Smart technological tools for rising damp on monumental buildings for cultural heritage conservation. A proposal for smart villages implementation in the Madonie montains (Sicily)

The Madonie district, in the inner Sicily, is composed of 21 villages, custodians of heritage, traditions, and values that constitute the identity of this area, now exclusively entrusted to the collective memory of an increasingly elderly and inactive population. In the study area, full of tangible and intangible heritage, technological tools, can revitalize and reuse examples of architecture, especially monumental, whose main problem is a deep rising damp affecting the masonry. That is particularly critical for the historic/traditional architectures. This research implements, in one of the villages of the enclave, a new technology system, namely Information and Commu- nication Technology (ICT) tool, like Charge neutralisation Technology (CNT), in contrast to the usual application of the classic and well-known resolution systems. This kind of methodology has been already applied in many monumental buildings in Italy with brilliant results and supporting the protection, enhancement, and promotion of cultural heritage. In Sicily it was never used and represents, in line with the smart village approach, a viable technology to be applied. The smart village model is one of the increasingly popular research topics globally and provides technologies aimed at preserving the identity of the territory and the historical buildings. Culture, if usable and accessible to all, results as an economic resource, a tourist attraction, and a factor of identity. The goal is to develop these inner areas through the smart villages approach by implementing smart technologies and establishing a synergic union of centers to be more competitive in the Sicilian hinterland, but also at the national level, with respect to the wise use of administrative, political, and governmental strategies. Cultural heritage and innovation, together, retrace the past with a view to modernity. The country’s cultural heritage recovered and enhanced is a virtuous strategy to safeguard the identity and value of historic places such as that one of ancient villages and a way to find smart resilient strategies and a sustainability assessment for future communities

Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting

Immunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general immunosuppression, which can be identified in terms of high expression of mannose receptor (MR or CD206). Immunosuppressive TAMs, like other macrophage sub-populations, display functional plasticity that allows them to be re-programmed to inflammatory macrophages. In order to mitigate immunosuppression at the TME, several efforts are ongoing to effectively re-educate pro-tumoral TAMs. Extracellular vesicles (EVs), released by both normal and tumor cells types, are emerging as key mediators of the cell to cell communication and have been shown to have a role in the modulation of immune responses in the TME. Recent studies demonstrated the enrichment of high mannose glycans on the surface of small EVs (sEVs), a subtype of EVs of endosomal origin of 30–150 nm in diameter. This characteristic renders sEVs an ideal tool for the delivery of therapeutic molecules into MR/CD206-expressing TAMs. In this review, we report the most recent literature data highlighting the critical role of TAMs in tumor development, as well as the experimental evidences that has emerged from the biochemical characterization of sEV membranes. In addition, we propose an original way to target immunosuppressive TAMs at the TME by endogenously engineered sEVs for a new therapeutic approach against solid tumors

Awareness and attitude among general dentists and orthodontists toward obstructive sleep apnea in children

AimThis study aimed to investigate Italian dentists’ knowledge of and attitudes toward obstructive sleep apnea (OSA) in children.MethodsAn anonymous questionnaire was prepared using Google Forms and sent to dentists in Italy through private social platforms. The first part of the questionnaire contained basic demographic data questions, and the second part included items about pediatric OSA.ResultsA total of 125 responses were collected within 1 month. The interviews revealed gaps in undergraduate and post-graduate training on OSA, and consequently, low self-evaluation of knowledge and self-confidence in managing young patients with OSA. Dentists showed unfavorable attitudes and poor knowledge of the general findings, risk factors, and consequences of pediatric OSA but demonstrated good knowledge of the beneficial effects of rapid maxillary expansion. Orthodontists showed a more favorable attitude and better recognition of the craniofacial features associated with OSA. In addition, a comparison was made between dentists who had graduated more than 5 years ago and new graduates, and differences were found in undergraduate education, which was better for new graduates, and a small number of questions were better answered by experienced dentists.ConclusionThis study showed a lack of knowledge about pediatric OSA and its management among Italian dentists, revealing the need to update the dentistry curriculum and organize educational interventions

Does the Hyperglycemia Impact on COVID-19 Outcomes Depend upon the Presence of Diabetes?-An Observational Study

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An in vitro strategy to assess mitigation of hazardous properties of engineered metal nanoparticles

The huge progress in the nanotechnology field has requested the production of increasingly advanced engineered nanoparticles (NPs). In particular, metal-based advanced NPs are widely used in several industrial applications. However, their potential effects on human health during occupational exposure are still incompletely characterized thus far and possible strategies to decrease their hazardous properties are not yet clearly defined. In this project we are developing an in vitro approach to test the cytotoxic effects of metal-based NPs, as derived from production lines or modified through coating with organic or inorganic moieties. We have used two cell models widely employed in toxicological studies, the human alveolar cell line A549 and the murine macrophage cell line RAW264.7, to avoid possible limitations due to cell specific effects. Moreover, in order to evaluate the effectiveness of mitigation approaches for NPs endowed with little acute cytotoxicity, additional endpoints, alternative to viability, have also been assessed. Colloidal suspensions of Ag, TiO2 and ZrO2 NPs were tested as provided by industries or modified with SiO2 NPs or citrate used as coating remediation agents. Heterocoagulation of opposite charged phases was applied in order to promote the coating of pristine surfaces by modifying agents. Heterocoagulated sols were obtained by ball milling sols of positive charged Ag, TiO2 and ZrO2 NPs with negative charged SiO2 NPs or citrate ions. Modified samples, obtained by spray-drying and re- dispersing in water the corresponding sols, were also obtained in order to compare reactivity. Original and modified NPs were added to culture media starting from water colloidal suspensions. Viability was determined with the resazurin method in a range of doses from 2.5 to 80 nfg/cm2 (0.3125 to 20 g/cm2 for Ag NPs) of monolayer surface at three experimental times (24, 48 and 72h). The expression of the inducible form of nitric oxide synthase (Nos2), an indicator of macrophage activation and, hence, of pro-inflammatory activity, was assessed with RT-PCR as an end-point alternative to viability. Among the NPs tested, only Ag NP caused a significant loss of viability, with an IC50 of about 0.8 g/cm2 for Raw264.7 cells and 2.4 g/cm2 for A549 cells at the 24h-experimental time. In a preliminary experiment, SiO2 NPs were demonstrated to have no significant effect on cell viability. The comparison between original and SiO2-coated Ag NPs, performed in the same experiment, suggested a coating-independent mitigation effect of bioreactivity exerted by the spray drying procedure. However, once corrected for the actual Ag content of the spray- dried powder, no significant difference was found in the IC50 values, indicating that neither silica coating nor spray drying mitigate cytotoxicity. The effects on viability of original TiO2 and ZrO2 NPs were assessed using P25 Aeroxide TiO2 NPs as a reference material. These materials did not affect significantly cell viability at any time point tested, so that it was not possible to estimate IC50 values for either cell line. However, titania produced a clear-cut induction of Nos2 expression in Raw264.7 cells, thus indicating their potential pro- inflammatory activity. Citrate coating did not produce any significant attenuation of the biological effect. In summary, these preliminary results showed no mitigating effect of the surface modifications tested on the biological effects of the engineered NPs investigated. However, the exploitation of this in vitro experimental strategy can be useful for the preliminary assessment of the mitigation potential of surface modifications of both low-toxic and high-toxic engineered NPs. Supported by EU Grant NMP4-SL-2012-280716 (Sanowork Project

VA residential substance use disorder treatment program providers’ perceptions of facilitators and barriers to performance on pre-admission processes

Abstract Background In the U.S. Department of Veterans Affairs (VA), residential treatment programs are an important part of the continuum of care for patients with a substance use disorder (SUD). However, a limited number of program-specific measures to identify quality gaps in SUD residential programs exist. This study aimed to: (1) Develop metrics for two pre-admission processes: Wait Time and Engagement While Waiting, and (2) Interview program management and staff about program structures and processes that may contribute to performance on these metrics. The first aim sought to supplement the VA’s existing facility-level performance metrics with SUD program-level metrics in order to identify high-value targets for quality improvement. The second aim recognized that not all key processes are reflected in the administrative data, and even when they are, new insight may be gained from viewing these data in the context of day-to-day clinical practice. Methods VA administrative data from fiscal year 2012 were used to calculate pre-admission metrics for 97 programs (63 SUD Residential Rehabilitation Treatment Programs (SUD RRTPs); 34 Mental Health Residential Rehabilitation Treatment Programs (MH RRTPs) with a SUD track). Interviews were then conducted with management and front-line staff to learn what factors may have contributed to high or low performance, relative to the national average for their program type. We hypothesized that speaking directly to residential program staff may reveal innovative practices, areas for improvement, and factors that may explain system-wide variability in performance. Results Average wait time for admission was 16 days (SUD RRTPs: 17 days; MH RRTPs with a SUD track: 11 days), with 60% of Veterans waiting longer than 7 days. For these Veterans, engagement while waiting occurred in an average of 54% of the waiting weeks (range 3–100% across programs). Fifty-nine interviews representing 44 programs revealed factors perceived to potentially impact performance in these domains. Efficient screening processes, effective patient flow, and available beds were perceived to facilitate shorter wait times, while lack of beds, poor staffing levels, and lengths of stay of existing patients were thought to lengthen wait times. Accessible outpatient services, strong patient outreach, and strong encouragement of pre-admission outpatient treatment emerged as facilitators of engagement while waiting; poor staffing levels, socioeconomic barriers, and low patient motivation were viewed as barriers. Conclusions Metrics for pre-admission processes can be helpful for monitoring residential SUD treatment programs. Interviewing program management and staff about drivers of performance metrics can play a complementary role by identifying innovative and other strong practices, as well as high-value targets for quality improvement. Key facilitators of high-performing facilities may offer programs with lower performance useful strategies to improve specific pre-admission processes

Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction

Background: Phosphorylation of diacylglycerol by diacylglycerol-kinases represents a major inhibitory event constraining T cell activation upon antigen engagement. Efficient TCR signalling requires the inhibition of the alpha isoform of diacylglycerol kinase, DGKα, by an unidentified signalling pathway triggered by the protein adaptor SAP. We previously demonstrated that, in SAP absence, excessive DGKα activity makes the T cells resistant to restimulation-induced cell death (RICD), an apoptotic program counteracting excessive T cell clonal expansion. Results: Herein, we report that the Wiskott-Aldrich syndrome protein (WASp) inhibits DGKα through a specific interaction of the DGKα recoverin homology domain with the WH1 domain of WASp. Indeed, WASp is necessary and sufficient for DGKα inhibition, and this WASp function is independent of ARP2/3 activity. The adaptor protein NCK-1 and the small G protein CDC42 connect WASp-mediated DGKα inhibition to SAP and the TCR signalosome. In primary human T cells, this new signalling pathway is necessary for a full response in terms of IL-2 production, while minimally affecting TCR signalling and restimulation-induced cell death. Conversely, in T cells made resistant to RICD by SAP silencing, the enhanced DAG signalling due to DGKα inhibition is sufficient to restore apoptosis sensitivity. Conclusion: We discover a novel signalling pathway where, upon strong TCR activation, the complex between WASp and DGKα blocks DGKα activity, allowing a full cytokine response