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Glial cells are fundamental players in the central nervous system (CNS) development and homeostasis, both in health and disease states. In Parkinson's disease (PD), a dysfunctional glia-neuron crosstalk represents a common final pathway contributing to the chronic and progressive death of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc). Notably, glial cells communicating with each other by an array of molecules, can acquire a "beneficial" or "destructive" phenotype, thereby enhancing neuronal death/vulnerability and/or exerting critical neuroprotective and neuroreparative functions, with mechanisms that are actively investigated. An important way of delivering messenger molecules within this glia-neuron cross-talk consists in the secretion of extracellular vesicles (EVs). EVs are nano-sized membranous particles able to convey a wide range of molecular cargoes in a controlled way, depending on the specific donor cell and the microenvironmental milieu. Given the dual role of glia in PD, glia-derived EVs may deliver molecules carrying various messages for the vulnerable/dysfunctional DAergic neurons. Here, we summarize the state-of-the-art of glial-neuron interactions and glia-derived EVs in PD. Also, EVs have the ability to cross the blood brain barrier (BBB), thus acting both within the CNS and outside, in the periphery. In these regards, this review discloses the emerging applications of EVs, with a special focus on glia-derived EVs as potential carriers of new biomarkers and nanotherapeutics for PD.

Advanced applications of digital mammography such as dual-energy and tomosynthesis require multiple exposures and thus deliver higher dose compared to standard mammograms. A straightforward manner to reduce patient dose without affecting image quality would be removal of the anti-scatter grid, provided that the involved reconstruction algorithms are able to take the scatter figure into account [1]. Monte Carlo simulations are very well suited for the calculation of X-ray scatter distribution and can be used to integrate such information within the reconstruction software. Geant4 is an open source C++ particle tracking code widely used in several physical fields, including medical physics [2,3]. However, the coherent scattering cross section used by the standard Geant4 code does not take into account the influence of molecular interference. According to the independent atomic scattering approximation (the so-called free-atom model), coherent radiation is indistinguishable from primary radiation because its angular distribution is peaked in the forward direction. Since interference effects occur between x-rays scattered by neighbouring atoms in matter, it was shown experimentally that the scatter distribution is affected by the molecular structure of the target, even in amorphous materials. The most important consequence is that the coherent scatter distribution is not peaked in the forward direction, and the position of the maximum is strongly material-dependent [4]. In this contribution, we present the implementation of a method to take into account inter-atomic interference in small-angle coherent scattering in Geant4, including a dedicated data set of suitable molecular form factor values for several materials of clinical interest. Furthermore, we present scatter images of simple geometric phantoms in which the Rayleigh contribution is rigorously evaluated., (Copyright © 2017.)

Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p < 0.001) and higher chance of good functional outcome (OR 4.58, p < 0.001). Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p < 0.001) and lateral (+19.2%; p = 0.016) MCA territory compared to pretreatment during MCA occlusion. Safety indicators were treatment-related mortality and cardiorespiratory effects. The highest efficacy and safety profile was observed for HDT. Our findings suggest that acute modulation of cerebral collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

Background: Excessively long clamping time and suboptimal position of stitches can influence the anastomosis patency and the clinical outcome in cerebral bypass surgery. Coronary intravascular micro-shunts could represent an innovative solution for neurosurgical bypass, but the hemodynamic properties of these devices should be extensively studied before their translational application. We created an experimental in-vivo model and we analyzed the blood flow and pressure modification induced by the micro-shunt., Methods: After laparotomy, an intravascular micro-shunt was placed into the aorta of 8 adult rats, simulating a neurosurgical setting in which the shunt is temporary placed inside the receiving cerebral vessel. A fiber-optic pressure sensor was placed in the femoral artery and the blood pressure continuously recorded during the procedure. Using an ultrasound vascular probe, blood flow velocity in aorta was measured at baseline and both proximally and distally to the shunt., Results: After shunt positioning, no significant decrease in blood pressure was observed (mean value 68.57 versus 80.00 mmHg; P=0.48). Distal aortic blood flow, expressed as peak systolic velocity, showed a significant decrease after shunt positioning (mean value 51.88 versus 86.88 cm/sec; P=0.04), with a mean residual blood flow of 63%. Blood flow values recorded immediately upstream to the shunt did not differ from baseline., Conclusions: This is the first in-vivo experimental study concerning the hemodynamic properties of an intravascular micro-shunt. Our results demonstrate that this device provides a considerable blood out-flow without significant changes in blood pressure, suggesting that specific neurosurgical micro-shunts might be developed.

Intracranial collaterals are dynamically recruited after arterial occlusion and are emerging as a strong determinant of tissue outcome in both human and experimental ischemic stroke. The relationship between collateral flow and ischemic penumbra remains largely unexplored in pre-clinical studies. The aim of the present study was to investigate the pattern of collateral flow with regard to penumbral tissue after transient middle cerebral artery (MCA) occlusion in rats. MCA was transiently occluded (90min) by intraluminal filament in adult male Wistar rats (n=25). Intracranial collateral flow was studied in terms of perfusion deficit and biosignal fluctuation analyses using multi-site laser Doppler monitoring. Molecular penumbra was defined by topographical mapping and quantitative signal analysis of Heat Shock Protein 70kDa (HSP70) immunohistochemistry. Functional deficit and infarct volume were assessed 24h after ischemia induction. The results show that functional performance of intracranial collaterals during MCA occlusion inversely correlated with HSP70 immunoreactive areas in both the cortex and the striatum, as well as with infarct size and functional deficit. Intracranial collateral flow was associated with reduced areas of both molecular penumbra and ischemic core and increased areas of intact tissue in rats subjected to MCA occlusion followed by reperfusion. Our findings prompt the development of collateral therapeutics to provide tissue-saving strategies in the hyper-acute phase of ischemic stroke prior to recanalization therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: The abuse of anabolic steroids is emerging as a psychosocially significant issue. In the last few years the use of the substances has shifted from professional sports to amateur sports and certain occupations (bouncers, models, etc.). In the literature, steroid users are portrayed as multidrug users who engage in dangerous and aggressive behavior towards themselves and others. This study looks into the habits, lifestyles and psychological profiles of a group of subjects who make regular use of sports centres in the city of Palermo, Italy, with the aim of establishing how the abuse of anabolic substances is associated with a specific lifestyle and particular psychosocial behaviour., Methods: A revision of the American Massachusetts Youth Risk Survey questionnaire (1993), adapted for the Italian context, and a personality assessment scale, The Adjective Check List (1980), were administered to a group of 71 subjects., Results: Fifteen of these subjects admitted taking steroids with differing frequencies. Using Spearman's rho rank correlation, repeated use of anabolic steroids was found to be correlated with abuse of other types of drugs, risk behavior and a distinct personality pattern. Steroid abuse was found to be significantly correlated (r = 0.35, 0.31, 0.30, 0.28, P < 0.01) with illegal drug use (LSD, cocaine and heroin)., Conclusions: It is therefore imperative to develop studies and analyses to investigate more thoroughly the phenomenon and its related psychological and social context in order to lay the foundations for a targeted prevention programme, especially in countries such as Italy where this type of drug abuse is still largely unrecognised and risks degenerating into a new, full-blown social disease.

A study by National Health Unit - U.S.S.L. 32 on 28 patients suffering from manic depressive psychosis has shown the great importance of social and environment factors in the treatment of this disease. In two test groups given the same quantity of lithium salts, the one also receiving a social and environmental assistance revealed a net reduction in the number of hospital admissions for manic symptoms whereas no significant improvement was obtained in the other group.