Differential Inhibition by Cenobamate of Canonical Human Nav1.5 Ion Channels and Several Point Mutants.

Cenobamate is a new and highly effective antiseizure compound used for the treatment of adults with focal onset seizures and particularly for epilepsy resistant to other antiepileptic drugs. It acts on multiple targets, as it is a positive allosteric activator of γ-aminobutyric acid type A (GABA) receptors and an inhibitor of neuronal sodium channels, particularly of the late or persistent Na current. We recently evidenced the inhibitory effects of cenobamate on the peak and late current component of the human cardiac isoform hNav1.

Mapping O- and N-Glycosylation in Transmembrane and Interface Regions of Proteins: Insights from a Database Search Study.

Glycosylation is a critical post-translational modification that influences protein folding, stability and function. While extensively studied in extracellular and intracellular regions, glycosylation within transmembrane (TM) regions and at membrane interfaces remains poorly understood. This study aimed to map O- and N-glycosylation sites in these regions using a comprehensive database search and structural validation where possible.

ZnSnO@SiO@5-FU Nanoparticles as an Additive for Maxillary Bone Defects.

This study investigates the synthesis of ZnSnO@SiO@5-FU nanoparticles as an additive for bone fillers in dental maxillofacial reconstruction. ZnSnO nanoparticles were synthesized and coated with a SiO shell, followed by the incorporation of 5-Fluorouracil (5-FU), aimed at enhancing the therapeutic properties of classical fillers. Structural analysis using X-ray diffraction confirmed that ZnSnO was the single crystalline phase present, with its crystallinity preserved after both SiO coating and 5-FU incorporation.

The Interplay Between High Cumulative Doses of Radioactive Iodine and Type 2 Diabetes Mellitus: A Complex Cardiovascular Challenge.

Starting from the metabolic profile of type 2 diabetes mellitus (T2DM), we hypothesized that the mechanisms of ¹³¹I-induced cardiotoxicity differ between patients diagnosed with differentiated thyroid cancer (DTC) with/without T2DM, with metformin potentially acting as a cardioprotective agent by mitigating inflammation in patients with T2DM. To address this hypothesis, we quantified, using ELISA, the serum concentration of several key biomarkers that reflect cardiac injury (NT-proBNP, NT-proANP, ST2/IL-33R, and cTn I) in 74 female patients with DTC/-T2DM and 25 with DTC/+T2DM treated with metformin. All patients received a cumulative oral dose of I exceeding 150 mCi (5.

In Vitro and In Vivo Evaluation of rPET/Cu-Alg Nanofibers for Anti-Infective Therapy.

With the growing interest in nanofibers and the urgent need to address environmental concerns associated with plastic waste, there is an increasing focus on using recycled materials to develop advanced healthcare solutions. This study explores the potential of recycled poly(ethylene terephthalate) (PET) nanofibers, functionalized with copper-enhanced alginate, for applications in wound dressings. Nanofibers with desirable antimicrobial properties were developed using chemical recycling and electrospinning techniques, offering a sustainable and effective option for managing wound infections and promoting healing.

Zinc Oxide-Loaded Recycled PET Nanofibers for Applications in Healthcare and Biomedical Devices.

Polyethylene terephthalate (PET) is a widely utilized synthetic polymer, favored in various applications for its desirable physicochemical characteristics and widespread accessibility. However, its extensive utilization, coupled with improper waste disposal, has led to the alarming pollution of the environment. Thus, recycling PET products is essential for diminishing global pollution and turning waste into meaningful materials.

Synthesis, Physicochemical Properties, and Ion Recognition Ability of Azulene-Based Bis-(Thio)Semicarbazone.

Azulene-1,3-bis(semicarbazone), , and azulene-1,3-bis(thiosemicarbazone), , were synthesized by the acid-catalyzed condensation reactions of semicarbazide and thiosemicarbazide, respectively, with azulene-1,3-dicarboxaldehyde in stoichiometric amounts. Compounds and were identified by high-resolution mass spectrometry and characterized by IR, H-NMR, C-NMR, and UV-vis spectroscopic techniques. Crystal structure determination of azulene-1,3-bis(thiosemicarbazone) shows that the thiosemicarbazone units exhibit a -closed conformation, with both arms oriented in the same direction and adopting an configuration with respect to the imine linkages.

Novel 3-Sulfonamide Dual-Tail Pyrrol-2-one Bridged Molecules as Potent Human Carbonic Anhydrase Isoform Inhibitors: Design, Synthesis, Molecular Modeling Investigation, and Anticancer Activity in MeWo, SK-BR-3, and MG-63 Cell Lines.

Novel 3-sulfonamide pyrrol-2-one derivatives containing two sulfonamide groups were synthesized via a one-pot, three-component method using trifluoroacetic acid as a catalyst. Structural confirmation was achieved using spectroscopic techniques. The compounds were tested against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX, and hCA XII).

Well-being factors. An item-level analysis of the positive cognitive triad role, in the relationship between resilience and well-being.

This study examines the impact of resilience and the positive cognitive triad (consisting of three components: view of the self, view of the world, and view of the future) on well-being, a subject that is presently understudied. The present study investigated well-being models that take into consideration the role of the positive cognitive triad, in the relationship between resilience and several concepts of well-being: subjective (general) happiness, subjective (hedonic) well-being, and psychological (eudaimonic) well-being (N = 742). Eudaimonic and hedonic well-being contribute to overall happiness through different mechanisms, while subjective happiness is people's assessment of their happiness.

Implications of Biomaterials for Chronic Wounds.

The use of biomaterials in treating and managing chronic wounds represents a significant challenge in global healthcare due to the complex nature of these wounds, which are slow to heal and can lead to complications such as frequent infections and diminished quality of life for patients. Chronic wounds, which can arise from conditions like diabetes, poor circulation, and pressure sores, pose distinct challenges in wound care, necessitating the development of specialized dressings. The pathophysiology of chronic wounds is thoroughly examined in this article, with particular attention paid to the cellular and molecular defects at work and the therapeutic guidelines.

Poly(3-hydroxybutyrate) Modified with Thermoplastic Polyurethane and Microfibrillated Cellulose: Hydrolytic Degradation and Thermal and Mechanical Properties.

Blending poly(3-hydroxybutyrate) (PHB) with other polymers could be a rapid and accessible solution to overcome some of its drawbacks. In this work, PHB was modified with microfibrillated cellulose (MC) and a thermoplastic polyurethane containing biodegradable segments (PU) by two routes, using a masterbatch and by direct mixing. The PU and MC modifiers improved the thermal stability of PHB by up to 13 °C and slightly decreased its melt viscosity and crystallinity, thus improving the melt processability.

The Potential of TRPA1 as a Therapeutic Target in Cancer-A Study Using Bioinformatic Tools.

The expression of the transient receptor potential 1 (TRPA1) gene is increased in many solid tumours, and its function relates to inflammation, oxidative stress or the presence of toxic substances. However, little is known about the correlation of clinical parameters with patients' cancer stages, metastases and the degree of tumour infiltration by immune cells. We performed a bioinformatic analysis, using databases and public resources to investigate TRPA1 for many available samples.

: A Comprehensive Review of Its Therapeutic Potential, Pharmacological Properties, and Clinical Applications.

(NS) is an annual herb belonging to the Ranunculaceae family, also known as black cumin or black seed. This plant has been used since ancient times due to its therapeutic properties and has proven effective in gastrointestinal, respiratory, cardiovascular, infectious, and inflammatory conditions. In this review, the aim is to highlight the therapeutic effects of the plant known in Arab countries as "the plant that cures any disease", which are provided by the phytochemical compounds in its composition, such as thymoquinone, p-cymene, α-thujene, longifolene, β-pinene, α-pinene, and carvacrol.

Bisindole Compounds-Synthesis and Medicinal Properties.

The indole nucleus stands out as a pharmacophore, among other aromatic heterocyclic compounds with remarkable therapeutic properties, such as benzimidazole, pyridine, quinoline, benzothiazole, and others. Moreover, a series of recent studies refer to strategies for the synthesis of bisindole derivatives, with various medicinal properties, such as antimicrobial, antiviral, anticancer, anti-Alzheimer, anti-inflammatory, antioxidant, antidiabetic, etc. Also, a series of natural bisindole compounds are mentioned in the literature for their various biological properties and as a starting point in the synthesis of other related bisindoles.

Synthesis, Spectroscopic Characterization, Structural Analysis, and Evaluation of Anti-Tumor, Antimicrobial, and Antibiofilm Activities of Halogenoaminopyrazoles Derivatives.

New haloaminopyrazole derivatives differing in the number of pyrazole nuclei - and -, respectively, were synthesized and characterized by H-NMR, C-NMR, IR, UV-Vis, and elemental analysis. The single-crystal X-ray diffraction method was used to describe compounds and . When tested on normal NCTC fibroblasts in vitro, the newly synthesized derivatives were shown to be non-cytotoxic at a dosage of 25 μg/mL.

Inhibitory Effects of Cenobamate on Multiple Human Cardiac Ion Channels and Possible Arrhythmogenic Consequences.

Cenobamate is a novel third-generation antiepileptic drug used for the treatment of focal onset seizures and particularly for multi-drug-resistant epilepsy; it acts on multiple targets: GABA receptors (EC 42-194 µM) and persistent neuronal Na currents (IC 59 µM). Side effects include QT interval shortening with >20 ms, but not <300 ms. Our in vitro cardiac safety pharmacology study was performed via whole-cell patch-clamp on HEK293T cells with persistent/inducible expression of human cardiac ion channel isoforms hNav1.

Tackling Cardiovascular Care Deserts in Romania: Expanding Population Access in Underserved Areas.

Background: Cardiovascular deserts are areas that lack medical facilities, specialists and equipment to effectively diagnose, treat and manage cardiovascular diseases (CVDs). Romania registers the highest incidence and the highest mortality due to CVDs in Europe. Population ageing is a significant concern, as it increases the risk of CVDs and the demand for specialised care.

Long-term impact of tillage on microbial communities of an Eastern European Chernozem.

As conservation agricultural practices continue to spread, there is a need to understand how reduced tillage impacts soil microbes. Effects of no till (NT) and disk till (DT) relative to moldboard plow (MP) were investigated in a long-term experiment established on Chernozem. Results showed that conservation practices, especially NT, increased total, active and microbial biomass carbon.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Regulations of activities and protection levels in marine protected areas of the European Union: A dataset compiled from multiple data sources.

The dataset gathers available regulations of human activities and protection levels of Marine Protected Areas (MPAs) of the European Union (EU). The MPA list and polygons were extracted from the MPA database of the European Environment Agency (EEA) and completed with available zoning systems (all were filtered for their marine area reported under the Marine Strategy Framework Directive). Fully-overlapping MPAs were merged.

Internet- and mobile-based aftercare and relapse prevention interventions for anxiety and depressive disorders: a systematic review.

Background: Digital interventions present potential solutions for aftercare and relapse prevention in anxiety and depressive disorders. This systematic review synthesizes evidence on the efficacy of internet- and mobile-based interventions for post-acute care in these conditions.

Methods: A systematic search was conducted in electronic databases (MEDLINE, CENTRAL, Scopus, Web of Science, PsycINFO, PsycARTICLES, PsycEXTRA, ProQuest Dissertations and Theses Open, Open Access Theses and Dissertations, and Open Grey) for randomized controlled trials evaluating digital aftercare or relapse prevention interventions for adults with anxiety or depressive disorders.

Ictal semiology in temporo-frontal epilepsy: A systematic review and meta-analysis.

We performed a systematic review of the ictal semiology of temporo-frontal seizures with the aim to summarize the state-of-the-art anatomo-clinical correlations in the field, and help guide the interpretation of ictal semiology within the framework of presurgical evaluation. We conducted the systematic review and meta-analysis, and reported its results according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We searched electronic databases (Scopus, PUBMED, Web of Science, and EMBASE) using relevant keywords related to temporal, frontal and sublobar structures, semiology, and electroencephalography/stereoelectroencephalography exploration.

Uncovering deep-rooted conflicts: the role of psychoanalytic psychotherapy in treating athletes' social media-related psychological distress.

The use of social media by athletes can support them in difficult moments, but it can also become a source of negative emotions and psychological distress. This perspective critically examines psychoanalytic psychotherapy as a method for restoring athletes' psychological well-being after experiencing negative effects from social media use. The paper characterizes the key elements of psychoanalytic psychotherapy relevant to athletes, discusses the role of the psychoanalytic psychotherapist in working with athletes and describes the specifics of the psychoanalytic therapeutic process in this context.

qDATA - an R application implementing a practical framework for analyzing quantitative real-time PCR data.

Gene expression assays that are based on quantitative real-time PCR (qRT-PCR) method are still very popular, therefore, we developed qDATA, an open-source R-based bioinformatics application that offers a quick and intuitive analysis of raw cycle threshold (Ct) values. The application relies on a straightforward data input consisting in Ct values and on other mandatory fields specifying the experimental and control groups. qDATA automatically performs descriptive statistics, normality and statistical testing on 2 (or ΔCt) and 2 terms calculated with Livak's method.

Investigating stress, anxiety, and coping strategies among higher education students in extreme contexts: insights from Romania during the COVID-19 pandemic.

Background: Using the perspective of the recent COVID-19 pandemic, which represents a public health challenge that also affects education and the psychological well-being of students, this paper aims to assess the vulnerability to anxiety and stress of the Romanian students from the Faculty of Administration and Business of the University of Bucharest pursuing their degrees in administration and business.

Methods: Our study is based on the results of the survey that was administered to a sample of 422 students (39.6% females and 60.