Search Results (971)

Background: Preclinical dental training requires simulation-based tools to develop fine motor skills, but traditional models like plastic teeth often lack realistic tactile feedback, and systematic evaluations of multi-layered drilling plates are scarce. This study aimed to evaluate the educational utility and perceived realism of a novel multi-layered drilling plate designed to simulate enamel, dentin, and pulp, with null hypotheses that it would not differ in realism from natural dental tissues or in educational utility from existing tools. Methods: Seventy dental educators (mean preclinical teaching experience: 112.9 ± 116.7 months) from 14 institutions across four continents assessed the plates using standardized protocols. Statistical analysis (Mann–Whitney U Test) was performed to analyze the results. Results: Quantitative ratings (1–10 scale) showed high mean scores for drilling quality (enamel: 7.80 ± 1.55, dentin: 7.27 ± 1.94, pulp: 7.48 ± 2.33), surface smoothness (enamel: 8.17 ± 1.55, dentin: 8.17 ± 1.57), and ergonomic visibility (8.56 ± 1.58), with 90% passing grades, rejecting the null hypothesis of no difference in educational utility. Tissue transition scores (enamel/dentin: 7.09 ± 2.56; dentin/pulp: 6.86 ± 2.46) showed significant differences (p < 0.05) in realism from natural tissues, rejecting the null hypothesis of no difference. Inter-rater reliability was poor (Krippendorff’s alpha: 0.449 for failing scores, 0.211 for passing scores). Qualitative feedback praised ease of use but noted limitations in dentin haptic simulation. Conclusions: The drilling plate shows promise for skill development, though without controlled comparisons to existing tools, its relative efficacy remains preliminary. Further research on student outcomes and tool refinement is needed to validate its use in dental education. Full article

This study investigates the evolution of strain-induced martensite (SIM) and its effect on magnetic Barkhausen noise (MBN) in AISI 321 austenitic stainless steel subjected to uniaxial tensile testing. Using X-ray diffraction and the Barkhausen noise technique, the formation and distribution of SIM were analysed as functions of plastic strain and strain rate. The results show that MBN is primarily governed by plastic deformation and strain rate rather than residual stress. The martensite fraction increases from 10% at low strains to 42.5% at high strains; however, accelerated strain rates significantly reduce martensite formation to approximately 25%. The increase in martensite density enhances the magnetic exchange interactions among neighbouring islands, resulting in stronger and more numerous MBN pulses. The anisotropy of MBN is also influenced by the initial crystallographic texture of the austenite. These findings highlight the strong correlation between MBN and SIM evolution, establishing MBN as a sensitive, non-destructive tool for assessing martensitic transformation and optimising deformation parameters in austenitic steels. Full article

Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic cellular dysfunction. While autophagy and inflammation are key dysregulated pathways in HGPS, the role of microRNAs (miRNAs) in these processes remains poorly understood. Methods: We performed an extensive literature review to identify miRNAs involved in autophagy and inflammation. Through stem-loop RT-qPCR in aging HGPS and control fibroblast strains, we identified significant miRNAs and focused on the most prominent one, miR-181a-5p, for in-depth analysis. We validated our in vitro findings with miRNA expression studies in skin biopsies from an HGPS mouse model and conducted functional assays in human fibroblasts, including immunofluorescence staining, β-Galactosidase assay, qPCR, and Western blot analysis. Transfection studies were performed using an miR-181a-5p mimic and its inhibitor. Results: We identified miR-181a-5p as a critical regulator of premature senescence in HGPS. miR-181a-5p was significantly upregulated in HGPS fibroblasts and an HGPS mouse model, correlating with Sirtuin 1 (SIRT1) suppression and induction of senescence. Additionally, we demonstrated that TGFβ1 induced miR-181a-5p expression, linking inflammation to miRNA-mediated senescence. Inhibiting miR-181a-5p restored SIRT1 levels, increased proliferation, and alleviated senescence in HGPS fibroblasts, supporting its functional relevance in disease progression. Conclusions: These findings highlight the important role of miR-181a-5p in premature aging and suggest its potential as a therapeutic target for modulating senescence in progeroid syndromes. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background/Objectives: Respectful maternity care involves privacy, dignity, and informed choice within the process of delivery as stipulated by the World Health Organization (WHO). Informed consent is a cornerstone of patient-centered care, representing not just a formal document, but an ongoing ethical and clinical process through which women are offered objective, understandable information to support autonomous, informed decision-making. Methods: This narrative review critically examines the literature on informed consent in maternity care, with particular attention to both obstetric-led and midwifery-led models of care. In addition to identifying institutional, cultural, and systemic obstacles to its successful implementation, the review examines the definition and application of informed consent in perinatal settings and evaluates its effects on women’s autonomy and satisfaction with care. Results: Important conclusions emphasize that improving women’s experiences and minimizing needless interventions require active decision-making participation, a positive provider–patient relationship, and ongoing support from medical professionals. However, significant gaps persist between legal mandates and actual practice due to provider attitudes, systemic constraints, and sociocultural influences. Women’s experiences of consent can be more effectively understood through the use of instruments such as the Mothers’ Respect (MOR) Index and the Mothers’ Autonomy in Decision Making (MADM) Scale. Conclusions: To promote genuinely informed and considerate maternity care, this review emphasizes the necessity of legislative reform and improved provider education in order to close the gap between policy and practice. Full article

An anion exchange-assisted technique was used for the synthesis of platinum-decorated SnO₂ supports, providing nanocatalysts with enhanced activity for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). In this study, a series of SnO₂ supports, namely SnA (synthesized almost at room temperature), SnB (hydrothermally treated at 180 °C), and SnC (annealed at 600 °C), are systematically investigated, all loaded with 1 mol% Pt from H₂PtCl₆ under identical mild conditions. The chloride ions from the SnCl₄ precursors were efficiently removed via a strong-base anion exchange reaction, resulting in highly dispersed, crystalline ~5 nm cassiterite SnO₂ particles. All Pt/SnO₂ composites displayed mesoporous structures with type IVa isotherms and H₂-type hysteresis, with SP1a (Pt on SnA) exhibiting the largest surface area (122.6 m²/g) and the smallest pores (~3.5 nm). STEM-HAADF imaging revealed well-dispersed PtOx domains (~0.85 nm), while XPS confirmed the dominant Pt⁴⁺ and Pt²⁺ species, with ~25% Pt⁰ likely resulting from photoreduction and/or interactions with Sn–OH surface groups. Raman spectroscopy revealed three new bands (260–360 cm⁻¹) that were clearly visible in the sample with 10 mol% Pt and were due to the vibrational modes of the PtOx species and Pt-Cl bonds introduced due the addition and hydrolysis of H₂PtCl₆ precursor. TGA/DSC analysis revealed the highest mass loss for SP1a (~7.3%), confirming the strong hydration of the PtOx domains. Despite the predominance of oxidized PtOx species, SP1a exhibited the highest catalytic activity (k_app = 1.27 × 10⁻² s⁻¹) and retained 84.5% activity for the reduction of 4-NP to 4-AP after 10 cycles. This chloride-free low-temperature synthesis route offers a promising and generalizable strategy for the preparation of noble metal-based nanocatalysts on oxide supports with high catalytic activity and reusability. Full article

Current temperature sensors require regular recalibration to maintain reliable temperature measurement. Photonic/quantum-based approaches have the potential to radically change the practice of thermometry through provision of in situ traceability, potentially through practical primary thermometry, without the need for sensor recalibration. This article gives an overview of the European Partnership in Metrology (EPM) project: Photonic and quantum sensors for practical integrated primary thermometry (PhoQuS-T), which aims to develop sensors based on photonic ring resonators and optomechanical resonators for robust, small-scale, integrated, and wide-range temperature measurement. The different phases of the project will be presented. The development of the integrated optical practical primary thermometer operating from 4 K to 500 K will be reached by a combination of different sensing techniques: with the optomechanical sensor, quantum thermometry below 10 K will provide a quantum reference for the optical noise thermometry (operating in the range 4 K to 300 K), whilst using the high-resolution photonic (ring resonator) sensor the temperature range to be extended from 80 K to 500 K. The important issues of robust fibre-to-chip coupling will be addressed, and application case studies of the developed sensors in ion-trap monitoring and quantum-based pressure standards will be discussed. Full article

(1) Background: Our study investigates the green synthesis of Ag₂O/Ag nanoparticles using the isoflavone Puerarin as a bioreductor. (2) Methods: The PUE@Ag₂O/Ag nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), electronic microscopy (TEM, SEM), energy dispersive X-ray spectroscopy (EDX), and dynamic light scattering (DLS). Biological activities were assessed through antimicrobial testing, cytotoxicity assays on human keratinocytes and melanoma cells, and an in ovo screening using the HET-CAM assay. (3) Results: The formation of crystalline Ag₂O/Ag nanoparticles with sizes below 100 nm was accomplished with Puerarin. Despite their high cytotoxicity at all tested concentrations, the nanoparticles showed antioxidant activity with IC₅₀ 981.5 ± 94.2 μg/mL, antibacterial activity against several clinically relevant nosocomial strains (Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa), and no local irritant effects or inhibition of angiogenesis in the HET-CAM assay. (4) Conclusions: This study provides insights into the synthesis, characterization, and biological profile of PUE@Ag₂O/Ag nanoparticles for potential biomedical applications. Full article

Background/Objectives: Early diagnosis and oral or, in severe cases, intravenous antibiotics are usually effective for Lyme disease, but some patients have persistent symptoms unresponsive to standards of care, requiring alternative therapies. Disulfiram (DIS), a drug for alcoholism, is under investigation as a potential adjunctive treatment, but its low bioavailability, rapid metabolism, and safety concerns urge the development of improved formulations for clinical translation. Methods: Screening dissolution and permeation studies were investigated for vehicle and excipient selection, following the pharmacopeia perspectives to develop and optimize the low-dose DIS rectal suppository intended for application in post-treatment Lyme disease syndrome (PTLDS). Further characterizations were carried out by differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. Results: Cyclodextrin (CD) encapsulation was investigated to improve the aqueous solubility of the hydrophobic drug. The dissolution of DIS from fatty base suppository was very slow; it was remarkably improved by the molecular encapsulation of the drug with CDs. The dissolution of DIS from a water-soluble base was more favorable, but incomplete. In the polyethylene glycol (PEG) based suppositories, the addition of CDs already in a physical mixture ensured the dissolution of the drug. The presented drug delivery system relates to a novel preparation for rectal administration comprising a low-dose disulfiram with improved solubility and permeability by the PEG and hydroxypropyl-β-cyclodextrin (HPBCD) synergistic matrix. Conclusions: The rectal dosage form containing the drug and CD in the physical mixture is advantageous, avoiding the hepatic first-pass effect, minimizing dose-limiting toxicity, simplifying production, and fasting the availability of the repositioned drug. Full article

Background: We assessed the frequency and causes of discrepancies in CT dose indices such as dose-length product (DLP), size-specific dose estimate (SSDE), and effective dose (ED), as calculated by CT dose-monitoring systems. Our secondary aim was to demonstrate the estimation of size-specific ED (SED) from the patients’ dose records. Methods: The retrospective study included dosimetric data of 79,383 consecutive CT exams performed on two CT scanners. The following dose values were recorded from both the locally developed dose-monitoring system (DMS) and a commercial dose-monitoring program (DW^TM): DLP, SSDE, and ED. Only the DMS provided bodyweight-corrected effective dose (SED_DMS) and the SED based on previous published data. Results: Without body-region-specific analysis, there were no tendentious differences between the DLP, ED, or SSDE values obtained from DW^TM and DMS. However, the body region-based correlation revealed substantial differences between ED_DMS and ED_DW, primarily related to inadequate identification of the body. SSDE showed strong correlation to each anatomical category and CT device, except for the head region, where inadequate consideration of CT inclination was the reason for the biased SSDE_DW value. Furthermore, by analyzing the SED_DMS, SSDE, and SED correlations, we concluded that SED_DMS is a promising figure for estimating the SED value. Conclusions: SED provides suitable supplementary size-specific dose data to SDDE and may be a preferable choice for estimating cumulative doses in routine radiological practice. Full article

Background and objectives: Post-operative pain (POP) is a common complication after root canal treatment and is influenced by various clinical and patient-related factors. The present study evaluated the incidence and intensity of POP following root canal treatment using a bioceramic sealer performed by operators with different levels of experience. Methods: A total of 115 patients were included in this prospective observational study. Patients were treated by operators with different levels of experience: postgraduate students (PGSs) and endodontic specialists (ESs). Standardized protocols were used in two distinct appointments: an instrumentation visit and an obturation visit. Obturation was performed using the continuous wave condensation technique and Total Fill Hi-Flow BC Sealer (TFHF). POP, mastication discomfort, and sleep disturbance were assessed at 24, 48, and 72 h after the instrumentation and obturation phases using a numeric rating scale (NRS). Results: The results indicate significantly higher POP after the instrumentation phase, compared to the obturation phase (p < 0.001). The pain intensity progressively decreased over time for both phases. No significant differences were observed between the PGS and ES groups regarding POP, mastication discomfort, or sleep disturbance at any time. Sealer extrusion did not significantly impact POP (p > 0.05). Conclusions: This study found that operator experience does not significantly influence POP when a standardized protocol is followed. The use of TFHF with the continuous wave condensation technique was associated with minimal POP. Full article

Background/Objectives: Vitamin D₃ is predominantly sequestered in adipose tissue, where it is slowly mobilized under conditions of deficiency in vivo. However, the kinetics of its uptake, release, and interaction with its major metabolites, 25(OH)D₃ and 1,25(OH)₂D₃, remain poorly understood. Given the close relationship between obesity, low-grade chronic inflammation, and disrupted vitamin D metabolism, a clearer understanding of these dynamics in adipocytes is essential. Thus, we sought to characterize time-dependent uptake and metabolites in differentiated human adipocytes. Methods: Human pre-adipocytes were differentiated in vitro and exposed to either vitamin D₃ and 1,25(OH)₂D₃ or the combination of vitamin D₃, 25(OH)D₃ and 1,25(OH)₂D₃. Intracellular concentrations were quantified through HPLC at various time points. A separate efflux experiment assessed vitamin D₃ release under basal and isoproterenol-stimulated conditions using ³H-vitamin D₃ and scintillation counting. Results: Vitamin D₃ uptake showed a gradual and sustained increase over 96 h, suggesting ongoing accumulation within lipid-rich compartments. In contrast, 25(OH)D₃ and 1,25(OH)₂D₃ peaked rapidly within the first hour and declined sharply. Isoproterenol stimulation significantly enhanced vitamin D₃ release into the extracellular medium from the adipocytes, indicating increased efflux during lipolytic activation. Conclusions: Adipocytes selectively retain vitamin D₃ while rapidly clearing its hydroxylated forms. These findings highlight the distinct intracellular handling of vitamin D metabolites and suggest that tailored supplementation strategies—particularly in individuals with excess adiposity—may improve bioavailability and metabolic efficacy. Full article

Multiple myeloma (MM or plasma cell myeloma) is a heterogenous B-cell malignant tumor that typically exhibits a high recurrence rate, resistance to drugs, and molecular diversity of tumor subclones. Given the limited efficacy of standard therapy options, cellular immunotherapy featuring a chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of MM. The rational choice of a tumor target which shows high selectivity, stable expression, and biological significance is key to the successful implementation of CAR therapy. This review has summarized and analyzed data from the literature on biological properties, the features of expression, and the clinical development stages of CAR cell products for MM treatment which target BCMA, GPRC5D, FcRH5, SLAMF7, CD38, CD138, TACI, APRIL, CD19, TNFR2, CD44v6, CD70, NKG2D ligands, etc. Special focus is on strategic approaches to overcoming antigenic escape, such as multi-specific CAR constructs, logical activation sequences, and controlled safety systems. The analysis underscores the need for integrating the molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising the efficacy, stability, and safety of cellular therapy in the case of MM. Full article

Choosing the optimal first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangements can be challenging in daily practice. Although clinical trials with next-generation ALK-tyrosine kinase inhibitors (TKIs) have played a key role in evaluating their efficacy and safety, which patients benefit from a specific ALK-TKI may still be questioned. The methodological inconsistencies in these trials, which led to the inclusion of different patient populations, appear to have been inadequately addressed. ALK-rearranged NSCLC is a heterogeneous disease, and co-existing molecular alterations may affect the outcome. The questions explored in these trials appear insufficient to support a personalized approach to the first-line treatment, while defining long-term responders and early progressors would be clinically useful. This narrative review presents several considerations from oncologists’ and pathologists’ perspectives. We propose defining favorable and unfavorable features, such as histology, type of ALK fusion, co-existing molecular alterations, plasma circulating tumor DNA (ctDNA, performance status, and brain metastases, to help identify patients with lower and higher risk of progression. Consequently, the most potent ALK-TKI to date, Lorlatinib, may be considered as the first-line treatment for high-risk patients with unfavorable features, while sequencing of ALK-TKIs may be appropriate for low-risk patients with favorable features. Although ALK signal inhibition is critical in this disease, it may not be sufficient for clinical control due to de novo co-alterations. A more personalized approach to first-line therapy requires consideration of risk factors for each patient. Full article

Background: Psychological impacts of the coronavirus disease 2019 (COVID-19) pandemic on individuals with chronic medical conditions remain understudied. Chronic kidney disease (CKD) is one of the chronic conditions associated with an increased risk of severe COVID-19 outcomes. The aim of this study was to define the psychological burden of individuals with CKD during the COVID-19 pandemic. Methods: In this cross-sectional study, 219 individuals with CKD were recruited from the Nephrology Outpatient Unit at the University Hospital Essen, Germany, and completed anonymous surveys incorporating validated psychological assessment tools for generalized anxiety (GAD-7) and depressive symptoms (PHQ-2), along with self-generated items addressing COVID-19-specific concerns and behavioral changes. These participants were propensity score matched with controls from the general German population. Results: Individuals with CKD exhibited lower levels of generalized anxiety and depressive symptoms compared to the general population. However, they reported significantly greater risk perceptions regarding the likelihood of experiencing symptoms, a severe disease course, and death from COVID-19. COVID-19-related fear and associated behavioral changes were more frequently reported among CKD patients. Adherent and dysfunctional safety behaviors predominated among the CKD cohort. Conclusions: This study underscores psychological challenges faced by individuals with CKD during the COVID-19 pandemic. The increased risk perceptions and fears of severe disease and mortality from COVID-19 emphasize the need for mental health interventions aimed at improving coping strategies alongside physical health management in this vulnerable population. Full article