Cognitive and functional connectivity alterations in Friedreich's ataxia

Objective: The aim of this study was to perform the first resting-state func- tional MRI (RS-fMRI) analysis in Friedreich’s ataxia (FRDA) patients to assess possible brain functional connectivity (FC) differences in these patients, and test their correlations with neuropsychological performances. Methods: In total, 24 FRDA patients (M/F: 15/9, mean age 31.3 15.0) and 24 healthy controls (HC; M/F: 15/9, mean age 30.7 15.5) were enrolled in this cross-sectional study. All patients underwent a thorough neuropsychological battery, investigat- ing different cognitive domains. RS-fMRI data were analyzed using a seed-based approach, probing the FC of cortical areas potentially referable to specific exec- utive and cognitive functions compromised in FRDA. Results: Compared to HC, FRDA patients showed overall worse neuropsychological scores in several domains, including global cognitive assessment, spatial memory, visuopercep- tion and visuospatial functions, and executive functions. Analysis of RS-fMRI data showed a higher FC in FRDA patients compared to HC between paracin- gulate gyri and the medial frontal gryrus, between the superior frontal gyrus and bilateral angular gyri, and between the middle temporal gyrus and the cin- gulate gyrus, with a reduced FC between the medial frontal gryrus and the cere- bellum. Interpretation: We found a reduction in FC between frontal areas and the contralateral cerebellar cortex in FRDA, in line with the known alteration in cerebello-cortical pathway in this condition. On the other hand, a higher FC between different cortical areas was shown, possibly reflecting a compensatory phenomenon. These results, in conjunction with clinical findings, may shed new light on the pattern of supratentorial and infratentorial involvement, and on dynamics of brain plasticity in this disease

Antitumoral potential, antioxidant activity and carotenoid content of two Southern Italy tomato cultivars extracts: San Marzano and Corbarino

Gastric cancer represents a diffuse and aggressive neoplasm, whose mortality index is among the highest in the world. Predisposing factors are E-cadherin mutations, Helicobacter pylori infection, and a diet rich in salted and smoked food, with a low intake of fresh fruits and vegetables. Here, we analyzed the effect of total lipophilic extracts of two Southern Italy tomato varieties, San Marzano and Corbarino, on an in vitro model of gastric cancer, YCC-1, YCC-2 and YCC-3 cell lines, characterized by different aggressiveness. Our results showed a possible role of these two varieties of tomatoes against typical neoplastic features. The treatment with tomato extracts affected cancer cell ability to grow both in adherence and in semisolid medium, reducing also cell migration ability. No toxic effects were observed on non-tumoral cells. We found, on gastric cancer cell lines, effects on both cell cycle progression and apoptosis modulation. The extent of antineoplastic effects, however, did not seem to correlate with the carotenoid content and antioxidant activity of the two tomato varieties. Our data indicate that San Marzano and Corbarino intake might be further considered as nutritional support not only in cancer prevention, but also for cancer patient diet

Cinnamic anilides as new mitochondrial permeability transition pore inhibitors endowed with ischemia-reperfusion injury protective effect in vivo

In this account, we report the development of a series of substituted cinnamic anilides that represents a novel class of mitochondrial permeability transition pore (mPTP) inhibitors. Initial class expansion led to the establishment of the basic structural requirements for activity and to the identification of derivatives with inhibitory potency higher than that of the standard inhibitor cyclosporine-A (CsA). These compounds can inhibit mPTP opening in response to several stimuli including calcium overload, oxidative stress, and thiol cross-linkers. The activity of the cinnamic anilide mPTP inhibitors turned out to be additive with that of CsA, suggesting for these inhibitors a molecular target different from cyclophylin-D. In vitro and in vivo data are presented for (E)-3-(4-fluoro-3-hydroxy-phenyl)-N-naphthalen-1-yl- acrylamide 22, one of the most interesting compounds in this series, able to attenuate opening of the mPTP and limit reperfusion injury in a rabbit model of acute myocardial infarction

The real TiO 2

We present a multiscale simulation of charge transport in a solid-state dye-sensitized solar cell, where the real morphology between TiO2 and the hole transport material is included