Search Results (23,181)

Understanding antimicrobial resistance (AMR) within a One Health framework requires examining how human–animal–environment interactions shape bacterial populations, and captive wildlife offers a unique context to explore these dynamics. This study aimed to characterise the phenotypic resistance and virulence profiles of Escherichia coli isolated from faecal samples of captive non-domestic felids housed in a wildlife sanctuary in the United Kingdom and evaluate the influence of captive conditions in E. coli traits. A total of 41 faecal samples were collected from 36 animals representing 11 non-domestic felid species, from which it was possible to obtain 108 E. coli isolates identified using IMViC testing. The isolates were characterised regarding their susceptibility to 12 antibiotics by disc diffusion and screened for the phenotypic expression of six virulence factors, including protease, DNase, gelatinase, lecithinase, haemolysins, and biofilm formation. The highest resistance rates were observed for tetracycline (19.4%) and ampicillin (10.2%), while isolates presented complete susceptibility regarding half of the tested antibiotics. Also, 9.3% of the isolates presented a multidrug-resistant profile. Biofilm formation was the only virulence factor expressed by the isolates under study (8.3%). Significant associations were detected between resistance outcomes and levels of human proximity and enclosure type. These findings suggest that captivity-related factors may influence AMR profiles in wild felids and highlight the importance of continued AMR surveillance and appropriate management practices to reduce selective pressures in captive wildlife. Full article

Background/Objectives: Reverse total shoulder arthroplasty (RTSA), a commonly performed procedure in elderly patients with osteoarthritis, is frequently complicated by postoperative infections—primarily caused by Cutibacterium acnes and coagulase-negative staphylococci (CoNS)—which remain a major clinical challenge. While standard antiseptic skin protocols can reduce the bacterial load at the surgical site, they often fail to achieve complete eradication, particularly with C. acnes, a resident species of the shoulder microbiome. Recent evidence indicates that intraoperative povidone–iodine irrigation is effective in significantly decreasing microbial burden; however, a thorough characterization of the virulence factors of the isolated strains remains essential. Methods: A total of 187 clinical strains isolated immediately after RTSA were characterized with respect to their antibiotic resistance profiles and biofilm-forming capacity, and the impact of intraoperative povidone–iodine irrigation on the reduction in bacteria that express these virulence traits was evaluated. Results: Of the 120 C. acnes isolates, 97.67% were susceptible to the tested antimicrobial agents, while only 3.33% exhibited resistance, specifically to clindamycin. In contrast, 53% of CoNS isolates were classified as susceptible, whereas the remaining 47% demonstrated multidrug resistance. Biofilm production was detected in 24% (29/120) of C. acnes and 39% (25/64) of CoNS isolates, with a statistically significant reduction observed after irrigation only for C. acnes. No association was found between biofilm formation and clindamycin resistance in C. acnes, likely due to the low number of resistant isolates. Conversely, among CoNS, a correlation was observed, with the 17.2% of biofilm-producing strains also exhibiting resistance to antimicrobial agents. Conclusions: Notwithstanding the presence of these virulence factors, povidone–iodine irrigation proved effective in substantially reducing the number of bacterial isolates recovered at the surgical site without selecting for strains with enhanced pathogenicity. Notably, the majority of resistant bacteria were detected prior to intraoperative irrigation. This intraoperative procedure may be a key approach to reducing prosthetic joint infections frequently caused by more virulent pathogens, which are unlikely to be selected following this disinfection strategy. Full article

Background: Streptococcus pneumoniae (Spn) is a leading bacterial pathogen responsible for severe invasive diseases, including meningitis, sepsis, and pneumonia. Current pneumococcal vaccines, which are all based on capsular polysaccharide antigens, provide limited protection and are further compromised by post-vaccination serotype replacement. Pneumococcal surface protein A (PspA), a highly conserved virulence factor expressed across diverse serotypes, has emerged as a promising candidate antigen for novel protein-based vaccines. However, progress in this field has been hindered by the absence of standardized in vitro functional antibody assays. Methods: This study established a robust functional antibody detection method for PspA-based protein vaccines by modifying the conventional multiplex opsonophagocytic killing assay (MOPA), originally designed for polysaccharide-based vaccines. Using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) typing, a target strain panel was selected and developed to include representative strains from PspA Family 1-Clade 2 and Family 2-Clades 3 and 4. The MOPA protocol was optimized by extending the phagocytic reaction time to enhance sensitivity. Specificity was confirmed through recombinant PspA competitive inhibition assays. Results: The assay demonstrated high linearity (R² ≥ 0.98) between opsonophagocytic index (OI) and serum dilution, along with acceptable repeatability (CV ≤ 30%) and intermediate precision (CV ≤ 50%). Both preclinical and clinical serum samples exhibited potent bactericidal activity against diverse PspA families, independent of capsule type. Conclusion: This study provided a standardized framework to support the development and regulatory assessment of protein-based pneumococcal vaccines. Full article

Background and Objectives: The purpose of this study was to investigate whether high ethmoid sinus volume (ESV) constitutes a risk factor for the formation of orbital blowout fractures (OBFs) after craniofacial trauma and whether it affects the fracture pattern. Materials and Methods: This retrospective case–control study included patients aged ≥15 years who presented with craniofacial trauma to the emergency department of a Turkish university hospital between 1 October 2022 and 1 September 2023. The predictor variable was the presence of OBF (yes/no). The primary outcome variable was mean ESV, measured on computed tomography using the fully automated 3D Slicer software. Statistical analyses were performed with a significance level set at p < 0.05. Results: The case group consisted of 108 (median age: 41.5 years; 76 males, 70.38%), and the control group consisted of 122 (median age: 38 years; 84 males, 68.85%) subjects. OBFs were more frequent in males (69%), most commonly detected in the orbital floor (68.2%), and were bilateral in two (1.8%) subjects. The mean ESV in the case group (3.91 ± 1.39 cm³) was significantly higher than that in the control group (2.82 ± 0.94 cm³) (p < 0.001). Unlike the cases with medial wall fractures and those with orbital floor fractures, there was no significant difference in mean ESV between the cases with medial wall and orbital floor fractures and the control group (p = 0.562). Conclusions: A large ethmoid sinus not only increases the risk of orbital blowout fracture but also has an impact on the fracture pattern. Based on the data obtained from our study, we demonstrated a significant association between ethmoid sinus volume and the incidence of orbital blowout fracture. Full article

Bovine respiratory disease (BRD) remains one of the most consequential health and economic challenges in U.S. beef production, particularly within integrated systems where microbial, environmental, and management factors intersect. This review synthesizes contemporary epidemiological insights, emphasizing BRD’s multifactorial pathogenesis driven by dynamic host–pathogen–environment interactions involving agents such as Mannheimia haemolytica, Pasteurella multocida, and Mycoplasma bovis, alongside stressors from transportation, weaning, and commingling. BRD imposes annual losses exceeding two billion dollars through diminished feed efficiency, reduced carcass yield, increased treatment costs, and mortality. Despite progress in vaccination, biosecurity, and therapeutic interventions, BRD persists due to diagnostic subjectivity and limitations of traditional control measures. The review underscores emerging innovations, including precision livestock technologies, AI-enabled surveillance, and metabolomic biomarkers as transformative tools for early detection and targeted mitigation, while noting barriers related to cost, data harmonization, and scalability. The rising threat of antimicrobial resistance further highlights the need for stewardship frameworks that balance therapeutic effectiveness and public health priorities. Additionally, the paper analyzes policy and economic considerations, arguing for coordinated efforts among producers, veterinarians, researchers, and regulators. BRD is reframed as a systems-level challenge requiring integrated scientific, operational, and regulatory strategies to enhance resilience and sustainability across U.S. beef production. Full article

Food-borne diseases affect nearly 10% of the global population annually, with Salmonella being a major cause, particularly impacting children, the elderly, and populations in low- and middle-income countries. This study aimed to assess the prevalence, serotype distribution, antibiotic resistance profiles, and genetic determinants of resistance and virulence of Salmonella enterica in humans and poultry in the Nanoro health district. A community-based cross-sectional study involving humans and poultry was conducted in the Nanoro health district. Fresh stool samples (human and poultry cloacal/cecal) were collected, transported under sterile conditions, and processed within two hours using standard bacteriological methods. Phenotypic antibiotic resistance was determined by the Kirby–Bauer disk diffusion method, and whole-genome sequencing (Illumina) identified serotypes, resistance genes, and virulence factors. Logistic regression analyzed associations between Salmonella carriage and host or environmental factors. Salmonella enterica carriage was detected in 8.7% of humans and 7.2% of poultry. Human isolates showed 24% resistance to cephalosporins, while poultry isolates showed 36.8% resistance. Resistance genes, including fosA7, qnrB19, and a cryptic aminoglycoside resistance gene, and virulence genes encoding T3SS-1 and T3SS-2, were detected in both hosts. Logistic regression indicated that residence in Sitaon and Zimidin was associated with ~70% lower odds of carriage (aOR = 0.3), while individuals aged 11–20 and 51–60 years had 2.8-fold higher odds. Carriage was also 60% higher during the rainy season. These findings suggest possible cross-transmission of Salmonella between humans and poultry and the circulation of resistant, potentially virulent strains in the community. Seasonal and age-related variations highlight environmental and behavioral influences on asymptomatic carriage. Integrated One Health surveillance and targeted hygiene interventions are essential to reduce Salmonella transmission and antimicrobial resistance in rural settings. Full article

The significance of gut epithelial cell autoantibodies (GECAs), human leukocyte antigen (HLA) alleles, and other scientifically relevant factors has been largely overlooked, despite their potential importance in the medical management of HIV-infected individuals, in understanding the pathogenesis of AIDS, and in improving epidemiological and diagnostic approaches. This review may be considered as a hypothesis-driven narrative paper mostly considering GECAs and some easily detectable genetic markers. Thus, the aim is to highlight these neglected medical and scientific issues. Addressing them may contribute to a deeper understanding of HIV pathology at both the individual and population levels. Autoantibodies against enterocytes (GECAs) are present in the majority of HIV-positive patients. These intestinal epithelial cells are crucial for nutrient absorption and because of their role as antigen-presenting cells (APCs) within the immune system. Furthermore, the number of CD4-positive lymphocytes depends largely on daily antigenic stimulation rather than on thymic function, which becomes residual or inactive after puberty. The fall of CD4+ lymphocyte counts observed in HIV-infected patients may therefore be exacerbated by enterocyte dysfunction/damage, as indicated by the presence of GECAs. These autoantibodies either cause or reflect damage to these important antigen-presenting cells, which may impair intestinal antigen presentation by their surface HLA proteins to the clonotypic T-cell receptor of lymphocytes. Additionally, the association between specific HLA alleles and a CCR5 variant affects HIV disease progression or transmission and should be considered in both adults and mother–infant pairs. In particular, HLA-B35 and HLA-B57 allelic groups have been implicated in influencing both the transmission and progression of HIV infection. Moreover, several aspects of the natural history of HIV infection remain unresolved and controversial, and these issues warrant urgent clarification. For instance, diagnostic tests are not yet standardised globally, and viral abundance in HIV-infected individuals or AIDS patients’ cells may be relatively low. In summary, the neglected facets of HIV infection demand renewed investigation, particularly now that an HIV diagnosis is no longer the devastating prognosis it once was. The objective of this work is to emphasise additional factors that may influence the course of AIDS, such as enterocyte injury reflected by presence of GECAs. Ultimately, we propose that GECAs may impair enterocytes’ HLA (MHC II)-mediated antigen presentation by enterocytes to CD4+ T lymphocytes (through T-cell receptors), thereby diminishing T-cell proliferation, reducing CD4+ cell numbers, and impairing immune function. Full article

Hemostatic biomaterials are widely used in surgical and trauma settings, yet their influence on early wound healing remains incompletely understood. This in vivo study investigated the effects of cellulose- and gelatin-based hemostatic biomaterials on early wound healing using a murine skin wound model. Oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a porcine gelatin-based matrix (GELA) were left in situ following standardized subcutaneous implantation and compared with sham-treated controls. Tissue responses were analyzed at postoperative days 3 and 7 using histology, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR). Cellulose-based materials persisted as eosinophilic remnants, whereas fibrous matrix structures and enhanced extracellular matrix deposition were observed in the GELA group. Immunohistochemical analysis revealed increased cluster of differentiation 68 (CD68)–positive macrophage presence in the ORC group at day 3 and in the GELA group at day 7, indicating biomaterial-dependent modulation of macrophage involvement during early wound healing. Expression of Kiel 67 (Ki-67), a marker of cellular proliferation, was significantly elevated in the epidermis of the GELA group at day 7, suggesting enhanced proliferative activity during the reparative phase. In contrast, no significant differences were detected in the expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), or cluster of differentiation 14 (CD14) between groups. Overall, none of the investigated biomaterials impaired early wound healing, while the gelatin-based material demonstrated features consistent with enhanced reparative cellular responses without excessive inflammation. Full article

The dynamic characteristics of bridges are not only influenced by structural damage but also by ambient environmental variations. If environmental factors are not incorporated into the detection algorithm, they may lead to false positives or false negatives. In recent years, vibration-based damage detection methods have gained significant attention in structural health monitoring (SHM), particularly for assessing structural integrity under varying temperature conditions. This study introduces a deep-learning framework for identifying damage in composite bridges by utilizing both time-domain and frequency-domain vibration signals while explicitly accounting for temperature effects. Two deep learning models—Convolutional Neural Network (CNN) and Artificial Neural Network (ANN)—were implemented and compared. The effectiveness of the proposed damage identification approach was evaluated using an experimental dataset obtained from a composite bridge structure. Furthermore, statistical evaluation metrics—including accuracy, precision, recall, F1 score, and the ROC curve—were used to compare the damage detection performance of the two deep learning models. The results reveal that the CNN model consistently outperforms the ANN in terms of classification accuracy. Moreover, frequency-domain analysis was shown to be more effective than time-domain analysis for damage classification, and integrating temperature data with vibration signals improved the performance of all model architectures. Full article

Background: Intimate partner violence (IPV) represents a major public health problem in Europe, with significant physical, psychological, and social consequences. Nurses are often the first professionals capable of detecting early signs of IPV, yet they lack validated instruments to assess their clinical competency in detection, evaluation, documentation, and intervention. This study aimed to develop and validate the Intimate Partner Violence Nursing Competency Scale (IPVNCS), aligned with the Nursing Intervention Classification (NIC 6403). Methods: A cross-sectional psychometric study was conducted among registered nurses in the Community of Madrid. A 30-item Likert-type self-administered instrument (1–5 scale) was developed based on NANDA, NIC 6403, and NOC frameworks. A total of 202 nurses participated. Reliability was assessed through Cronbach’s alpha. Construct validity was examined using exploratory factor analysis (EFA) with Promax rotation and confirmatory factor analysis (CFA) using AMOS 26. Ethical approval was obtained (CEU San Pablo, code 843/24/104). Results: After item refinement, 26 items remained across four dimensions: (1) Intervention and Referral, (2) Detection and Assessment, (3) Documentation and Recording-keeping, (4) Psychosocial Support. The instrument showed excellent reliability ($\alpha$ = 0.97). KMO was 0.947 and Bartlett’s test was significant (p < 0.001). CFA demonstrated satisfactory fit: ${\chi }^2$/df = 2.066, RMSEA = 0.073, CFI = 0.92, TLI = 0.91, NFI = 0.86. The final model adequately represented the latent structure. After debugging, its psychometric properties were significantly improved. Four redundant items were eliminated, achieving internal consistency ($\alpha$ = 0.97), a KMO value of 0.947 and a significant Bartlett’s test of sphericity. It showed a better fit, according to ${\chi }^2$/df = (2.066); Parsimony = (720.736); RMR (0.0529; RMSEA (0.073); NFI (0.860); TLI (0.910) and CFI (0.920). The final model provides an adequate representation of the latent structure of the data. This study provides initial evidence of construct validity and internal consistency reliability of the IPVNCS. Conclusions: The IPVNCS is a valid and reliable tool to assess nursing competencies for clinical management of IPV. It supports structured evaluation across four core nursing domains, enabling improved educational planning, clinical decision-making, and quality of care for victims. The scale fills a gap in clinical nursing assessment tools and can support protocol development in emergency, primary care, and hospital settings. Full article

Background: Neurodegeneration and dementia are key factors in Alzheimer’s disease (AD). The deposition of amyloid-ß into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA) are the main clinical parameters of AD. Acute myocardial infarction (AMI) and AD share a comparable pathophysiology. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date. Methods: AD transgenic APP23 mice were analyzed in experimental AMI using the closed-chest model. Results: APP23 mice displayed significantly decreased left ventricular function as detected by FS/MPI (fractional shortening/myocardial performance index) after 24 h and 3 weeks after ligation of the LAD compared to WT controls. No differences have been observed in infarct and scar size. The analysis of cardiac remodeling after 3 weeks showed an altered composition of the collagen tissue of the scar with elevated tight but reduced fine collagen in APP23 mice. Altered scar formation was accompanied by elevated degranulation of platelets following activation of the collagen receptor GPVI. Conclusions: These results suggest that AD patients are at higher risk for cardiac damage after AMI. This implies the need for a personalized therapy of AMI in AD patients. Full article

Background/Objectives: Neuroblastoma cells are phenotypically plastic, transitioning between mesenchymal and adrenergic states. Core functional genes (e.g., YAP1) mark the mesenchymal state, which is linked to unfavorable prognosis. We and others previously demonstrated relapse-specific Hippo-YAP pathway activation in matched primary/relapsed neuroblastomas. Here we explored the role of YAP1 in neuroblastoma aggressiveness and response to therapy. Methods: RT-qPCR and immunoblotting assessed YAP1 expression in neuroblastoma cell lines. RNA-sequencing detected YAP1-dependent gene signatures in Tet-ON SK-N-AS and SH-EP neuroblastoma cell models expressing wildtype YAP1 or constitutively activated YAP1^S127A. Data from cell models were compared with our published YAP1 expression data from neuroblastomas. Efficacy of commonly used chemotherapeutics was comparatively analyzed in the cell models. Results: YAP1 expression showed marked variability across a panel of neuroblastoma cell lines, assessed by mRNA analysis in 10 cell lines and protein analysis in a subset of 9 cell lines. RNA sequencing in constitutively activated YAP1^S127A mutant and wildtype YAP1 models detected 2162 and 1837 significantly differentially expressed genes in the SK-N-AS and SH-EP backgrounds, respectively. Continuously activating YAP1 in SK-N-AS cells upregulated mesenchymal signature genes and mesenchymal-associated transcription factors. Gene expression influenced by YAP1 activity in the cell models significantly overlapped with YAP1-associated genes (e.g., CYR61 and SPRY4) in published tumor data. Functionally, YAP1^S127A expression rendered neuroblastoma cells resistant to chemotherapy. Conclusions: Findings corroborate the idea of a mechanistic role for YAP1 in neuroblastoma adrenergic to mesenchymal reprogramming and therapy resistance. The YAP1-mediated plastic switch towards a mesenchymal expression state in neuroblastoma cells may provide the molecular basis for novel therapeutic avenues. Full article

In recent years, remarkable progress in nanomedicine has been achieved, leading to the development of several nanocarriers which aim to enhance the therapeutic efficacy in cancer treatment. Owing to their high versatility and highly tunable physicochemical properties, alumina (Al₂O₃) and silica (SiO₂) substrates represent promising and innovative nanoplatforms that are widely used in biomedical applications, such as drug-delivery, diagnosis, and biosensing in cancer. In particular, such platforms possess multiple advantageous properties, including mechanical stability, high loading capacity, tunable porosity, excellent biocompatibility, and in vitro and in vivo low toxicity. In this review article, we discuss their emerging role as biosensing platforms and drug delivery systems in oncology. As such, we describe how these substrates enable the incorporation of antibodies against various cancer biomarkers [e.g., cancer antigen 15-3 (CA15-3), serum amyloid A1 (SAA1), epithelial cell adhesion molecule (EpCAM), or human epidermal growth factor receptor 2 (HER2)] for the detection of multiple malignancies. Furthermore, we highlight the development of highly promising alumina- and silica-based platforms for drug delivery (e.g., chemotherapeutics, photosensitizers, or gene delivery agents) in cancer. Ultimately, by providing a comprehensive overview alongside a critical analysis, we demonstrate that such nanostructures represent promising platforms for potential clinical translation in cancer medicine, helping to mitigate the limitations of conventional cancer therapies. Full article

Melanoma was once considered ‘incurable’; however, drug therapy for the condition has dramatically transformed with the advent of immune checkpoint inhibitors and molecular targeted therapies. In this review, we summarize the published literature on melanoma drug therapy, presenting the current landscape of melanoma treatments, and discuss potential future transformations in melanoma therapy. Although the prognosis of advanced-stage melanoma had been extremely poor in the past, new-age immunotherapy has made long-term survival possible. Several immunotherapies and their combinations, as well as personalized vaccines, cell therapies, and intratumoral agents, have been tested with success; however, adverse toxicities have also been detected. Therefore, patient selection and management are critical. Furthermore, new approaches to overcome the limitations of the current treatments are also being developed. To implement these therapies clinically, guideline-recommended treatment algorithms should be followed while optimizing the therapies by considering factors such as presence of BRAF mutations which may lead to treatment resistance, increased disease burden/progression rate, toxicity tolerance, and the presence of brain metastases. In practice, the choice of the initial therapy should depend on the patient, leading to personalized therapy and minimal adverse effects. Full article

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become one of the most serious problems confronting modern healthcare, particularly in intensive care units where patients are highly susceptible, procedures are frequent, and antibiotic exposure is often prolonged. In this review, carbapenem resistance in K. pneumoniae is presented not as a fixed feature of individual bacteria, but as a process that is constantly changing and closely interconnected. We bring together evidence showing how the spread of successful bacterial lineages, the exchange of resistance genes, and gradual genetic adjustment combine to drive both the rapid spread and the long-lasting presence of resistance. A major focus is placed on mobile genetic elements, including commonly encountered plasmid backbones, transposons, and insertion sequences that carry carbapenemase genes such as blaKPC, blaNDM, and blaOXA-48-like. These elements allow resistance genes to move easily between bacteria and across different biological environments. The human gut plays a particularly important role in this process. Its microbial community serves as a largely unseen reservoir where resistance genes can circulate and accumulate well before infection becomes clinically apparent, making prevention and control more difficult. This review also discusses the key biological factors that shape resistance levels, including carbapenemase production, changes in the bacterial cell membrane, and systems that expel antibiotics from the cell, and explains how these features work together. Advances in molecular testing have made it possible to identify resistance more quickly, supporting earlier clinical decisions and infection control measures. Even so, current tests remain limited by narrow targets and may miss low-level carriage, hidden genetic reservoirs, or newly emerging resistance patterns. Finally, we look ahead to approaches that move beyond detection alone, emphasizing the need for integrated surveillance, thoughtful antibiotic use, and coordinated system-wide strategies to lessen the impact of CRKP. Full article