An overview of trends in the regulation of clinical ethics committee; an opinion from the Italian National Bioethics Committee [Una visión general de las tendencias en la regulación por los comités de ética clínica: una opinión del Comité Nacional Italiano de Bioética]

In 2017, the Italian National Bioethics Commttee (INBC) released an opinion paper titled "Clinical ethics committees". Said document advocates for the creation of "clinical bioethics committees" in every suitable setting and lays out a set of guidelines aimed at regulationg such committees' function. The recommendations deal primarily with the independence, requirements for counselling, structures, composition, tasks, placement, coordination, requisite competences, regulations. In the opinion's contents there are: a) the need to entrust counselling and training on ethical issues within clinical practice to different committees than those that deal with ethical assessment of scientific trial and experimentation; b) the laying out of all the various functions and related competences required of the ethics committes' members; c) the necessity that all counselling pratices be carried out by each committee as a whole, rather than a single expert member; d) Committee's independece. The authors elaborate on each one of the above mentioned aspects and highlight the importance of INBC's recommendations in order to improve the quality standards of care delivered "to each patient's bed".En el 2017, el Comité Nacional Italiano de Bioética (CNIB) publicó un artículo de opinión titulado “Comités de Ética Clínica”. Dicho documento aboga por la creación de “comités clínicos de bioética” en cada entorno adecuado, y establece un conjunto de directrices destinadas a regular las funciones de tales comités. Las recomendaciones se refieren principalmente a la independencia, los requisitos para el asesoramiento, las estructuras, la composición, las tareas, la ubicación, la coordinación, las competencias requeridas, las regulaciones. En los contenidos de la opinión se plantean: a) la necesidad de confiar el asesoramiento y la capacitación en cuestiones éticas dentro de la práctica clínica a diferentes comités que aquellos que se ocupan de las evaluaciones éticas de los ensayos científicos y la experimentación; b) la presentación de las diversas funciones y competencias requeridas por los miembros de los comités de ética; c) la necesidad de que todas las prácticas de asesoramiento sean llevadas a cabo por cada comité como un todo, y no por un solo miembro experto; d) independencia del comité. Los autores detallan cada uno de los aspectos mencionados anteriormente y resaltan la importancia de las recomendaciones de CNIB para mejorar los estándares de calidad de la atención brindada “a la cabecera de la cama de cada paciente”

Biological systems interact with Engineered NanoMaterials (ENMs): Possible environmental risks

There is a growing and controversial public debate on the potential risk of NanoMaterials (NMs) to living organisms, including humans. In particular, the processes of dispersion and bioaccumulation of Engineered NanoMaterials (ENMs) into the environment are poorly investigated. Biological systems interact with ENMs in a very complex dynamic way whose comprehension is still at its infancy. Thus the evaluation of the environmental impact of ENMs may be useful to minimize or eliminate ENMs toxicity and/or ecotoxicity, and to help authorities to draw directives and regulations for a safe production and use of ENMs. Here we briefly review biotoxicity and environmental risks of ENMs (like carbon- and metalnanoparticles) reporting also our experience in the cytotoxicity of carbon (C) and silver (Ag) NanoParticles (NPs) on HeLa cells and nanoecotoxicity on Paracentrotus lividus

HF-SCA: Hands-Free Strong Customer Authentication Based on a Memory-Guided Attention Mechanisms

Strong customer authentication (SCA) is a requirement of the European Union Revised Directive on Payment Services (PSD2) which ensures that electronic payments are performed with multifactor authentication. While increasing the security of electronic payments, the SCA impacted seriously on the shopping carts abandonment: an Italian bank computed that 22% of online purchases in the first semester of 2021 did not complete because of problems with the SCA. Luckily, the PSD2 allows the use of transaction risk analysis tool to exempt the SCA process. In this paper, we propose an unsupervised novel combination of existing machine learning techniques able to determine if a purchase is typical or not for a specific customer, so that in the case of a typical purchase the SCA could be exempted. We modified a well-known architecture (U-net) by replacing convolutional blocks with squeeze-and-excitation blocks. After that, a memory network was added in a latent space and an attention mechanism was introduced in the decoding side of the network. The proposed solution was able to detect nontypical purchases by creating temporal correlations between transactions. The network achieved 97.7% of AUC score over a well-known dataset retrieved online. By using this approach, we found that 98% of purchases could be executed by securely exempting the SCA, while shortening the customer’s journey and providing an elevated user experience. As an additional validation, we developed an Alexa skill for Amazon smart glasses which allows a user to shop and pay online by merely using vocal interaction, leaving the hands free to perform other activities, for example driving a car

Long-term clinical impact of permanent pacemaker implantation in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis

AIMS: The aims of this study is to assess by an updated meta-analysis the clinical outcomes related to permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) at long-term (≥12 months) follow-up (LTF). METHODS AND RESULTS: A comprehensive literature research was performed on PubMed and EMBASE. The primary endpoint was all-cause death. Secondary endpoints were rehospitalization for heart failure, stroke, and myocardial infarction. A subgroup analysis was performed according to the Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score. This study is registered with PROSPERO (CRD42021243301). A total of 51 069 patients undergoing TAVI from 31 observational studies were included. The mean duration of follow-up was 22 months. At LTF, PPI post-TAVI was associated with a higher risk of all-cause death [risk ratio (RR) 1.18, 95% confidence interval (CI) 1.10-1.25; P < 0.001] and rehospitalization for heart failure (RR 1.32, 95% CI 1.13-1.52; P < 0.001). In contrast, the risks of stroke and myocardial infarction were not affected. Among the 20 studies that reported procedural risk, the association between PPI and all-cause death risk at LTF was statistically significant only in studies enrolling patients with high STS-PROM score (RR 1.25, 95% CI 1.12-1.40), although there was a similar tendency of the results in those at medium and low risk. CONCLUSION: Patients necessitating PPI after TAVI have a higher long-term risk of all-cause death and rehospitalization for heart failure as compared to those who do not receive PPI

Association of plasma Aβ40/Aβ42 ratio and brain Aβ accumulation: testing a whole-brain PLS-VIP in individuals at risk of Alzheimer's disease

Molecular and brain regional/network-wise pathophysiological changes at preclinical stages of Alzheimer's disease (AD) have primarily been found through knowledge-based studies conducted in late-stage mild cognitive impairment/dementia populations. However, such an approach may compromise the objective of identifying the earliest spatial-temporal pathophysiological processes. We investigated 261 individuals with subjective memory complaints, a condition at increased risk of AD, to test a whole-brain, non-a-priori method based on partial least squares, in unraveling the association between plasma Aβ42/Aβ40 ratio and an extensive set of brain regions characterized through molecular imaging of Aβ accumulation and cortical metabolism. Significant associations were mapped onto large-scale networks, identified through an atlas and by knowledge, to elaborate on the reliability of the results. Plasma Aβ42/40 ratio was associated with Aβ-PET uptake (but not FDG-PET) in regions generally investigated in preclinical AD such as those belonging to the default mode network, but also in regions/networks normally not accounted - including the central executive and salience networks - which likely have a selective vulnerability to incipient Aβ accumulation. The present whole-brain approach is promising to investigate early pathophysiological changes of AD to fully capture the complexity of the disease, which is essential to develop timely screening, detection, diagnostic, and therapeutic interventions

The Amyloid-beta Pathway in Alzheimer's Disease

Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer’s disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aβ species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aβ-targeting therapeutic strategies in development for the early treatment of AD

Interplay between myocardial bridging and coronary spasm in patients with myocardial ischemia and non-obstructive coronary arteries: Pathogenic and prognostic implications

BACKGROUND: Myocardial bridging (MB) may represent a cause of myocardial ischemia in patients with non-obstructive coronary artery disease (NOCAD). Herein, we assessed the interplay between MB and coronary vasomotor disorders, also evalu-ating their prognostic relevance in patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) or stable NOCAD. METHODS AND RESULTS: We prospectively enrolled patients with NOCAD undergoing intracoronary acetylcholine provocative test. The incidence of major adverse cardiac events, defined as the composite of cardiac death, non-fatal myocardial infarc-tion, and rehospitalization for unstable angina, was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires summary score. We enrolled 310 patients (mean age, 60.6±11.9; 136 [43.9%] men; 169 [54.5%] stable NOCAD and 141 [45.5%] MINOCA). MB was found in 53 (17.1%) patients. MB and a positive acetylcholine test coexisted more frequently in patients with MINOCA versus stable NOCAD. MB was an independent predictor of positive acetylcholine test and MINOCA. At follow-up (median, 22 months; interquartile range, 13–32), patients with MB had a higher rate of major adverse cardiac events, mainly driven by a higher rate of hospitalization attributable to angina, and a lower Seattle Angina Questionnaires summary score (all P<0.001) compared with patients without MB. In particular, the group of patients with MB and a positive acetylcholine test had the worst prognosis. CONCLUSIONS: Among patients with NOCAD, coronary spasm associated with MB may predict a worse clinical presentation with MINOCA and a higher rate of hospitalization attributable to angina at long-term follow-up with a low rate of hard events

Plasma β-secretase1 concentrations correlate with basal forebrain atrophy and neurodegeneration in cognitively healthy individuals at risk for AD

BACKGROUND: Increased β-secretase 1 (BACE1) protein concentration, in body fluids, is a candidate biomarker of Alzheimer's disease (AD).We reported that plasma BACE1 protein concentrations are associated with the levels of brain amyloidβ (Αβ) accumulation in cognitively healthy individuals with subjective memory complaint (SMC). METHODS: In 302 individuals from the same cohort, we investigated the cross-sectional and longitudinal association between plasma BACE1 protein concentrations and AD biomarkers of neurodegeneration (plasma t-tau and Neurofilament light chain (NfL), fluorodeoxyglucose-positron emission tomography (FDG-PET), brain volumes in the basal forebrain [BF], hippocampus, and entorhinal cortex). RESULTS: We report a positive longitudinal correlation of BACE1 with both NfL and t-tau, as well as a correlation between annual BACE1 changes and bi-annual reduction of BF volume. We show a positive association between BACE1 and FDG-PET signal at baseline. CONCLUSIONS: The association between plasma BACE1 protein concentrations and BF atrophy we found in cognitively healthy individuals with SMC corroborates translational studies, suggesting a role of BACE1 in neurodegeneration

Analysis of the effect of locally applied inhomogeneous static magnetic field-exposure on mouse ear edema - a double blind study

The effect static magnetic field (SMF)-exposure may exert on edema development has been investigated. A 6 h long whole-body (WBSMF) or local (LSMF), continuous, inhomogeneous SMF-exposure was applied on anesthetized mice in an in vivo model of mustard oil (MO)-induced ear edema. LSMF was applied below the treated ear, below the lumbar spine, or below the mandible. Ear thickness (v) was checked 8 times during the exposure period (at 0, 0.25, 1, 2, 3, 4, 5, and 6 h). The effect size of the applied treatment (eta) on ear thickness was calculated by the formula eta = 100% x (1-vj/vi), where group i is the control group and j is the treated group. Results showed that MO treatment in itself induced a significant ear edema with an effect of 9% (p11% in both cases compared to SMF-exposure alone (p<0.001). In these cases SMF-exposure alone without MO treatment reduced ear thickness significantly (p<0.05), but within estimated experimental error. In cases of LSMF-exposure on the head, a significant SMF-exposure induced ear thickness reduction was found (eta = 5%, p<0.05). LSMF-exposure on the spine affected ear thickness with and without MO treatment almost identically, which provides evidence that the place of local SMF action may be in the lower spinal region