The digitization process and the evolution of Clinical Risk Management concept: The role of Clinical Engineering in the operational management of biomedical technologies.

Introduction: Digital transformation and technological innovation which have influenced several areas of social and productive life in recent years, are now also a tangible and concrete reality in the vast and strategic sector of public healthcare. The progressive introduction of digital technologies and their widespread diffusion in many segments of the population undoubtedly represent a driving force both for the evolution of care delivery methods and for the introduction of new organizational and management methods within clinical structures. Methods: The CS Clinical Engineering of the "Spedali Civili Hospital in Brescia" decided to design a path that would lead to the development of a software for the management of biomedical technologies within its competence inside the hospital. The ultimate aim of this path stems from the need of Clinical Engineering Department to have up-to-date, realistic, and systematic control of all biomedical technologies present in the company. "Spedali Civili Hospital in Brescia" is not just one of the most important corporate realities in the city, but it is also the largest hospital in Lombardy and one of the largest in Italy. System development has followed the well-established phases: requirement analysis phase, development phase, release phase and evaluating and updating phase. Results: Finally, cooperation between the various figures involved in the multidisciplinary working group led to the development of an innovative management software called "SIC Brescia". Discussion: The contribution of the present paper is to illustrate the development of a complex implementation model for the digitization of processes, information relating to biomedical technologies and their management throughout the entire life cycle. The purpose of sharing this path is to highlight the methodologies followed for its realization, the results obtained and possible future developments. This may enable other realities in the healthcare context to undertake the same type of pathway inspired by an accomplished model. Furthermore, future implementation and data collection related to the proposed Key Performance Indicators, as well as the consequent development of new operational management models for biomedical technologies and maintenance processes will be possible. In this way, the Clinical Risk Management concept will also be able to evolve into a more controlled, safe, and efficient system for the patient and the user.

Eomesodermin requires transforming growth factor-beta/activin signaling and binds Smad2 to activate mesodermal genes.

The T-box gene Eomesodermin (Eomes) is required for early embryonic mesoderm differentiation in mouse, frog (Xenopus laevis), and zebrafish, is important in late cardiac development in Xenopus, and for CD8+ T effector cell function in mouse. Eomes can ectopically activate many mesodermal genes. However, the mechanism by which Eomes activates transcription of these genes is poorly understood. We report that Eomes protein interacts with Smad2 and is capable of working in a non-cell autonomous manner via transfer of Eomes protein between adjacent embryonic cells. Blocking of Eomes protein transfer using a farnesylated red fluorescent protein (CherryF) also prevents Eomes nuclear accumulation. Transfer of Eomes protein between cells is mediated by the Eomes carboxyl terminus (456-692). A carbohydrate binding domain within the Eomes carboxyl-terminal region is sufficient for transfer and important for gene activation. We propose a novel mechanism by which Eomes helps effect a cellular response to a morphogen gradient.

Forced expression of RDH10 gene retards growth of HepG2 cells.

The constitutive over-expression of the retinol dehydrogenase 10 (RDH10) gene, involved in retinoic acid (RA) biosynthesis, produced in HepG2 cells a significant antiproliferative response, but not signs of apoptosis. An indirect assay based on the Chloramphenicol AcetylTransferase (CAT) reporter gene driven by a retinoic acid responsive element (RARE) suggests in genetically modified HepG2 cells an increase of the endogenous RA concentration. Furthermore, the growth arrest of HepG2 cells over-expressing the RDH10 gene was associated with the upregulation and downregulation of, respectively, RARbeta/p21(Cip1) and CycE/CdK2 mRNAs. These results indicated that forced expression of RDH10 produces antiproliferative effects highly comparable to those achieved by retinoids treatment and thus the development of a gene therapy, finalized at the restoration of the enzymatic and receptorial machinery of the RA pathway, could be a possible curative strategy for hepatocellular carcinoma (HCC).