Search Results (8,052)

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Antimicrobial resistance (AMR) is a growing global health threat, with wild birds increasingly recognized as potential reservoirs of resistant pathogens and as sentinels of environmental AMR. This study investigated the occurrence and AMR profiles of Gram-negative bacteria isolated from wild birds that died at the Wildlife Rescue Center in Vanzago, Lombardy, in 2024. Cloacal swabs were collected from 112 birds representing various ecological categories. A total of 157 Gram-negative bacteria were isolated and identified, including clinically relevant genera and species, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Salmonella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Antimicrobial susceptibility testing revealed resistance to first-line and critically important antimicrobials, including those exclusively authorized for human use. Notably, a phenotype compatible with Extended-Spectrum Beta-Lactamase (ESBL) production was detected in four out of ten (40%) K. pneumoniae isolates. In addition, 20 out of the 157 (12.7%) isolated bacteria phenotypically exhibited a resistance profile indicative of AmpC beta-lactamase (AmpC) production, including Enterobacter spp. and P. aeruginosa. Resistance patterns were particularly interesting in birds with carnivorous, scavenging, or migratory-associated behaviors. These findings highlight the role of wild birds in the ecology and dissemination of antimicrobial-resistant bacteria (ARB) and highlight the need for wildlife-based AMR monitoring programs as part of a One Health approach. Full article

The perianal skin is a unique “skin–gut” boundary that serves as a critical hotspot for the exchange and evolution of antibiotic resistance genes (ARGs). However, its role in the dissemination of antimicrobial resistance (AMR) has often been underestimated. To characterize the resistance patterns in the perianal skin environment of patients with perianal diseases and to investigate the drivers of AMR in this niche, a total of 51 bacterial isolates were selected from a historical strain bank containing isolates originally collected from patients with perianal diseases. All the isolates originated from the skin site and were subjected to antimicrobial susceptibility testing, whole-genome sequencing, and co-occurrence network analysis. The analysis revealed a highly structured resistance pattern, dominated by two distinct modules: one representing a classic Staphylococcal resistance platform centered around mecA and the bla operon, and a broad-spectrum multidrug resistance module in Gram-negative bacteria centered around tet(A) and predominantly carried by IncFIB and other IncF family plasmids. Further analysis pinpointed IncFIB-type plasmids as potent vehicles driving the efficient dissemination of the latter resistance module. Moreover, numerous unexplained resistance phenotypes were observed in a subset of isolates, indicating the potential presence of emerging and uncharacterized AMR threats. These findings establish the perianal skin as a complex reservoir of multidrug resistance genes and a hub for mobile genetic element exchange, highlighting the necessity of enhanced surveillance and targeted interventions in this clinically important ecological niche. Full article

(1) Background: Monomorphic intestinal epitheliotropic T-cell lymphoma (MEITL) is a very rare subtype of lymphoma, being involved in less than 5% of lymphomas of the digestive tract. Accurate diagnosis is extremely challenging due to the lack of specific clinical symptoms and the low specificity of the diagnostic approaches. (2) Methods: We present the case of a patient admitted to the Neurology Clinic of the Emergency Clinical Hospital of Galati, Romania, with progressive cranial nerve impairment. (3) Results: Analyzing clinical and paraclinical data and corroborating the previous known diagnosis of MEITL, the positive diagnosis was that of meningitis with atypical lymphocytes with MEITL as starting point. The cytology of CSF was the basis for the diagnostic confirmation. (4) Conclusions: The present case is a rare situation of secondary dissemination of MEITL. We were not able to identify a similar report in the available literature that associated urothelial carcinoma with leptomeningeal MEITL-sourced neoplastic lesions. Full article

Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control and in lowering death rates at both individual and population levels. Although diagnostic methods have improved sufficiently in recent decades, TB can still present with ambiguous laboratory and imaging features. This ambiguity can lead to diagnostic pitfalls and potentially disastrous outcomes due to delayed diagnosis. In this article, we present a case of TB that was difficult to diagnose. The disease had invaded the mediastinum, right atrium, right coronary artery, and inferior vena cava (IVC), resulting in Budd–Chiari syndrome. This rare presentation created clinical, laboratory, and radiological confusion, resulting in a diagnostic dilemma that ultimately led to open cardiac surgery. The patient initially presented with progressive shortness of breath on exertion and fatigue, which suggested possible heart disease. This suspicion was reinforced by computed tomography (CT) imaging, which showed infiltrative mass lesions predominantly in the right side of the heart, invading the right coronary artery and IVC, with imaging features mimicking angiosarcoma. Although laboratory findings revealed an exudative effusion with lymphocyte predominance and elevated adenosine deaminase (ADA), the Gram stain was negative for bacteria, and an acid-fast bacilli (AFB) smear was also negative. These findings contributed to diagnostic uncertainty and delayed the confirmation of TB. Open surgery with excisional biopsy and histopathological analysis ultimately confirmed TB. We conclude that TB should not be ruled out solely based on negative Mycobacterium bacteria in pericardial effusion or AFB smear. TB can mimic aggressive tumors such as angiosarcoma or lymphoma with invasion of the surrounding tissues and blood vessels. Awareness of the clinical presentation, imaging findings, and potential diagnostic pitfalls of TB is essential, especially in endemic regions. Full article

Achieving food security for a growing population under a changing climate is a key concern in Senegal, where agriculture employs 77% of the workforce with a majority of small farmers who rely on the production of crops for their subsistence and for income generation. Moreover, due to the underproductive soils and variable rainfall, Senegal depends on imports to fulfil 70% of its food requirements. In this research, we considered four crops that are crucial for Senegalese agriculture: millet, sorghum, peanuts and rice. We used crop simulation models to explore existing yield gaps and optimal agronomic practices. Improving the N fertilizer management in sorghum and millet resulted in 40–100% increases in grain yields. Improved N symbiotic fixation in peanuts resulted in yield increases of 20–100% with highest impact in wetter locations. Optimizing irrigation management and N fertilizer use resulted in 20–40% gains. The best N fertilizer strategy for sorghum and millet included applying low rates at sowing and in early development stages and adjusting a third application, considering the expected rainfall. Peanut yields of the variety 73-33 were higher than Fleur-11 in all locations, and irrigation showed no clear economic advantage. The best N fertilizer management for rainfed rice included applying 30 kg N/ha at sowing, 25 days after sowing (DAS) and 45 DAS. The best combination of sowing dates for a possible double rice crop depended on irrigation costs, with a first crop planted in January or March and a second crop planted in July. Our work confirmed results obtained in field research experiments and identified management practices for increasing productivity and reducing yield variability. Those crop management practices can be implemented in pilot experiments to further validate the results and to disseminate best management practices for farmers in Senegal. Full article

During the transition of culture-featured district planning from static conservation to innovation-driven models, existing research remains constrained by mechanistic paradigms, reducing districts to functional containers and neglecting human perceptual interactions and meaning-production mechanisms. This study explores and quantifies the generative mechanisms of spatial communicability and cultural dissemination efficacy within human-centered frameworks. Grounded in humanistic urbanism, we analyze Harbin Central Street as a case study integrating historical heritage with contemporary vitality, developing a tripartite communicability assessment framework comprising perceptual experience, infrastructure utility, and behavioral dynamics. Machine learning-based threshold analysis reveals that spatial encoding elements govern communicability through significant nonlinear mechanisms. The conclusion shows synergies between street view-quantified greenery visibility and pedestrian accessibility establish critical human-centered design thresholds. Spatial data analysis integrating physiologically sensed emotional experiences and topologically analyzed spatial morphology resolves metric fragmentation while examining spatial encoding’s impact on interaction efficacy. This research provides data-driven decision support for sustainable urban renewal and enhanced cultural dissemination, advancing heritage sustainability. Full article

Background: Various predisposing factors contribute to the emergence and dissemination of the multidrug-resistant (MDR) phenotype in Escherichia coli and Klebsiella pneumoniae. Understanding these factors is crucial for guiding appropriate antimicrobial therapy and infection control strategies. This study investigated the predisposing factors contributing to the MDR characteristics of E. coli and K. pneumoniae isolated in a community hospital in northeastern Thailand. Methods: This case–control study utilized retrospective data from bacterial culture, as well as demographic, clinical, and antibiotic susceptibility records collected during 5 years (January 2016–December 2020). E. coli and K. pneumoniae isolates were analyzed from various clinical samples, including blood, urine, pus, sputum, and other body fluids. Data were analyzed using descriptive statistics and univariate logistic regression. Results: In total, 660 clinical isolates were analyzed (421 E. coli and 239 K. pneumoniae). Blood was the most common source of the detection of E. coli (63.0%) and sputum was the most common source of K. pneumoniae (51.0%). The median ages of patients were 67 and 63 years for E. coli and K. pneumoniae, respectively. E. coli cases were significantly associated with prior antibiotic use (OR = 1.79, 95% CI: 1.17–2.74 p = 0.008). MDR was observed in 50.1% of E. coli and 29.7% of K. pneumoniae (p < 0.001). E. coli compared to K. pneumoniae had lower resistance to third-gen cephalosporins (64.9% versus 95.8%) and carbapenems (8.0% versus 6.9%). ICU admission was the only factor significantly associated with MDR E. coli (OR = 2.40, 95% CI: 1.11–5.20 p = 0.026). No significant differences were observed in gender, age, or comorbidities between MDR cases. Antibiotic usage patterns also differed, with E. coli more likely to receive third-gen cephalosporins compared to carbapenems (OR = 3.02, 95% CI:1.18–7.74 p = 0.021). Conclusions: The use of third-generation cephalosporin may drive MDR E. coli more than K. pneumoniae. Prior antibiotic exposure was linked to E. coli bloodstream infections, while MDR E. coli showed greater clinical severity. These findings highlighted the need for improved antibiotic stewardship in rural hospitals. Full article

Mpox has become a significant health concern since the global outbreak that began in 2022. The aim of this study is to present the epidemiological situation of Mpox in Romania during 2022–2023 and to describe a severe case of Mpox in a patient who survived despite multiple co-pathologies. Forty-seven confirmed cases were reported at the national level, all in men, in 2022. The median age was 33 years. Twenty-six cases involved men who have sex with men (MSM), and twenty-three tested positive for HIV. We also describe a severe case involving a 34-year-old bisexual male with newly diagnosed AIDS who developed severe Mpox with persistent necrotic skin lesions, respiratory involvement, and multiple opportunistic infections: tuberculosis, pneumocystis pneumonia, syphilis, and oral candidiasis. The patient presented with fever, night sweats, weight loss, and dyspnea, with a single ulcerative facial lesion that later disseminated. Mpox infection was confirmed through PCR from skin lesion, serum, saliva, urine, rectal, nasal, and pharyngeal swab samples, with high viral loads persisting despite prolonged Tecovirimat therapy. The patient developed immune reconstitution inflammatory syndrome following the initiation of antiretroviral therapy. This case emphasizes the challenges of treating Mpox in immunocompromised patients. Full article

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article

Promoting energy efficiency in the Italian production sector is significantly hampered by the lack of knowledge, the scarcity and the limited distribution of tools for supporting energy audits in small and medium-sized enterprises (SMEs) in a wide range of Italian economic sectors (industry, tertiary sector, transport). The Advanced Tool for ENErgy Audit for SMEs, ATENEA4SME, is intended to help SMEs promote energy-efficiency projects, supports energy audits and self-evaluation of energy consumption. The tool uses an original mathematical model that takes into account the results of questionnaires and a multi-criteria analysis to generate recommendations for energy efficiency investments. This article will give a thorough explanation of the tool, emphasizing and outlining the sections as well as the procedures to get the ultimate summary of the energy usage of the enterprises under investigation and the potential for energy saving. From a technological and financial perspective, the tool helps to remove obstacles to the development of energy-efficiency measures. In this article, the IT and methodological structure of the tool will therefore be extensively described, and its operation for the context of SMEs will be illustrated, with application cases. Ample space will be allocated to the dissemination campaign and the replicability of the tool for all economic sectors of the industrial and tertiary sectors. Full article

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its rapid nosocomial dissemination, limited therapeutic options, and elevated mortality rates. This study aimed to characterize the epidemiology, carbapenemase profiles, and antimicrobial susceptibility patterns of CRKP isolates, as well as the clinical features and outcomes observed in infected or colonized patients. Materials and Methods: We conducted a retrospective analysis of clinical and microbiological data from patients with CRKP infections or colonization admitted between January 2023 and January 2024. Descriptive statistics were used to assess prevalence, resistance patterns, and patient outcomes. Two binary logistic regression models were applied to identify independent predictors of sepsis and in-hospital mortality. Results: Among 89 CRKP isolates, 45 underwent carbapenemase typing. More than half were metallo-β-lactamase (MBL) producers, with 44.4% co-harbouring NDM and OXA-48-like enzymes. Surgical intervention was associated with a significantly lower risk of sepsis (p < 0.01) and in-hospital mortality (p = 0.045), whereas intensive care unit (ICU) stay was a strong predictor of both outcomes. ICU admission conferred a 10-fold higher risk of sepsis (95%Cl 2.4–41.0) and a 40.8-fold higher risk of in-hospital death (95% Cl 3.5–473.3). Limitations: This single-center retrospective study included a limited number of isolates in certain groups. Additionally, cefiderocol (FDC) susceptibility was assessed by disk diffusion rather than by the broth microdilution method. Conclusions: Our study underscores the increasing prevalence of metallo-beta-lactamase-producing CRKP, particularly strains harbouring dual carbapenemases. Timely recognition of high-risk patients, combined with the implementation of targeted infection control measures and the integration of novel therapeutic options, is crucial to optimize clinical management and reduce mortality associated with CRKP. Full article

Bone is the most frequent site of distant metastasis in advanced prostate cancer (PCa), contributing substantially to patient morbidity and mortality. Hypoxia, a defining feature of the solid tumour microenvironment, plays a pivotal role in driving bone-tropic progression by promoting epithelial-to-mesenchymal transition (EMT), cancer stemness, extracellular matrix (ECM) remodelling, and activation of key signalling pathways such as Wingless/Integrated (Wnt) Wnt/β-catenin and PI3K/Akt. Hypoxia also enhances the secretion of extracellular vesicles (EVs), enriched with pro-metastatic cargos, and upregulates bone-homing molecules including CXCR4, integrins, and PIM kinases, fostering pre-metastatic niche formation and skeletal colonisation. In this review, we analysed current evidence on how hypoxia orchestrates PCa dissemination to bone, focusing on the molecular crosstalk between HIF signalling, Wnt activation, EV-mediated communication, and cellular plasticity. We further explore therapeutic strategies targeting hypoxia-related pathways, such as HIF inhibitors, hypoxia-activated prodrugs, and Wnt antagonists, with an emphasis on overcoming therapy resistance in castration-resistant PCa (CRPC). By examining the mechanistic underpinnings of hypoxia-driven bone metastasis, we highlight promising translational avenues for improving patient outcomes in advanced PCa. Full article

Recent years have seen frequent heavy rainfall events in Japan, often linked to Baiu fronts and typhoons. These events are exacerbated by global warming, leading to an increased frequency and intensity. As floods represent a serious threat to sustainable urban development and community resilience, this study contributes to sustainability-focused risk reduction through integrated analysis. This study focuses on the 2 June 2023 heavy rain disaster in Toyohashi City, Japan, which caused extensive damage due to flooding from the Yagyu and Umeda Rivers. Using numerical models, this study accurately reproduces flooding patterns, revealing that high tides amplified the inundation area by 1.5 times at the Yagyu River. A resident questionnaire conducted in collaboration with Toyohashi City identifies key trends in evacuation behavior and disaster information usage. Traditional media such as TV remain dominant, but younger generations leverage electronic devices for disaster updates. These insights emphasize the need for targeted information dissemination and enhanced disaster preparedness strategies, including online materials and flexible training programs. The methods and findings presented in this study can inform local and regional governments in building adaptive disaster management policies, which contribute to a more sustainable society. Full article

With the increasing application of digital interactive installations in museums, their role in enhancing audience engagement and cultural dissemination effectiveness has become prominent. However, ensuring the sustained use of these technologies remains challenging. Based on distributed cognition and perceived value theories, this study investigates key factors influencing users’ continuous usage of digital interactive installations using the Capital Museum in Beijing as a case study. A theoretical model was constructed and empirically validated through Bayesian Structural Equation Modeling (Bayesian-SEM) with 352 valid samples. The findings reveal that perceived ease of use plays a critical direct predictive role in continuous usage intention. Environmental factors and peer interaction indirectly influence user behavior through learner engagement, while user satisfaction serves as a core mediator between perceived ease of use and continuous usage intention. Notably, perceived usefulness and entertainment showed no direct effects, indicating that convenience and social experience outweigh functional benefits in this context. These findings emphasize the importance of optimizing interface design, fostering collaborative environments, and enhancing user satisfaction to promote sustained participation. This study provides practical insights for aligning digital innovation with audience needs in museums, thereby supporting the sustainable integration of technology in cultural heritage education and preservation. Full article