Search

Bovine herpesvirus 4 (BoHV-4) is a Gammaherpesvirus belonging to the Rhadinovirus genus. The bovine is BoHV-4's natural host, and the African buffalo is BoHV-4's natural reservoir. In any case, BoHV-4 infection is not associated with a specific disease. Genome structure and genes are well-conserved in Gammaherpesvirus, and the orf 45 gene and its product, ORF45, are one of those. BoHV-4 ORF45 has been suggested to be a tegument protein; however, its structure and function have not yet been experimentally characterized. The present study shows that BoHV-4 ORF45, despite its poor homology with other characterized Rhadinovirus ORF45s, is structurally related to Kaposi's sarcoma-associated herpesvirus (KSHV), is a phosphoprotein, and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV-4 lytic replication and is associated with the viral particles, as for the other characterized Rhadinovirus ORF45s. Finally, the impact of BoHV-4 ORF45 on cellular transcriptome was investigated, an aspect poorly explored or not at all for other Gammaherpesvirus. Many cellular transcriptional pathways were found to be altered, mainly those involving p90 ribosomal S6 kinase (RSK) and signal-regulated kinase (ERK) complex (RSK/ERK). It was concluded that BoHV-4 ORF45 has similar characteristics to those of KSHV ORF45, and its unique and incisive impact on the cell transcriptome paves the way for further investigations.

A literature search on the in vitro testing of anti-inflammatory compounds of natural origin revealed a considerable number of studies adopting a similar template for data reporting in the years up to 2019. Sixty-five such reports appear to have been published between the years 2008 and 2019. Interestingly, this format template was clearly recognizable by a few hallmarks, such as a precise way of plotting cell viability data, extremely consistent endpoints, and the way these were graphically represented. In some instances the similarities extended to some textual features, such as in the case of figure legends. The similarity was so high that chance can be excluded and these studies can be safely assumed to have intentionally followed a template. By 2020, however, no new reports following this format have been published. Although a consistent and reproducible formatting for data reporting may improve report readability, this phenomenon should also be closely scrutinized to assess the rationale why it occurred, the validity of the endpoints that were chosen and why it was then abandoned. The present report reviewed the mean features of this format, traced its origin and its evolution over time, while discussing the limitations of this model.

The combination of servitization and digitalization is increasingly changing the economy and society at the global level towards sustainability goals. Companies are shifting their business models, typically oriented to selling products, towards providing bundles of products and services and integrating them with technologies enabling data collection and analysis, resulting in the so-called smart Product Service Systems (PSS). Different approaches and techniques have been put forth to design PSS and, more recently, smart PSS, but they continue to primarily concentrate on establishing value propositions and ignore the question of what sort of operational data can be gathered and used to deliver the PSS solution. Therefore, manufacturing companies willing to expand their portfolio with new advanced services nowadays still face multiple challenges. To address this gap, this study proposes the Service Engineering Methodology for the engineering of smart PSS (SEEM-Smart), which takes into account the trade-off between customer satisfaction and internal efficiency with a focus on data gathering and information flow. The methodology is then applied in a real-world setting. The case study shows the application of the SEEM-Smart for engineering a new data-driven service offering enabled by a cloud-based platform supporting the service provision.

A new Ru

In the contention of the current industrial landscape, an increasing number of manufacturing firms are experimenting with the transition from product-centric offerings to service-based value concepts and product-service bundles as high-value integrated customer solutions to increase their revenues and build sustainable competitive advantages; a phenomenon known as the “servitization” of manufacturing. Nowadays, consistently with the Industry 4.0 paradigm, these companies have therefore started a process of integrating their traditional value offerings with digital services. This recent strategy is known as “Digital Servitization” and consists of developing new services and/or improving existing ones through digital technologies. However, this transformation is challenging, and companies often struggle to achieve their expectations. Thus, this study aims to shed light on the current state of Digital Servitization strategies in the manufacturing sector based on a survey addressed to the top and middle management. The results obtained by the analysis of the data collected from the survey show an increasing trend towards the adoption of digital technologies for enabling innovation and differentiation in service delivery processes.

Data availability is changing the way companies make decisions at various levels (e.g., strategical and operational). Researchers and practitioners are exploring how product–service system (PSS) providers can benefit from data availability and usage, especially when it comes to making decisions related to service delivery. One of the services that are expected to benefit most from data availability is maintenance. Through the analysis of the asset health status, service providers can make informed and timely decisions to prevent failures. Despite this, the offering of data-based maintenance service is not trivial, and requires providers to structure themselves to collect, analyze and use historical and real-time data properly (e.g., introducing suitable information flows, methods and competencies). The paper aims to investigate how a manufacturing company can re-engineer its maintenance service delivery process in a data-driven fashion. Thus, the paper presents a case study where, based on the Dual-perspective, Data-based, Decision-making process for Maintenance service delivery (D3M), an Italian manufacturing company reengineered its maintenance service delivery process in a data-driven fashion. The case study highlights the benefits and barriers coming with this transformation and aims at helping manufacturing companies in understanding how to address it.

A new Ru3(CO)12-catalyzed directed alkenylation of 2-carboxaldimine-heterocyclopentadienes has been accomplished. This process allows to couple furan, pyrrole, indole and thiophene 2-carboxaldimines with electron-poor alkenes such as acrylates, vinylsulfones, and styrenes. This regio- and chemoselective oxidative C–H coupling does not require the presence of an additional sacrificial oxidant. Density functional theory (DFT) calculations allowed to propose a mechanism and unveiled the nature of the H2 acceptor.

Manufacturing companies are revolutionizing the way they deal with customers, trying to satisfy their emerging needs with new, Product-Service System-centered (PSS), offerings. The shift towards this offering and its implementation are not easy since the proposal of badly structured offerings leads to unsatisfactory results for all the stakeholders. To obtain the maximum value in use, the way products and services are sold and delivered must be configured properly. In view of this, proper conceptualization, design and engineering methodologies must be adopted, along with suitable Decision Support Systems (DSS) to support them. DSS could help decision-makers in improving the service delivery process, proposing its scheduling, or deciding which kind service and how to provide it to customers. To be effective, DSS must be fed with right data and, in this sense, the implementation of Industry 4.0 technologies results crucial since the availability and exploitation of new, big, and structured datasets could improve DSS reliability. The aim of this work is to investigate how the presence of a DSS focused on service delivery process can enhance PSS offering in the context of Industry 4.0. The authors used a set of keywords related to PSS, service delivery process, DSS and Industry 4.0 to perform the research on the Scopus database. Following, they filtered results according to parameters of interest and, after reviewing the papers’ pool, they identified the final set for the review. The analysis highlighted a gap in literature due to the lack of researches around the improvements in the service delivery process achievable through the implementation of smarter DSS exploiting the Industry 4.0 technologies.

Objective: The main focus of this in vitro study was to highlight possible differences between outcomes of photobiomodulation performed in the presence or absence of growth factors derived from pla...

Maintenance service delivery constitutes one of the most problematic tasks for companies offering such service. Besides dealing with customers expecting to be served as soon as possible, companies must consider the penalties they are incurring if the service is delivered later than the deadline, especially if the service suppliers want to establish long and lasting relationships with customers. Despite being advisable to use appropriate tools to schedule such activity, in many companies, planners rely only on simple tools (e.g., Excel sheets) to schedule maintenance interventions. Frequently, this results in a suboptimal allocation of the interventions, which causes customer satisfaction problems. This paper, contextualised in the Balance Systems case study, proposes an optimisation model that can be used by planners to perform the intervention allocation. The optimisation model has been developed in the context of the Dual-perspective, Data-based, Decision-making process for Maintenance service delivery (D3M) framework, which aims to improve the maintenance service delivery by making a proper use of real-time and historical data related to the asset status and the service resources available. The proposed model tries to cope with the current problems present in the company’s service delivery process by proposing the introduction of a mathematical instrument in support of the planner. Being strongly influenced by the contextual setting, the model discussed in this paper originates from the D3M framework logic and is adapted to the company necessities.

Background: Scientific research on atrial fibrosis in atrial fibrillation (AF) has mainly focused on quantitative or molecular features. The purpose of this study was to perform a clinicoarchitectural/structural investigation of fibrosis to provide one key to understanding the electrophysiological/clinical aspects of AF. Methods: We characterized the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting persistent AF (group 1; 59 males; 60±11 years; 91 mitral disease–related AF, 30 nonmitral disease–related AF) and from 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59±12 years). Ten autopsy hearts served as controls. Results: Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which we arbitrarily subdivided into 4 stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and at a more advanced stage in group 1 versus group 2 and, within group 1, in patients with rheumatic disease versus nonrheumatic cases. In patients with AF with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69–150 cells/mm 2 , depending on the areas in AF biopsies). A few fibrocytes—circulating and bone marrow-derived mesenchymal cells—were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. Conclusions: Atrial fibrosis is an evolving and inhomogeneous histological/architectural change that progresses through different stages ranging from isolated foci to confluent sclerotic zones which—seemingly—constrain impulse conduction across restricted regions of electrotonically coupled cardiomyocytes. The fibrotic areas mainly consist of type I collagen extracellular matrix and, only to a lesser extent, mesenchymal cells.

A wide range of methodologies for the preparation of organic azides has been reported in the literature for many decades, due to their interest as building blocks for different transformations and their applications in biology as well as in materials science. More recently, with the spread of the use of transition metal-catalyzed reactions, new perspectives have also materialized in azidation processes, especially concerning the azidation of C–H bonds and direct difunctionalization of multiple carbon-carbon bonds. In this review, special emphasis will be placed on reactions involving substrates bearing a leaving group, hydroazidation reactions and azidation reactions that proceed with the formation of more than one bond. Further reactions for the preparation of allyl and vinyl azides as well as for azidations involving the opening of a ring complete the classification of the material.

Objectives Cytomegalovirus (CMV)‐related encephalitis is a rare but potentially life‐threatening complication of CMV infection in immunocompromised patients. The high mortality rate is associated with deficient immune system reconstitution after hematopoietic stem cell transplant (HSCT) and poor bioavailability of antiviral drugs in cerebrospinal fluid (CSF). CMV‐related central nervous system (CNS) infection may occur with aspecific symptoms, without evidence of either blood viral load or magnetic resonance imaging (MRI) signs of encephalitis. Methods Here, we describe a 10‐year‐old girl who underwent an allogeneic HSCT and subsequently developed CMV encephalitis. Because of the absence of CMV antigen in the blood, the diagnosis of encephalitis was proposed only after a delay, following the onset of immune reconstitution inflammatory syndrome (IRIS). Two months of combined dual antiviral therapy with ganciclovir and foscarnet proved ineffective against CMV and caused significant bone marrow and renal toxicity. To avoid further toxicity, the girl was given daily treatment with CMV‐hyperimmune globulins alone. Results After three weeks, the CSF viral load dropped significantly and was undetectable within three more weeks. In the meantime, the renal impairment resolved, and there was a complete bone marrow recovery. Conclusion We suggest that this patient succeeded in achieving CMV CSF clearance with high dose of CMV‐hyperimmune globulin, given alone, because of the ability of immunoglobulins to penetrate the blood–brain barrier (BBB)., This case describes the high‐dose anti‐cytomegalovirus (CMV) hyperimmune globulin treatment of CMV‐induced encephalitis after allogeneic hematopoietic stem cell transplant. After two months of combined dual antiviral therapy with ganciclovir and foscarnet, the CSF viral load remained very high; meanwhile, the patient, a 10‐year‐old girl, developed severe bone marrow and renal toxicity. Complete CSF clearance was obtained with high doses of anti‐CMV hyperimmune globulins given alone. We suggest this treatment succeeded because of the ability of immunoglobulins to penetrate the blood–brain barrier.

The palladium-catalyzed aminoazidation of aminoalkenes yielding azidomethyl-substituted nitrogen-containing heterocycles was developed. The procedure requires oxidative conditions and occurs at room temperature in the presence of hydrogen peroxide and NaN

The design of Product-Service Systems (PSS) has been approached from several perspectives like the process, innovation, engineering and operational ones providing, for each one of those, a specific view on the problem. This paper proposes a Data-Driven Product-Service System Design and Delivery (4DPSS) methodology focusing on the collection and exploitation of delivery data to feed the design phase. The logic of the methodology relies on aggregating operational data (collected in the delivery phase) to build a consistent body of knowledge to be exploited in iterative PSS design activities, thanks to better identification of customer needs, and product and service process design issues. This paper presents the 4DPSS methodology at a theoretical level, the implementations of the different methods constituting the methodology are referred to in the text, while its implementation and test as a whole are demanded to future work. © 2020, IFIP International Federation for Information Processing.

Many manufacturing companies are now facing the transition towards the development of a structured service offering in the servitization fashion. Especially in the case of a service like maintenance, the definition of a coherent process, able to collect and exploit in the right way the data from the field for decision-making scopes constitutes the base to run an economically sustainable offering. The authors proposed a structured framework that, considering a dual perspective (asset and service), aims to address this problem and to improve the maintenance decision-making. The paper, using as a case study an Italian manufacturing company willing to accelerate its servitization process, addresses the testing and improvement of the framework. Company A service department’s employees were interviewed in the scope of validating the framework and identify improvements for its structure and the related decision-making instruments.

International audience; The Murai reaction is a ruthenium-catalyzed transformation leading to alkylated arenes through the CC bond formation between an alkene and an arene bearing a directing group. Discovered in the nineties, this useful C-H activation based coupling has been the object of intense study since its discovery. After having studied the Murai reaction on 2-formylfurans of biomass derivation, we describe here the carbonylative version applied to 2-formylfurans, 2-formylpyrrols and 2-formylthiophenes. This acylation reaction takes place regioselectively at C3 position of the heterocyclopentadienes thanks to the installation of removable imine directing groups. The transformation can be achieved by treating the two reaction partners with a catalytic amount of Ru 3 (CO) 12 , in toluene at 120-150 °C, after CO bubbling, at atmospheric pressure. DFT computations of the full catalytic cycle help in deciphering the mechanism of this transformation, and to rationalize the different behaviors depending on the nature of imine directing groups.

Optimal autonomic regulation and stress resilience might be considered critical elements of athletic performance. We hypothesize that a novel unitary autonomic index for sports (ANSIs), together with a somatic stress related symptom score (4SQ) might help characterize athletes who were eventually selected for the Rio 2016 Olympic Games Italian team (Rio +). In this retrospective study we examined 778 athletes (age 24.4 ± 6.7 yrs) who underwent a planned yearly pre-participation screening. All athletes underwent clinical, autonomic and exercise ECG evaluation. The combination of vagal and sympathetic indices from RR variability into ANSIs was performed by radar plot and percent ranking of index variables. We assessed (Rio +) versus (Rio −) athletes also after subdivision into three sport intensity groups (low, mid and high intensity). Overall there were no significant differences between (Rio +) and (Rio −) athletes when considering individual spectral derived variables. Conversely, the unitary Index ANSIs was significantly higher in (Rio +) compared to (Rio −) athletes (respectively 54.5 ± 29.5 and 47.9 ± 28.4 p = 0.014). This difference was particularly evident (p = 0.017) in the group of athletes characterized by both high static and dynamic components. 4SQ was smaller in the (Rio +) group, particularly in the groups of athletes characterized by both low-medium static and dynamic components. ANSIs, a proxy of integrated cardiac autonomic regulation and simple assessment of resilience to stress, may differentiate Italian athletes who were eventually selected for participation in the 2016 Rio Olympic Games from those who were not, suggesting the possibility of a “winning functional phenotype”.

Scientization of the Social - Politization of Knowledge? On a Narrative of the History of the Twentieth Century. The spread of scientific methods and expert cultures in the social, political and economic fields represents a key aspect of twentieth century history. In German-speaking historiography, the "scientization of the social" (Lutz Raphael) has advanced to an influential concept for research into the role of social and human sciences within this development. Exploring this analytical framework against the background of methodological debates, this paper raises the question of how the relationship between the academic and the political spheres in modern societies can be theoretically conceived.

Background Spectral analysis of Heart Rate Variability (HRV) is a simple, non-invasive technique that is widely used in sport to assess sympatho-vagal regulation of the heart. Its employment is increasing partly due to the rising usage of wearable devices. However data acquisition using these devices may be suboptimal because they cannot discriminate between sinus and non-sinus beats and do not record any data regarding respiratory frequency. This information is mandatory for a correct clinical interpretation. Methods This study involved 974 elite athletes, all of them underwent a complete autonomic assessment, by way of Autoregressive HRV analysis. Results In 91 subjects (9% of the total population) we observed criticalities of either cardiac rhythm or respiration. Through perusal of one-lead ECG analysis we observed that 77 subjects had atrial or ventricular ectopy, i.e. conditions which impair stationarity and sinus rhythm. Running anyway autonomic nervous system analysis in this population, we observed that RR variance and raw values of LF and HF regions are significantly higher in arrhythmic subjects. In addition 14 subjects had slow (about 6 breath/min, 0.1Hz) respiration. This condition clouds the separation between LF from HF spectral regions of RR interval variability, respectively markers of the prevalent sympathetic and vagal modulation of SA node and of their synergistic interaction. Conclusions Caution must be payed when assessing HRV with non-ECG wearable devices. Recording ECG signal and ensuring that respiratory rate is higher than 10 breath/min are both prerequisites for a more reliable analysis of HRV particularly in athletes.

Nell’immediato secondo dopoguerra enormi sconvolgimenti scossero la struttura demografica della Germania occidentale, dapprima sotto l’occupazione degli alleati, poi come stato autonomo. Oltre alle perdite subite durante la guerra, il paese dovette far fronte all’arrivo di milioni di profughi degli ex territori del Reich che dopo il 1945 furono annessi dai paesi dell’Europa orientale e di rifugiati provenienti dalla Repubblica democratica tedesca. Negli anni Cinquanta questo problema rappresento forse la principale sfida sociale per la giovane Repubblica Federale Tedesca. Anche se discriminazione e isolamento sociale condizionarono profondamente il destino dei profughi, la loro integrazione avvenne nel medio termine con grande successo. Questo articolo sostiene che il collocamento sul mercato del lavoro ebbe un ruolo fondamentale nelle politiche per l’integrazione e che cio rappresenta un’importante chiave di lettura per comprendere la storia di profughi e rifugiati sullo sfondo degli intensi movimenti di popolazione nell’Europa del secondo dopoguerra. Le politiche occupazionali attuate dal "Servizio Nazionale di Collocamento" rivelarono infatti lo stato ambivalente dei profughi tedeschi: essi avrebbero dovuto essere integrati, in quanto cittadini tedeschi; tuttavia l’afflusso di massa mise a dura prova l’idea di una comunita nazionale solidale.

The digital transformation of the manufacturing industry is currently unlocking new possibilities in terms of automation and improvement of existing business processes. Service is currently one of the key areas that are being affected by it and, while many use cases are proposed, their operational implementation often remains a challenge. This paper, focusing on the impact of information transparency on the formulation of an effective maintenance plan, is proposing a progressive implementation roadmap for a dynamic failure mode, effect and criticality analysis (FMECA), according to the digital maturity of the organization.

The Product-Service Systems (PSS) offering is spreading on the market. Companies are becoming aware that selling bundles of products and services can create additional value for them and for the customers. Despite this, the provision of additional services not natively designed to improve products usage is not trivial. In fact, not only services must be correctly customized on the customers’ necessities but also the way they are provided must be redesigned. An effective service delivery process is fundamental if companies want to create additional value from their service portfolio. The way they manage the phases leading to the service provision influences the way and the time required to deliver them. This work compares the service delivery process of two manufacturing companies headquartered in different parts of the world and selling products for the B2B market. The analyses performed on the service delivery processes highlighted how, despite the technological complexity the products, the management of the service delivery process is not automated, but it is still managed by humans without any Decision Support System (DSS) by the companies’ service departments. For this reason, authors proposed improvements for the two service delivery processes through the introduction of DSS able to handle part of the process and, in turn, smooth them, shortening the time required to deliver services to customers and, so, increasing their satisfaction.

Due to the commodisation and globalization of the markets, manufacturing companies have been pursuing new business models based on product- service bundles, which in literature have been investigated under the broad term of Product-Service Systems (PSS). Efficient provision of PSS is not immediate since it requires as a first condition a deep integration of product and service components and the related delivery processes. As regards durable equipment, maintenance is one of the most relevant and common services offered to the market. The identification of the best maintenance policy, and the expected improvement of availability and productivity of the industrial asset depends upon the knowledge, cognition, and expertise that the provider has on the machine and the related operating conditions. With this regard, it is fundamental to wisely collect and analyze data related to the machine and its delivery process, extracting useful information guiding the policy selection. By investigating the case of a durable equipment manufacturer, the paper focuses on the problem related to the creation of a proper engineering process and data infrastructure for supporting a gradual and robust transition towards a PSS-based business model. A dual perspective vision for ensuring a continuous improvement of maintenance services is proposed and discussed, based on a cross-analysis of the on-field collected data from the industrial asset and the maintenance delivery processes.

Myeloablative conditioning is a well‐established procedure that precedes hematopoietic stem cell transplantation (HSCT), particularly in pediatric patients. In the period directly following transplantation, several factors may contribute to complications that lead to the activation or damage of endothelial cells, involved in the pathogenesis of vascular endothelial syndromes (VES). However, to date, sufficiently specific and sensitive diagnostic markers for the various forms of VES have not been identified. This was a retrospective single‐center study of patients who underwent allogeneic HSCT. For this cohort of patients, parameters including type of engraftment, donor characteristics, and cytokine production were measured and correlated with a high prevalence of short‐term complications after HSCT. The aim of this study was to identify specific parameters useful for improving diagnostics and predicting adverse effects in VES. We confirmed that monocyte‐predominant engraftment was related to a higher risk for an early transplant‐related complication termed sinusoidal obstruction syndrome (SOS). The increased production of specific cytokines, in particular RANTES, represents a marker associated with prevalent engraftment. In addition, patients undergoing prophylaxis with defibrotide had “classical” engraftment, a common cytokine profile and a lower incidence of life‐threatening transplant‐related complications. The beneficial effect of defibrotide might be a starting point for developing selective prophylaxis for patients with monocyte engraftment to prevent severe early transplant‐related complications., The onset of vascular endothelial syndromes after hematopoietic stem cell transplantation is significantly associated with monocyte‐predominant engraftment (P

Background The exact pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is still unknown. The aim of this paper was to investigate the effects of zoledronic acid and dexamethasone on the early phases of socket healing in rats subjected to tooth extractions. Material and Methods Thirty male Sprague-Dawley rats were divided into 2 groups: pharmacologically treated group (T, n=20) and non-pharmacologically treated group (C, n=10). T group rats received 0.1 mg/Kg of zoledronic acid (ZOL) and 1 mg/Kg of dexamethasone (DEX) three times a week for 10 consecutive weeks. C group rats were infused with vehicle. After 9 weeks from the first infusion, first maxillary molars were extracted in each of the rats. Quantitative macroscopic and microscopic analysis was performed to evaluate socket healing 8 days after extraction. Results Pharmacologically treated rats showed significant inhibition of bone remodeling. Connective tissue/alveolar bone ratio, osteoclast number and woven bone deposition were significantly reduced in group T compared to group C. Conversely, the proportion of necrotic bone was higher in group T compared to group C (0.8% and 0.3%, respectively. P=0.031). ZOL plus DEX do not cause gross effects on socket healing at a macroscopic level. Conclusions Our findings confirmed that exposure to ZOL plus DEX impairs alveolar wound repair. Inhibition of osteoclastic resorption of socket walls after tooth extraction and the inability to dispose of the necrotic bone may be considered the initial steps of MRONJ onset. Key words:Medication-related osteonecrosis of the jaw, zoledronic acid, dexamethasone, tooth extraction, rat.

Stanozolol (ST) is a synthetic androgen with high anabolic potential. Although it is known that androgens play a positive role in bone metabolism, ST action on bone cells has not been sufficiently tested to support its clinical use for bone augmentation procedures. Objective: This study aimed to assess the effects of ST on osteogenic activity and gene expression in SaOS-2 cells. Material and Methods: SaOS-2 deposition of mineralizing matrix in response to increasing doses of ST (0-1000 nM) was evaluated through Alizarin Red S and Calcein Green staining techniques at 6, 12 and 24 days. Gene expression of runt-related transcription factor 2 (RUNX2), vitamin D receptor (VDR), osteopontin (SPP1) and osteonectin (ON) was analyzed by RT-PCR. Results: ST significantly influenced SaOS-2 osteogenic activity: stainings showed the presence of rounded calcified nodules, which increased both in number and in size over time and depending on ST dose. RT-PCR highlighted ST modulation of genes related to osteogenic differentiation. Conclusions: This study provided encouraging results, showing ST promoted the osteogenic commitment of SaOS-2 cells. Further studies are required to validate these data in primary osteoblasts and to investigate ST molecular pathway of action.

The evidence that extracellular matrix (ECM) components could represent new targets for drugs designed to approach degenerative disease, requires their analysis. Before the analysis, proteins should be extracted from ECM and solubilized. Currently, few protocols for ECM proteins extraction and solubilization are available in literature, and most of them are based mainly on the use of proteolytic enzymes, such as trypsin, which often lead to proteins damage. Moreover, no methods have been so far proposed to solubilize Schwann Cell ECM, which may represent an important target for the therapy of neurodegenerative disorders. In our study, we propose to solubilize SC ECM through the use of surfactants and urea. We compared our method of solubilization, with one of that proposed in literature for a general ECM, mainly based on the use of enzymes. We want to highlight the benefit of solubilizing SC ECM, avoiding the use of proteolytic enzymes. To compare the amount of proteins extracted with both methods, MicroBCA assay was used, while the quality of the proteins extracted was observed through the SDS-PAGE. The results obtained confirm a better solubilization of SC ECM proteins with the proposed protocol, both quantitatively and qualitatively, showing a higher concentration of proteins extracted and a better enrichment of protein fractions, if compared to the enzyme-based protocol. Our results show that SC ECM could be efficiently solubilized through the use of surfactant and urea, avoiding the use of enzyme-base methods. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3175-3180, 2016.

Aim Reflex alterations of cardiac autonomic modulation have been described after acute myocardial infarction (AMI). The non-homogeneous autonomic innervation of the heart gives reason of different patterns of autonomic modulation depending upon the site of AMI. Conflicting data are available on cardiac autonomic modifications after primary percutaneous coronary intervention (pPCI). We evaluated cardiac autonomic changes in patients with ST-elevation myocardial infarction (STEMI) after pPCI, either within 24 h after revascularization (T0) and at clinical stability (T1, 6 ± 2 days), taking into account the site of infarction. Methods and results We enrolled 33 consecutive patients with STEMI treated with pPCI (25 males, mean age 61 ± 12.1 yr); 15 had an anterior wall STEMI (ANT) and 18 had an inferior wall STEMI (INF). ECG and respiration were recorded at T0 and at T1. Cardiac autonomic modulation was evaluated by means of symbolic analysis of heart rate variability. At T0, At T0, 0V% (marker of sympathetic modulation) was higher in INF compared to ANT [31% (18–43) vs 18% (7–32), p = 0.014]. Moreover, ANT had a higher 2LV%, index of vagal modulation, compared to INF [8% (7–15) vs 5% (2–8), p = 0.006]. Conclusion After pPCI, these preliminary results suggest that patients with INF were characterized by a sympathetic predominance, while ANT by a predominant vagal modulation. Our data suggest that pPCI can be associated with specific autonomic patterns, which are different for ANT and INF STEMI, according to the different autonomic innervation. Future ad hoc studies are needed to confirm these preliminary observations.

δ‑like ligand 4 (DLL4)‑Notch signaling is associated with tumor resistance to anti‑vascular endothelial growth factor (VEGF) therapy. Furthermore, Notch signaling is critical for the maintenance of colon cancer stem cells (CSCs), which are relevant in drug resistance and tumor angiogenesis. CD44 is a transmembrane glycoprotein and is considered a putative marker of CSCs. To assess the association of Notch intracellular cleaved domain (NICD), DLL4 and CD44 expression with the efficacy of anti‑angiogenic drugs, a series of samples derived from patients with advanced colon cancer enrolled in prospective clinical trials were analyzed. Histological samples from 51 primary tumors that originated from patients treated with bevacizumab‑based first‑line chemotherapy were analyzed by immunohistochemistry for NICD, DLL4 and CD44 expression, and CD31 for microvessel count. The expression levels of genes relevant for angiogenesis [angiopoietin (ANGPT)1, ANGPT2, fibroblast growth factor (FGF)1, FGF2, epidermal growth factor, placental growth factor, VEGFA and DLL4] were detected by reverse transcription‑quantitative PCR using RNA extracted from the frozen tissues of four tumors with low and four tumors with high NICD expression. Strong NICD levels were observed in 12/51 (24%) of the patients, whereas 16/51 (31%) of the colon cancer subjects exhibited high CD44 expression. Strong CD44 staining was associated with high NICD levels compared with the CD44 expression levels noted in samples with low NICD levels (67 vs. 20%, P=0.005). No association was observed with regards to the expression levels of NICD, CD44 and the other aforementioned biomarkers. High expression levels of NICD and CD44 predicted reduced progression‑free survival (P

Everybody, regardless of their role, is aware that biomedical research is rapidly evolving, and the demand for reproducibility is increasing together with the amount of novel information. “Before reproducibility must come pre-producibility” “Checklists work to improve science”, just to quote some of the articles querying how to find a new bridge between ethics in science and the urgency for publishing. Looking for papers on anti-inflammatory compounds in periodontics, we came across a significant number of articles that could be considered a prototype of a consistent study format. The literature on the testing of active compounds on lipopolysaccharides- (LPS)-induced inflammation in gingival fibroblasts was searched to identify studies that followed a consistent format, to better understand their similarities and assess the appropriateness of their methods. Several studies were identified with a degree of similarity in their methods and formatting that was so high that it was possible to rule out that it was due to chance, and a format template common to these studies was outlined. Although this was most likely beyond the intentions of their authors, these studies may pose the basis for an in-vitro testing standard for anti-inflammatory compounds; however, the dangers of acritical uniformity are also apparent.

Since the seminal studies by Sayers (Ergonomics 16:17-32, 1973) and Akselrod et al. (Science 213:220-222, 1981) a few decades ago, it became clear that beat-by-beat oscillations in RR interval length (i.e. heart-rate variability [HRV]) contain information on underlying neural-control mechanisms based on the instantaneous balance between parasympathetic and sympathetic innervation. Over the years, the number of studies addressing HRV has increased markedly and now outnumbers 23,000. Despite such a large interest, there is still a continuing debate about interpretation of indices produced by computer analysis of HRV.The main part of studies relies on spectral techniques to extract parameters that are linked to hidden information. The general idea is that these proxies of autonomic regulation can be useful to clinical applications in various conditions in which autonomic dysregulation may play a role. There are, however, serious shortcomings related to algorithms, interpretation, and the hidden value of individual indices. In particular, it appears that specific training is necessary to interpret the hidden informational value of HRV. This technical complexity represents a severe barrier to large-scale clinical applications. Moreover, important differences in HRV separate the sexes, and age plays an additional confounding role.We present here a preliminary application of a novel unitary index of RR variability (Autonomic Nervous System Index of cardiac regulation) capable of providing information on the performance of autonomic regulation using a percentile rank position as projected on a large benchmark population. A summary of the underlying sympatho-vagal model is also presented.

Purpose Nowadays manufacturers companies are increasingly compelled to navigate towards servitization. Different methods and approaches were proposed in literature to support them to switch from traditional product-based business model to product service systems (PSSs). However, new knowledge, capabilities and skills were needed to consistently develop PSSs, since they need a joint focus on both customer’s perspective and company’s internal performance and at the same time a proper support for the integration of product and service design. The purpose of this paper is to propose the Product Service System Lean Design Methodology (PSSLDM), a structured methodology to develop PSSs along their entire lifecycle. Design/methodology/approach Retrieving concepts from interpretative, interactive and system development research traditions, and strongly reminding the design research methodology framework, the adopted research methodology is composed of three main phases (observation and conceptualization, theory building and tool development, validation) and involved three heterogeneous companies. Findings This paper provides an overview of the PSSLDM, explaining how the different methods supporting its conduction should contribute to properly design an integrated PSS. Moreover, companies highlighted several benefits in the different stages along the PSS lifecycle deriving by the adoption of the PSSLDM. Research limitations/implications The development of a platform based on the PSSLDM methodology raises a discussion on the possible changes needed by current Product Lifecycle Management (PLM) models and systems when they have to do with PSSs. Originality/value The PSSLDM enriches the already proposed SErvice Engineering Methodology, introducing new several components linked by lean rules in each of its phases (starting from customer analysis, going through solution concept and detailed design, until the offering analysis) and better supprting the deatil design of both prodcut and service components.

In the recent years, Product Service Systems (PSSs) and smart products are surging in the market and acquiring a strategic role for companies’ survival. Their relevance is constantly pushed by technological progress, increased customers’ demand for always different functionalities and manufacturers’ need for improving their position on the market. Manufacturers, compelled towards the transformation process into PSS providers, have to face the challenge of building up knowledge for successfully providing such complex solutions, also resorting to the help of more effective IT systems and tools. The need to adopt a collaborative design platform, typically used in product engineering processes, is starting to be raised also in the PSS context, since manufacturing companies often have a lack of knowledge for providing PSS. This work, grounded on a combination of Lean and DfX-based theories, is aimed at contributing to improve the knowledge formalization and sharing with the support of IT tools. In this sense, a tool able to manage PSS design knowledge, the Lean Content Design Guidelines and Rules generated and referring to the Design for Product Service Supportability (DfPSSu) approach, is proposed. Finally, to fully exploit design knowledge through a structured engineering workflow, the Lean Design Rules tool (LDRT) is integrated in a more holistic engineering environment able to interact with Product Lifecycle Management (PLM) systems.

Since the seminal studies by Sayers (Ergonomics 16:17–32, 1973) and Akselrod et al. (Science 213:220–222, 1981) a few decades ago, it became clear that beat-by-beat oscillations in RR interval length (i.e. heart-rate variability [HRV]) contain information on underlying neural-control mechanisms based on the instantaneous balance between parasympathetic and sympathetic innervation. Over the years, the number of studies addressing HRV has increased markedly and now outnumbers 23,000. Despite such a large interest, there is still a continuing debate about interpretation of indices produced by computer analysis of HRV.