Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Medical device regulation in vascular ageing assessment: a VascAgeNet survey exploring knowledge and perception.

BACKGROUND: Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment. The aim of this work is to explore knowledge and perception of medical device regulatory framework in vascular ageing field. RESEARCH DESIGN AND METHODS: A survey was developed within VascAgeNet and distributed in the community by means of the EUSurvey platform. RESULTS: Results were derived from 94 participants (27% clinicians, 62% researchers, 11% companies) and evidenced mostly a fair knowledge of MDR (despite self-judged as poor by 51%). Safety (83%), validation (56%), risk management (50%) were considered relevant and associated with the regulatory process. Structured support and regulatory procedures connected with medical devices in daily practice at the institutional level are lacking (only 33% report availability of a regulatory department). CONCLUSIONS: Regulation was recognized relevant by the VascAgeNet community and specific support and training in medical device regulatory science was considered important. A direct link with the regulatory sector is not yet easily available.

Graphene Oxide/Silver Nanoparticles Platforms for the Detection and Discrimination of Native and Fibrillar Lysozyme: A Combined QCM and SERS Approach.

We propose a sensing platform based on graphene oxide/silver nanoparticles arrays (GO/AgNPs) for the detection and discrimination of the native and toxic fibrillar forms of an amyloid-prone protein, lysozyme, by means of a combination of Quartz Crystal Microbalance (QCM) and Surface Enhanced Raman Scattering (SERS) measurements. The GO/AgNPs layer system was obtained by Langmuir-Blodgett assembly of the silver nanoparticles followed by controlled adsorption of GO sheets on the AgNPs array. The adsorption of native and fibrillar lysozyme was followed by means of QCM, the measurements provided the kinetics and the mechanism of adsorption as a function of protein concentration as well as the mass and thickness of the adsorbed protein on both nanoplatforms. The morphology of the protein layer was characterized by Confocal Laser Scanning Microscopy experiments on Thioflavine T-stained samples. SERS experiments performed on arrays of bare AgNPs and of GO coated AgNP after native, or fibrillar, lysozyme adsorption allowed for the discrimination of the native form and toxic fibrillar structure of lysozyme. Results from combined QCM/SERS studies indicate a general construction paradigm for an efficient sensing platform with high selectivity and low detection limit for native and amyloid lysozyme.

Technical Validation and Usability of a Portable Ultrasound-Based System for Carotid Assessment of Vascular Ageing: A Pilot Study.

OBJECTIVE: The objective of this work was to investigate technical validation and usability of an innovative, technically simple, easy-to-use, and portable integrated system to assess carotid function and structure by ultrasound. METHODS: The studied system integrated a hardware (the Interson SP-L01 embedded ultrasound probe [Interson, Pleasanton, CA, USA]) and a software measuring the instantaneous diameter of the carotid artery in real-time from B-mode ultrasound image sequences (Carotid Studio, by Quipu Srl [Pisa, Italy]). Technical validation was evaluated by intra-operator reproducibility of two measurements acquired by an expert operator, and agreement with state-of-the-art technique (Mylab25 by Esaote SpA [Genova, Italy], Carotid Studio 4.3 by Quipu Srl) was evaluated in laboratory settings in 12 healthy volunteers; usability of the portable integrated system was investigated by administering questionnaires to users and the results were reported with scores based on a five-point scale. RESULTS: Twelve (12) healthy volunteers (five men, mean age 44.5±13.6 years, free of cardiovascular disease or risk factors), were recruited. Agreement with state-of-the-art technique was satisfactory, with no significant bias. Coefficient of variation (intra-operator reproducibility) was 3.2% (2.5% SD) for intima-media thickness, 0.9% (0.7% SD) for diameter, and 2.5% (2.2% SD) for distension. Usability questionnaires showed an overall positive judgement of the integrated system with respect to the traditional one, obtaining an average score greater than 4 (on a five-point scale). CONCLUSIONS: A portable, innovative prototype to easily assess ultrasound carotid parameters of vascular ageing was successfully designed, developed, and demonstrated to be comparable with state-of-the art technique. Usability was also satisfactory.

Multifunctional Magnetic Nanocolloids for Hybrid Solar-Thermoelectric Energy Harvesting.

Present environmental issues force the research to explore radically new concepts in sustainable and renewable energy production. In the present work, a functional fluid consisting of a stable colloidal suspension of maghemite magnetic nanoparticles in water was characterized from the points of view of thermoelectrical and optical properties, to evaluate its potential for direct electricity generation from thermoelectric effect enabled by the absorption of sunlight. These nanoparticles were found to be an excellent solar radiation absorber and simultaneously a thermoelectric power-output enhancer with only a very small volume fraction when the fluid was heated from the top. These findings demonstrate the investigated nanofluid's high promise as a heat transfer fluid for co-generating heat and power in brand new hybrid flat-plate solar thermal collectors where top-heating geometry is imposed.

Blocking the FKBP12 induced dendrimeric burst in aberrant aggregation of α-synuclein by using the ElteN378 synthetic inhibitor.

α-Synuclein (α-syn), a disordered cytoplasmatic protein, plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Here, we have shown, using photophysical measurements, that addition of FKBP12 to α-syn solutions, dramatically accelerates protein aggregation, leading to an explosion of dendritic structures revealed by fluorescence and phase-contrast microscopy. We have further demonstrated that this aberrant α-syn aggregation can be blocked using a recently discovered non-immunosuppressive synthetic inhibitor of FKBP12, ElteN378. The role of FKBP12 and of ElteN378 in the α-syn aggregation mechanism has been elucidated using molecular dynamics simulations based on an effective coarse-grained model. The reported data not only reveal a new potent synthetic drug as a candidate for early stage treatment of α-syn dependent neurodegenerations but also pave the way to a deeper understanding of the mechanism of action of FKBP12 on α-syn oligomeric aggregation, a topic which is still controversial.

Extraction, recovery and characterization of structural extracellular polymeric substances from anammox granular sludge.

The composition and colloidal properties of extracellular polymeric substances (EPS) from anammox granular sludge were investigated through a complete set of spectroscopic and scattering techniques. To fully characterize EPS, we developed a robust and reproducible extraction/recovery protocol specific for anammox biofilms, based on the change of water affinity under alternated alkaline and acidic conditions, each monitored with Z-potential and dynamic light scattering analysis. This method enabled both extraction as a colloidal suspension and recovery as a solid of large amounts of EPS (0.38 ±â€¯0.04 and 0.21 ±â€¯0.02 g/g, respectively), including for the first time its structural components. The dominance of the proteinaceous fraction was revealed by all methods tested, resulting in the highest protein/carbohydrates ratio reported for biofilms applied in the wastewater sector. The abundance of proteinaceous ordered structures and in particular of cross-ß motifs was detected, indicating for the first time the presence of amyloid-like aggregates in anammox EPS, and suggesting the key role of the protein fraction in determining the mechanical properties of the parent biofilm. The robustness and reproducibility of the proposed method fill the current gap towards a reliable full-scale recovery as well as towards an accurate and meaningful investigation of anammox EPS and pave the way for further exploration of their applicative potential thus stimulating the desirable shift from the current wastewater treatment perspective towards biorefinery in a circular economy context.

The precise chemical-physical nature of the pharmacore in FK506 binding protein inhibition: ElteX, a New class of nanomolar FKBP12 ligands.

Due to its central role in immunosuppression and cell proliferation and due to its specific peptidyl-prolyl-isomerase (PPI) function, the FKBP protein family is at the crossroad of several important metabolic pathways. Members of this family, and notably FK506 binding protein (FKBP12), are thought to be involved in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, as well as in proliferation disorders and cancer. Using an interdisciplinary approach based on computational, synthetic, and experimental techniques, we show that the best potential binders for FKBP proteins optimally expose the two contiguous carbonyl oxygen in the proline-mimetic chain for FKBP docking and are characterized by the abundance of rigid quasi-cyclic structures stabilized in aqueous solution by intraligand hydrophobic interactions mimicking the macrolide structure of the natural FKBP binders FK506 and Rapamycin. These peculiar structural and chemical-physical features define at the same time an ElteX compound and the minimal pharmacore in the FKBP family, shedding new light on the isomerization mechanism of the PPI domain. On the basis of the above hypothesis, we have successfully designed and synthesized several nanomolar ElteX FKBP12 ligands. Among these, ElteN378 is a new low atomic weight ligand with affinity comparable to that of the macrolide Rapamycin.

Light-responsive nanocomposite sponges for on demand chemical release with high spatial and dosage control.

We present a biocompatible device for on demand chemical release in the form of a light-activated sponge-like nanocomposite scaffold, which ensures excellent control over the principal parameters of chemical release and dosage in order to sustain effective therapeutic action. The sponge consists of a porous biopolymer scaffold containing a dispersion of gold nanorods, which acts as an absorber of the incoming laser light, and of thermosensitive micelles, which serve as a reservoir for the drug molecules to be released. The photothermal response of the nanoparticles contained inside the sponge triggers a contraction in proximal micelles, thus promoting the expulsion of the drug that in turn is released from the sponge to the external environment. The peculiar physiochemical and structural properties of the nanocomposite sponges impart a number of interesting features to the proposed drug release system, including the possibility of spatially confining the therapeutic treatment as well as precise control of the amount of released drug as a function of duration and power of the excitation light.