67 research outputs found
How to design decentralisation to curb secessionist pressures? Top-down vs. bottom-up reforms
No full textThis paper looks at decentralisation as an institutional solution for curbing secessionist pressures by making potentially seceding regions strictly better off by staying in the union. We show that a bottom-up decentralisation reform, where single regions that can opt to assume or not stronger fiscal responsibilities on the basis of bilateral negotiations with the central government, may be more successful in avoiding instability and a secessionist conflict than more standard top-down decentralisation, where the central government assigns identical fiscal powers to all regions. The example of the decentralisation process in Spain over the last 40 years illustrates the relevance of the institutional pattern we analyse in the paper
Topiramate efficacy in an infant with partial seizures refractory to conventional antiepileptic drugs.
No full textRationale, relevance, and limits of stress-induced psychopathology in rodents as models for psychiatry research : an introductory overview
No full textEmotional and cognitive information processing represent higher-order brain functions. They require coordinated interaction of specialized brain areas via a complex spatial and temporal equilibrium among neuronal cell-autonomous, circuitry, and network mechanisms. The delicate balance can be corrupted by stressful experiences, increasing the risk of developing psychopathologies in vulnerable individuals. Neuropsychiatric disorders affect twenty percent of the western world population, but therapies are still not effective for some patients. Elusive knowledge of molecular pathomechanisms and scarcity of objective biomarkers in humans present complex challenges, while the adoption of rodent models helps to improve our understanding of disease correlate and aids the search for novel pharmacological targets. Stress administration represents a strategy to induce, trace, and modify molecular and behavioral endophenotypes of mood disorders in animals. However, a mouse or rat model will only display one or a few endophenotypes of a specific human psychopathology, which cannot be in any case recapitulated as a whole. To override this issue, shared criteria have been adopted to deconstruct neuropsychiatric disorders, i.e., depression, into specific behavioral aspects, and inherent neurobiological substrates, also recognizable in lower mammals. In this work, we provide a rationale for rodent models of stress administration. In particular, comparing each rodent model with a real-life human traumatic experience, we intend to suggest an introductive guide to better comprehend and interpret these paradigms
Termination of acute stress response by the endocannabinoid system is regulated through LSD1-mediated transcriptional repression of 2-AG hydrolases ABHD6 and MAGL
No full textAcute environmental stress rarely implies long-lasting neurophysiological and behavioral alterations. On the contrary, chronic stress exerts a potent toxic effect at the glutamatergic synapse whose altered physiology has been recognized as a core trait of neuropsychiatric disorders. The endocannabinoid system (ECS) plays an important role in the homeostatic response to acute stress. In particular, stress induces synthesis of endocannabinoid (eCB) 2-arachidonyl glycerol (2-AG). 2-AG stimulates presynaptic cannabinoid 1 (CB1) receptor contributing to stress response termination through inhibition of glutamate release, restraining thereafter anxiety arousal. We employ mouse models of stress response coupled to gene expression analyses, unravelling that in response to acute psychosocial stress in the mouse hippocampus, ECS-mediated synaptic modulation is enhanced via transcriptional repression of two enzymes involved in 2-AG degradation: α/β-hydrolase domain containing 6 (ABHD6) and monoacylglycerol lipase (MAGL). Such a process is orchestrated by the epigenetic corepressor LSD1 who directly interacts with promoter regulatory regions of Abhd6 and Magl. Remarkably, negative transcriptional control of Abhd6 and Magl is lost in the hippocampus upon chronic psychosocial stress, possibly contributing to trauma-induced drift of synapse physiology toward uncontrolled glutamate transmission. We previously showed that in mice lysine-specific demethylase 1 (LSD1) increases its hippocampal expression in response to psychosocial stress preventing excessive consolidation of anxiety-related plasticity. In this work, we unravel a nodal epigenetic modulation of eCB turn over, shedding new light on the molecular substrate of converging stress-terminating effects displayed by ECS and LSD1
Lafora disease : spectroscopy study correlated with neuropsychological findings
No full textPURPOSE:
To evaluate the metabolic changes both in grey and white matter in Lafora disease using proton magnetic resonance spectroscopy and to determine the possible correlation with the pattern of cognitive impairment.
METHODS:
Five patients with Lafora disease and six healthy controls were included in the study. Patients underwent at the same time-point neuropsychological testing and 1[H]MRS, using PRESS sequences (TE=136 and 25 ms) positioned in the frontal and posterior cingulate gyrus cortexes and in the adjacent frontal and parietal white matter.
RESULTS:
Neuropsychological testing showed in all patients a prevalent involvement of performance abilities--with partial sparing of verbal competences--and of executive functions, suggesting a major involvement of frontal areas. Analysis of 1[H]MRS showed a statistically significant reduction in NAA/mI and NAA/Cr in grey matter of patients compared to controls, more significant in frontal regions. In white matter, a significant reduction of NAA/mI ratio was observed both in the frontal and parietal regions, associated with a reduction of the NAA/Cr only in the frontal white matter. NAA/mI was found to be the most statistically significant altered parameter in all regions studied and the only significantly altered ratio in strong correlation with all sets of neuropsychological parameters.
CONCLUSIONS:
Our study confirmed the predominant metabolic damage in the frontal cortex, also demonstrating NAA/mI ratio to be the most sensitive parameter to detect metabolic brain changes in Lafora disease; moreover, it evidenced frontal white matter spectroscopic changes. Both spectroscopy values and clinical features of cognitive impairment showed a prevalent frontal impairment
Corrosion and oxidation behavior of a Fe-Al-Mn-C duplex alloy
No full textThe low-density steels represent a topic of great interest within the scientific world because of the great demand from the steel market of increasingly lighter materials, also featured by an optimal mix of the mechanical properties. In this work, the corrosion and hot oxidation resistance of a Fe-15%Mn-9.5%Al-6.5%Ni-1%Cr-0.43%C were analyzed and related to the microstructural features. The material behavior was analyzed both in the as-cast and in the heat-treated state. For the corrosion test, the experimental plan was fulfilled using four different concentrations of HCl and four temperatures. In the case of hot oxidation resistance, the exposure time and the temperature effects were evaluated. The corrosion resistance in HCl was comparable to the stainless steel, and the iso-corrosion curves showed excellent resistance of the 1300 degrees C solution-treated material, especially at low temperatures, but it is also good at high temperatures due to the hot oxidation
Ketogenic diet in Lafora disease: a long term follow-up pilot study
No full textPURPOSE: Lafora body disease (LBD) is severe and rapidly worsening progressive myoclonus epilepsy (PME), not treatable with specific therapy. In LBD patients, typical polyglucosan accumulations result from alterations of proteins involved in the regulation of glycogen metabolism. Thus, a ketogenic regimen might reasonably be expected to counteract the disease progression. We set out to assess the feasibility and tolerability of a long-term ketogenic diet (KD) in LBD patients and to make a preliminary evaluation of its effect on the disease course. METHODS: We treated five LBD patients with KD and evaluated the changes in the clinical, neuropsychological and neurophysiological findings over 10-30 months. RESULTS: The KD was well tolerated in all the patients for the first 16 months. Nutritional measures and laboratory findings remained substantially stable. The disease progressed in all the patients, reaching an advanced stage in one. Electrophysiological findings indicated the presence of increased cortical excitability in four patients, paralleling the worsening of the myoclonus.
CONCLUSION: KD was unable to stop the disease progression. However, given the considerable heterogeneity of the natural history of LBD, we cannot exclude the possibility that KD has the potential to slow down the disease progression. The application of this nutritional approach should be further evaluated in larger case series
Insights into cental and peripheral factors affacting the "oxidative performance" of skeletal muscle in aging
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