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Background: Occupational therapy (OT) is an essential component of patient care, and it is especially beneficial if focused on meaningful activities. For ataxic patients, traditional procedures are currently the most efficient, although without specific guidelines and suggestions for virtual reality integration. In this context, this study proposes Hybrid Smart Rehabilitation (HSR) based on mixed reality (MR) as an aid in overcoming limitations of the traditional OT procedures., Methods: MR-HSR is designed specifically for ataxic patients and developed in Unity with the Holographic Remoting setting for run-time intervention on the scene. The subject reaches a book and grabs it with their hand inside a holographic guide with audio-visive feedback. Hand trajectories acquired from eight ataxic patients and eight healthy subjects were compared and new variables were analyzed to evaluate the performance. The Trust in Automation questionnaire was submitted to assess the opinion of the patients., Results: Patients confirmed their trust in the developer and in the improvement that this system can bring to their rehabilitation. The "total time" and "sway area" of the trajectory were statistically significant and, together with the deviation of the trajectory from the main axis of the guide, although not statistically significant, made it possible to build a classifier., Conclusions: The patient-specific MR-HSR can be considered as an integrative tool for assessing the subject's condition by analyzing new quantitative variables which, if matched to the Scale for the Assessment and Rating of Ataxia (SARA), could be the basis of a new index to assess the progressiveness of ataxia.

Background: Surgery involving implantable devices is widely used to solve several health issues. National registries are essential tools for implantable device surveillance and vigilance. In 2017, the European Union encouraged Member States to establish "registries and databanks for specific types of devices" to evaluate device safety and performance and ensure their traceability. Spine-implantable devices significantly impact patient safety and public health; spine registries might help improve surgical outcomes. This study aimed to map existing national spine surgery registries and highlight their features and organisational standards to provide an essential reference for establishing other national registries., Methods: A scoping search was performed using the Embase, PubMed/Medline, Scopus, and Web of Science databases for the terms "registry", "register", "implantable", and all terms and synonyms related to spinal diseases and national registries in publications from January 2000 to December 2020. This search was later updated and finalised through a web search and an ad hoc survey to collect further detailed information., Results: Sixty-two peer-reviewed articles were included, which were related to seven national spine registries, six of which were currently active. Three additional active national registries were found through the web search. The nine selected national registries were set up between 1998 and 2021. They collect data on the procedure and use patient-reported outcome measures (PROMs) for the follow-up., Conclusion: Our study identified nine currently active national spine surgery registries. However, globally accepted standards for developing a national registry of spine surgery are yet to be established. Therefore, an international effort to increase result comparability across registries is highly advisable. We hope the recent initiative from the Orthopaedic Data Evaluation Panel (ODEP) to establish an international collaboration will meet these needs., (© 2023. Societa Italiana di Ortopedia e Traumatologia (Italian Society of Orthopaedics and Traumatology SIOT).)

Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma cells. Here, we show that oncogenic BRAF localises to the nucleus of these cells, and the compound decreases BRAF levels in both the nuclear and cytosolic compartments. Although mutations in the tumour suppressor p53 gene are not equally frequent in melanomas compared to BRAF, the functional impairment of the p53 pathway may also contribute to melanoma development and aggressiveness. To understand whether oncogenic BRAF and p53 may cooperate, a possible interplay was considered in the two cell lines displaying a different p53 status, being p53 mutated into an oncogenic form in SK-MEL-28 and wild-type in A375 cells. Immunoprecipitation revealed that BRAF seems to preferentially interact with oncogenic p53. Interestingly, ITF2357 not only reduced BRAF levels but also oncogenic p53 levels in SK-MEL-28 cells. ITF2357 also targeted BRAF in A375 cells but not wild-type p53, which increased, most likely favouring apoptosis. Silencing experiments confirmed that the response to ITF2357 in BRAF-mutated cells depends on p53 status, thus providing a rationale for melanoma-targeted therapy.

Background: Guidelines for degenerative cerebellar ataxia neurorehabilitation suggest intensive coordinative training based on physiotherapeutic exercises. Scientific studies demonstrate virtual exergaming therapeutic value. However, patient-based personalization, post processing analyses and specific audio-visual feedbacks are not provided. This paper presents a wearable motion tracking system with recording and playback features. This system has been specifically designed for ataxic patients, for upper limbs coordination studies with the aim to retrain movement in a neurorehabilitation setting. Suggestions from neurologists and ataxia patients were considered to overcome the shortcomings of virtual systems and implement exergaming., Methods: The system consists of the mixed-reality headset Hololens2 and a proprietary exergaming implemented in Unity. Hololens2 can track and save upper limb parameters, head position and gaze direction in runtime., Results: Data collected from a healthy subject are reported to demonstrate features and outputs of the system., Conclusions: Although further improvements and validations are needed, the system meets the needs of a dynamic patient-based exergaming for patients with cerebellar ataxia. Compared with existing solutions, the mixed-reality system is designed to provide an effective and safe therapeutic exergaming that supports both primary and secondary goals of an exergaming: what a patient should do and how patient actions should be performed.

Histone deacetylase inhibitors (HDACI) are epigenetic compounds that have been widely considered very promising antitumor agents. Here, we focus on the effects of the pan-HDAC inhibitor ITF2357 (Givinostat) in comparison with SAHA (Vorinostat) in melanoma cells bearing BRAF V600E oncogenic mutation. Our results indicate both ITF2357 and SAHA dose-dependently reduce the viability of BRAF-mutated SK-MEL-28 and A375 melanoma cells. The comparison of IC50 values revealed that ITF2357 was much more effective than SAHA. Interestingly, both inhibitors markedly decreased oncogenic BRAF protein expression levels, ITF2357 being the most effective compound. Moreover, the BRAF decrease induced by ITF2357 was accompanied by a decrease in the level of phospho-ERK1/2. The inhibitor of upstream MEK activity, U0126, reduced ERK1/2 phosphorylation and dramatically potentiated the antitumor effect of ITF2357, exacerbating the reduction in the BRAF level. ITF2357 stimulated an early pro-survival autophagic response, which was followed by apoptosis, as indicated by apoptotic markers evaluation and the protective effects exerted by the pan-caspase inhibitor z-VADfmk. Overall, our data indicate for the first time that ITF2357 targets oncogenic BRAF in melanoma cells and induces a switch from autophagy to classic apoptosis, thus representing a possible candidate in melanoma targeted therapy.

Unlabelled: Self-cleaning photocatalytic coatings for biocalcarenite stones, based on TiO2 nanoparticles obtained by sol-gel processes at different pH values and also adding gold particles, have been investigated. The selected test material is a biocalcarenite named "pietra di Lecce" (Lecce stone), outcropping in Southern Italy. Scanning electron microscopy with energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, and Raman investigations were carried out to characterize the TiO2 nanoparticles and coatings. Nanocrystalline anatase and, to a lesser extent, brookite phases are obtained. Photocatalytic activity of the TiO2 sols and of the coatings on "pietra di Lecce" was assessed under ultraviolet irradiation, monitoring methyl orange (MeO) dye degradation as a function of time. To evaluate the harmlessness of the treatment, colorimetric tests and water absorption by capillarity were performed. The results show good photodegradation rates for titania nanosols, particularly when putting in Au particles, whereas a satisfactory chromatic compatibility between the sol and the surface of the calcarenite is found only without Au addition., Highlights: Sols of nanocrystalline titania at different pH values and with Au particles were prepared and characterized. Satisfactory photodegradation of MeO by the sols in solution and on calcarenite-coated surfaces is obtained. The addition of Au particles improves the photodegradation activity but gives poor chromatic results on "pietra di Lecce."