Effectiveness of equine-assisted activities and therapies for improving adaptive behavior and motor function in autism spectrum disorder

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7-15 years as well as the impact of EAAT on the magnitude of stress in the parent-child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p 64 0.01) as well as a progressive improvement in the child's abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples

Prokineticin 2 upregulation in the peripheral nervous system has a major role in triggering and maintaining neuropathic pain in the chronic constriction injury model

The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI) of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7) reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi) and in the ipsilateral DRG since 6 dpi. PROK2 protein overexpression was evident in Schwann Cells, infiltrating macrophages and axons in the peripheral nerve and in the neuronal bodies and some satellite cells in the DRG. Therapeutic treatment of neuropathic mice with the PKR-antagonist, PC1, impaired the PROK2 upregulation and signalling. This fact, besides alleviating pain, brought down the burden of proinflammatory cytokines in the damaged nerve and prompted an anti-inflammatory repair program. Such a treatment also reduced intraneural oedema and axon degeneration as demonstrated by the physiological skin innervation and thickness conserved in CCI-PC1 mice. These findings suggest that PROK2 plays a crucial role in neuropathic pain and might represent a novel target of treatment for this disease

Halogenated triazinediones behave as antagonists of PKR1: in vitro and in vivo pharmacological characterization

Different prokineticin receptor antagonists, based on the triazinedione scaffold, were synthesized by a new efficient method. Here we demonstrated that 5-benzyltriazinedionessubstituted in position para of the benzyl group with halogens provide compounds endowed with interesting selectivity for the Prokineticin receptor 1 (PKR1). BRET technology indicates that such substitutionresults in increased affinity for thePKR1.The affinity for PKR2, always in M range, was never significantly affected by the para-halogen-benzyl pharmacophores. The analog bearing a para-bromobenzyl pharmacophore (PC-25) displayed the highest affinity for PKR1 (~18 times higher than the reference PC-1 that bears apara-ethyl benzyl group) and the highest selectivity (~300 times). The other halogen substitutedanalogs (PC-7, PC-18 and PC-35), showed selectivity for PKR1 more than 100 times higher than for PKR2. Using transgenic mice lacking one of the two PKRs we demonstrated that all these compounds were able to abolish the Bv8-induced hyperalgesia in mice still expressing the PKR1 at doses lower than those necessary to abolish hyperalgesia in mice expressing only the PKR2. The dose ratio reflected the in- vitro evaluated receptor selectivity

Reports about 8 selected benchmark cases of model hierarchies : Deliverable number: D5.1 - Version 0.1

Based on the multitude of industrial applications, benchmarks for model hierarchies will be created that will form a basis for the interdisciplinary research and for the training programme. These will be equipped with publically available data and will be used for training in modelling, model testing, reduced order modelling, error estimation, efficiency optimization in algorithmic approaches, and testing of the generated MSO/MOR software. The present document includes the description about the selection of (at least) eight benchmark cases of model hierarchies.EC/H2020/765374/EU/Reduced Order Modelling, Simulation and Optimization of Coupled Systems/ROMSO

Il naturalismo oggi. Abbozzo di una mappa e alcune riflessioni

This paper tries to draw a map of the various versions of naturalism to which the current philosophical debate aims – from the most radical, or ‘hard’ ones, to the mild-est, or liberal ones – and of the different projects of naturalization that are associated to them. In particular, in the first paragraphs, the present article will consider Timothy Williamson’s and Penelope Maddy’s attempts to inherit the demands of naturalism with-out declaring to be a naturalist (Williamson), or without making naturalism an empty slogan or a kind of masked first philosophy (Maddy). In the second part, the connec-tions between epistemological naturalism and ontological or metaphysical naturalism will be analysed. The questions will be: (1) is it possible to be naturalist with regard to epistemology without being naturalist with regard to ontology?; (2) is it possible to be ontologically naturalist without being epistemologically naturalist