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Alcohol is responsible for an ever-increasing number of deaths worldwide, and many road accidents are caused by irresponsible drinking and driving. The use of biomarkers that can support a diagnosis of alcohol abuse is a very important tool that can improve the prevention of many alcohol-related diseases and serious traffic accidents. The main aim of our study was the full validation of a rapid and simple method by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to detect ethyl glucuronide in hair (hEtG). The method was successfully applied to n = 171 real hair samples collected from drivers convicted of driving while impaired by alcohol or drugs. A comparison of hEtG and serum Carbohydrate-Deficient Transferrin percentages (% CDT) was also performed to carefully evaluate the data in relation to the specific detection windows of the two different biomarkers. Most of the drivers with hEtG > 30 pg/mg were males in their thirties. None of the hEtG-positives had a serum % CDT above the cutoff (≥2%). Although some researchers suggest caution until solid data are available on the possible effects of interindividual variability that may influence EtG incorporation and metabolism, hEtG is a very useful biomarker of long-term alcohol exposure that shows greater reliability than traditional blood markers. [ABSTRACT FROM AUTHOR]

Amniotic fluid is a complex and dynamic biological matrix that surrounds the fetus during the pregnancy. From this fluid, is possible to isolate various cell types with particular interest directed towards stem cells (AF-SCs). These cells are highly appealing due to their numerous potential applications in the field of regenerative medicine for tissues and organs as well as for treating conditions such as traumatic or ischemic injuries to the nervous system, myocardial infarction, or cancer. AF-SCs, when subcultured in the presence of basic Fibroblast Growth Factor (bFGF), have been shown to survive and migrate when transplanted into the striatum of the rat brain, exhibiting behavior characteristics of neuronal/glial progenitor cells. In this work, we performed an electrophysiological characterization to ascertain the propensity of AF-SCs to differentiate into glial and neuronal cells by bFGF. By using patch clamp technique we characterized a fibroblast-like morphology that display a barium-sensitive inward-rectifying potassium current (Kir) and calcium-activated potassium currents (KCa). The electrophysiological and calcium dynamics of histamine, a marker of undifferentiated neural progenitors, was further studied. Histamine promoted intracellular calcium increase by Fura-2 recording and calcium-activated potassium current activation with a similar temporal profile in AF-SC. The data presented in this paper ultimately confirm the expression in AF-SCs of the Kir and KCa currents, also showing regulation by endogenous stimuli such as histamine for the latter. [ABSTRACT FROM AUTHOR]

Brain abscesses are invasive infections of the central nervous system with a high level of treatment complexity especially in pediatric patients. Here, we describe a 3-month-old infant with multiple brain abscesses caused by methicillin-susceptible Staphylococcus aureus (MSSA). The patient was initially treated with empirical antibiotics (ceftriaxone, metronidazole, vancomycin). Upon MSSA identification, therapy was optimized by switching vancomycin to linezolid to improve tissue penetration. Therapeutic drug monitoring (TDM) was performed to check linezolid levels in the plasma and pus of the abscess, confirming drug penetration into brain tissue. A two-stage surgical drainage approach, consisting of repeated pus aspiration through an intracystic catheter, was then performed to achieve a significant reduction in abscess size. After nine weeks of antibiotic therapy, the patient was discharged in good clinical condition. This case highlights the role of linezolid for the treatment of complicated CNS infections and the importance of a multidisciplinary approach, combining TDM-based antibiotic therapy with timely and eventually repeated surgery, in order to effectively treat brain abscesses. [ABSTRACT FROM AUTHOR]

Background/Objectives: We aimed to establish biatrial and biventricular reference ranges using cardiac magnetic resonance (CMR) parameters in SCD patients without heart damage. Methods: This study compared CMR parameters, quantified by cine SSFP sequences, in 48 adult SCD patients without apparent cardiac involvement (defined by the absence of known risk factors, normal electrocardiogram, and no macroscopic myocardial fibrosis or significant cardiac iron on T2* CMR) to matched cohorts of 96 healthy controls and 96 thalassemia major (TM) patients without cardiac damage. Nine paediatric SCD patients were also analysed and compared to age- and gender-matched groups of nine TM patients and nine healthy subjects. Results: In all groups, studied males displayed higher biventricular volumes and mass indexes than females. Male SCD patients showed significantly higher left ventricular (LV) end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), LV stroke volume index (SVI), cardiac index, LV and right ventricular (RV) mass index, and atrial areas than healthy subjects. Females with SCD exhibited increased LV EDVI, LV SVI, RV mass index, and left atrial area index compared to healthy controls. SCD and TM patients showed comparable biatrial areas and biventricular volumes and function. When compared to TM, SCD males exhibited a larger mass index, while SCD females showed an increased RV mass index. CMR parameters were similar across all paediatric groups. Conclusions: By establishing the biatrial and biventricular reference ranges through CMR for adult male and female SCD patients, we aimed to prevent possible misdiagnosis of cardiomyopathy in this population by taking into account cardiac adaptation due to anaemia. [ABSTRACT FROM AUTHOR]

Cultural diversity often complicates the understanding of sustainability, sometimes making its concepts seem vague. This issue is particularly evident in food systems, which rely on both renewable and nonrenewable resources and drive significant environmental changes. The widespread impacts of climate change, aggravated by the overuse of natural resources, have highlighted the urgency of balancing food production with environmental preservation. Society faces a pivotal challenge: ensuring that food systems produce ample, accessible, and nutritious food while also reducing their carbon footprint and protecting ecosystems. Agriculture 5.0, an innovative approach, combines digital advancements with sustainability principles. This study reviews current knowledge on digital agriculture, analyzing scientific data through an undirected bipartite network that links journals and author keywords from articles retrieved from Clarivate Web of Science. The main goal is to outline a framework that integrates various sustainability concepts, emphasizing both well-studied (economic) and underexplored (socioenvironmental) aspects of Agriculture 5.0. This framework categorizes sustainability concepts into material (tangible) and immaterial (intangible) values based on their supporting or influencing roles within the agriculture domain, as documented in the scientific literature. [ABSTRACT FROM AUTHOR]

The increasing adoption of distributed recycling via additive manufacturing (DRAM) has facilitated the revalorization of materials derived from waste streams for additive manufacturing. Recycled materials frequently contain impurities and mixed polymers, which can degrade their properties over multiple cycles. This degradation, particularly in rheological properties, limits their applicability in 3D printing. Consequently, there is a critical need for a tool that enables the rapid assessment of the flowability of these recycled materials. This study presents the design, development, and manufacturing of an open-source melt flow index (MFI) apparatus. The open-source MFI was validated with tests on virgin polylactic acid pellets, shredded recycled poly(ethylene) terephthalate glycol flakes, and high-density polyethylene/poly(ethylene) terephthalate blends to demonstrate the range of polymer types and recyclability. The proposed MFI tool offers a user-friendly and cost-effective solution for evaluating the flow properties of materials from waste streams, thereby enhancing their viability for additive manufacturing applications. [ABSTRACT FROM AUTHOR]

Background: Drugged driving is associated with an increased risk of road accidents worldwide. In Italy, driving under the influence (DUI) of alcohol and drugs is a reason for driving disqualification or revocation of the driving license. Drivers charged with driving under the influence of alcohol and drugs must attend a Local Medical Commission (LMC) to undergo mandatory examinations to regain the suspended license. Our study mainly aims to report on the analysis performed on hair samples collected from 7560 drivers who had their licenses suspended for drugged or drunk driving between January 2019 and June 2024. Methods: A rapid, sensitive, and selective method for the determination of ethyl glucuronide in hair by UPLC/MS-MS was developed and fully validated. Results: The most frequently detected substances were cocaine (ecgonine methyl ester, norcocaine, and benzoylecgonine) and cannabinoids (Δ9-tetrahydrocannabinol, cannabidiol, and cannabinol), followed by opiates (codeine, morphine, and 6-MAM), methadone (EDDP), and amphetamines (amphetamine, methamphetamine, MDA, MDMA, and MDEA). To perform a more in-depth analysis, we also compared hair color with the drug classes that tested positive. The results showed a significant prevalence of dark hair that tested positive for one or more substances, followed by gray/white hair and light hair. Conclusions: Our study provides an interesting and alarming insight into drug exposure in the general population with serious public health threats, discussing the main aspects of hair matrix analysis and focusing on its advantages and reliability in the interpretation of results. [ABSTRACT FROM AUTHOR]

This paper presents the removal of a non-original varnish from the surface of a painting by Wassily Kandinsky based on prior experimentation carried out on mock-ups, which were made according to the original artistic technique and painting stratigraphy. Due to a generally serious state of conservation, the artwork underwent several treatments over the years that have changed its original appearance. This work focused on the study and characterization of the ketone-based varnish present on the surface to outline how this non-original film layer interacted with paint layers and increased deterioration phenomena. Aiming to identify the most suitable approach for the artwork, some preliminary cleaning tests were made on artificially aged mock-ups. A multi-analytical investigation was carried out through non-invasive and invasive techniques to support all steps of the conservation treatment. By comparing cleaning results on mock-ups, a suitable protocol was developed and applied to the original painting. The best results were obtained by using the Nanorestore Gel® Dry MWR (Medium Water Retention) with ethanol. The project has shown that the dissolving power of the solvent can effectively be controlled and limited at the surface by confining it to the nanostructure of the gel, thus minimizing the risk of interaction with the original paint layers. [ABSTRACT FROM AUTHOR]

This study evaluated ethosomes as a novel nanodelivery system for nutlin-3a, a known MDM2 inhibitor and activator of the p53 pathway, to improve nutlin-3a's poor solubility, limiting its bio-distribution and therapeutic efficacy. The potential of nutlin-3a-loaded ethosomes was investigated on two in vitro models of melanoma: the HT144 cell line p53wild-type and the SK-MEL-28 cell line p53mutated. Nutlin-3a-loaded ethosomes were characterized for their physicochemical properties and used to treat melanoma cells at different concentrations, considering nutlin-3a solution and empty ethosomes as controls. The biological effects on cells were evaluated 24 and 48 h after treatment by analyzing the cell morphology and viability, cell cycle, and apoptosis rate using flow cytometry and the p53 pathway's activation via Western blotting. The results indicate that ethosomes are delivery systems able to maintain nutlin-3a's functionality and specific biological action, as evidenced by the molecular activation of the p53 pathway and the biological events leading to cell cycle block and apoptosis in p53wild-type cells. Nutlin-3a-loaded ethosomes induced morphological changes in the HT144 cell line, with evident apoptotic cells and a reduction in the number of viable cells of over 80%. Furthermore, nutlin-3a-loaded ethosomes successfully modulated two p53-regulated proteins involved in survival/apoptosis, with up to a 2.5-fold increase in membrane TRAIL-R2 and up to an 8.2-fold decrease in Notch-1 (Notch intracellular domain, NICD) protein expression. The expression of these molecules is known to be altered or dysfunctional in a large percentage of melanoma tumors. Notably, ethosomes, regardless of their nutlin-3a loading, exhibited the ability to reduce HT144 melanoma cellular migration, as assessed in real time using xCELLigence, likely due to the modification of lipid rafts, suggesting their potential antimetastatic properties. Overall, nutlin-3a delivery using ethosomes appears to be a significantly effective means for upregulating the p53 pathway and downregulating active Notch-1, while also taking advantage of their unexpected ability to reduce cellular migration. The findings of this study could pave the way for the development of specific nutlin-3a-loaded ethosome-based medicinal products for cutaneous use. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor–receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence. [ABSTRACT FROM AUTHOR]

Additive Manufacturing has significantly impacted circular design, expanding the opportunities for designing new artifacts following circular economy principles, e.g., using secondary raw materials. Small-format 3D printing has reached a broader audience of stakeholders, including end-users, when dealing with filament feedstocks from plastic and biomass waste. However, using large-format extrusion-based additive manufacturing with recycled feedstocks remains challenging, resulting in limited applications and awareness among practitioners. This work analyzes the most relevant product applications using large-format material extrusion additive manufacturing with recycled plastics and biomass waste feedstocks. It reviews the case studies from 2010 to mid-2024 dealing with new materials and applications from academic research and practical contexts. The applications were analyzed to outline the current situation and trends for large-format 3D printing with recycled plastics- and biomass-based feedstocks, focusing on secondary raw materials, manufacturability, impact on product aesthetics, application fields, and products. Despite more consolidated sectors, new technical applications using granulate feedstock systems, e.g., transportation, are emerging. Academic research studies new secondary raw materials and distributed practices through large-format 3D printing. Practitioners are exploiting different approaches to design products, optimizing building times, costs, and material usage through different manufacturing strategies, strengthening the product identity by highlighting circularity. Spreading specific expertise could enlarge the range of application sectors and products, as well as foster real-world collaborations and scaling-up. Thanks to this work, new synergies between the research and practical contexts can be encouraged for new circular economy practices, detecting and exploring new scraps, material categories, or Additive Manufacturing processes in the future. [ABSTRACT FROM AUTHOR]

Calcification refers to the deposition of calcium-containing crystals either intracellularly or within the extracellular matrix. Physiologic calcification is a normal process occurring during bone and tooth development and growth. In contrast, pathologic calcification occurs in soft tissues that typically do not undergo mineralization, such as blood vessels, cartilage, tendons, and skin. Pathological calcification is significantly associated with tissue impairment and the development of secondary diseases, such as atherosclerosis, osteoarthritis, tendinopathy, and skin ulcers. Aging, a natural process linked to numerous pathologic conditions, is one of the most recognized risk factors for pathological calcification. In this manuscript, we review the current state of knowledge regarding the role of aging in calcification across different tissues. We focus on the mechanisms activated during normal aging, including cellular senescence, decreased pyrophosphate levels, increased secretion of extracellular vesicles, elevated oxidative stress, and higher levels of pro-mineralizing cytokines, all of which can contribute to pathological calcification. Finally, we discuss the available animal models used to study the impact of aging on calcification. [ABSTRACT FROM AUTHOR]

Short-term pediatric psychiatric hospitalization is used to manage acute-crisis behaviors. Few studies have detailed their clinical model and key metrics such as patient behavioral health outcomes and staff experience. This study describes a model which emphasizes group therapy based on dialectical behavior therapy during brief inpatient stays (average length of stay of 8 days). The study variables assessed included patient symptoms of depression, anxiety, and anger at discharge, patient satisfaction, and staff safety. The program produced significant improvements in adolescent depression, anxiety, and anger, and patients reported high satisfaction with the services received. However, there was a high rate of staff injuries, correlated with staffing ratios and the time of day. The key findings from this study demonstrate the effectiveness of brief inpatient programs and highlight variables that may impact staff experiences on these units, which could serve as further discussion points to improve clinical care. [ABSTRACT FROM AUTHOR]

The etiology of neurodevelopmental disorders and epilepsy is very heterogeneous and partly still unknown, and the research of causative genes related to these diseases is still in progress. In 2020, pathogenic variants of the TET3 gene were associated with Beck–Fahrner syndrome, which is characterized by neurodevelopmental delay, intellectual and learning disabilities of variable degree, growth abnormalities, hypotonia and seizures. Variants of TET3 have been described having both an autosomal dominant with a milder phenotype and an autosomal recessive pattern. To date, in the literature, only 28 patients are reported with pathogenic variants of the TET3 gene, and only 9 of them have epilepsy. We describe a 31-year-old woman with macrocephaly, mild neurodevelopmental delay and a long history of epilepsy. Trio-based exome sequencing identified a de novo heterozygous TET3 variant, c.2867G>A p.(Arg956Gln), never described before, absent in the general population and predicted to be potentially pathogenetic by bioinformatics tools. This report aims to describe the clinical history of our patient, the pharmacological treatment and clinical response, as well as the biological characteristics of this new variant. [ABSTRACT FROM AUTHOR]

Hypertension is a major risk factor for heart disease and stroke. Garlic has a long history of use in traditional medicine for various conditions, including hypertension. This narrative review examined the scientific evidence on the efficacy of garlic in lowering blood pressure. It explores the historical uses of garlic in different cultures for medicinal purposes and delves into the phytochemical composition of garlic, highlighting key components, like allicin and ajoene, that are believed to contribute to its potential health benefits. Clinical studies that investigated the effects of garlic and garlic-based supplements on blood pressure are presented, with the findings suggesting that garlic consumption may modestly reduce blood pressure, particularly in individuals with mild hypertension. Potential mechanisms of action include increased nitric oxide production, improved endothelial function, and antioxidant properties. While garlic may offer some benefits for blood pressure management, it should not be considered a substitute for conventional antihypertensive medications. Further large-scale, long-term clinical trials are warranted to establish the efficacy of garlic in managing hypertension, including the optimal dosage and formulation. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then to exert tight control over a much broader range of processes, including neurotransmitter release, neuronal excitability, and synaptic plasticity. Endothelial NO synthase (eNOS) is usually far from the mind of synaptic neurophysiologists, who have focused most of their attention on neuronal NO synthase (nNOS) as the primary source of NO at the neurovascular unit (NVU). Nevertheless, the available evidence suggests that eNOS could also contribute to generating the burst of NO that, serving as volume intercellular messenger, is produced in response to neuronal activity in the brain parenchyma. Herein, we review the role of eNOS in both the regulation of cerebral blood flow and of synaptic plasticity and discuss the mechanisms by which cerebrovascular endothelial cells may transduce synaptic inputs into a NO signal. We further suggest that eNOS could play a critical role in vascular-to-neuronal communication by integrating signals converging onto cerebrovascular endothelial cells from both the streaming blood and active neurons. [ABSTRACT FROM AUTHOR]

Pulsars (PSRs) and Pulsar Wind Nebulae (PWNe) form some of the most interesting high-energy astrophysical systems. Their prominent synchrotron emission makes them ideal candidates for polarimetry. Here, after briefly summarizing the scientific rationale underpinning the importance of their polarimetric studies, we review the current status and achievements obtained by the IXPE mission. For the first time, we have space- and phase-resolved X-ray data that allow us to set constraints on the geometry and level of turbulence of the magnetic field which, in turn, can help us to better understand which acceleration and radiation model(s) might be at work in these systems. Interestingly, PWNe show a large variety in terms of polarization degree that might indicate key physical differences, still to be further investigated. [ABSTRACT FROM AUTHOR]

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity. [ABSTRACT FROM AUTHOR]

Anderson–Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations. [ABSTRACT FROM AUTHOR]

Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA. [ABSTRACT FROM AUTHOR]

Simple Summary: Coccinellidae, commonly known as ladybirds, comprise a diverse group of insects with varied dietary preferences. Ladybirds typically feed on plants or prey on various insects, resulting in distinct morphological adaptations in their mandibles. Investigation of the ultrastructural organization of mandibles enables the identification of specific adaptations adopted by different species in response to their feeding modalities and preferences. In this study, we examined the ultrastructural organization of mandibles in two widely distributed and economically important ladybird species: the entomophagous Harmonia axyridis and the phytophagous Subcoccinella vigintiquatuorpunctata. Significant differences in mandible organization were observed between the two species. H. axyridis exhibited larger mandibles with a distinctive tooth pattern, whereas S. vigintiquatuorpunctata displayed multiple teeth on its apical region. Furthermore, variations in the metal content of the mandibles were identified, highlighting how dietary preferences influence mandible metal compositions. The mandibles are among the most important appendages of insects' mouthparts. Their morpho-functional organization is correlated with the variation in dietary preferences. In this study, we investigated the ultrastructural organization and metal composition of the mandibles of two ladybird species with different dietary habits: Harmonia axyridis (an entomophagous species) and Subcoccinella vigintiquatuorpunctata (a phytophagous species). The ultrastructural organization was studied using Scanning and Transmission Electron Microscopy, whereas the metal composition was investigated using Energy-Dispersive X-ray spectroscopy (EDX). Significant differences were observed in the general organization and metal enrichment pattern between the two species. The mandibles of H. axyridis are large and present a molar part with two teeth, with the apical one showing a bifid apex. In contrast, S. vigintiquatuorpunctata exhibited a molar region with several teeth on its apical part. The study revealed significant differences in metal content between the teeth and the prostheca of H. axyridis. Mn was the most abundant element in teeth, whereas Cl was more abundant in the prostheca. In the case of S. vigintiquatuorpunctata, Si was the most abundant element in the prostheca, while Mn was more present in the teeth. A comparison between the two species revealed that both teeth and prostheca showed significant variation in the elemental composition. These findings underscore the role of dietary preferences in shaping the structural and metal composition variations in the mandibles of these two ladybird species. [ABSTRACT FROM AUTHOR]

Thoracentesis is one of the most important invasive procedures in the clinical setting. Particularly, thoracentesis can be relevant in the evaluation of a new diagnosed pleural effusion, thus allowing for the collection of pleural fluid so that laboratory tests essential to establish a diagnosis can be performed. Furthermore, thoracentesis is a maneuver that can have therapeutic and palliative purposes. Historically, the procedure was performed based on a physical examination. In recent years, the role of ultrasound has been established as a valuable tool for assistance and guidance in the thoracentesis procedure. The use of ultrasound increases success rates and significantly reduces complications. The aim of this educational review is to provide a detailed and sequential examination of the procedure, focusing on the two main modalities, the ultrasound-assisted and ultrasound-guided form. [ABSTRACT FROM AUTHOR]

The use of benzodiazepines is strongly associated with an increased risk of traffic accidents due to their side effects of sedation and drowsiness, which can significantly impair driving performance. The main aim of our study was to investigate the trend of benzodiazepine use over nine years (2015–2023) in a population of 15,988 subjects who had their license suspended for driving under the influence (DUI) of alcohol or drugs. Among the 15,988 users accessed to our laboratory, 924 tested positive for at least one benzodiazepine. An increase in the number of positive-testing users was observed in the period 2015–2018, followed by a slight decrease in 2019. Overall, the trend of benzodiazepine use was stable over the next four years (2020–2023), with the highest incidence in 2022. The most common benzodiazepines, and/or metabolites, found in urine samples were α-OH-alprazolam (28.66%; n = 366) and oxazepam (27.25%; n = 348). Several cases of mixed positivity were observed in the study population. The main substances taken with benzodiazepines were cocaine and Δ9-tetrahydrocannabinol. Our findings suggest that people taking benzodiazepines should be monitored, as these have a relevant impact on driving ability in addition to significant interindividual differences in the behavioral effects of benzodiazepines on driving performance. [ABSTRACT FROM AUTHOR]

The expression "twice-exceptionality" has been used to describe conditions in which giftedness and specific disorders coexist. Our study offers a retrospective analysis of clinical reports of gifted children evaluated for suspected specific learning disorders (SLD) or attention-deficit/hyperactivity disorder (ADHD). The initial sample included 456 school-aged children referred to our clinic for suspected SLD and/or ADHD over a two-year interval. The inclusion criteria were: a General Ability Index score above 120 in the cognitive assessment; age 6–18 years; and not satisfying diagnostic criteria for autism spectrum disorder. Forty children were selected for the study. We grouped patients according to the final diagnosis: neurodevelopmental disorder (SLD and/or ADHD) (n = 15), psychopathological disorder (n = 8), mixed neurodevelopmental and psychopathological (n = 13), no emerging disorder (n = 4). The study included 36 (90%) males. Mean age was 9.3 years (SD 1.62). Mean Full-Scale Intelligence Quotient was 121.7 (SD 7.77), mean General Ability Index was 130.2 (SD 6.79). Furthermore, the cognitive assessment of the different groups highlighted a non-homogeneous profile in all groups, with lower scores on working memory and processing speed indexes. Our results support the hypothesis that difficulties in gifted children's adaptation to scholastic and social settings could be misinterpreted as a manifestation of a clear disease. [ABSTRACT FROM AUTHOR]

Research progresses have led to the development of different kinds of nanoplatforms to deliver drugs through different biological membranes. Particularly, nanocarriers represent a precious means to treat skin pathologies, due to their capability to solubilize lipophilic and hydrophilic drugs, to control their release, and to promote their permeation through the stratum corneum barrier. A crucial point in the development of nano-delivery systems relies on their characterization, as well as in the assessment of their interaction with tissues, in order to predict their fate under in vivo administration. The size of nanoparticles, their shape, and the type of matrix can influence their biodistribution inside the skin strata and their cellular uptake. In this respect, an overview of some characterization methods employed to investigate nanoparticles intended for topical administration is presented here, namely dynamic light scattering, zeta potential, scanning and transmission electron microscopy, X-ray diffraction, atomic force microscopy, Fourier transform infrared and Raman spectroscopy. In addition, the main fluorescence methods employed to detect the in vitro nanoparticles interaction with skin cell lines, such as fluorescence-activated cell sorting or confocal imaging, are described, considering different examples of applications. Finally, recent studies on the techniques employed to determine the nanoparticle presence in the skin by ex vivo and in vivo models are reported. [ABSTRACT FROM AUTHOR]

UV radiation was combined with the incorporation of fish protein hydrolysates to improve the performance of active bio-based films for food packaging. UV radiation was not used previously to enhance the packaging performance of blend films of starch/protein, and fish protein hydrolysates were not incorporated in bio-based polymer surfaces previously. Rice starch and fish proteins (from Whitemouth croaker muscle) were utilized to prepare films by the casting technique, which were UV-radiated under different exposure times (1, 5, and 10 min). The packaging performance of the films was determined according to the mechanical and barrier performance, solubility, and color. Fish protein hydrolysates (from Argentine croaker muscle) were then incorporated into the films (bulk structure or surface). The results showed that UV radiation for 1 min increased the tensile strength and modified the optical properties of films. It also altered the structure of the polymeric matrix, as demonstrated by the microstructure and thermal analysis, in agreement with the data obtained in packaging properties. The evaluation of antioxidant capacity through 2,2-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and reducing power indicated that incorporating fish protein hydrolysates either in the films' bulk structure or film surface promoted antioxidant properties; control films (produced with rice starch/fish proteins without hydrolysates) also presented antioxidant potential. According to the peroxide value and thiobarbituric acid reactive substance (TBARS) assays, control films and the films containing hydrolysates in their bulk structure or on the surface could prevent the lipid oxidation of Italian salami. Thus, combining UV radiation to shape the characteristics of bio-based materials with fish protein hydrolysates to reduce lipid oxidation contributes to the performance of active bio-based films for food packaging. [ABSTRACT FROM AUTHOR]

State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focus on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the Motor Network (MN) and how the MN state affects responses to the transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to the left M1 in eight subjects at rest, with simultaneous EEG. Motor-evoked potentials (MEPs) were measured from the right hand. The source space functional connectivity of the left M1 to the whole brain was assessed using the imaginary part of the phase locking value at the frequency of the sensorimotor μ-rhythm in a 1 s window before the pulse. Group-level connectivity revealed functional links between the left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At the single-subject level, this relation is more highly expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity-based NIBS. [ABSTRACT FROM AUTHOR]

Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca2+ entry and activity-dependent change in the strength of synaptic transmission, as well as by metabotropic glutamate receptors (mGluRs), which mediate slower postsynaptic responses through the recruitment of second messenger systems. A wealth of evidence reported over the last three decades has shown that this dogmatic subdivision between iGluRs and mGluRs may not reflect the actual physiological signaling mode of the iGluRs, i.e., α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA) receptors (AMPAR), kainate receptors (KARs), and N-methyl-D-aspartate (NMDA) receptors (NMDARs). Herein, we review the evidence available supporting the notion that the canonical iGluRs can recruit flux-independent signaling pathways not only in neurons, but also in brain astrocytes and cerebrovascular endothelial cells. Understanding the signaling versatility of iGluRs can exert a profound impact on our understanding of glutamatergic synapses. Furthermore, it may shed light on novel neuroprotective strategies against brain disorders. [ABSTRACT FROM AUTHOR]

The removal of non-original superimposed layers covering the original pictorial layer in paintings is a common practice to restore the authentic appearance of surfaces and mitigate potential risks to artwork preservation. Contemporary assessments of the effectiveness of such cleaning treatments often employ non-destructive analytical methods. However, many existing techniques face limitations, either lacking specificity in compound identification or analyzing very limited areas (

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children. [ABSTRACT FROM AUTHOR]

The Sertoli cells (SeCs) of the seminiferous tubules secrete a multitude of immunoregulatory and trophic factors to provide immune protection and assist in the orderly development of germ cells. Grafts of naked or encapsulated SeCs have been proved to represent an interesting therapeutic option in a plethora of experimental models of diseases. However, whether SeCs have immunosuppressive or immunomodulatory effects, which is imperative for their clinical translatability, has not been demonstrated. We directly assessed the immunopotential of intraperitoneally grafted microencapsulated porcine SeCs (MC-SeCs) in murine models of fungal infection (Aspergillus fumigatus or Candida albicans) or cancer (Lewis lung carcinoma/LLC or B16 melanoma cells). We found that MC-SeCs (i) provide antifungal resistance with minimum inflammatory pathology through the activation of the tolerogenic aryl hydrocarbon receptor/indoleamine 2,3-dioxygenase pathway; (ii) do not affect tumor growth in vivo; and (iii) reduce the LLC cell metastatic cancer spread associated with restricted Vegfr2 expression in primary tumors. Our results point to the fine immunoregulation of SeCs in the relative absence of overt immunosuppression in both infection and cancer conditions, providing additional support for the potential therapeutic use of SeC grafts in human patients. [ABSTRACT FROM AUTHOR]

Patients with cystic fibrosis (PwCF) have recently experienced an unprecedented breakthrough with the adoption of modulator therapy in clinical practice. This remarkable achievement has led to the reconsideration of disease management as the increased life expectancy has gradually shifted the attention over a spectrum of extra-pulmonary manifestations that become prevalent in the aging population. It comes to be that complementary approaches that target patient co-morbidities are needed for the optimal clinical management of PwCF. A strategy would be to adjuvate the cystic fibrosis transmembrane conductance regulator (CFTR) in performing its functions in the different organs in which it is expressed. Solute carrier family 26 (SLC26) members appear ideal in this context. Indeed, they not only cooperate with CFTR in the organ-dependent regulation of ion fluxes but physically interact with it to reciprocally modulate their function. In this opinion, we summarize available evidence pointing to a physical and functional interaction between CFTR and SLC26 members, with a particular focus on SLC26A6 for its wider expression and broader anion selectivity, and then discuss how restoring the physical interaction between CFTR and SLC26A6 might be beneficial in the treatment of PwCF in the era of modulator therapy. [ABSTRACT FROM AUTHOR]

Population-based metaheuristics can be seen as a set of agents that smartly explore the space of solutions of a given optimization problem. These agents are commonly governed by movement operators that decide how the exploration is driven. Although metaheuristics have successfully been used for more than 20 years, performing rapid and high-quality parameter control is still a main concern. For instance, deciding the proper population size yielding a good balance between quality of results and computing time is constantly a hard task, even more so in the presence of an unexplored optimization problem. In this paper, we propose a self-adaptive strategy based on the on-line population balance, which aims for improvements in the performance and search process on population-based algorithms. The design behind the proposed approach relies on three different components. Firstly, an optimization-based component which defines all metaheuristic tasks related to carry out the resolution of the optimization problems. Secondly, a learning-based component focused on transforming dynamic data into knowledge in order to influence the search in the solution space. Thirdly, a probabilistic-based selector component is designed to dynamically adjust the population. We illustrate an extensive experimental process on large instance sets from three well-known discrete optimization problems: Manufacturing Cell Design Problem, Set covering Problem, and Multidimensional Knapsack Problem. The proposed approach is able to compete against classic, autonomous, as well as IRace-tuned metaheuristics, yielding interesting results and potential future work regarding dynamically adjusting the number of solutions interacting on different times within the search process. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic strained healthcare systems around the world. This study aims to understand the preparedness of private remote hospitals in Lebanon to respond to the pandemic and evaluate the impact of inter-hospital collaborations on the hospitals' readiness. Methods: A multi-centered study was conducted between August 2020 and June 2021 in ten Lebanese private remote hospitals based on a mixed-methods embedded approach where the quantitative supported the qualitative. Through the AUB-USAID (American University of Beirut-United States Agency for International Development) COVID-19 project, these hospitals received personal protective equipment and medical equipment in addition to COVID-19-related training using the Train-the-Trainer model. The quantitative part used knowledge and evaluation questionnaires and a pre–post-intervention hospital preparedness checklist. The qualitative approach adopted semi-structured interviews with a purposive sample from key hospital personnel. Quantitative data were analyzed using SPSS version 27, and a p-value of <0.05 was considered to be statistically significant. For the qualitative data, a thematic analysis was performed by adopting the six-phase process described by Braun and Clarke. Results: Of the 393 healthcare workers who attended the training and completed the evaluation questionnaire, 326 completed the pre- and post-training knowledge questionnaire. A significant improvement was observed in mean knowledge scores following training for infection control, nursing, and polymerase chain reaction sampling staff (p-value < 0.001, p-value < 0.001, and p-value = 0.006, respectively), but not for housekeeping staff. More than 93% of the participants showed high trainer and content evaluation scores. As for the hospitals' preparedness assessments, there was a clear improvement in the pre- and post-assessment scores for each hospital, and there was a significant difference in the mean of the total scores of partner hospitals pre- and post-USAID-AUB project (p-value = 0.005). These findings were supported by the qualitative analysis, where nine hospitals expressed the positive impact of the USAID-AUB intervention in improving their preparedness to respond to the COVID-19 pandemic at a critical time when it was highly needed. Despite the intervention, persistent challenges remained. Conclusions: A timely and proactive collaborative program between academic/tertiary care centers and remote community hospitals that includes sharing supplies and expertise is feasible and highly effective during public health emergencies. [ABSTRACT FROM AUTHOR]

Background: Infections caused by antimicrobial-resistant (AMR) pathogens are increasing worldwide, representing a serious global public health issue with high morbidity and mortality rates The treatment of Pseudomonas aeruginosa (PA) infections has become a significant challenge due to its ability to develop resistance to many of the currently available antibiotics, especially in intensive care unit (ICU) settings. Among the very few therapeutic lines available against extensively drug-resistant (XDR)-PA and/or with difficult-to-treat resistance (DTR)-PA, cefiderocol is an injectable siderophore cephalosporin not licensed for use in pediatric patients. There are only a few case reports and two ongoing trials describing the administration of this cephalosporin in infants. Case presentation: This report describes the case of a critically ill 8-month-old girl affected by ventilator-associated pneumonia (VAP) infection complicated by bloodstream infection (BSI) sustained by VIM-producing PA. She was treated with cefiderocol as a salvage therapy during ECMO and CRRT support. Conclusions: In healthcare settings, treating multidrug-resistant, Gram-negative bacteria poses a serious challenge, especially in pediatric patients. Our findings suggest that cefiderocol can be considered as an off-label rescue therapy in selected pediatric cases. [ABSTRACT FROM AUTHOR]

Simple Summary: COVID-19, an emerging infectious disease of possible animal origin due to SARS-CoV-2, which has caused a severe pandemic, has also affected some zoo animals. Since non-human primates are considered susceptible hosts, we tested 43 lemurs (20 black-and-white ruffed lemur Varecia variegata and 23 ring-tailed lemur Lemur catta) from a Spanish zoological institution, which were in close contact with humans during the pandemic period, for SARS-CoV-2 infection in both 2022 and 2023. We used molecular techniques for viral RNA detection in oropharyngeal and rectal swabs and blood anti-SARS-CoV-2 serology. The molecular assays were negative, but one animal was seropositive, strongly suggesting previous infection by SARS-CoV-2 of that animal. These data, while not pinpointing a high susceptibility of lemurs to SARS-CoV-2 infection, add to existing information on the need for surveillance of that virus in animals. In the setting of the recent COVID-19 pandemic, transmission of SARS-CoV-2 to animals has been reported in both domestic and wild animals and is a matter of concern. Given the genetic and functional similarities to humans, non-human primates merit particular attention. In the case of lemurs, generally considered endangered, they are believed to be susceptible to SARS-CoV-2 infection. We have conducted a study for evidence of SARS-CoV-2 infection among the 43 lemurs of Mundomar, a zoological park in Benidorm, Spain. They belong to two endangered lemur species, 23 black-and-white ruffed lemurs (Varecia variegata) and 20 ring-tailed lemurs (Lemur catta). Health assessments conducted in 2022 and 2023 included molecular analyses for SARS-CoV-2 RNA of oral and rectal swabs using two different RT-qPCR assays, always with negative results for SARS-CoV-2 in all animals. The assessment also included serological testing for antibodies against the receptor-binding domain (RBD) of the spike protein (S) of SARS-CoV-2, which again yielded negative results in all animals except one black-and-white ruffed lemur, supporting prior infection of that animal with SARS-CoV-2. Our data, while not indicating a high susceptibility of lemurs to SARS-CoV-2 infection, show that they can be infected, adding to the existing information body on potential ways for SARS-CoV-2 virus spreading in zoos, highlighting the need for animal surveillance for the virus. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to describe the trajectories of bone mineral density (BMD) and trabecular bone score (TBS) changes throughout pre-menopause (reproductive phase and menopausal transition) and post-menopause (early and late menopause) in women with HIV (WWH) undergoing different antiretroviral therapies (ARTs) and explore the risk factors associated with those changes. Methods: This was an observational longitudinal retrospective study in WWH with a minimum of two DEXA evaluations comprising BMD and TBS measurements, both in the pre-menopausal and post-menopausal periods. Menopause was determined according to the STRAW+10 criteria, comprising four periods: the reproductive period, menopausal transition, and early- and late-menopausal periods. Mixed-effects models were fitted to estimate the trajectories of the two outcomes (BMD and TBS) over time. Annualized lumbar BMD and TBS absolute and percentage changes were calculated in each STRAW+10 time window. A backward elimination procedure was applied to obtain the final model, including the predictors that affected the trajectories of BMD or TBS over time. Results: A total of 202 WWH, all Caucasian, were included. In detail, 1954 BMD and 195 TBS data were analyzed. The median number of DEXA evaluations per woman was 10 (IQR: 7, 12). The median observation periods per patient were 12.0 years (IQR = 8.9–14.4) for BMD and 6.0 years (IQR: 4.3, 7.9) for TBS. The prevalence of osteopenia (63% vs. 76%; p < 0.001) and osteoporosis (16% vs. 36%; p < 0.001) increased significantly between the pre-menopausal and post-menopausal periods. Both BMD (1.03 (±0.14) vs. 0.92 (±0.12) g/cm2; p < 0.001) and TBS (1.41 (IQR: 1.35, 1.45) vs. 1.32 (IQR: 1.28, 1.39); p < 0.001) decreased significantly between the two periods. The trend in BMD decreased across the four STRAW+10 periods, with a slight attenuation only in the late-menopausal period when compared with the other intervals. The TBS slope did not significantly change throughout menopause. The delta mean values of TBS in WWH were lower between the menopausal transition and reproductive period compared with the difference between menopause and menopausal transition. Conclusions: Both BMD and TBS significantly decreased over time. The slope of the change in BMD and TBS significantly decreased in the menopausal transition, suggesting that this period should be considered by clinicians as a key time during which to assess bone health and modifiable risk factors in WWH. [ABSTRACT FROM AUTHOR]

A monolayer of endothelial cells lines the innermost surface of all blood vessels, thereby coming into close contact with every region of the body and perceiving signals deriving from both the bloodstream and parenchymal tissues. An increase in intracellular Ca2+ concentration ([Ca2+]i) is the main mechanism whereby vascular endothelial cells integrate the information conveyed by local and circulating cues. Herein, we describe the dynamics and spatial distribution of endothelial Ca2+ signals to understand how an array of spatially restricted (at both the subcellular and cellular levels) Ca2+ signals is exploited by the vascular intima to fulfill this complex task. We then illustrate how local endothelial Ca2+ signals affect the most appropriate vascular function and are integrated to transmit this information to more distant sites to maintain cardiovascular homeostasis. Vasorelaxation and sprouting angiogenesis were selected as an example of functions that are finely tuned by the variable spatio-temporal profile endothelial Ca2+ signals. We further highlighted how distinct Ca2+ signatures regulate the different phases of vasculogenesis, i.e., proliferation and migration, in circulating endothelial precursors. [ABSTRACT FROM AUTHOR]

Alcohol abuse is still one of the leading causes of death worldwide. Early diagnosis of alcohol abuse enables preventive intervention on the effects and risks associated with its consumption. Carbohydrate-deficient transferrin (CDT) is one of the most reliable biomarkers of chronic alcohol misuse. We retrospectively studied a population of 12,624 subjects who had their driving license suspended for driving under the influence of alcohol or drugs from 2016 to 2022. The analytical determination of CDT was performed following a certified high-performance liquid chromatography (HPLC) method. Data were split by year, age and gender. The majority of subjects with positive %CDT were male, although the trend of positivity was similar between males and females. A steady increase in both the number of tests performed and the number of positives was observed over the years. Patients aged 41–50 years had the highest prevalence, followed by 51–60, 31–40 and 18–30 years. CDT continues to be a steady marker for diagnosis of alcohol abuse in the majority of cases. Data emerging from our study are in line with the increasing national trends on traffic accidents, injuries and deaths related to alcohol and drug DUI (driving under the influence), requiring the implementation of preventive measures to limit this ever-growing phenomenon. [ABSTRACT FROM AUTHOR]

The pathogenesis of coronavirus disease 2019 (COVID-19) is associated with a hyperinflammatory response. The mechanisms of SARS-CoV-2-induced inflammation are scantly known. Methylglyoxal (MG) is a glycolysis-derived byproduct endowed with a potent glycating action, leading to the formation of advanced glycation end products (AGEs), the main one being MG-H1. MG-H1 exerts strong pro-inflammatory effects, frequently mediated by the receptor for AGEs (RAGE). Here, we investigated the involvement of the MG-H1/RAGE axis as a potential novel mechanism in SARS-CoV-2-induced inflammation by resorting to human bronchial BEAS-2B and alveolar A549 epithelial cells, expressing different levels of the ACE2 receptor (R), exposed to SARS-CoV-2 spike protein 1 (S1). Interestingly, we found in BEAS-2B cells that do not express ACE2-R that S1 exerted a pro-inflammatory action through a novel MG-H1/RAGE-based pathway. MG-H1 levels, RAGE and IL-1β expression levels in nasopharyngeal swabs from SARS-CoV-2-positive and -negative individuals, as well as glyoxalase 1 expression, the major scavenging enzyme of MG, seem to support the results obtained in vitro. Altogether, our findings reveal a novel mechanism involved in the inflammation triggered by S1, paving the way for the study of the MG-H1/RAGE inflammatory axis in SARS-CoV-2 infection as a potential therapeutic target to mitigate COVID-19-associated pathogenic inflammation. [ABSTRACT FROM AUTHOR]

In this work, an approach is proposed to solve binary combinatorial problems using continuous metaheuristics. It focuses on the importance of binarization in the optimization process, as it can have a significant impact on the performance of the algorithm. Different binarization schemes are presented and a set of actions, which combine different transfer functions and binarization rules, under a selector based on reinforcement learning is proposed. The experimental results show that the binarization rules have a greater impact than transfer functions on the performance of the algorithms and that some sets of actions are statistically better than others. In particular, it was found that sets that incorporate the elite or elite roulette binarization rule are the best. Furthermore, exploration and exploitation were analyzed through percentage graphs and a statistical test was performed to determine the best set of actions. Overall, this work provides a practical approach for the selection of binarization schemes in binary combinatorial problems and offers guidance for future research in this field. [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder that may lead patients to sudden cell death through the occurrence of ventricular arrhythmias. ACM is characterised by the progressive substitution of cardiomyocytes with fibrofatty scar tissue that predisposes the heart to life-threatening arrhythmic events. Cardiac mesenchymal stromal cells (C-MSCs) contribute to the ACM by differentiating into fibroblasts and adipocytes, thereby supporting aberrant remodelling of the cardiac structure. Flecainide is an Ic antiarrhythmic drug that can be administered in combination with β-adrenergic blockers to treat ACM due to its ability to target both Nav1.5 and type 2 ryanodine receptors (RyR2). However, a recent study showed that flecainide may also prevent fibro-adipogenic differentiation by inhibiting store-operated Ca2+ entry (SOCE) and thereby suppressing spontaneous Ca2+ oscillations in C-MSCs isolated from human ACM patients (ACM C-hMSCs). Herein, we briefly survey ACM pathogenesis and therapies and then recapitulate the main molecular mechanisms targeted by flecainide to mitigate arrhythmic events, including Nav1.5 and RyR2. Subsequently, we describe the role of spontaneous Ca2+ oscillations in determining MSC fate. Next, we discuss recent work showing that spontaneous Ca2+ oscillations in ACM C-hMSCs are accelerated to stimulate their fibro-adipogenic differentiation. Finally, we describe the evidence that flecainide suppresses spontaneous Ca2+ oscillations and fibro-adipogenic differentiation in ACM C-hMSCs by inhibiting constitutive SOCE. [ABSTRACT FROM AUTHOR]

We report on the far-infrared, temperature-dependent optical properties of a CrI 3 transition metal halide single crystal, a van der Waals ferromagnet (FM) with a Curie temperature of 61 K. In addition to the expected phonon modes determined by the crystalline symmetry, the optical reflectance and transmittance spectra of CrI 3 single crystals show many other excitations as a function of temperature as a consequence of the combination of a strong lattice anharmonicity and spin–phonon coupling. This complex vibrational spectrum highlights the presence of entangled interactions among the different degrees of freedom in CrI 3 . [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze maternal risk factors associated with negative outcomes of COVID-19 and association with socioeconomic indicators in Brazil. Methods: A cross-sectional study, with data from the Influenza Epidemiological Surveillance Information System (SIVEP-Flu) of pregnant women with COVID-19 and cases of hospitalization and death. For the analysis of risk factors and outcomes, the multiple logistic regression method was used. Results: Pregnant women who had some risk factor represented 47.04%. The chance of death was 2.48 times greater when there was a risk factor, 1.55 for ICU admission and 1.43 for use of ventilatory support. The percentage of cure was 79.64%, 15.46% without any negative outcome, 4.65% death and 0.26% death from other causes. Pregnant women who did not take the vaccine represented 30.08%, 16.74% took it and 53.18% were not specified. The variables HDI, illiteracy, per capita income and urbanization did not influence the cases of COVID-19. Conclusions: Factors such as age, obesity, asthma and pregnancy were responsible for the increase in hospitalizations, respiratory complications and death. Vaccination reduced the risk of negative outcomes by 50%. There were no correlations between socioeconomic indicators and the negative outcomes of COVID-19 in pregnant women. [ABSTRACT FROM AUTHOR]