A BIM-based PSS approach for the management of maintenance operations of building equipment

The service-centered economy has grown considerably in the last few years, shifting from product-based solutions towards service centered offerings, i.e., Product-Service System (PSS) solutions. Such an approach is also emerging in the context of building equipment, where maintenance activities play a fundamental role in facility management. In this field, Building Information Modeling (BIM) based tools are diffusely used to improve the performances of facility management. However, few studies have addressed the above issues while considering a shift from product-based approaches in favor of more advanced servitization models. The study aims at integrating BIM based approaches in a PSS context for the improvement of the management of maintenance operations of building equipment. A general framework for maintenance management has been developed, merging the implementation of the PSS components in a BIM model for the definition of maintenance management. A first application of this methodology to a real case study concerning the elevators of an existing building has shown the efficacy of the proposed approach. The study highlighted the benefits that can be achieved, especially in terms of reduced periods of equipment unavailability, reduced costs and augmented customer satisfaction, while enhancing the information exchange between the PSS actors. Hence, although further research is still needed for its validation, the proposed approach can offer practical insights for the development of promising BIM-based PSS solutions for facility management in the construction industry

A novel signalling mechanism regulating telomere length in cardiomyocytes

Clinical management and treatment of human diseases are continuously improving, with a progressive elongation of life expectancy in Western countries. As a consequence of the elevation of the average age of the population, the incidence of ageing-related diseases will progressively in- crease in the next years. Among ageing-related diseases, cardiovascular diseases still represent the first of cause of death in the Western world

SARS-CoV-2 and COVID-19. Facing the pandemic together as citizens and cardiovascular practitioners

Despite their highbrow name, coronarvirus have proved eminently disruptive in recent years. Since the epidemic of severe respiratory distress syndrome (SARS) due to the SARS-related coronavirus (SARS-CoV) infection and the Middle East respiratory syndrome (MER S) due to the MER S-related coronavirus (MER S-CoV), several experts could expect the advent of additional epidemics due to coronaviruses. Yet, the ongoing pandemic of coronavirus-associated disease 2019 (COVID -2019) due to the infection from SARS-CoV-2 (also known as 2019-nCoV) has wreaked havoc worldwide (Figure 1). As Italian citizens and cardiovascular practitioners, we are now facing this storm, with a mix of incredulity, fear, boldness, and sense of duty

VST - VLT Survey Telescope Integration Status

The VLT Survey Telescope (VST) is a 2.6m aperture, wide field, UV to I facility, to be installed at the European Southern Observatory (ESO) on the Cerro Paranal Chile. VST was primarily intended to complement the observing capabilities of VLT with wide-angle imaging for detecting and pre-characterising sources for further observations with the VLT.Comment: 2 pages, 2 figures, conferenc

Cell clearing systems as targets of polyphenols in viral infections: Potential implications for COVID-19 pathogenesis

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated the ongoing coronavirus disease-2019 (COVID-19) pandemic, still with an uncertain outcome. Besides pneumonia and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), other features became evident in the context of COVID-19. These includes endothelial and coagulation dysfunction with disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS), along with the occurrence of neurological alterations. The multi-system nature of such viral infection is a witness to the exploitation and impairment of ubiquitous subcellular and metabolic pathways for the sake of its life-cycle, ranging from host cell invasion, replication, transmission, up to a cytopathic effect and overt systemic inflammation. In this frame, alterations in cell-clearing systems of the host are emerging as a hallmark in the pathogenesis of various respiratory viruses, including SARS-CoV-2. Indeed, exploitation of the autophagy and proteasome pathways might contribute not only to the replication of the virus at the site of infection but also to the spreading of either mature virions or inflammatory mediators at both cellular and multisystem levels. In this frame, besides a pharmacological therapy, many researchers are wondering if some non-pharmacological substances might counteract or positively modulate the course of the infection. The pharmacological properties of natural compounds have gained increasing attention in the field of alternative and adjunct therapeutic approaches to several diseases. In particular, several naturally-occurring herbal compounds (mostly polyphenols) are reported to produce widespread antiviral, anti-inflammatory, and anti-oxidant effects while acting as autophagy and (immuno)-proteasome modulators. This article attempts to bridge the perturbation of autophagy and proteasome pathways with the potentially beneficial effects of specific phytochemicals and flavonoids in viral infections, with a focus on the multisystem SARS-CoV-2 infection

An International Survey on Taking Up a Career in Cardiovascular Research: Opportunities and Biases toward Would-Be Physician-Scientists

Background Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey. Methods and Results We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, geographic area, training and full-time researcher status. Specifically, women proved significantly less satisfied than men, disclosed access to fewer resources and less support from mentors (all P Conclusions Several potential biases appear to be present in the way training in cardiovascular research is provided worldwide, including one against women. If confirmed, these data require proactive measures to decrease discriminations and improve the cardiovascular research training quality

Neurotrophin/Trk receptor signaling mediates C/EBPα, -β and NeuroD recruitment to immediate-early gene promoters in neuronal cells and requires C/EBPs to induce immediate-early gene transcription

BACKGROUND: Extracellular signaling through receptors for neurotrophins mediates diverse neuronal functions, including survival, migration and differentiation in the central nervous system, but the transcriptional targets and regulators that mediate these diverse neurotrophin functions are not well understood. RESULTS: We have identified the immediate-early (IE) genes Fos, Egr1 and Egr2 as transcriptional targets of brain derived neurotrophic factor (BDNF)/TrkB signaling in primary cortical neurons, and show that the Fos serum response element area responds to BDNF/TrkB in a manner dependent on a combined C/EBP-Ebox element. The Egr1 and Egr2 promoters contain homologous regulatory elements. We found that C/EBPα/β and NeuroD formed complexes in vitro and in vivo, and were recruited to all three homologous promoter regions. C/EBPα and NeuroD co-operatively activated the Fos promoter in transfection assays. Genetic depletion of Trk receptors led to impaired recruitment of C/EBPs and NeuroD in vivo, and elimination of Cebpa and Cebpb alleles reduced BDNF induction of Fos, Egr1 and Egr2 in primary neurons. Finally, defective differentiation of cortical dendrites, as measured by MAP2 staining, was observed in both compound Cebp and Ntrk knockout mice. CONCLUSION: We here identify three IE genes as targets for BDNF/TrkB signaling, show that C/EBPα and -β are recruited along with NeuroD to target promoters, and that C/EBPs are essential mediators of Trk signaling in cortical neurons. We show also that C/EBPs and Trks are required for cortical dendrite differentiation, consistent with Trks regulating dendritic differentiation via a C/EBP-dependent mechanism. Finally, this study indicates that BDNF induction of IE genes important for neuronal function depends on transcription factors (C/EBP, NeuroD) up-regulated during neuronal development, thereby coupling the functional competence of the neuronal cells to their differentiation

Comparative indoor pollution from Glo, Iqos, and Juul, using traditional combustion cigarettes as benchmark. Evidence from the randomized sur-vapes air trial

Modified risk products (MRP) such as electronic vaping cigarettes (EVC) and heat-not-burn cigarettes (HNBC) are appealing alternatives to combustion cigarettes. Limited between-and within-device comparative data are available on MRP. We aimed at comparing indoor particulate matter (PM) emissions measured in a randomized trial enforcing standardized smoking sessions, testing different devices and flavors of MRP, using traditional combustion cigarettes (TCC) as benchmark. Overall, MRP yielded significantly lower levels of indoor PM in comparison to TCC (with median PM levels during smoking for MRP < 100 µg/m3, and for TCC > 1000 µg/m3). Despite this, significant differences among MRP were found, with Iqos appearing associated with a significantly lower burden of emissions for all the monitored fractions of PM, including total PM (all p < 0.05). Precisely, during use, PM ≤ 1 µm (PM1) emissions were 28 (16; 28) µg/m3 for Glo, 25 (15; 57) µg/m3 for Iqos, and 73 (15; 559) µg/m3 for Juul (p < 0.001 for Glo vs. Iqos, p <0.001 for Glo vs. Juul, and p = 0.045 for Iqos vs. Juul). Exploratory within-MRP analyses suggested significant differences between flavors, favoring, for instance, Ultramarine for Glo, Bronze for Iqos, and Mango for Juul, even if results varied substantially according to individual smoker. In conclusion, leading MRP have significantly less intense and persistent effects on indoor pollution in comparison to TCC. Yet, when focusing solely on MRP, between-product and between-flavor differences appear, with quantitative estimates suggesting lower polluting effects with Iqos. These results, if confirmed externally, could be used to individualize product and flavor choice to minimize the untoward effects of EVC and HNBC on indoor pollution

“Discovery of promising 1,2,4-oxadiazoles hits for the development of new anti-inflammatory agents interfering with eicosanoid biosynthesis pathways”

Prostaglandin E2 (PGE2) is an inflammatory mediator that plays a pivotal role in the evolvement and progression of inflammatory and tumor diseases.1The identification of novel inhibitors of eicosanoids biosynthesis with unexplored scaffolds is of great demand to develop a next generation of anti-inflammatory or anti-cancer drugs. Following a multidisciplinary protocol that involves virtual combinatorial screening, chemical synthesis, and validation of the biological activities we afforded to the identification of 1,2,4-oxadiazole-based hits, as a novel class of anti-inflammatory agents able to inhibit several enzymes involved in the progression of inflammation. 1,2,4-oxadiazoles represent a versatile “privileged scaffold” in drug discovery, due to the possibility of modifying and opportunely decorating the nucleus,2 and are never explored for their inhibitory activity on eicosanoid biosynthesis. This multidisciplinary scientific approach led to the identification of a multi-target inhibitor of cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LO) and microsomal prostaglandin E2 synthase-1 (mPGES-1). Moreover, in vivo studies on the disclosed hit demonstrate that it attenuates leukocytes migration in a model of zymosan-induced peritonitis and modulates the production of IL-1β and TNF-α. These promising outcomes pave the way toward a medicinal chemistry optimization campaign of the disclosed hit characterized by a promising and safer pharmacological profile

Interplay between Nox2 activity and platelet activation in patients with sepsis and septic shock. a prospective study

Background. Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls. Methods and Results. Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls (n=10, age 67.8±3.2, male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, p<0.001), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, p<0.001), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, p<0.001), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, p<0.001). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed. Conclusions. Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock