compared to the WT littermates. Consistently, olfactory perception test highlighted that Prep1 hypomorphic heterozygous mice display a scant ability to distinguish odors, which significantly impacts on feeding behavior, as Prep1i/+ mice revealed a reduced preference for high-fat food. Analysis of BDNF signaling, which represents the main molecular mediator of olfactory plasticity, showed that Prep1i/+ mouse olfactory bulbs feature a 30% reduction of TrkB receptor levels and a decreased activation of ERK1/2. Similarly, overexpression of Prep1 in mouse neuronal cells (N2A) caused an increase of TrkB expression levels, BDNF-induced ERK phosphorylation, and cell viability, compared to control cells. We conclude that Prep1 deficiency alters olfactory morpho-functional integrity and olfaction-mediated eating behavior by affecting BDNF-TrkB signaling. Prep1 could, therefore, play a crucial role in behavioral dysfunctions associated to impaired responsiveness to BDNF. Electronic supplementary material The online version of this article (10.1007/s12035-018-0873-7) contains supplementary material, which is available to authorized users.

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p < 0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p = 0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r = 0.418 and p = 0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.

The present study was aimed to evaluate the malvidin’s protective effects on damage induced by 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion in rat pial microcirculation. Rat pial microcirculation was observed using fluorescence microscopy through a closed cranial window. Western blotting analysis was performed to investigate the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) and matrix metalloproteinase 9 (MMP-9) expression. Moreover, MMP-9 activity was evaluated by zymography. Finally, neuronal damage and radical oxygen species (ROS) formation were assessed. In all animals, pial arterioles were classified in five orders of branching according to Strahler’s method. In hypoperfused rats, 30 min BCCAO and 60 min reperfusion caused a decrease in arteriolar diameter, an increase in microvascular leakage and leukocyte adhesion, accompanied by decreased capillary perfusion and red blood cell velocity (VRBC). Moreover, marked neuronal damage and evident ROS generation were detected. Conversely, malvidin administration induced arteriolar dilation in dose-related manner, reducing microvascular leakage as well as leukocyte adhesion. Capillary perfusion and VRBC were protected. Nitric oxide synthase inhibition significantly attenuated malvidin’s effects on arteriolar diameter. Western blotting analysis revealed an increase in eNOS and p-eNOS expression, while zymography indicated a decrease in MMP-9 activity after malvidin’s administration. Furthermore, malvidin was able to prevent neuronal damage and to decrease ROS generation. In conclusion, malvidin protects rat pial microcirculation against BCCAO/reperfusion injury, preventing blood-brain impairment and neuronal loss. Malvidin’s effects appear to be mediated by eNOS activation and scavenger activity.

Matrix metallo-proteinases (MMPs) are a family of zinc-dependent endopeptidases, capable of degrading all the molecular components of extracellular matrix. A class of MMPs is gelatinases which includes gelatinase A or MMP-2 (72 kDa) and gelatinase B or MMP-9 (92 kDa), which have been shown to play critical roles in pathophysiology of many human disease and, in particular, cancer progression. For these reasons they obtained a great interest as potential non-invasive biomarker in providing useful clinical information in cancer diagnosis and therapy. A sensitive and unexpensive method for analysis of gelatinases is the gelatine zymography, which allows to measure the relative amounts of active and inactive enzymes in body fluids and tissue extracts. The procedure involves the electrophoretic separation of proteins under denaturing but non reducing conditions through a polyacrylamide gel containing a synthetic substrate (gelatin). The aim of this mini-review has been to describe the general principles of gelatine zymography technique, underling the main advantages and disadvantages. Even though an improvement of this method is necessary for a better applicability in laboratory medicine, gelatine zymography represents the most convenient method to detect the activity of the different gelatinases from a wide range of biological samples.

The identification of biomarkers in urine or serum samples from patients with bladder cancer is urgently required for the development of non-invasive methods for the diagnosis of bladder carcinoma and to facilitate follow-up surveillance, to combat the high progression and recurrence rates of this type of cancer. The current study measured the content of matrix metalloproteinase (MMP)-2 and -9, as well as tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in the urine and sera of 41 patients with bladder cancer by ELISA. The association between levels of MMP-2 and -9 and TIMP-1 and -2, and tumor grade and stage were investigated to verify whether these molecules are involved in tumor differentiation. Statistical analysis of the data revealed that urinary TIMP-1 levels were significantly higher in the high grade group compared with those of the low grade samples (P=0.022). The results also revealed a significantly differing distribution of TIMP-1 expression between Ta and T1 stage specimens (P=0.040). The corresponding area under the curves (AUCs) were 0.72, with a sensitivity of 0.70 and specificity of 0.75. In addition, neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex levels in the sera were measured. All molecules evaluated were detected in the sera of the patients studied. In particular, tumors staged as non-muscle invasive (Ta and T1), demonstrated significantly higher NGAL levels compared with those of muscle invasive (>T1) bladder cancer (32.8 ng/ml vs. 16.2 ng/ml; P=0.029). The discriminatory ability of NGAL expression was confirmed by receiver operating characteristic curve analysis that revealed an AUC of 0.75, a sensitivity of 0.88 and a specificity of 0.67. These data indicated that urinary TIMP-1 and serum NGAL may be useful non-invasive biomarkers to provide clinical information for bladder cancer disease management. Multicenter, prospective studies are required to confirm these preliminary results.