Introductory editorial: drug-eluting stents or drug-eluting grafts? Insights from proteomic analysis

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Aspects of geodesical motion with Fisher-Rao metric: classical and quantum

The purpose of this article is to exploit the geometric structure of Quantum Mechanics and of statistical manifolds to study the qualitative effect that the quantum properties have in the statistical description of a system. We show that the end points of geodesics in the classical setting coincide with the probability distributions that minimise Shannon's Entropy, i.e. with distributions of zero dispersion. In the quantum setting this happens only for particular initial conditions, which in turn correspond to classical submanifolds. This result can be interpreted as a geometric manifestation of the uncertainty principle.Comment: 15 pages, 5 figure

Hamilton-Jacobi approach to Potential Functions in Information Geometry

The search for a potential function $S$ allowing to reconstruct a given metric tensor $g$ and a given symmetric covariant tensor $T$ on a manifold $\mathcal{M}$ is formulated as the Hamilton-Jacobi problem associated with a canonically defined Lagrangian on $T\mathcal{M}$. The connection between this problem, the geometric structure of the space of pure states of quantum mechanics, and the theory of contrast functions of classical information geometry is outlined.Comment: 16 pages. A discussion on the Kullback-Leibler divergence has been added. To appear in Journal of Mathematical Physic

oxidative stress and proteostasis network culprit and casualty of alzheimer s like neurodegeneration

Free radical-mediated damage to proteins is particularly important in aging and age-related neurodegenerative diseases, because in the majority of cases it is a non-reversible phenomenon that requires clearance systems for removal. Major consequences of protein oxidation are loss of protein function and the formation of large protein aggregates, which are often toxic to cells if allowed to accumulate. Deposition of aggregated, misfolded, and oxidized proteins may also result from the impairment of protein quality control (PQC) system, including protein unfolded response, proteasome, and autophagy. Perturbations of such components of the proteostasis network that provides a critical protective role against stress conditions are emerging as relevant factor in triggering neuronal death. In this outlook paper, we discuss the role of protein oxidation as a major contributing factor for the impairment of the PQC regulating protein folding, surveillance, and degradation. Recent studies from our group and from others aim to better understand the link between Down syndrome and Alzheimer's disease neuropathology. We propose oxidative stress and alteration of proteostasis network as a possible unifying mechanism triggering neurodegeneration

Pharmacologic approaches against advanced glycation end products (ages) in diabetic cardiovascular disease

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports

Soft Tissue Contour Impression with Analogic or Digital Work Flow: A Case Report

Transferring precise information to the dental laboratory is one of the key factors to achieving clinical success. The aim of the present study was to describe classical and digital work-flows used to rehabilitate an implant with a convergent collar in the aesthetic zone following the BOPT (biologically oriented preparation technique) approach and to report the three years follow-up outcomes of two patients rehabilitated following such procedures

It Is All About (U)biquitin: Role of Altered Ubiquitin-Proteasome System and UCHL1 in Alzheimer Disease

Free radical-mediated damage to macromolecules and the resulting oxidative modification of different cellular components are a common feature of aging, and this process becomes much more pronounced in age-associated pathologies, including Alzheimer disease (AD). In particular, proteins are particularly sensitive to oxidative stress-induced damage and these irreversible modifications lead to the alteration of protein structure and function. In order to maintain cell homeostasis, these oxidized/damaged proteins have to be removed in order to prevent their toxic accumulation. It is generally accepted that the age-related accumulation of “aberrant” proteins results from both the increased occurrence of damage and the decreased efficiency of degradative systems. One of the most important cellular proteolytic systems responsible for the removal of oxidized proteins in the cytosol and in the nucleus is the proteasomal system. Several studies have demonstrated the impairment of the proteasome in AD thus suggesting a direct link between accumulation of oxidized/misfolded proteins and reduction of this clearance system. In this review we discuss the impairment of the proteasome system as a consequence of oxidative stress and how this contributes to AD neuropathology. Further, we focus the attention on the oxidative modifications of a key component of the ubiquitin-proteasome pathway, UCHL1, which lead to the impairment of its activity

Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol (InRapa) that maximizes brain delivery and reduce systemic side effects. Methods: Ts65Dn mice were administered with InRapa for 12 weeks, starting at 6 months of age demonstrating, at the end of the treatment by radial arms maze and novel object recognition testing, rescued cognition. Results: The analysis of mTOR signalling, after InRapa, demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR (reduced to physiological levels), which led, through the rescue of autophagy and insulin signalling, to reduced APP levels, APP processing and APP metabolites production, as well as, to reduced tau hyperphosphorylation. In addition, a reduction of oxidative stress markers was also observed. Discussion: These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis, thus ultimately resulting in improved cognition. Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals

P3‐179: ABERRANT PERK ACTIVATION IS ASSOCIATED WITH THE DEPLETION OF NRF2 SIGNALING AND THE INCREASE OF OXIDATIVE BURDEN IN DS PATHOLOGY

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DIEP flap perfusion assessment using microdialysis versus Doppler ultrasonography. A comparative study

BackgroundThe increasing number of buried free-tissue transfer procedures and the need for an objective method to evaluate vascular complications of free flaps has led to the development of new technologies. Microdialysis has been used to monitor free flaps using interstitial biological markers. Previous uses mainly focused on muscular flaps. Our aim is to compare external Doppler ultrasonography (EDU) evaluation versus microdialysis in the early follow-up of adipocutaneous flaps, and propose an efficient postoperative monitoring protocol. MethodsWe retrospectively assessed 68 consecutive DIEP flaps (50 patients) performed between January 2019 and March 2021. All flaps received standardized post-operative monitoring using clinical signs, EDU and microdialysis. Glucose and lactate concentrations were assessed using glucose 6 mmol/L as ischemic trend thresholds. We calculated Glucose/Lactate ratio as a new parameter for the assessment of flap viability. ResultsAmong all the 68 flaps, two flaps returned to the operative theater when a combination of unsatisfactory microdialysis values and clinical/EDU signs identified vascular impairment; only one developed total flap necrosis. Reoperation rate was 2.94% with an overall flap success rate of 98.53%. External Doppler ultrasonography had 100% sensitivity and 82% specificity, while microdialysis had 100% sensitivity and 100% specificity. ConclusionsMicrodialysis values proved flap viability sooner than external Doppler ultrasonography, making it an excellent tool for post-operative monitoring. With the appropriate thresholds for glucose and lactate concentrations, and glucose/lactate ratio used as a new parameter, it can help potentially avoiding unnecessary re-explorations, and reducing flap ischemia times