Search Results (92,893)

Large bone defects resulting from trauma, tumor resection, infection, or degenerative diseases pose a major clinical challenge in orthopedic surgery and regenerative medicine. Despite advances in biomaterials and surgical techniques, successful outcomes are often compromised by poor vascularization, limited osteoinduction, and donor-site morbidity associated with autografts or allografts. However, conventional delivery systems suffer from burst release, rapid clearance, off-target effects, and supraphysiologic dosing, which can lead to undesirable complications such as ectopic ossification and inflammation, with some reports raising concerns about the long-term tumorigenic risk. Heparin, a naturally highly sulfated glycosaminoglycan structurally related to heparan sulfate, has emerged as a particularly attractive candidate for affinity-based biomaterial systems. It naturally binds over 300 growth factors, including bone morphogenetic proteins. By protecting these proteins from enzymatic degradation, enhancing their bioavailability, and mediating receptor clustering, heparin provides both biochemical stability and biofunctional modulation. This review provides a comprehensive overview of heparin-based delivery strategies in bone tissue engineering. We begin by describing the biological functions of heparin in modulating growth factor activity. We then discuss in detail the different heparin-based biomaterials designed to sustain the release of growth factors for bone tissue engineering, including the heparin–polycation coacervate system; heparin-based supramolecules; and heparin-based hydrogels, nanoparticles, and microspheres for sustained release of bone morphogenic proteins and other growth factors for bone tissue engineering. Finally, we assess the clinical and translational relevance of heparin-based systems, identify key challenges, and outline future perspectives, highlighting the potential of these biomaterials for providing safer and more effective therapies for bone regeneration. Full article

Reconstruction of the ear and temporal region presents unique challenges due to the complex anatomy of the lateral skull base and the need to restore both structural integrity and auditory function. Historically managed as separate entities, auricular reconstruction and hearing rehabilitation are increasingly approached in an integrated manner, supported by advances in microsurgical techniques and implantable hearing technologies. This narrative review synthesizes contemporary evidence on microsurgical reconstruction of the ear and temporal region in conjunction with hearing rehabilitation, analyzing a wide range of existing surgical techniques in an integrative manner. Reconstructive techniques discussed include local and regional flaps, free tissue transfer, auricular framework reconstruction using autologous cartilage or alloplastic materials, external auditory canal reconstruction, and subtotal petrosectomy. Hearing rehabilitation options reviewed encompass bone-anchored hearing systems, active and passive transcutaneous devices, middle ear implants, and cochlear implantation. Simultaneous reconstruction and implantation may reduce surgical burden and enable earlier hearing restoration in carefully selected patients, while staged approaches remain advantageous in complex or high-risk scenarios, particularly in the presence of chronic infection or extensive temporal bone surgery. Multidisciplinary collaboration, meticulous preoperative planning, and long-term follow-up are essential to optimize outcomes. Full article

Urinary tract infections (UTIs) are the most frequent infections in hospitalized and outpatient settings, where Escherichia coli is the predominant pathogen. Conventional diagnostic and antimicrobial susceptibility testing (AST) methods are time-consuming, often requiring 48 h, leading to empirical antibiotic therapy and contributing to antimicrobial resistance (AMR). FASTinov^® developed a rapid phenotypic method that enables AST directly from urine samples within two hours using flow cytometry. In this study, 154 inoculated urine samples were analyzed to evaluate the performance of two diagnostic panels: FASTgramneg for Gram-negative bacteria and FASTgrampos for Gram-positive bacteria. Data analysis was performed using bioFAST^® software (version 3.0), providing results in accordance with EUCAST guidelines. The FASTgramneg panel allows detection of resistance mechanisms, including extended-spectrum β-lactamases (ESBLs), and screening of AmpC β-lactamases and carbapenemases; the FASTgrampos panel additionally determines the minimal inhibitory concentration (MIC) of vancomycin for Staphylococcus aureus. Overall agreement with conventional AST methods was 97.5% for Gram-negative bacteria and 95.0% for Gram-positive bacteria. All resistance mechanisms were correctly identified with no false positives. The essential agreement for vancomycin’s MIC was 95.2%, with a BIAS of +14.3%. Reproducibility was 99.5% for FASTgramneg and 95.0% for FASTgrampos. These results demonstrate that the FASTinov^® kit significantly reduces turnaround time while maintaining high accuracy, supporting improved UTI management and antimicrobial stewardship. Full article

Bacterial wilt caused by Ralstonia solanacearum is a major constraint on tomato (Solanum lycopersicum L.) production, yet the molecular basis of quantitative resistance remains poorly understood. In this study, comparative transcriptome profiling was performed on resistant (‘ZM3’) and susceptible (‘ZM86’) tomato inbred lines following pathogen inoculation in roots, stems, and leaves. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify resistance-associated regulatory modules and hub genes. The results revealed distinct gene expression patterns between the two genotypes after infection. Several co-expression modules were significantly associated with resistance or susceptibility traits. Functional enrichment analysis showed that differentially expressed genes were mainly involved in plant hormone signal transduction, plant–pathogen interaction, phenylpropanoid biosynthesis, and cell wall modification. Genes related to ethylene and salicylic acid signaling were strongly induced following infection, whereas brassinosteroid-associated genes showed genotype-dependent expression patterns. Network analysis further identified several hub genes within defense-related modules, including ACO (Solyc04g007980), ERF1 (Solyc09g091950), MAPK9, receptor-like kinase RLK (Solyc07g006770), and a dirigent family gene (Solyc10g008900). Taken together, our results suggest that tomato resistance to Ralstonia solanacearum involves a coordinated defense network integrating hormone-mediated transcriptional regulation and structural reinforcement, and provides candidate genes for breeding bacterial wilt-resistant cultivars. Full article

Anthrax is one of the most significant zoonotic diseases in Albania due to its endemic presence in livestock, the potential for occupational exposure, and human cases. Although the implementation of risk-based livestock immunization, animal movement restrictions, and appropriate carcass disposal, the efficacy of targeted management remains limited in certain outbreaks due to insufficient enforcement of these measures. Their efficacy is specifically diminished by insufficient disinfection, the absence of grazing bans in contaminated pastures, and the absence of designated burial sites for the safe disposal of dead animals. District-level data on animal anthrax control programs were collected and analyzed for the period 2021–2025. In addition, a retrospective analysis of national datasets covering the same period was conducted using data from the national surveillance system, alongside a review of the relevant scientific and grey literature and aggregated program and routine surveillance data. Analysis showed that anthrax affected 149 animals in 97 farms, and the average number of animals per infected farm declined from 1.70 to 1.08, indicating a slight reduction within-farm outbreak. Hotspots for human anthrax were aligned with the animal cases and persisted particularly in the southern districts. The peak of outbreaks was in 2023, primarily driven by cattle (n = 32) and sheep (n = 24). Equine cases appeared only in 2024, with small clusters of 3 cases in both 2024 and 2025. Caprine cases remained consistently low throughout the period. Nevertheless, the number of outbreaks and within-herd cases are decreasing due to more rapid identification and response. Targeted surveillance on animal outbreaks provides critical insights into disease spread and links among affected farms in Albania. Therefore, One Health genomic surveillance and antibiotic susceptibility testing of Bacillus anthracis isolates are essential for understanding its epidemiology, transmission routes, and for tracing the sources of infection across humans, animals, and the environment. Full article

Background: Oral gene delivery vectors, such as those derived from attenuated Salmonella strains, have shown great promise in oral vaccine development against various human diseases. Human cytomegalovirus (CMV) is a herpesvirus capable of affecting the global population and establishing lifelong infection. Generation of an anti-CMV vaccine is a major public health priority. Methods: This study reports the development of a novel weakened Salmonella strain, S713, and the effects of this strain as an oral vaccine candidate against murine cytomegalovirus (MCMV) infection in mice. Results: The weakened Salmonella strain S713 was attenuated in killing mice in vivo by >500,000 fold compared to a clinical strain, following intragastric instillation in animals. Mice intragastrically immunized with S713 that produced MCMV M24 protein exhibited elevated anti-MCMV mucosal IgA and serum IgG titers and enhanced anti-MCMV T cell responses. Moreover, immunization with the generated vaccine in MCMV-challenged mice not only suppressed viral replication in lungs, spleens, livers, and salivary glands but also increased animal survival. Conclusions: These findings demonstrate strong and effective anti-MCMV immune responses induced by the generated M24-expressing vaccine. Furthermore, our results reveal the promising capability of weakened strain S713 expressing different CMV proteins to act as oral vaccines against CMV infections and diseases. Full article

Cassava brown streak disease (CBSD), caused by cassava brown streak virus (CBSV; Ipomovirus brunusmanihotis) and Ugandan cassava brown streak virus (UCBSV; Ipomovirus manihotis) (family Potyviridae, genus Ipomovirus), is increasingly becoming a threat to cassava production in several parts of Africa, especially in Eastern, Central and Southern Africa. In Kenya, the disease continues to wreak havoc on cassava production leading to a significant reduction in crop yields and economic losses of up to USD 1 billion. Variation in virus populations make the control of CBSD challenging as virus genomic variation can affect the accuracy of diagnostic tests, lead to resistance breaking isolates and jeopardize strategies of breeding for resistance. CBSV and UCBSV populations obtained from cassava fields in Kenya were characterized. In total, 44 new complete sequences of CBSV and UCBSV were assembled and 40 sequences successfully submitted to GenBank. Single Nucleotide Polymorphism (SNP) analysis revealed that the cylindrical inclusion protein (CI) is the most stable region across the genome of CBSV and UCBSV. In contrast, protein 1 (PI) and the coat protein (CP) were the most hypervariable regions. Phylogenetic analysis showed three major geographical groupings for both UCBSV and CBSV isolates, suggesting a continued spread of the viruses through human-mediated movement of infected planting materials. The data obtained in this study can support the development of disease management strategies through improved molecular diagnostic tests and targets for breeding for resistance against CBSD. Full article

(1) Brucellosis is a zoonotic infection that remains a significant public health concern in endemic regions. This study aimed to determine the seroprevalence of brucellosis in a tertiary care hospital, analyze associated risk factors, and evaluate the diagnostic performance of commonly used serological tests. (2) The study was based on the serological test results of 24,545 samples collected between 2020 and 2023. Rose Bengal, standard tube agglutination, and Brucellacapt tests were used for the diagnosis of brucellosis. Data were analyzed according to age, sex, clinical department, and seasonal distribution using SPSS version 25.0. (3) Overall, 367 cases (1.5%) tested positive. When the 367 seropositive cases were evaluated by year, the annual distribution showed a declining trend, decreasing from 2.5% in 2020 to 1.2% in 2023. Among the positive cases, 57.8% were female, and 36% were aged between 41 and 64 years. The infectious diseases department had the highest positivity rate (37.1%). Brucellacapt showed the highest positivity rate (90.2%), followed by Rose Bengal (76.2%). The highest monthly positivity rate was observed in October (11.4%), and seasonally in autumn (31.3%). (4) The Brucellacapt test has demonstrated high sensitivity and serves as a valuable supplementary diagnostic tool in the evaluation of brucellosis. However, its low specificity underscores the necessity for careful interpretation of positive results and supports its use in conjunction with other serological tests to enhance diagnostic accuracy. Considering seasonal and departmental variations, a combined testing approach may improve overall diagnostic accuracy. Full article

Background: Burn injuries have both physical and psychological impacts on patients. Factors such as personal beliefs, prior experiences, and geographic, economic, or cultural barriers, as well as fear of hospitals, can contribute to delays in seeking specialized care. When combined with inadequate first aid or the inappropriate use of pharmaceutical or traditional remedies, these delays may worsen burn severity, prolong healing, and negatively affect quality of life. From a clinical perspective, delayed presentation following burn injury has been linked to burn wound progression, which increases the risk of local infection, hypertrophic scarring and prolonged functional impairment. Methods: This analytical cross-sectional study was conducted at the Clinical Emergency Hospital of Bucharest between January and September 2025. The primary objective was to characterize adult burn patients presenting more than 24 h after injury (Group A) and to describe self-reported psychosocial/behavioral characteristics and explore unadjusted patterns among delayed presenters. Data were collected from medical records and a structured questionnaire administered to delayed presenters. A secondary descriptive comparison was performed with patients presenting within 24 h (Group B) to provide contextual reference. Results: The majority of patients were male (62.2%) and of working age (18–65 years, 82.4%). Thermal burns from domestic accidents were most common (58.8%), with scalds predominating. Second-degree burns were the most frequent (60.5%), primarily affecting the upper and lower limbs. Mean total body surface area (TBSA) was low (2.86 ± 1.91%), although higher values were observed in radiation burns and closed-space accidents. More than half of the patients did not receive any first aid, while the remainder used various pharmaceutical or natural products, some of which were inappropriate for burn treatment. The main reasons for delaying specialized care were the expectation that injuries would heal spontaneously, negligence, and fear of the hospital. In contrast, escalating pain, edema, and family insistence were the primary motivators for seeking professional medical attention. Delayed presentation was associated with older burn lesions, higher burn severity and an increased likelihood of hospitalization or refusal of recommended admission. Conclusions: Burn injuries predominantly affect working-age males and most frequently arise from domestic thermal accidents. Delayed presentation and inadequate first aid are common and influenced by behavioral, social, and demographic factors. Targeted public education, improved first aid practices, and timely healthcare-seeking are essential to reduce burn severity and improve patient outcomes. Full article

Background: Hepatitis B virus infection has been linked to liver cancer and may influence metastasis in other malignancies, but its role in gastric cancer liver metastasis (GCLM) is unclear. Methods: We retrospectively analyzed 776 gastric cancer patients with HBV testing. HBV infection was defined as HBsAg+ (chronic HBV, CHB) or HBsAg− with HBcAb/HBeAb+ (occult HBV, OHB). Among the 776 patients, 300 (38.6%) were classified as HBV+. The association between HBV infection and GCLM was evaluated, and propensity score matching (PSM) was performed to adjust for age and gender. Furthermore, the impact of HBV infection on overall survival (OS) was analyzed. Results: GCLM occurred in 19.5% of patients. HBV+ patients had a higher GCLM prevalence than HBV− patients (25.3% vs. 15.8%; p = 0.001), persisting after PSM (25.3% vs. 15.3%; p = 0.002). HBV infection was an independent risk factor for GCLM (OR = 2.563, p < 0.001). Both OHB and CHB groups showed significantly higher GCLM rates than HBV− patients in univariate and multivariate analyses. However, OS did not differ between groups (p = 0.737). Conclusion: HBV infection significantly increases the risk of liver metastasis in gastric cancer. Enhanced surveillance for liver metastasis is warranted in these patients. Full article

Background: Hepatitis B virus (HBV) is an infection proven to increase the risk of gastric cancer, especially among hepatitis B virus surface antigen (HBsAg) seropositive patients. However, the route through which HBV injures gastric mucosa and its mechanism of gastric carcinogenesis are still under investigation. Aims: The present study aimed to observe and evaluate associations between HBV infection with Helicobacter pylori, atrophic gastritis, and some other high-risk events for gastric cancer development. Methods: A retrospective cross-sectional study recruited participants undergoing a health check-up between 2018 and 2020 in the West China Hospital of Sichuan University. Participants were stratified into three statuses, including Group A (non-HBV infection), Group B (resolved HBV infection), and Group C (chronic HBsAg carriers or active HBV infection). Additionally, Groups A and B were categorized as HBsAg-seronegative, whereas Group C was defined as HBsAg-seropositive. High-risk events of gastric cancer included a history of gastric ulcer, Helicobacter pylori infection, serological atrophic gastritis (serum pepsinogens), hypergastrinemia (serum gastrin-17), and endoscopic findings of atrophic gastritis, gastric polyps, and gastric ulcer. Associations of HBV infection status or HBsAg seropositivity with Helicobacter pylori infection, atrophic gastritis and other high-risk events of gastric cancer were analyzed. Results: A total of 21,505 eligible observations were included, with Group C accounting for 6.1%. In Group C, the prevalence of gastric ulcer (p = 0.002) and very-high serum gastrin-17 level (p = 0.002) was significantly greater than in Group A. In multivariate analysis, both Helicobacter pylori infection (aOR = 2.79, 95% CI 2.44–3.21) and HBsAg seropositivity (aOR = 1.28, 95% CI 1.02–1.59) were significant risk factors for hypergastrinemia. No interaction was found between Helicobacter pylori co-infection risks and Group B (aOR = 1.10, 95% CI 0.84–1.43) or Group C (aOR = 1.40, 95% CI 0.66–2.95). Helicobacter pylori infection was identified as an independent risk factor for atrophic gastritis (aOR = 1.85, 95% CI 1.44–2.39). However, HBsAg seropositivity did not show a similar association with atrophic gastritis (aOR = 1.15, 95% CI 0.75–1.74). Moreover, HBV co-infection did not exert a synergistic effect on the risk of atrophic gastritis in individuals with Helicobacter pylori (aOR = 1.09, 95% CI 0.54–2.22). Additionally, multivariate analyses did not identify significant associations between HBV infection statuses and gastric polyps or ulcers. Conclusions: HBsAg seropositivity was not associated with increased risk of atrophic gastritis, gastric polyps or ulcers, or Helicobacter pylori infection, with the exception of hypergastrinemia. Additionally, HBV co-infection did not exert a synergistic effect on increasing the risk of atrophic gastritis in patients with Helicobacter pylori. Collectively, these findings suggest that the mechanism underlying the increased risk of gastric cancer in individuals with HBV may not be predominantly mediated via Helicobacter pylori infection and atrophic gastritis. Theories regarding HBV-induced genotoxicity or confounding effects warrant further investigation. Full article

Cytomegalovirus (CMV) remains a major opportunistic pathogen in individuals with HIV. The aim of this study was to investigate the seroprevalence and reactivation rates of CMV among HIV-positive individuals. A total of 300 people with HIV presenting to the Istanbul Faculty of Medicine were enrolled. Serological assessments were performed using enzyme-linked immunosorbent assay (ELISA), while molecular analyses were conducted through PCR-based methods. Sociodemographic and clinical characteristics of the patients were also evaluated. Of the participants, 90% were male, with an age range of 18–76 years. Serological testing demonstrated CMV IgG positivity in 292 patients (97.3%) and CMV IgM positivity in 11 patients (4.07%). CMV DNA was detected in 91 patients (30.3%) by molecular assays, with viral loads ranging from <150 to 2,404,678 copies/mL. CMV DNA positivity was significantly more frequent in older patients (p < 0.05) and was associated with lower CD4+ T lymphocyte counts. CMV disease was identified in 50 patients (16.7%), with organ involvement (64%) representing the most common clinical manifestation. CMV seropositivity is remarkably high in HIV-positive individuals, and reactivation rates are increased, particularly in older patients and those with advanced immunosuppression. These findings underscore the clinical relevance of routine CMV surveillance in the management of HIV infection. Full article

Respiratory syncytial virus (RSV), a member of the genus Orthopneumovirus, is an etiological agent in infant lower respiratory tract infections (LRTIs) producing substantial global morbidity. Here, secretoglobin (Scgb1a1)-derived progenitors play a primary role in triggering innate, inflammatory, and cell state transitions in response to RSV LRTIs. Whether RSV activation of innate signaling in this epithelial sentinel population leads to chronic airway disease is unknown. To understand the role of innate signaling in Scgb1a1-derived progenitors, a model of RSV post-viral disease (PVLD) was developed and studied in the presence or absence of RelA conditional knockout (CKO). Single-cell RNA sequencing (scRNA-seq) studies showed that RSV-PVLD induced a transition of atypical, differentiation-intermediate, alveolar type 2 (aAT2) cells characterized by tumor protein 63 (TRP63), aquaporin 3 (AQP3), and Itgβ4 expression, as well as changes in PDGFRβ mesenchyme. A single-cell trajectory analysis and lineage-tracing experiments using Scgb1a1 CreER^TM X mTmG mice demonstrated that the Scgb1a1+ populations were precursors to the aAT2 population. Mechanistically, we found that the formation of the aAT2 population was prevented by RelA CKO. A differential gene expression analysis revealed that RSV-PVLD coordinately upregulates nuclear receptor subfamily 1 group D (Nr1d1/2), clock and basic helix-loop-helix ARNT-like 1 (Bmal) genes both in the aAT2 cell and in its Pdgfrα+ mesenchymal niche in a RelA-dependent manner. A systematic analysis of intercellular epithelial–mesenchymal communication in the scRNA-seq data showed that the clock-dysregulated epithelial–mesenchymal niche produces aberrant ANGPTL4 expression. ANGPTL4 upregulation was confirmed by the measurement of both its mRNA and protein. Moreover, ANGPTL4 is biologically active in the BALF of RSV-PVLD mice, inhibiting lipoprotein lipase activity. We conclude that RSV-PVLD is mediated, at least in part, by RelA signaling in Scgb1a1-derived epithelial progenitors, dysregulating ANGPTL4 signaling in an epithelial–mesenchymal niche, resulting in persistence of atypical alveolar epithelial cells with dysregulated of clock gene expression. Full article

The high incidence of Candida albicans infections and the limited efficacy of current antifungal therapies highlight the need for new antifungal agents. In this study, we present a bio-based hybridization strategy aimed at enhancing the antifungal activity of natural product scaffolds, with a particular focus on trans-ferulic acid. A library of twenty-nine hybrid molecules was rationally generated by grafting naturally occurring lipophilic moieties onto either the phenolic or carboxylic acid functions of ferulic acid. The antifungal activity of these molecules was then assessed against C. albicans. While the parent natural compounds exhibited weak activity (MIC > 500 µM), several hybrid derivatives (ATF19, ATF20, and MB22) demonstrated enhanced potency, with MIC values of <50 µM. Esters of the carboxylic acid or phenol group were essential for activity, with the most potent effects observed for short linear or mildly branched lipophilic chains. These active compounds exerted a multifaceted anti-virulence effect, including mitochondrial membrane depolarization, inhibition of hyphal morphogenesis, alterations in cell wall composition, and strong suppression of biofilm formation. Additionally, lead compounds showed no detectable cytotoxicity in human macrophages and intestinal epithelial cells and significantly improved host survival in a Caenorhabditis elegans model of C. albicans infection. Overall, the ferulic acid, citronellol, and sinapic hybrid molecules emerged as promising lead compounds for the development of antifungals against C. albicans. Full article

Based on the follow-up of patients who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, several reports of people who re-tested positive have been described. This may result from viral reactivation, true reinfection, superinfection, or an initial infection by more than one virus (multiple infection). These scenarios can only be correctly distinguished through viral quasispecies analysis. Herein, 26 cancer patients under extended follow-up for SARS-CoV-2 infection were submitted to multiple longitudinal analyses through nucleic acid isolation, PCR amplification and high-throughput sequencing. SARS-CoV-2 classification and the definition of cases as persistent or repeated infections were based on phylogenetic reconstruction. Supported by their viral complete genomes and intrahost quasispecies over time, the different scenarios were identified. Nine confirmed and 12 plausible persistence cases were identified. Virus evolution dynamics in the intrahost population from patients with persistent infection was shown for the first time. Regarding reinfection, three confirmed and two plausible cases were identified, including one case of multiple infection. Altogether, this is the first study that analyzes the plethora of SARS-CoV-2 within-host minor variants and describes reinfections, multiple infections and viral evolution across time in cancer patients, contributing to the understanding of SARS-CoV-2’s within-host population dynamics in the natural history of COVID-19. Full article