Interoperability Standards for Data Sharing as a Basis to Fill in a Tailored EHR for Undiagnosed Rare Diseases.

Undiagnosed rare diseases include diseases with a well-characterised phenotype, diseases with unknown molecular causes or due to non-genetic factors, and pathological condition that cannot be named. Several initiatives have been launched for healthcare of patients with undiagnosed rare diseases. A project for development of medical records with special reference to the HL7 standards is being carried out in Genoa (Italy), taking into account regional and national regulations. The project is based on the integration of functionality related to patient diagnostics, taking into account omic sciences for disease prevention and risk assessment. Considering the evolution of standards, the use of FHIR is being considered in order to increase the elasticity of the system also in view of foreseeable adoption of this standard by the Italian healthcare system.

Semantics Management for a Regional Health Information System in Italy by CTS2 and FHIR.

An infrastructure for the management of semantics is being developed to support the regional health information exchange in Veneto - an Italian region which has about 5 million inhabitants. Terminology plays a key role in the management of the information fluxes of the Veneto region, in which the management of electronic health record is given great attention. An architecture for the management of the semantics of laboratory reports has been set up, adopting standards by HL7. The system has been initially developed according to the common terminology service release 2 (CTS2) standard and, in order to overcome complexities of CTS2 is being revised according to the Fast Healthcare Interoperability Resources (FHIR) standard, which has been subsequently introduced. Aspects of CST2 and of FHIR have been considered in order to retain most suitable aspects of both. This integration can be regarded as most worthwhile.

Integrating an Electronic Health Record System into a Regional Health Information System: An HL7 FHIR Architecture.

This paper presents an architecture which has been developed in order to integrate a routinely used cardiologic EHR system into the health information infrastructure system of the region where the EHR is used. A Service Oriented Approach based on HL7 and FHIR was used, achieving interoperability, security and confidentiality at all levels. The system has been used for about a year and has brought about significant improvements in the provision of care.

Healthcare Associated Infections: An Interoperable Infrastructure for Multidrug Resistant Organism Surveillance.

Prevention and surveillance of healthcare associated infections caused by multidrug resistant organisms (MDROs) has been given increasing attention in recent years and is nowadays a major priority for health care systems. The creation of automated regional, national and international surveillance networks plays a key role in this respect. A surveillance system has been designed for the Abruzzo region in Italy, focusing on the monitoring of the MDROs prevalence in patients, on the appropriateness of antibiotic prescription in hospitalized patients and on foreseeable interactions with other networks at national and international level. The system has been designed according to the Service Oriented Architecture (SOA) principles, and Healthcare Service Specification (HSSP) standards and Clinical Document Architecture Release 2 (CDAR2) have been adopted. A description is given with special reference to implementation state, specific design and implementation choices and next foreseeable steps. The first release will be delivered at the Complex Operating Unit of Infectious Diseases of the Local Health Authority of Pescara (Italy).

Sustained delivery of growth factors with high loading efficiency in a layer by layer assembly.

Layer by layer (LBL) assembly has garnered considerable interest due to its ability to generate multifunctional films with high tunability and versatility in terms of substrates and polyelectrolytes, allowing the option to use complex devices and drugs. Polyelectrolytes, such as growth factors (GFs), are essential, but costly, delicate, biological molecules that have been used in various tissue regeneration applications. For this reason, the controlled drug delivery of efficiently loaded GFs via LBL assembly (GF-LBL) can contribute to the establishment of cost-effective biologically triggered biomedical applications. We have developed an LBL method to load GFs (specifically, transforming growth factor beta 1, platelet-derived growth factor ßß, and insulin growth factor 1), with up to 90% efficiency approximately, by gas plasma surface activation and tuning the pH to increase the ionic strength of polyelectrolytes. Poly(styrenesulfonate) (PSS) and poly(ethyleneimine) (PEI) have been used to provide the initial necessary charge for multilayer build-up. Heparin and dextran sulphate have been investigated as counter polyelectrolytes to enhance the activity of GFs by protecting their ligands, where heparin resulted in the highest achievable loading efficiency for all GFs. Oxygen gas plasma and acidic pH levels also resulted in a significant increase in GF loading efficiency. The three GFs were released by diffusion and erosion in a controlled manner over lengthy time scales and the bioactivity was maintained for up to 14 days. When tested as implants in vitro, GF-LBL constructs increased fibroblast proliferation, influenced cell morphology and migration, and enhanced myofibroblast differentiation, indicating that the biological functionalities of the GFs were preserved. In conclusion, this developed LBL assembly method can provide a simple drug delivery system, which may yield more effective applications for tissue regeneration as well as biomedical sciences at large.

Medical Equipment Replacement Prioritisation: A Comparison Between Linear and Fuzzy System Models.

In hospital management, health technology assessment techniques are being increasingly developed. This paper presents a comparison of the results obtained using two models for replacement priority value calculation applied to the Galliera hospital in Genoa (Italy). One the models was developed at the Galliera Hospital along the lines of the model by Fennigkoh and addresses four primary replacement issues: equipment service and support, equipment function, cost benefits and clinical efficacy, by a "yes-no" scheme. This model is compared with a model based on fuzzy logic. The comparison between the two models shows a conservative behaviour by the Galliera model, according to which 77.4% of the analysed instrumentation is maintained, whereas the classification by the fuzzy model allows for a better discrimination among the devices.

Information Technology System Including Patient Generated Health Data for Cancer Clinical Care and Research.

This paper presents the extension of a service-oriented architecture framework for precision oncology to the management of patient generated health data from wearables. The solution follows the indication provided by the Health Level 7 (HL7) and Object Management Group (OMG) initiative Healthcare Service Specification Project (HSSP) and is compliant to Retrieve Locate and Update Service (RLUS) Release 1 standard adopting Clinical Document Architecture Release 2 (CDA R2) as semantic signifier. The system which has been developed supports the management of visits, the setting up of a clinical diary and a comprehensive view of the patients from the wearables data for improve clinical care and for research. The system structure is highly modular and the parameters relating to wearables data are only present in one module. Extension of the systems to other aspects, such as genomics and immune therapy, are planned following the same modular design criteria.

Cancer precision medicine today: Towards omic information in healthcare systems.

INTRODUCTION:: This article focuses on the integration of omics data in electronic health records and on interoperability aspects relating to big data analysis for precision medicine. METHODS:: Omics data integration methods for electronic health record and for systems interoperability are considered, with special reference to the high number of specific software tools used to manage different aspects of patient treatment. This is an important barrier against the use of this integrated approach in daily clinical routine. RESULTS:: The correct use of all three levels of interoperability (technical, semantic, and process interoperability) plays a key role in order to achieve an easy access to a significant amount of data, all with correct contextualization, which is the only way to obtain a real value from data for precision medicine. CONCLUSIONS:: The proposed architecture could improve the potentialities of data routinely collected in many health information systems to form a real patient center information environment.

Optimizing Texture Modified Foods for Oro-pharyngeal Dysphagia: A Difficult but Possible Target?

Dysphagia is a swallowing disorder characterized by the difficulty in transferring solid foods and/or liquids from the oral cavity to the stomach, imparing autonomous, and safe oral feeding. The main problems deriving from dysphagia are tracheo-bronchial aspiration, aspiration pneumonia, malnutrition and dehydration. In order to overcome dysphagia-induced problems, over the years water and food thickening has been used, focusing specifically on viscosity increase, but limited results have been obtained. Elastic components and their effects on the cohesiveness on the bolus should be taken into account in the first place. We provide an analysis of dysphagia and suggest possible corrections to the protocols which are being used at present, taking into account rheological properties of food and the effect of saliva on the bolus. We reckon that considering such aspects in the dysphagia management market and healthcare catering would result in significant clinical risk reduction.

Image-Based Tracking of Anticancer Drug-Loaded Nanoengineered Polyelectrolyte Capsules in Cellular Environments Using a Fast Benchtop Mid-Infrared (MIR) Microscope.

Drug delivery monitoring and tracking in the human body are two of the biggest challenges in targeted therapy to be addressed by nanomedicine. The ability of imaging drugs and micro-/nanoengineered drug carriers and of visualizing their interactions at the cellular interface in a label-free manner is crucial in providing the ability of tracking their cellular pathways and will help understand their biological impact, allowing thus to improve the therapeutic efficacy. We present a fast, label-free technique to achieve high-resolution imaging at the mid-infrared (MIR) spectrum that provides chemical information. Using our custom-made benchtop infrared microscope using a high-repetition-rate pulsed laser (80 MHz, 40 ps), we were able to acquire images with subwavelength resolution (0.8 × λ) at very high speeds. As a proof-of-concept, we embarked on the investigation of nanoengineered polyelectrolyte capsules (NPCs) containing the anticancer drug, docetaxel. These NPCs were synthesized using a layer-by-layer approach built upon a calcium carbonate (CaCO3) core, which was then removed away with ethylenediaminetetraacetic acid. The obtained MIR images show that NPCs are attached to the cell membrane, which is a good step toward an efficient drug delivery. This has been confirmed by both three-dimensional confocal fluorescence and stimulated emission depletion microscopy. Coupled with additional instrumentation and data processing advancements, this setup is capable of video-rate imaging speeds and will be significantly complementing current super-resolution microscopy techniques while providing an unperturbed view into living cells.

Prediction of potential barcoding sites on ITS1 by wavelet transform.

For sustainable development, biodiversity conservation and life-quality improvement must be simultaneously considered. Molecular techniques have greatly impacted biotechnology. These methods have, in particular, improved the capability to investigate the fine differences among organisms and, as a consequence, to better investigate the effects on environmental factors on them. We propose an approach to support the optimal selection of molecular probes for barcoding application in many biotechnological fields. The aim of our work is specificity maximization. To this purpose, we have integrated a filter system based on wavelet transforms with biological knowledge about the sequence proneness to mutation and post-translational modification. Specifically, we have tested the proposed method on ITS1 sequences that are a region of the rRNA locus. Our analysis has shown the presence of other local relative stable conformations in addition to known cleavage site. Their characteristics differ within the group of mammals selected for our analysis. These variations could be used to design new species-specific barcoding probes or other quick molecular screening tools.

Peroxidated olive oil nanoemulsion for cancer targeted therapy.

A reactive oxygen species-mediated targeting system has been used to selectively kill cancer cells. Two different cell lines, normal and cancer cells, have been cultured and treated with a peroxide olive oil (K600) in simple solution and in form of nanoemulsion (N-K600). Preliminary results of both treatments have been compared.

Chitosan/dextran multilayer microcapsules for polyphenol co-delivery.

Polysaccharide-based nanostructured polymeric microcapsules were fabricated by the electrostatic layer-by-layer self-assembly technique and used to encapsulate mixtures of four different polyphenols in order to achieve their controlled release. The real-time fabrication of the dextran/chitosan multilayer was monitored by quartz crystal microbalance with dissipation monitoring, and the morphology of the nanostructured polymeric capsules was characterized by scanning electron microscopy. The polyphenol encapsulation was obtained by reversible permeability variation of the capsule shell in ethanol:water mixtures. The loading efficiency in different water:ethanol mixtures and the release rate in acidic conditions were characterized by UV spectroscopy and HPLC. The higher loading efficiency was obtained with an ethanol:water 35:65 phenolic solution, equal to 42.0±0.6%, with a total release of 11.5±0.7 mg of total polyphenols per 11.3 µL of microcapsules after 240 min of incubation in acidic environment. The results suggest that polysaccharide-based capsules can be successfully used to encapsulate and release low water-soluble molecules, such as polyphenols.

Multilayered polyelectrolyte microcapsules: interaction with the enzyme cytochrome C oxidase.

Cell-sized polyelectrolyte capsules functionalized with a redox-driven proton pump protein were assembled for the first time. The interaction of polyelectrolyte microcapsules, fabricated by electrostatic layer-by-layer assembly, with cytochrome c oxidase molecules was investigated. We found that the cytochrome c oxidase retained its functionality, that the functionalized microcapsules interacting with cytochrome c oxidase were permeable and that the permeability characteristics of the microcapsule shell depend on the shell components. This work provides a significant input towards the fabrication of an integrated device made of biological components and based on specific biomolecular functions and properties.

Functionalized biocompatible polyelectrolyte multilayers for drug delivery: in situ investigation of mechanical properties by dissipative quartz crystal microbalance.

Nanostructured polymeric capsules have been applied in different fields, and specifically are regarded as promising for smart drug delivery applications. The physical-chemical and mechanical properties, and thus the permeability of the polyelectrolyte multilayer shell, play an important role in efficient delivery. Quartz crystal microbalance working in liquid has been used for the characterization of the buildup process and of the viscoelastic properties of biocompatible multilayers and of their functionalization by S-layer proteins. Optical and scanning electron microscopy have been used for the morphological characterization of nanostructured capsules obtained at physiological conditions by the assembly of the characterized multilayers onto spherical cores and by their subsequent removal. The proposed functionalized biocompatible capsules can be regarded as promising candidates for smart drug delivery applications.

Oriented collagen nanocoatings for tissue engineering.

Collagens are among the most widely present and important proteins composing the human total body, providing strength and structural stability to various tissues, from skin to bone. In this paper, we report an innovative approach to bioactivate planar surfaces with oriented collagen molecules to promote cells proliferation and alignment. The Langmuir-Blodgett technique was used to form a stable collagen film at the air-water interface and the Langmuir-Schaefer deposition was adopted to transfer it to the support surface. The deposition process was monitored by estimating the mass of the protein layers after each deposition step. Collagen films were then structurally characterized by atomic force, scanning electron and fluorescent microscopies. Finally, collagen films were functionally tested in vitro. To this aim, 3T3 cells were seeded onto the silicon supports either modified or not (control) by collagen film deposition. Cells adhesion and proliferation on collagen films were found to be greater than those on control both after 1 (p<0.05) and 7 days culture. Moreover, the functionalization of the substrate surface triggered a parallel orientation of cells when cultured on it. In conclusion, these data demonstrated that the Langmuir-Schaefer technique can be successfully used for the deposition of oriented collagen films for tissue engineering applications.

Adhesion and proliferation of osteoblast-like cells on anodic porous alumina substrates with different morphology.

We have fabricated nanoporous alumina surfaces by means of anodization in oxalic acid in different conditions and used them as the substrates for the growth of cells from a human osteoblast-like cell line. The rough nanoporous alumina substrates have been compared both with smooth standard Petri dishes used as the control and with commercial substrates of similar material. The viability of the cells has been assessed at different culture times of 4, 11, 18, and 25 days in vitro. It turned out that the porous side of the galvanostatically fabricated alumina performed similar to the control and better than the commercial porous alumina, whereas the potentiostatically fabricated porous alumina performed better than all the other substrates at all times, and in particular at the two shortest time periods of 4 and 11 days in vitro. The best performance of the substrates is associated with intermediate surface roughness and feature spacing.

Polyelectrolyte based molecular carriers: the role of self-assembled proteins in permeability properties.

Polyelectrolyte capsules are seen as promising nanotechnology based drug delivery systems. In previous works, we have demonstrated the possibility to fabricate bio-activated surface layer containing capsules with improved features in terms of biocompatibility. In this study, we have characterized the permeability properties of such capsules towards low and high molecular weight molecules, including proteins. The results indicated that the presence of the surface layer strongly affects the permeability properties of the capsules in terms of loading capacity which was found to be higher compared to that of plain capsules. These properties make such systems interesting candidates as drug delivery platforms.

Comparative analysis of Rac1 binding efficiency with different classes of ligands: morpholines, flavonoids and imidazoles.

The focal adhesion pathway has a great impact on cellular growth and survival. Its disregulation is correlated with the loss of cellular mechanical properties. Such modifications are, in many cases, associated with pathologies such as cancer and cardiovascular diseases. Actin remodeling is a critical reaction cascade embedded in focal adhesion pathway, and Rac1 is one of the proteins involved in actin remodeling. In order to design highly selective pharmacophores against this target, it is necessary to maximize the binding affinity of chemical entities against Rac1. To this purpose we propose an integrative chemo-bioinformatics tool to screen ligand specificity for a target protein. Our integrative workflow includes chemo-informatics data mining (Chemical System), structural bioinformatics and combined exploratory data analysis. We have applied this integrative chemo-bioinformatics workflow to a comparative analysis of three different classes of ligands (morpholines, flavonoids and imidazoles) against the Rac1 protein. Our analysis emphasizes the presence of several ligands that preferentially dock Rac1 in the domain that seems to be responsible for Rac1-phospholipase C gamma 1 interaction. Recent studies have highlighted the Rac1 and PLC interactions in platelet adhesion. Our study has highlighted the role of Rac1-PLC gamma1 interaction in cytoskeleton remodeling associated with cardiovascular diseases. Rac1 PLC interaction is Calcium dependent. This suggest that some of the analysed ligands, could be used to control the Calcium dependent cytoskeleton remodeling since they dock Rac1 in the switch 2 domain. Our results, in a nanotechnology perspective, also endorse the use Rac1's switch 2 domain suitable for new highly specific biosensors.

Potential MiRNAs recognition site identification in 3' UTR regions by DSP methods.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate fundamental cellular processes in diverse organisms and that have an important function in gene expression regulation. miRNAs seem capable to concurrently modulate hundreds of target genes. Their abnormal expression is emerging as important element in many pathological conditions. The identification of microRNA binding sites on those proteins that can be disease biomarker is fundamental to design synthetic artificial oligomers. In this paper we suggest a method, based on signal processing, to filter out potential miRNA recognition sites in the 3' UTR region of mRNAs.