Cerebellum in timing control: Evidence from contingent negative variation after cerebellar tDCS

Background and aims Timing control is defined as the ability to quantify time. The temporal estimation of supra-seconds range is generally seen as a conscious cognitive process, while the sub-seconds range is a more automatic cognitive process. It is accepted that cerebellum contributes to temporal processing, but its function is still debated. The aim of this research was to better explore the role of cerebellum in timing control. We transitorily inhibited cerebellar activity and studied the effects on CNV components in healthy subjects. Methods Sixteen healthy subjects underwent a S1-S2 duration discrimination motor task, prior and after cathodal and sham cerebellar tDCS, in two separate sessions. In S1-S2 task they had to judge whether the duration of a probe interval trial was shorter (Short-ISI-trial:800 ms), longer (long-ISI-trail:1600 ms), or equal to the Target interval of 1200 ms. For each interval trial for both tDCS sessions, we measured: total and W2-CNV areas, the RTs of correct responses and the absolute number of errors prior and after tDCS. Results After cathodal tDCS a significant reduction in total-CNV and W2-CNV amplitudes selectively emerged for Short (p < 0.001; p = 0.003 respectively) and Target-ISI-trial (total-CNV: p < 0.001; W2-CNV:p = 0.003); similarly, a significant higher number of errors emerged for Short (p = 0.004) and Target-ISI-trial (p = 0.07) alone. No differences were detected for Longer-ISI-trials and after sham stimulation. Conclusions These data indicate that cerebellar inhibition selectively altered the ability to make time estimations for second and sub-second intervals. We speculate that cerebellum regulates the attentional mechanisms of automatic timing control by making predictions of interval timing

Mental flexibility in Parkinson's disease with central fatigue: Data from the frontal assessment battery

Background and aims Central fatigue is defined as a reduced energy level or an increased perception of effort, often associated to a failure in initiating and maintaining tasks that require self-motivation. It is common in Parkinson's disease population and it has been hypothesized to be related to a dysfunction in the striato-talamo- prefrontal loop. The aim of the present study was to explore the association between fatigue and executive functions as index of integrity of the striato-thalamo-prefrontal loop. Methods Twenty-nine non-demented PD patients without fatigue - PDnF, 28 non-demented PD patients with fatigue - PDF and 26 age and sex- matched controls underwent an evaluation with the Frontal Assessment Battery (FAB), MMSE, PSQI, BDI, STAI Y1-2, PDQ-39. Differences between groups in FAB scores (total and subitems) were analyzed by means of Kruskal-Wallis test. Moreover, a correlation between fatigue and FAB was also analyzed. Results Overall parkinsonian population displayed worse performance than controls in frontal scores especially inhibitory control (p = 0.008) and sensitivity to interference (p = 0.014). PDF displayed significantly worse than PDnF in verbal fluency (p = 0.05). Fatigue severity inversely correlated with executive performance (p b 0.001). Conclusions Phonemic fluency tasks are thought to reflect the simultaneous engagement of several executive functions such as attention, working memory, retrieval, information processing. The association of central fatigue with a deficit in mental flexibility, could support the hypothesis that central fatigue is a reliable index of the impairment of higher executive functions needed in order to effectively assess costs and benefits related to adaptive decision- making behavior

Electro-Thermal Parameters of Graphene Nano-Platelets Films for De-Icing Applications

This paper provides a study of some relevant electro-thermal properties of commercial films made by pressed graphene nano-platelets (GNPs), in view of their use as heating elements in innovative de-icing systems for aerospace applications. The equivalent electrical resistivity and thermal emissivity were studied, by means of models and experimental characterization. Macroscopic strips with a length on the order of tens of centimeters were analyzed, either made by pure GNPs or by composite mixtures of GNPs and a small percentage of polymeric binders. Analytical models are derived and experimentally validated. The thermal response of these graphene films when acting as a heating element is studied and discussed

Analysis of dynamic wireless power transfer systems based on behavioral modeling of mutual inductance

This paper proposes a system-level approach suitable to analyze the performance of a dynamic Wireless Power Transfer System (WPTS) for electric vehicles, accounting for the uncertainty in the vehicle trajectory. The key-point of the approach is the use of an analytical behavioral model that relates mutual inductance between the coil pair to their relative positions along the actual vehicle trajectory. The behavioral model is derived from a limited training data set of simulations, by using a multi-objective genetic programming algorithm, and is validated against experimental data, taken from a real dynamic WPTS. This approach avoids the massive use of computationally expensive 3D finite element simulations, that would be required if this analysis were performed by means of look-up tables. This analytical model is here embedded into a system-level circuital model of the entire WPTS, thus allowing a fast and accurate analysis of the sensitivity of the performance as the actual vehicle trajectory deviates from the nominal one. The system-level analysis is eventually performed to assess the sensitivity of the power and efficiency of the WPTS to the vehicle misalignment from the nominal trajectory during the dynamic charging process

Basophil activation test for Staphylococcus aureus enterotoxins in severe asthmatic patients

Background: Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs—the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST-1)—can induce both polyclonal and specific IgE responses. Objective: The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT). Methods: 57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST-1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ basophils to SEs and to negative control) was >2. Two threshold values (>0.1 kU/L and >0.35 kU/L, respectively) were used to assess serum SEsIgE. Results: 36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35 kU/L (SEs IgE+) was associated with BAT SEs positivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE− SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations. Conclusions: The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma

Class II phosphoinositide 3-kinase C2 beta regulates a novel signaling pathway involved in breast cancer progression

It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focused on one specific isoform with very little known about the potential role of the other members of this family in cancer. Here we demonstrate that the class II enzyme PI3K-C2β is overexpressed in several human breast cancer cell lines and in human breast cancer specimens. Our data indicate that PI3K-C2β regulates breast cancer cell growth in vitro and in vivo and that PI3K-C2β expression in breast tissues is correlated with the proliferative status of the tumor. Specifically we show that downregulation of PI3K-C2β in breast cancer cell lines reduces colony formation, induces cell cycle arrest and inhibits tumor growth, in particular in an estrogen-dependent in vivo xenograft. Investigation of the mechanism of the PI3K-C2β-dependent regulation of cell cycle progression and cell growth revealed that PI3K-C2β regulates cyclin B1 protein levels through modulation of microRNA miR-449a levels. Our data further demonstrate that downregulation of PI3K-C2β inhibits breast cancer cell invasion in vitro and breast cancer metastasis in vivo. Consistent with this, PI3K-C2β is highly expressed in lymph-nodes metastases compared to matching primary tumors. These data demonstrate that PI3K-C2β plays a pivotal role in breast cancer progression and in metastasis development. Our data indicate that PI3K-C2β may represent a key molecular switch that regulates a rate-limiting step in breast tumor progression and therefore it may be targeted to limit breast cancer spread

Pathology and molecular analysis of ' Hapalotrema mistroides ' (Digenea: Spirorchiidae) infecting a Mediterranean loggerhead turtle ' Caretta caretta '

Turtle blood flukes belonging to the family Spirorchiidae (Digenea) represent a major threat for sea turtle health and are considered the most important parasitic cause of turtle stranding and mortality worldwide. Despite the large diversity of spirorchiid species found globally, there are only 2 records for free-ranging Mediterranean sea turtles that date back to the late 1800s involving just Hapalotrema mistroides Monticelli, 1896. This study describes the first fatal confirmed case of spirorchiidiasis in a free-ranging Mediterranean loggerhead turtle Caretta caretta (Linnaeus) and, owing to the complexities of taxonomic identification of these parasites, provides the first molecular characterization and phylogenetic analysis of H. mistroides from the Mediterranean Sea. The loggerhead turtle showed cachexia and digestive disorders associated with severe damage to the pancreas and intestinal ganglia, caused by deposition of Hapalotrema eggs forming granulomas. Massive Hapalotrema egg emboli in several tissues and organs and encephalitis were the most probable contributions to the death of the turtle. The congruence between the phylogenetic analysis of both the ITS2 and 28S rDNA resolved the Italian and USA H. mistroides as the same species, confirming the parasite identification. The case here described clearly indicates that the blood flukes should be considered in the differential diagnosis of Mediterranean sea turtle diseases