Problem statement. For conditions of asymmetric loads on underground structures caused by uneven weakening of rocks due to flooding and other natural and man-made factors, issues of substantiating rational forms and sizes of injection hardening zones require further comprehensive studies combining geomechanics, materials science and optimization methods. Purpose of the study. Justification of the parameters of injection rock hardening zones to improve the safety level of underground workings and buried structures under conditions of asymmetric loads on the support. Methods. Generalization of data on the asymmetry of loads on the support of underground structures; methodology for assessing the rock massif destruction; mathematical modeling using the finite element method. Research results. Hardening of rocks around underground workings and buried structures allows to reduce the probability of cracks, prevent the development of deformations and increase the overall resistance of objects to the impact of operational and natural loads. The issue of substantiation of rational forms and sizes of injection hardening zones for conditions of asymmetric loads on underground structures which are caused by uneven weakening of rocks due to flooding and other natural and man-made factors requires further research. The features of the formation process of loads asymmetry on the support of the underground structures are determined. The method of assessing the state of the polymer-saturated rock massif and forecasting its changes under the influence of certain measures to strengthen the rocks around the underground structure is substantiated. It has been established that rock hardening by means of injection and other hardening technologies allows for effective compensation of supporting deficiencies without a significant increase in capital expenditures. In addition, the use of various configurations and arrangement schemes of hardening zones allows for flexible adaptation to specific geological conditions, redistribution of stresses in rocks, reduction of their concentrations in potentially hazardous zones, prevention of local collapses, deformations and water inflows, which ensures long-term safe use of underground structures. For conditions of uneven loads on the supports, an asymmetric shape of the hard-ened zone is proposed, which can be used as a reserve for increasing the stability of the underground structure. It is established that the nearly elliptical shape of the hardened zone as an element of rock pressure control ensures an in-crease in the stability of the underground structure due to a 10‒35 % reduction in the inelastic deformation zone and a 0,5‒3,0 m deep displacement of the asymmetric support pressure zone. The displacement of the roof of the underground workings is reduced by 6‒13 % of the total displacements, and the workings floor by 7‒23 %. Scientific novelty. For the first time, in order to increase the level of safety in the operation of underground workings and buried structures under conditions of asymmetric loads on the support, patterns of changes in maximum principal stresses have been established when using various nearly elliptical shape of injection rock hardening zones. Practical significance. The proposed configurations of injection hardening zones reduce stress concentrations in rocks, which helps prevent sudden deformations of supports and ensure long-term safe use of underground structures.

Patent foramen ovale (PFO) is the most common inherited cardiac abnormality, with intermittent right-to-left (R-L) shunt of variable size. To study the quantification of R-L shunt (shunt) in PFO patients using an original thermodilution method in relationship to the morphology of the interatrial septum, measured by echocardiography and cardiopulmonary exercise tests before and after the occlusion of a PFO. A multicenter study enrolled a population of 151 patients, eligible for PFO closure in secondary prevention, underwent transthoracic echocardiography and contrast transesophageal echocardiography, cardiopulmonary exercise tests before and 6 months after the closure. The size of the shunt was measured by catheterization using the thermodilution Inntherm® system. Shunt was detected in 133 (90%) patients. Size of shunt >20% was present in 41 (28%) patients, 10%-20% in 33 (22%), and <10% in 49 (40%) patients. Shunt size >10% was associated with greater atrial septal separation during the Valsalva (P = 0.03) and respiration (P = 0.04), amplitude of septal displacement (P = 0.009), amount of contrast media in the left atrium (LA) (P = 0.03) and hypermobility of septum (P = 0.03). After PFO closure, work capacity increased in patients with shunt ≥20% (Δ +6.8; standard deviation [SD] 16.9 [W]) compared with those with <10% (Δ -2.1; SD 24.5 [W]; P = 0.02). Migraine occurrence decreased in 8 patients (62%) (P = 0.008). A decrease in saturation on exercise occurred in 12 cases (9%), after the PFO closure saturation normalized from 90.5% to 95.0% (P = 0.009), with no effect on exercise. We proved safe use of thermodilution for R-L shunt measurement. The main cause of inducible shunt severity is atrial septal mobility. A severe PFO shunt impacts work capacity.

Chloroplast genomes provide conserved yet informative sequences useful for inferring plant evolution and species identification. Genus Aconitum consists of around 300 traditional Indian and Chinese medicinal plant species, many native to mountainous regions, and known to be highly poisonous due to toxic diterpene alkaloids. Their accurate identification and classification are vital for traditional medicine systems, particularly for ensuring their safe use. A consistent quadripartite structure was identified across all chloroplast genomes, comprising the typical large single copy (LSC), small single copy (SSC), and two inverted repeats (IR) regions. Pan-plastome analysis unveiled 72 core and nine accessory genes, indicating an open pan-plastome characteristic. In-depth nucleotide-level homology analysis revealed that homologous genes of all accessory genes are present in all other genomes, implying the need for better chloroplast genome annotation tools that can identify all putative genes from such conserved genomes. Notably, the order of all core and accessory genes remained highly conserved across all analysed genomes, underscoring the overall evolutionary stability despite the diversity of accessory genes. Members of some core pathways are relatively absent on the chloroplast genome, suggesting their potential presence on the nuclear genome, which will be revealed after their nuclear genome sequencing. Our phylogenetic results largely supported the morphological classification, with distinct Lycoctonum and Aconitum subgenera clustering, further validating the gross accuracy except for A. flavum, suggesting a putative morphological classification discrepancy or inaccurate classification. This comparative analysis reveals a highly conserved chloroplast genome architecture across Aconitum while documenting measurable plastome-level variation among 73 species. The chloroplast phylogeny highlights instances of non-monophyletic clustering among conspecific accessions and unexpected placement of certain taxa, indicating complex evolutionary histories within the genus. Such patterns may reflect a combination of processes, including incomplete lineage sorting, chloroplast capture, or sample misidentification, rather than definitive phylogenetic incongruence. While chloroplast genomes alone cannot fully resolve evolutionary relationships in a group shaped by hybridization and polyploidy, the results provide valuable insights into plastome evolution and identify key lineages and taxa that warrant further investigation using nuclear genomic and integrative approaches.

Urinary tract infections (UTIs) are a prevalent health issue, particularly among women, and are commonly treated with antibiotics. However, increasing antimicrobial resistance has led to growing interest in complementary and alternative medicine (CAM) as a non-antibiotic approach to UTI prevention and management. This study aimed to assess the knowledge, practices, and perceptions of Jordanian adults regarding the use of CAM therapies, including herbal remedies and natural products, for the prevention and treatment of UTIs. A descriptive, cross-sectional study was conducted using an online survey distributed via social media platforms. The questionnaire assessed sociodemographic characteristics, medical history, awareness of UTI risk factors, sources of CAM information, and perceptions toward CAM use. Descriptive and inferential statistical analyses were performed. A total of 429 participants completed the survey. Nearly half had a medical-related background, and 46.9% reported a personal or familial history of UTIs. While 54.3% preferred antibiotics for treatment, 42.7% used herbal remedies such as parsley and green tea. Awareness of key risk factors like low water intake (87.9%) and urine retention (90.2%) was high, but knowledge gaps persisted regarding hormonal and behavioral risk factors. Participants with medical education had significantly higher awareness scores (p &lt; 0.001). Most participants perceived CAM as a culturally accepted practice. CAM therapies are widely used and culturally accepted in Jordan for UTI management. However, public education and professional guidance are essential to ensure their safe use.

Atezolizumab is a widely used immune checkpoint inhibitor (ICI) for cancer treatment, and postmarketing testing is important. This study aims to provide a reference for the safe and rational use of drugs in clinical practice by mining and analyzing the adverse event (AE) signals of atezolizumab on the basis of the FDA Adverse Event Reporting System (FAERS). This research extracted AE reports from the second quarter (Q2) of 2016 to Q2 of 2024 from the FAERS. AEs were standardized and classified on the basis of the System Organ Class (SOC) and Preferred Term (PT) from the Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. This study utilized disproportionality analysis (DPA) for signal mining and analysis, including the reporting odds ratio (ROR) method, the Medicines and Healthcare Products Regulatory Agency (MHRA) method, and the Bayesian confidence propagation neural network (BCPNN) method. We obtained a total of 3,124 AE signals and identified 640 PTs and 21 SOCs for atezolizumab. The highest signal intensity was systemic immune activation (n = 15, ROR = 449.20, PRR = 449.07, IC = 8.06), and the most frequently reported AEs were death, pyrexia, infectious pneumonia, anaemia, and febrile neutropenia. The top 100 PTs in terms of signal intensity involved a total of 16 SOCs, including those associated with endocrine disorders; respiratory, thoracic and mediastinal disorders; and renal and urinary disorders. This study revealed that AEs in the endocrine, respiratory and urinary systems need to be monitored in clinical practice.

Hexaconazole (HEX), a triazole fungicide extensively used in agriculture, raises concerns due to its potential nephrotoxicity. This study assessed the dose-dependent effects of HEX on kidney structure and function in Swiss albino male mice. Mice received graded oral doses of HEX for 30 days, followed by evaluation of serum renal markers, oxidative stress parameters, and kidney histopathology. Results revealed significant, dose-dependent increases in serum urea, uric acid, and creatinine levels, indicating impaired renal function. Antioxidant enzyme activities (SOD, catalase, GPx) were decreased and malondialdehyde (MDA) levels elevated in kidney tissue, supporting increased oxidative stress. Histological analysis showed progressive renal injury, from mild tubular changes in low dose groups to marked glomerular atrophy, tubular dilation, extensive vacuolar degeneration, and widespread necrosis at higher doses. These findings demonstrate that HEX induces clear nephrotoxic effects in mice through oxidative stress and disruption of renal architecture. The study underscores the importance of strict regulation and further research on the safe use and management of HEX to protect health and the environment.

Despite the widespread use of medications during pregnancy, ethical and methodological barriers to clinical trials make observational studies necessary for evaluating medication safety in this population. Observational studies are prone to biases that often limit their validity due to the lack of randomization; integrating genetic information through discordant sibling designs, polygenic scores, and Mendelian randomization can address several confounding issues. However, application of these three approaches in perinatal pharmacoepidemiology has been limited. Complementing traditional designs with these genetically informed research designs can tackle common biases and strengthen causal inference. This paper focuses on applying genetically informed research designs to child outcomes in perinatal pharmacoepidemiology by reviewing various methods, discussing their strengths and limitations, and examining their application to date, as well as considerations for implementing them in future research. Such considerations include the availability of genetic data, the complexity of integrating genetic data with existing epidemiological data, and selection of appropriate genetic instruments for analyses. Incorporating causal inference in perinatal pharmacoepidemiology can ultimately contribute to enhancing safe medication use during pregnancy.

Trust at risk: Why public health must lead the use of AI in pandemic preparedness.

A study on user satisfaction with medical devices for the elderly: The case of blood pressure monitors.

Existing and future use cases, and safety and ethical considerations for AI in body image, and eating disorder prevention.

Subchronic 90-days toxicity profile of Salicornia ramosissima extract in rats.

Assessment of regulatory compliance in diagnostic X-ray facilities based on a radiation safety audit in Zanzibar.

Safety evaluation of ursolic acid: Absence of acute oral and reproductive toxicity in a rodent model.

Background: Sodium fluoride is a widely utilized compound in industrial processes and oral health products, impacting biological systems across multiple hierarchical levels, including organs, tissues, cells, and subcellular structures. While its dental benefits are well established, chronic or excessive exposure disrupts enzymatic activity and function, impairs mitochondrial integrity, and perturbs redox balance, leading to apoptosis, inducing autophagy, and activating inflammatory responses. Understanding these mechanisms is critical for accurate toxicological assessment and for the development of safe, evidence-based applications. Objectives: This review critically evaluates sodium fluoride’s impact across multiple biological levels, from subcellular components to tissues and organs, integrating experimental, clinical, and toxicological evidence. It delineates its chemical properties, exposure pathways, and pharmacokinetics—including absorption, distribution, metabolism, and excretion—while highlighting molecular and cellular mechanisms underlying systemic effects. Dose–response dynamics, exposure duration, and cumulative risk frameworks are examined to distinguish therapeutic benefits from potential toxicity. The review addresses ongoing controversies, methodological limitations, and variability in findings, while discussing protective strategies, public health policies, and ethical and environmental considerations. By synthesizing multidisciplinary evidence, it provides a balanced foundation for safe fluoride use and future research priorities. أسفل النموذج Conclusion: This review synthesizes current evidence on sodium fluoride’s effects across molecular, cellular, tissue, organ, and systemic levels. Its biological impact is mediated via complex mechanisms, including enzyme modulation, oxidative stress, mitochondrial function, ion transport, and signaling cascades, with outcomes influenced by concentration, exposure duration, and developmental context. Systemic effects involve calcified tissues, endocrine organs, renal systems, and neural structures, with heightened vulnerability during prenatal and early postnatal stages. Risk assessment requires integration of dose–response data, exposure dynamics, and population variability. Evidence-based mitigation, ethical regulation, and interdisciplinary research are essential to optimize therapeutic benefits while minimizing biological and environmental risks.

This research provides a comprehensive elucidation of the molecular interaction between cefpodoxime (CFP) and bovine serum albumin (BSA) through an integrated approach combining computational docking and a suite of spectroscopic methods. Initial evidence from UV-Vis absorption spectroscopy confirmed a ground-state complex formation between the drug and the protein. Subsequent fluorescence quenching studies established a static quenching mechanism, with a binding constant (Kb) of 3.99 × 104 L·mol-1 determined at 298K, indicating moderate binding affinity. Analysis of the thermodynamic parameters, computed via the Van't Hoff equation, revealed that the binding process is both spontaneous and endothermic. The positive entropy change (ΔS°) identified hydrophobic interactions as the predominant driving force for the complex formation.The binding site was precisely localized to subdomain IIA (Site I) of BSA, a finding consistently supported by two independent lines of evidence: competitive site-marker displacement assays and molecular docking simulations. Collectively, these insights into the binding affinity, forces, and specific location are fundamental for advancing the understanding of CFP's pharmacokinetic profile. This knowledge is critical for predicting its distribution and elimination in vivo, thereby informing its safe clinical use and helping to mitigate potential adverse effects.

This registry-based study aimed to evaluate the long-term survivorship of dual-mobility components (DMCs) compared to conventional components (CCs) in primary total hip arthroplasty (THA), and to assess potential adverse effects, particularly in younger patients (aged < 75 years). Data from 58,314 primary THAs recorded between January 2006 and December 2023 in the French national SOFCOT/RENACOT registry were analyzed, including 25,545 DMCs (46%). The primary outcome was revision for any cause. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare implant survivorship, adjusting for age, sex, primary diagnosis, and fixation method. Among the 25,545 primary THAs performed with a DMC, 284 revisions (1.1%) were recorded. In adjusted Cox regression analysis, DMC use was not significantly associated with an increased risk of revision compared to CCs (hazard ratio 0.83 (95% CI 0.66 to 1.04); p = 0.118). Periprosthetic fracture was the leading cause of revision in the DMC group (98/284, 34.5%), occurring significantly more frequently than in the CC group (77/493, 15.6%; p < 0.001), while dislocation-related revisions were less common with DMCs. Overall, the combined proportion of revisions due to dislocation or fracture was lower in the DMC group (112/284, 39.4%) than in the CC group (254/493, 51.5%). No risk factors for implant failure were identified in multivariable Cox regression analysis. DMCs provide excellent long-term survivorship and effectively reduce the risk of dislocation in primary THA. Although a higher incidence of periprosthetic fractures was observed with DMCs, the overall outcomes support their safe and effective use. Nevertheless, ongoing surveillance remains important to monitor these risks.

A regional framework for the detection and management of ARIA with anti-amyloid therapies in early Alzheimer's disease in Asia.

Genotoxic, mutagenic, and DNA-protective properties of South American plant extracts: mechanisms and bioactive compounds.

Emerging trends in polysaccharide-based smart PEGylated hydrogels for biomedical applications.

Healthbots for conducting clinical screening and remote monitoring with patient mood assessment: A scoping review.