Search Results (6,358)

Pseudomonas aeruginosa poses significant health threats due to its multidrug-resistant profile, particularly affecting immunocompromised individuals. The pathogen’s ability to produce virulence factors and antibiotic-resistant biofilms, orchestrated through quorum-sensing (QS) mechanisms, complicates conventional therapeutic interventions. This review aims to critically assess the potential of anti-QS strategies as alternatives to antibiotics against P. aeruginosa infections. Comprehensive literature searches were conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies addressing QS inhibition strategies published recently. Anti-QS strategies significantly attenuate bacterial virulence by disrupting QS-regulated genes involved in biofilm formation, motility, toxin secretion, and immune evasion. These interventions reduce the selective pressure for resistance and enhance antibiotic efficacy when used in combination therapies. Despite promising outcomes, practical application faces challenges, including specificity of inhibitors, pharmacokinetic limitations, potential cytotoxicity, and bacterial adaptability leading to resistance. Future perspectives should focus on multi-target QS inhibitors, advanced delivery systems, rigorous preclinical validations, and clinical translation frameworks. Addressing current limitations through multidisciplinary research can lead to clinically viable QS-targeted therapies, offering sustainable alternatives to traditional antibiotics and effectively managing antibiotic resistance. Full article

Grapevine (Vitis vinifera L.) cultivation is an important agricultural sector worldwide. Its expansion into new areas, like Kazakhstan, brings significant phytosanitary risks. Viroids, such as grapevine yellow speckle viroid 1 (GYSVd-1) and hop stunt viroid (HSVd), are RNA pathogens that threaten vineyard productivity. They can cause a progressive decline through latent infections. Traditional diagnostic methods are usually targeted and therefore not suitable for thorough surveillance. In contrast, modern high-throughput sequencing (HTS) methods often face challenges due to their high costs and complicated sample preparation, such as ribosomal RNA (rRNA) depletion. This study introduces a simplified diagnostic workflow that overcomes these barriers. We utilized the latest Oxford Nanopore V14 cDNA chemistry, which is designed to prevent internal priming, by substituting a targeted oligo(dT)VN priming strategy to facilitate the sequencing of non-polyadenylated viroids from total RNA extracts, completely bypassing the rRNA depletion step and use of random oligonucleotides for c DNA synthesis. This method effectively detects and identifies both GYSVd-1 and HSVd. This workflow significantly reduces the time, cost, and complexity of HTS-based diagnostics. It provides a powerful and scalable tool for establishing strong genomic surveillance and phytosanitary certification programs, which are essential for supporting the growing viticulture industry in Kazakhstan. Full article

Background: Neurogenic bladder (NB) in children may lead to recurrent urinary tract infections (UTIs), renal deterioration, and a reduced quality of life. Clean intermittent catheterization (CIC) is the standard of care, but in some patients, CIC may be unfeasible due to anatomical, sensory, or compliance issues. Button cystostomy (BC) has emerged as a minimally invasive, bladder-preserving alternative. This study aimed to assess the feasibility, safety, and outcomes in the long-term of BC in pediatric NB patients. Methods: Retrospective analysis was conducted on children with NB who underwent endoscopic BC placement between January 2020 and December 2024 in a tertiary pediatric center. Demographic data, operative time, complications, and follow-up outcomes were collected. All procedures used an endoscopic approach with cystoscopic guidance for safe device placement. Results: Thirty-three patients (25 males; median age 7.96 years) underwent BC placement. Most had spinal dysraphism (63.6%). The mean operative time was 48.5 ± 6 min. During a mean follow-up of 2.1 ± 1.4 years, five patients (15.2%) had febrile UTIs and two had minor leakage. No major complications occurred. Four buttons were removed due to clinical improvement (N = 1), the fashioning of a continent derivation (N = 1) and implantation of a sacral neuromodulator (N = 2); two patients accepted CIC. Satisfaction was reported by 93.9% of families. Conclusions: BC is an effective, minimally invasive alternative for urinary drainage in children with NB, even when compared to continent diversion techniques such as the Mitrofanoff, due to its lower invasiveness, greater feasibility, and lower complication rate. Broader adoption may be warranted, but prospective studies are needed to confirm long-term outcomes. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Objective: This study aimed to describe the perinatal and neonatal outcomes of chronic abruption oligohydramnios sequence in the Kanto region of Japan. Methods: This survey was conducted at 123 perinatal centers affiliated to this area. Data on the experience of managing chronic abruption oligohydramnios sequence between 1 January 2017, and 31 December 2022, were collected and analyzed. Results: Among the 82 cases of chronic abruption oligohydramnios sequence that were included in this study, there were seven miscarriages, five artificial abortions, and 70 deliveries beyond 22 gestational weeks (singleton: 68; twin: 2). In 82 patients, vaginal bleeding was the initial symptom of chronic abruption oligohydramnios sequence (88%). The mean gestational duration at the initial symptom onset was 17.3 ± 5.0 weeks. Of the 68 singleton pregnancies delivered after 22 gestational weeks, the mean gestational duration at delivery was 25.2 ± 2.8 weeks. In patients with chronic abruption oligohydramnios sequence, the mean white blood cell count at diagnosis and mean of the maximum white blood cell count during pregnancy were 11,589 ± 2885 and 15,357 ± 4745/μL, respectively; and the mean C-reactive protein at diagnosis and mean of the maximum C-reactive protein during pregnancy were 1.0 ± 1.2 and 2.0 ± 2.1 mg/L, respectively. Chorioamnionitis was identified in 43 patients (63%). All neonates were admitted to the neonatal intensive care unit. Of the 68 singleton neonates, 5 died immediately after birth. Conclusions: Chronic abruption oligohydramnios sequence is a rare perinatal complication that is possibly associated with infections, such as chorioamnionitis, and linked to adverse perinatal and neonatal outcomes. Full article

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

The association between COVID-19 vaccination and thromboembolic events has garnered significant research attention, particularly with the advent of vaccines based on adenoviral vectors, including AstraZeneca’s and Johnson & Johnson’s vaccines. This review underscores the uncommon occurrence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and vaccine-induced thrombotic thrombocytopenia (VITT) following COVID-19 vaccination. Although these complications are extremely rare compared to the heightened risk of thrombosis from COVID-19 infection, elements like age, biological sex, type of vaccine and underlying health conditions may contribute to their development. In addition, rare renal complications such as acute kidney injury and thrombotic microangiopathy have been documented, broadening the spectrum of potential vaccine-associated thrombotic manifestations. Current guidelines emphasize early detection, individualized risk assessment, and use of anticoagulation therapy to mitigate risks. Despite these events, the overwhelming majority of evidence supports the continued use of COVID-19 vaccines, given their proven efficacy in reducing severe illness and mortality. In addition, recent comparative data confirm that mRNA-based vaccines are associated with a significantly lower risk of serious thrombotic events compared to adenoviral vector platforms. Ongoing research is essential to further refine preventive and therapeutic strategies, particularly for at-risk populations. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

The aim of this retrospective clinical study was to assess surgical duration and surgical and post-operative complications associated with Video-Assisted Thoracoscopic Surgery (VATS) and lung biopsy in horses with severe Equine Pasture Asthma (EPA) and paired control horses. Twelve horses (6 EPA-affected, 6 control) were sex, age and breed matched. Twenty-four thoracic surgeries were performed. Surgery of each matched pair (EPA-affected and healthy) was performed during asthma exacerbation (summer) and remission (winter). Surgical times were shorter with uncomplicated thoracoscopy (85 min) and significantly longer (p < 0.001) when intra-operative complications necessitated conversion to thoracotomy (156 min). The overall surgical time of EPA-affected horses during asthma exacerbation was significantly longer than control horses at any time point, predicted mean difference of 78 min (p < 0.05). When comparing EPA-affected horses to themselves during asthma exacerbation and remission, surgical times were significantly longer (p < 0.01) with a predicted mean difference of 98 min; this effect of seasonality did not occur amongst control horses. Intra-operative surgical complications (6/24) were evenly divided between EPA and control horses, however, only severe EPA horses in exacerbation were noted to have lung hyperinflation. Post-operative complications: fever, colic, hemothorax, pneumothorax, subcutaneous emphysema, surgical site infection, and/or laminitis occurred in 13/24 surgical procedures (54%). No fatalities resulted from these procedures. Full article

Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (M^pro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of M^pro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of M^pro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 M^pro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the M^pro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under M^pro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 M^pro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article

Nosocomial infections caused by ESKAPE pathogens represent a significant burden to global health. These pathogens may exhibit multidrug resistance (MDR) mechanisms, of which mechanisms such as efflux pumps and biofilm formation are gaining significant importance. Multidrug resistance mechanisms in ESKAPE pathogens have led to an increase in the effective costs in health care and a higher risk of mortality in hospitalized patients. These pathogens utilize antimicrobial efflux pump mechanisms and bacterial biofilm-forming capabilities to escape the bactericidal action of antimicrobials. ESKAPE bacteria forming colonies demonstrate increased expression of efflux pump-encoding genes. Efflux pumps not only expel antimicrobial agents but also contribute to biofilm formation by bacteria through (1) transport of molecules and transcription factors involved in biofilm quorum sensing, (2) bacterial fimbriae structure transport for biofilm adhesion to surfaces, and (3) regulation of a transmembrane gradient to survive the difficult conditions of biofilm microenvironments. The synergistic role of these mechanisms complicates treatment outcomes. Given the mechanistic link between biofilms and efflux pumps, therapeutic strategies should focus on targeting anti-biofilm mechanisms alongside efflux pump inactivation with efflux pump inhibitors. This review explores the molecular interplay between efflux pumps and biofilm formation, emphasizing potential therapeutic strategies such as efflux pump inhibitors (EPIs) and biofilm-targeting agents. Full article

Background: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) globally, linked to severe complications such as pelvic inflammatory disease and infertility. In the Brazilian Amazon, socioeconomic vulnerability and the absence of screening policies exacerbate risks, particularly among female sex workers (FSWs). Objective: This study aimed to determine the seroprevalence of anti-C. trachomatis IgG antibodies among FSWs in five municipalities of Pará State, Brazilian Amazon, and identify epidemiological factors associated with infection. Methods: A retrospective cross-sectional study (2005–2007) included 348 FSWs recruited via convenience sampling. Sociodemographic and behavioral data were collected through questionnaires, and blood samples were analyzed by ELISA for anti-C. trachomatis IgG. Statistical analyses included Fisher’s exact tests, odds ratios (ORs), and 95% confidence intervals (CIs), using SPSS 21.0. Results: Overall seroprevalence was 93.9% (327/348; 95% CI: 83.1–90%). Significant associations included a household income of 1–3 minimum wages (98.4%; p = 0.0002), sexual partners from the same region (98.8%; p = 0.0421), and age >42 years (96.3%). Most reported inconsistent condom use (43.7%), multiple monthly partners (54.6%), and illicit drug use (53.4%). Discussion: The extremely high seroprevalence reflects chronic C. trachomatis exposure, driven by socioeconomic deprivation and limited healthcare access. Comparisons with global data underscore the urgent need for screening policies, absent in Brazil for FSWs, and highlight the vulnerability of this population. Conclusions: The findings reveal an alarming burden of C. trachomatis exposure among Amazonian FSWs. Integrated strategies, including routine screening, sexual health education, and inclusion of FSWs in priority health programs, are critical to reduce transmission and associated complications. Full article

Streptococcus pyogenes (GAS) is a leading cause of acute otitis media (AOM) and its complications. This study aimed to evaluate the antimicrobial resistance of all isolated bacterial agents recovered from children with AOM and to perform the emm typing of GAS isolates. Antibiotic susceptibility testing was evaluated according to EUCAST criteria. Phenotyping and genotyping were performed for the macrolide-resistant GAS isolates. All GAS isolates were subjected to emm typing. Among the 103 AOM cases considered, we identified GAS isolates (39.4%), Staphylococcus aureus (26.6%), Haemophilus influenzae (13.8%), Streptococcus pneumoniae (11.7%), Moraxella catarrhalis (7.4%), and Serratia marcescens (1.1%). GAS exhibited 32.4% macrolide resistance and 10.8% clindamycin resistance. The M phenotype and mefE gene (18.9%) were the most common, followed by cMLSB (10.8% with ermB), a combination of mefA and ermB (8.1%), and iMLSB (2.7% with ermA). The most prevalent emm types were emm12 (27.0%), emm1 (21.6%), and emm3 (16.2%). The most common GAS emm types identified among AOM patients in this study are found worldwide and are associated with invasive infections in various countries. This may influence the virulence and invasive potential of these strains. Full article

This study was conducted in Armenia and included 32 pregnant women with TV infection and 30 healthy controls. The vaginal virome includes viruses that infect human cells and unicellular eukaryotes such as Trichomonas vaginalis (TV). Among these are Trichomonas vaginalis viruses (TVVs), double-stranded RNA viruses from the Totiviridae family, and giant DNA viruses that replicate in protozoa. This study investigated the presence of TVVs and giant protozoan viruses in pregnant women with trichomoniasis in Armenia and explored their potential associations with adverse pregnancy outcomes. Vaginal and urethral samples were collected from 32 pregnant women with confirmed TV infection and 30 healthy pregnant controls. TVVs and giant viruses (Marseilleviridae, Mimiviridae, Phycodnaviridae) were detected using qRT-PCR. Viral RNA and DNA were extracted from clinical samples and TV cultures, followed by quantification and gene expression analysis. Selected TVVs were visualized via scanning electron microscopy. All TV-positive women carried at least one TVV strain, with 94% harboring multiple TVV types and TVV4 being the most common. TV infection was significantly associated with preterm birth and premature rupture of membranes (PPROM). Giant viruses were identified in all TV-positive cases but in only 40% of controls. Marseilleviridae gene expression was observed in TV cultures, suggesting possible interactions. These findings highlight a potential role for protozoan viruses in reproductive complications and warrant further investigation. Full article