An Information System for Brownfield Regeneration: providing customised information according to stakeholders' characteristics and needs.

In the EU brownfield presence is still considered a widespread problem. Even though, in the last decades, many research projects and initiatives developed a wealth of methods, guidelines, tools and technologies aimed at supporting brownfield regeneration. However, this variety of products had and still has a limited practical impact on brownfield revitalisation success, because they are not used in their entire potential due to their scarce visibility. Also, another problem that stakeholders face is finding customised information. To overcome this non-visibility and not-sufficient customisation of information, the Information System for Brownfield Regeneration (ISBR) has been developed, based on Artificial Neural Networks, which allows understanding stakeholders' information needs by providing tailored information. The ISBR has been tested by stakeholders from the EU project TIMBRE case studies, located in the Czech Republic, Germany, Poland and Romania. Data gained during tests allowed to understand stakeholders' information needs. Overall, stakeholders showed to be concerned first on remediation aspects, then on benchmarking information, which are valuable to improve practices in the complex field of brownfield regeneration, and then on the relatively new issue of sustainability applied to brownfield regeneration and remediation. Mature markets confirmed their interest for remediation-related aspects, highlighting the central role that risk assessment plays in the process. Emerging markets showed to seek information and tools for strategic and planning issues, like brownfield inventories and georeferenced data sets. Results led to conclude that a new improved platform, combining the ISBR functionalities with geo-referenced ones, would be useful and could represent a further research application.

NIM811, a cyclophilin inhibitor without immunosuppressive activity, is beneficial in collagen VI congenital muscular dystrophy models.

Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are inherited muscle diseases due to mutations in the genes encoding the extracellular matrix protein collagen (Col) VI. Opening of the cyclosporin A-sensitive mitochondrial permeability transition pore (PTP) is a causative event in disease pathogenesis, and a potential target for therapy. Here, we have tested the effect of N-methyl-4-isoleucine-cyclosporin (NIM811), a non-immunosuppressive cyclophilin inhibitor, in a zebrafish model of ColVI myopathy obtained by deletion of the N-terminal region of the ColVI α1 triple helical domain, a common mutation of UCMD. Treatment with antisense morpholino sequences targeting col6a1 exon 9 at the 1-4 cell stage (within 1 h post fertilization, hpf) caused severe ultrastructural and motor abnormalities as assessed by electron and fluorescence microscopy, birefringence, spontaneous coiling events and touch-evoked responses measured at 24-48 hpf. Structural and functional abnormalities were largely prevented when NIM811--which proved significantly more effective than cyclosporin A--was administered at 21 hpf, while FK506 was ineffective. Beneficial effects of NIM811 were also detected (i) in primary muscle-derived cell cultures from UCMD and BM patients, where the typical mitochondrial alterations and depolarizing response to rotenone and oligomycin were significantly reduced; and (ii) in the Col6a1(-/-) myopathic mouse model, where apoptosis was prevented and muscle strength was increased. Since the PTP of zebrafish shares its key regulatory features with the mammalian pore, our results suggest that early treatment with NIM811 should be tested as a potential therapy for UCMD and BM.

Comparison of international approaches to sustainable remediation.

Since mid-to-late 2000s growing interest for sustainable remediation has emerged in initiatives from several international and national organisations as well as other initiatives from networks and forums. This reflects a realisation that risk-management activities can about bring environmental, social, and economic impacts (positive or negative) in addition to achieving risk-based remediation goals. These ideas have begun to develop as a new discipline of "sustainable remediation". The various initiatives have now published a number of frameworks, standards, white papers, road maps and operative guidelines. The similarities and differences in the approaches by these outputs and general trends have been identified. The comparison is based on a set of criteria developed in discussion with members of these various initiatives, and identifies a range of similarities between their publications. Overall the comparison demonstrates a high level of consensus across definitions and principles, which leads to the conclusion that there is a shared understanding of what sustainable remediation is both across countries and stakeholder groups. Publications do differ in points of detail, in particular about the operational aspects of sustainable remediation assessment. These differences likely result from differences in context and legal framework. As this analysis was carried out its findings were debated with members of the various international initiatives, many of whom have been included as authors. Hence the outcomes described in this paper can be seen as the result of a sort of multi-level debate among international experts (authors) and so can offer a starting point to new sustainable remediation initiatives (for example in other countries) that aim to start developing their own documents.

Limb apraxia in individuals with multiple sclerosis: Is there a role of semi-immersive virtual reality in treating the Cinderella of neuropsychology?

BACKGROUND: Limb apraxia is an acquired cognitive-motor disorder characterized by spatial and temporal disorganization of limb movements, negatively affecting the quality of life of patients, including those with multiple sclerosis (MS). Although recent studies have shown the potential role of VR in increasing cognitive and motor functions, only a few studies have been carried out on the rehabilitation of upper limb apraxia. Hence, our study aims to evaluate the potential efficacy of VR training to improve upper limb ideomotor apraxia in patients with MS. METHODS: One hundred and six patients, affected by secondary progressive MS, who attended our Robotic and Behavioral Neurorehabilitation Service from March 2019 to February 2020, were enrolled in this study and randomly divided into two groups: the control group (CG: 53 patients) performed traditional therapy whereas the experimental group (EG:53 patients) received training using semi-immersive VR. All patients underwent the same amount of cognitive training, 3 times a week for 8 weeks. They were submitted to a specific neuropsychological assessment before (T0) and after the rehabilitation treatment (T1). RESULTS: The VR training led to a significant improvement in global cognitive functions, with regard to constructive and ideomotor apraxia. On the contrary, the CG achieved significant improvements only in ideomotor apraxia. Moreover, only in the EG, we observed an improvement in the mood at the end of training. CONCLUSION: The present study demonstrates that VR rehabilitation can be an effective tool for the treatment of apraxia, which is a neuropsychological problem often underestimated in MS patients. Further studies with long-term follow-up periods are needed to confirm the effect of this promising approach.

Melanocytes from Patients Affected by Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy have Dysfunctional Mitochondria That Can be Rescued with Cyclophilin Inhibitors.

Ullrich congenital muscular dystrophy and Bethlem myopathy are caused by mutations in collagen VI (ColVI) genes, which encode an extracellular matrix protein; yet, mitochondria play a major role in disease pathogenesis through a short circuit caused by inappropriate opening of the permeability transition pore, a high-conductance channel, which causes a shortage in ATP production. We find that melanocytes do not produce ColVI yet they bind it at the cell surface, suggesting that this protein may play a trophic role and that its absence may cause lesions similar to those seen in skeletal muscle. We show that mitochondria in melanocytes of Ullrich congenital muscular dystrophy and Bethlem myopathy patients display increased size, reduced matrix density, and disrupted cristae, findings that suggest a functional impairment. In keeping with this hypothesis, mitochondria (i) underwent anomalous depolarization after inhibition of the F-ATP synthase with oligomycin, and (ii) displayed decreased respiratory reserve capacity. The non-immunosuppressive cyclophilin inhibitor NIM811 prevented mitochondrial depolarization in response to oligomycin in melanocytes from both Ullrich congenital muscular dystrophy and Bethlem myopathy patients, and partially restored the respiratory reserve of melanocytes from one Bethlem myopathy patient. These results match our recent findings on melanocytes from patients affected by Duchenne muscular dystrophy (Pellegrini et al., 2013), and suggest that skin biopsies may represent a minimally invasive tool to investigate mitochondrial dysfunction and to evaluate drug efficacy in ColVI-related myopathies and possibly in other muscle wasting conditions like aging sarcopenia.

NG2/CSPG4-collagen type VI interplays putatively involved in the microenvironmental control of tumour engraftment and local expansion.

In soft-tissue sarcoma patients, enhanced expression of NG2/CSPG4 proteoglycan in pre-surgical primary tumours predicts post-surgical metastasis formation and thereby stratifies patients into disease-free survivors and patients destined to succumb to the disease. Both primary and secondary sarcoma lesions also up-regulate collagen type VI, a putative extracellular matrix ligand of NG2, and this matrix alteration potentiates the prognostic impact of NG2. Enhanced constitutive levels of the proteoglycan in isolated sarcoma cells closely correlate with a superior engraftment capability and local growth in xenogenic settings. This apparent NG2-associated malignancy was also corroborated by the diverse tumorigenic behaviour in vitro and in vivo of immunoselected NG2-expressing and NG2-deficient cell subsets, by RNAi-mediated knock down of endogenous NG2, and by ectopic transduction of full-length or deletion constructs of NG2. Cells with modified expression of NG2 diverged in their interaction with purified Col VI, matrices supplemented with Col VI, and cell-free matrices isolated from wild-type and Col VI null fibroblasts. The combined use of dominant-negative NG2 mutant cells and purified domain fragments of the collagen allowed us to pinpoint the reciprocal binding sites within the two molecules and to assert the importance of this molecular interaction in the control of sarcoma cell adhesion and motility. The NG2-mediated binding to Col VI triggered activation of convergent cell survival- and cell adhesion/migration-promoting signal transduction pathways, implicating PI-3K as a common denominator. Thus, the findings point to an NG2-Col VI interplay as putatively involved in the regulation of the cancer cell-host microenvironment interactions sustaining sarcoma progression.