Publications

Abstract With the goal of combating the multi-faceted Alzheimer's disease (AD), a series of Rivastigmine-Benzimidazole (RIV-BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-beta (A beta) aggregation. Herein, we moved forward in this project, studying their ability to chelate redox-active biometal ions, Cu(II) and Fe(III), with widely recognized roles in the generation of oxidative reactive species and in protein misfolding and aggregation in both AD and Parkinson's disease (PD). Although Cu(II) chelation showed higher efficiency for the positional isomers of series 5 than those of series 4 of the hybrids, the A beta-aggregation inhibition appears more dependent on their capacity for fibril intercalation than on copper chelation. Since monoamine oxidases (MAOs) are also important targets for the treatment of AD and PD, the capacity of these hybrids to inhibit MAO-A and MAO-B was evaluated, and they showed higher activity and selectivity for MAO-A. The rationalization of the experimental evaluations (metal chelation and MAO inhibition) was supported by computational molecular modeling studies. Finally, some compounds showed also neuroprotective effects in human neuroblastoma (SH-SY5Y cells) upon treatment with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxic metabolite of a Parkinsonian-inducing agent.

Abstract Amino acid ionic liquids have garnered significant attention for their potential in electrochemical energy storage due to their wide electrochemical stability windows and inherent safety. The performance of ChGly as an electrolyte for supercapacitors has been compared to that of highly efficient conventional ionic liquids. However, a thorough understanding of the microstructural characteristics responsible for the enhanced properties of ChGly aqueous solutions remains largely unexplored. In this study, ab initio molecular dynamics simulations were employed to investigate the energetic, structural, transport and spectroscopic properties of ChGly-based pure and aqueous electrolytes. A comprehensive analysis of the cation-anion and water-ion hydrogen bonding was conducted for both electrolyte systems. Structural features were examined using radial and spatial distribution functions, while the vibrational power spectra were analyzed to identify significant differences in intermolecular interactions between pure and aqueous electrolytes, stemming from modified solvation shell structures. The findings presented in this work shed light on crucial structural and spectroscopic distinctions between pure and aqueous ChGly electrolytes, providing valuable insights for further advancements in the field.

Abstract Although the lipophilic triphenylphosphonium (TPP+) cation is widely used to target antioxidants to mitochondria, TPP+- based derivatives have shown cytotoxicity in several biological in vitro models. We confirmed that Mito.TPP is cytotoxic to both human neuronal (SH-SY5Y) and hepatic (HepG2) cells, decreasing intra-cellular adenosine triphosphate (ATP) levels, leading to mitochondrial membrane depolarization and reduced mitochondrial mass after 24 h. We surpassed this concern using nitrogen-derived cationic carriers (Mito.PICO, Mito.ISOQ, and Mito.IMIDZ). As opposed to Mito.TPP, these novel compounds were not cytotoxic to SH-SY5Y and HepG2 cells up to 50 mu M and after 24 h of incubation. All of the cationic derivatives accumulated inside the mitochondrial matrix and acted as neuroprotective agents against iron(III), hydrogen peroxide, and tert-butyl hydroperoxide insults. The overall data showed that nitrogen-based cationic carriers can modulate the biological performance of mitochondria-directed antioxidants and are an alternative to the TPP cation.

Abstract Introduction: The infections by multidrug-resistant bacteria are a growing threat to human health, and the efficacy of the available antibiotics is gradually decreasing. As such, new antibiotic classes are urgently needed. Objectives: This study aims to evaluate the antimicrobial activity, safety and mechanism of action of phytochemical-based triphenylphosphonium (TPP') conjugates. Methods: A library of phytochemical-based TPP' conjugates was repositioned and extended, and its antimicrobial activity was evaluated against a panel of Gram-positive (methicillin-resistant Staphylococcus aureus - MRSA) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) and fungi (Candida albicans, Cryptococcus neoformans var. grubii). The compounds' cytotoxicity and haemolytic profile were also evaluated. To unravel the mechanism of action of the best compounds, the alterations in the surface charge, bacterial membrane integrity, and cytoplasmic leakage were assessed. Results: Structure-activity-toxicity data revealed the contributions of the different structural components (phenolic ring, carbon-based spacers, carboxamide group, alkyl linker) to the compounds' bioactivity and safety. Dihydrocinnamic derivatives 5 m and 5n stood out as safe, potent and selective antibacterial agents against S. aureus (MIC < 0.25 lg/mL; CC50 > 32 lg/mL; HC10 > 32 lg/mL). Mechanistic studies sug- gest that the antibacterial activity of compounds 5 m and 5n may result from interactions with the bac- terial cell wall and membrane. Conclusions: Collectively, these studies demonstrate the potential of phytochemical-based TPP+ conju- gates as a new class of antibiotics. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Nutrition has crucial effects and a significant role in disease prevention. Recently, nutraceuticals have attracted much attention in scientific research due to their pleiotropic effects and relatively non-toxic behavior. Among the biological effects displayed by plants belonging to the Lamiaceae family, such as antibacterial, anticancer, anti-inflammatory, and anticholinesterase, sage is well known for its antioxidant properties and is a rich source of numerous compounds that are biologically active, amongst them polyphenols, with more than 160 types identified. In this review we summarized some of the significant studies published in the last decade reporting the most employed extraction methods and the different assays that are useful for establishing the antioxidant properties of some sage species. Even though the scientific literature contains plenty of data regarding the antioxidant properties of many sage species, further studies are needed in order to gain a deeper understanding of the mechanism of action and the compounds responsible for their antioxidant activity. Finally, it should be taken into account that the data on the antioxidant properties of sage extracts are often difficult to compare with each other, since a series of variables in the extraction procedures, the type of assay used, and standardization may affect the final result.

Abstract <jats:p>As artificial intelligence driver monitoring systems gain momentum in intelligent mobility, it is critical to analyse how distraction is defined and induced. This systematic review was specifically focused on studies conducted in driving simulators. A Boolean query was iteratively developed to retrieve articles from Scopus that fulfil the following criteria: (1) being an empirical study, (2) addressing driver distraction, (3) using a driving simulator, (4) aiming at developing an artificial intelligence monitoring system. After screening, 34 articles remained and were analysed according to four general themes: definition of distraction, characteristics of the scenarios used in the driving simulator, sampling of participants, and procedures. Results showed that the most common definitions of distraction consider it as a shift in the driver’s attention towards a secondary task, which implicates in a degradation of the execution of the primary task (i.e., driving the vehicle), and, consequently, a reduction in driving safety. Most articles described the scenarios used in the simulator in greater detail and, in some cases, variations in traffic density, visibility, and environmental conditions were observed. Furthermore, scripted critical events in the scenario (e.g., car in front of the participant breaking) were also used. Recruitment and samples varied greatly between studies, with the smallest population consisting of two and the largest of 97 participants. Despite the sample size, participants still needed to meet eligibility criteria such as having a driver’s license, possessing minimum driving experience, health prerequisites, being part of a specific group, age, and gender. Procedures and tasks were not always described in detail. However, several studies described an initial moment where participants could familiarize themselves with the simulator without taking measurements, while fewer reported that participants were allowed to familiarize themselves with the tasks. Session length varied from eight to 90 minutes. Regarding the operationalization of distraction in experiments, some studies required drivers to perform a single type of distraction-inducing task (mental calculations, use of In-Vehicle Information System (IVIS), cell phone operation, and manual tasks) with varying difficulty levels. Still, most studies relied on a combination of different tasks, such as cell phone use, physical tasks (e.g., drinking, moving objects, and applying makeup), and IVIS use. Results showed studies favour the description of the digital systems over the experiment design and procedures and a preference for locating the studies at the individual level of analysis, precluding a broader understanding of human behaviour as socially constructed and signified. We argue that articulation with higher levels of analysis would bring relevant explanations for actual road behaviour and personal and social factors should be considered when developing driver monitoring systems aimed at reducing distraction. Our results may assist future studies within the same scope, guiding the definition of effective experimental designs to test artificial intelligence driving monitoring systems, while contributing to a more holistic understanding of driver’s behaviour.</jats:p>

Abstract <jats:p>Recent developments in vehicle automation are leading a paradigm change in respect to mobility of goods and people. Pushed by environmental concerns, researchers and practitioners seek new and innovative solutions. Nevertheless, the challenge of sustainable transport does not end with the use of clean fuels, as faster, cheaper, and more efficient transport is still desired by operators. The concepts behind truck automation and truck platooning technologies present potential for operations management efficiency and cost reduction. On the other hand, as drivers are still the main piece on a safe and efficient transport system, their working conditions must be ensured. Therefore, a multidisciplinary perspective on truck platooning is required, comprising the view of all the stakeholders involved in the development of safe and easily adopted technologies. In the context of the project TRAIN, we have developed exploratory research towards understanding and mapping the requirements for deploying truck platooning technology. Through a qualitative research, based on focus groups, we have identified three main areas of requirements from logistics companies: (i) labor, (ii) safety and liability, and (iii) transport and logistics. The analysis also showed that these areas are related to three research domains: (i) human factors and human-machine interaction, (ii) operations research and management, and (iii) policy and regulation.</jats:p>

Abstract In this work, we intend to reflect on digital media in science and ma- thematics teaching from theoretical readings and empirical works that consider, mainly, the Portuguese case. First, we will situate the debate in the internal con- tradictions of the representations of the school and the idea of crisis associated with digital media. Then we will address the problems specifically associated with the Internet and the way in which it is integrated into pedagogical practices and, subsequently, into the participatory culture. We will see how the gap between promises and reality is constant and significant. We will end our work with a brief reflection in which we call on those responsible for education to reflect on the role of the school in the appropriation of digital media and the Internet.

Abstract Background: Patients with immune-mediated inflammatory diseases (IMIDs) treated with immunomodulatory therapy present an increased susceptibility to infections. Vaccination is a crucial element in the management of IMID patients; however, rates remain suboptimal. This study intended to clarify the adherence to prescribed vaccines. Materials and methods: This prospective cohort study included 262 consecutive adults with inflammatory bowel disease and rheumatological diseases who underwent an infectious diseases evaluation before initiating or switching immunosuppressive/biological therapy. Vaccine prescription and adherence were assessed during an infectious diseases (ID) consultation using a real-world multidisciplinary clinical project. Results: At baseline, less than 5% had all their vaccines up-to-date. More than 650 vaccines were prescribed to 250 (95.4%) patients. The most prescribed were pneumococcal and influenza vaccines, followed by hepatitis A and B vaccines. Adherence to each of the vaccines ranged from 69.1-87.3%. Complete adherence to vaccines occurred in 151 (60.4%) patients, while 190 (76%) got at least two-thirds of them. Twenty patients (8%) did not adhere to any of the vaccines. No significant differences were found in the adherence rates of patients with different sociodemographic and health-related determinants. Conclusions: ID physicians can play a role in the process of increasing vaccine prescription and adherence. However, more data on patients' beliefs and vaccine hesitancy, along with mobilization of all health care professionals and adequate local interventions, shall be considered to improve vaccine adherence.