Search

Purpose: Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks). Materials and Methods: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers. Results: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CDIIb, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants. Conclusions: Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress. [ABSTRACT FROM AUTHOR]

It is crucial to precisely strike the bacterially infected area and avoid damaging healthy tissue in bacterial infection treatment. Herein, we report an acidity-triggered aggregation antibacterial nanoplatform based on biodegradable mesoporous organic silica nanoparticles (MON NPs). The surface of MON NPs modified with polydopamine (PDA) encapsulated ciprofloxacin (CIP) and methylene blue (MB) and was then further grafted with glycol chitosan to obtain MB/CIP@MON-PDA-GCS NPs (MCMPG NPs). In the bacterial infection environment with acidic characteristics, glycol chitosan (GCS) becomes positively charged. Consequently, the positively charged acidity-triggered GCS enables MCMPG NPs to accumulate on the negatively charged bacterial surfaces in the infected area and not in healthy tissue. The targeted method allows for the precise release of CIP and MB, ensuring the spatial accuracy of photodynamic therapy (PDT) and photothermal therapy (PTT) for effective bacteria-specific treatment. [ABSTRACT FROM AUTHOR]

Conventional bactericides struggle with biofilm barriers and inefficient deposition on hydrophobic leaves, resulting in undesirable control of plant bacterial diseases. To overcome these challenges, an innovative ferrocene‐based small‐molecule (FccA8R) is conceived, featuring biofilm disruption capabilities. Further optimizing FccA8R with seven‐membered oligosaccharide‐involved host–guest supramolecular strategy creates two kinds of biocompatible multifunctional supramolecular nanospheres (FccA8R@β‐CD and FccA8R@HP‐β‐CD). This manipulation efficiently eradicates mature biofilm barriers while enhancing droplet retention on hydrophobic leaves. At a concentration of 56.64 µg mL−1, the two materials remove Xanthomonas‐biofilms by 76.32–76.83%, notably surpassing that of single FccA8R (57.96%). Their versatility extends to the enhanced inhibition of bacterial motility, extracellular enzymes secretion, and exopolysaccharides production, all reducing the bacterial virulence. In vivo pot experiments, FccA8R@β‐CD and FccA8R@HP‐β‐CD demonstrate workable control efficacies of 48.91–52.03% against rice bacterial blight at 200 µg mL−1, superior to the commercial thiodiazole‐copper‐20%SC (36.42%) and FccA8R‐0.1%Tween (39.54%). Furthermore, these supramolecular assemblies disclose broad‐spectrum bactericidal efficacy (71.45–73.19%) against kiwifruit canker, significantly higher than thiodiazole‐copper‐20%SC (43.05%) and FccA8R‐0.1%Tween (57.24%). Besides, supramolecular bactericides are safe for plants and non‐target organisms like zebrafish and earthworms. Briefly, this research builds a key foundation for creating green bactericides from small‐molecule conception to eco‐friendly supramolecular assemblies, realizing the prevention of bacterial diseases and environmental safety. [ABSTRACT FROM AUTHOR]

Piezocatalytic therapy has aroused considerable attention in the treatment of bacterial infection due to its noninvasive and deep tissue penetration capabilities. The catalytic efficiency, however, is significantly constrained by the insufficient piezoresponse of sonosensitizers at low‐intensity ultrasound (LIU) accompanied poor separation efficiency of charges, resulting in unsatisfactory sterilization. To address the dilemma, a piezocatalytic bio‐heterojunction (P‐bioHJ) consisting of BiOI and few‐layered Mxene is constructed for rapid antibacterial. The engineered P‐bioHJ not merely possesses a relatively narrow‐bandgap for responding to the sonoluminescence emitted by the sonocavitation effect, but rather induces the interfacial polarization and the generation of oxygen vacancies to facilitate the effective separation of carriers, leading to a burst of radicals for rapid sterilization. Transcriptomic analysis reveals that P‐bioHJ instigates sterilization by interfering with bacterial electron transport chain, disrupting both metabolism and energy synthesis. In vitro experiments indicate excellent cytocompatibility of P‐bioHJ. Furthermore, in vivo assays demonstrate that P‐bioHJ exhibits outstanding antimicrobial properties in a cutaneous infection model with LIU, and promotes angiogenesis and osteogenesis in an infectious bone defect model by decorating with naringin. As envisaged, this work offers valuable insight to augment piezocatalytic therapy by harnessing sonocavitation effect, advancing the remediation of infected tissue regeneration. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria are commonly found in food, water, and soil, posing significant public health challenges globally. Therefore, early, rapid, and highly sensitive strategies for monitoring the bacterial proliferation are crucial for ensuring public health, medical diagnosis, and food safety. Compared to traditional techniques, microfluidic platforms provide powerful detective tools characterized by high integration, high throughput, ease of operation, low reagent consumption, and high sensitivity. Driven by substantial commercial demand, research and development in microfluidic‐based rapid detection methods and technologies has progressed significantly derived by the interdisciplinary integration of multiple disciplines. In this review, progress in clinical detection of pathogenic bacteria with microfluidic biosensors, including microfluidic devices for point‐of‐care (POC) testing, is summarized. Strategies for pathogenic bacteria detection, containing their advantages and disadvantages are discussed in detail. Advanced platforms for capturing and detecting pathogenic bacteria, such as microchannels, microarrays, digital microfluidics (DMF) and paper‐based platforms, are highlighted. The accomplishments and shortcomings of these microfluidic devices are also summarized. Additionally, case studies of biosensor‑based microfluidic devices used for detecting diseases caused by bacterial imbalances are listed. Finally, possible research perspectives for further development in highly effective biosensor‑based microfluidics for clinical detection of pathogenic bacteria are proposed. [ABSTRACT FROM AUTHOR]

Infection is one of the leading causes of death in patients with hematologic cancers. Hematologic cancer patients with compromised immune systems are already susceptible to infections, which come on even more rapidly and are difficult to control after they develop neutrophil deficiencies from high-dose chemotherapy. After patients have developed an infection, the determination of the type of infection becomes a priority for clinicians. In this review, we summarize the biomarkers currently used for the prediction of infections in patients with hematologic cancers; procalcitonin, CD64, cytokines, and CD14 et al. can be used to determine bacterial infections, and (1-3)-β-D-glucan and galactomannan et al. can be used as a determination of fungal infections. We have also focused on the use of metagenomic next-generation sequencing in infections in patients with hematologic cancers, which has excellent clinical value in infection prediction and can detect microorganisms that cannot be detected by conventional testing methods such as blood cultures. Of course, we also focused on infection biomarkers that are not yet used in blood cancer patients but could be used as a future research direction, e.g., human neutrophil lipocalin, serum amyloid A, and heparin-binding protein et al. Finally, clinicians need to combine multiple infection biomarkers, the patient's clinical condition, local susceptibility to the type of infection, and many other factors to make a determination of the type of infection. [ABSTRACT FROM AUTHOR]

Choline kinase alpha (ChoKα) is a therapeutic target being developed for a variety of diseases, from cancer to rheumatoid arthritis and from parasites to bacterial infections. Nevertheless, the therapeutic potential of this drug target seems not exhausted and may end up as a possible solution for a larger variety of conditions. Here we present our working model for how ChoKα could play a role in obesity and for how drugs being developed as therapeutics for other diseases using ChoKα as a target, could be repurposed as prophylactic treatments for obesity. We also present preliminary observations in support of our model. [ABSTRACT FROM AUTHOR]

Bacterial pathogens pose a major risk to human health, leading to tens of millions of deaths annually and significant global economic losses. While bacterial infections are typically treated with antibiotic regimens, there has been a rapid emergence of antimicrobial resistant (AMR) bacterial strains due to antibiotic overuse. Because of this, treatment of infections with traditional antimicrobials has become increasingly difficult, necessitating the development of innovative approaches for deeply understanding pathogen function. To combat issues presented by broad- spectrum antibiotics, the idea of narrow-spectrum antibiotics has been previously proposed and explored. Rather than interrupting universal bacterial cellular processes, narrow-spectrum antibiotics work by targeting specific functions or essential genes in certain species or subgroups of bacteria. Here, we generate a collection of genome-scale metabolic network reconstructions (GENREs) of pathogens through an automated computational pipeline. We used these GENREs to identify subgroups of pathogens that share unique metabolic phenotypes and determined that pathogen physiological niche plays a role in the development of unique metabolic function. For example, we identified several unique metabolic phenotypes specific to stomach pathogens. We identified essential genes unique to stomach pathogens in silico and a corresponding inhibitory compound for a uniquely essential gene. We then validated our in silico predictions with an in vitro microbial growth assay. We demonstrated that the inhibition of a uniquely essential gene, thyX, inhibited growth of stomach-specific pathogens exclusively, indicating possible physiological location-specific targeting. This pioneering computational approach could lead to the identification of unique metabolic signatures to inform future targeted, physiological location-specific, antimicrobial therapies, reducing the need for broad-spectrum antibiotics. The emergence of resistance to traditional antimicrobials increases the need to develop innovative approaches to understanding pathogen function. This study uses a computational data-driven approach to drug target discovery by identifying metabolic signatures of diverse pathogens conserved within body sites. In vitro validation shows that such site-targeted antimicrobials can effectively inhibit stomach-specific pathogens. [ABSTRACT FROM AUTHOR]

Since the discovery of antibiotics, they have served as a potent weapon against bacterial infections; however, natural evolution has allowed bacteria to adapt and develop coping mechanisms, ultimately leading to the concerning escalation of multidrug resistance. Bacterial persisters are a subpopulation that can survive briefly under high concentrations of antibiotic treatment and resume growth after lethal stress. Importantly, bacterial persisters are thought to be a significant cause of ineffective antibiotic therapy and recurrent infections in clinical practice and are thought to contribute to the development of antibiotic resistance. Therefore, it is essential to elucidate the molecular mechanisms of persister formation and to develop precise medical strategies to combat persistent infections. However, there are many difficulties in studying persisters due to their small proportion in the microbiota and their non-heritable nature. In this review, we discuss the similarities and differences of antibiotic resistance, tolerance, persistence, and viable but non-culturable cells, summarize the molecular mechanisms that affect the formation of persisters, and outline the emerging technologies in the study of persisters. [ABSTRACT FROM AUTHOR]

Background: Decompensated cirrhosis (DC) is prone to recurrent episodes of decompensation following the initial event. This study aimed to identify the risk factors for subsequent decompensation and assess their impact on the outcomes of patients hospitalized for DC. Methods: Patients with DC were divided into two groups based on the occurrence of new decompensated events during hospitalization. Logistic regression analysis was employed to identify risk factors for new decompensation. The Cox proportional hazards model was used to evaluate the relationship between new decompensation and short-term mortality risk in these patients. Results: The study cohort consisted of 339 patients with DC, with a median age of 57 years. During hospitalization, 83 patients (24.5%) experienced new decompensated events, with bacterial infections (BIs) being the most common (n = 46, 13.6%). Multivariate analysis revealed that the Model for End-Stage Liver Disease (MELD) score at admission (OR = 1.06, 95% CI: 1.02–1.11, P = 0.005) was the sole risk factor for new decompensation during hospitalization. Patients who experienced new decompensation had significantly higher 28-day (28.9% vs. 7.0%, P < 0.001) and 90-day (33.7% vs. 15.2%, P < 0.001) transplant-free mortality compared to those who did not. After adjusting for white cell count, C-reactive protein, and MELD score, new decompensation during hospitalization was identified as an independent risk factor for 28-day and 90-day mortality (HR = 2.63, 95% CI: 1.42–4.87, P = 0.002 and HR = 1.73, 95% CI: 1.04–2.88, P = 0.033, respectively). Conclusions: Patients with high MELD scores are susceptible to new decompensation during hospitalization, and the occurrence of new decompensation adversely affects short-term mortality in patients with DC. [ABSTRACT FROM AUTHOR]

Background Prompt differentiation of viral from bacterial infections in febrile children is pivotal in reducing antibiotic overuse. Myxovirus resistance protein A (MxA) is a promising viral biomarker. Methods We evaluated the accuracy of a point-of-care (POC) measurement for blood MxA level compared to the reference enzyme immunoassay in 228 febrile children aged between 4 weeks and 16 years, enrolled primarily at the emergency department (ED). Furthermore, we analyzed the ability of MxA to differentiate viral from bacterial infections. Results The mean difference between POC and reference MxA level was −76 µg/L (95% limits of agreement from −409 to 257 µg/L). Using a cutoff of 200 µg/L, POC results were uniform with the reference assay in 199 (87.3%) children. In ED-collected samples, the median POC MxA level was 571 (interquartile range [IQR], 240–955) µg/L in children with viral infections, 555 (IQR, 103–889) µg/L in children with viral-bacterial coinfections, and 25 (IQR, 25–54) µg/L in children with bacterial infections (P <.001). MxA cutoff of 101 µg/L differentiated between viral and bacterial infections with 92% sensitivity and 91% specificity. Conclusions POC MxA measurement demonstrated acceptable analytical accuracy compared to the reference method, and good diagnostic accuracy as a biomarker for viral infections. [ABSTRACT FROM AUTHOR]

Background The role of gasdermin D (GSDMD) in bloodstream infection (BSI) diagnosis is unknown. Methods Serum GSDMD levels were measured in patients with BSI. Endothelial cells and peripheral blood mononuclear cells were isolated and infected with bacteria/fungi, and intracellular/extracellular GSDMD concentrations were measured. An animal model was established to investigate the association between serum GSDMD levels and BSI incidence or progression. Results Receiver operating characteristic curve analysis indicated that GSDMD could be a potential early diagnostic biomarker for BSI (area under the curve [AUC],.9885). Combining GSDMD with procalcitonin improved the differential diagnosis of gram-positive and gram-negative bacteria (AUC, 0.6699; 66.15% specificity) and early diagnosis of gram-positive bacteria (98.46% sensitivity), while procalcitonin was not significantly elevated. The combined GSDMD and (1-3)-β-D glucan test (G test) had higher sensitivity (AUC, 0.7174) for differential diagnosis of bacterial and fungal infections and early detection of fungal infections (98.44% sensitivity). In vitro and in vivo experiments confirmed that GSDMD levels increased significantly within 2 hours, peaked at 16 hours, and exhibited a time-dependent upward trend. Conclusions Serum GSDMD, alone or combined with other biomarkers, has potential for early diagnosis and differential diagnosis of BSI caused by various pathogens. This finding offers a new strategy for early detection and treatment of BSI. [ABSTRACT FROM AUTHOR]

[Display omitted] Persistent inflammation and bacterial infection commonly occur during the wound healing process, necessitating urgent development of effective strategies for treating drug-resistant bacterial infections. In this study, bismuth vanadate (BiVO 4) was successfully synthesized as an antibacterial agent that promotes wound healing. Through In vitro antibacterial experiments, it was observed that the prepared BiVO 4 exhibited excellent performance in catalyzing H 2 O 2 to produce hydroxyl radicals (OH) at a lower concentration (0.2 mg mL−1), resulting in significant antibacterial effects against Gram-negative Extended-Spectrum β-Lactamases-Producing Escherichia coli (ESBL- E. coli) strains. Furthermore, biosafety tests, cell scratch experiments, and ESBL- E. coli infected wound rat model experiments demonstrated high biocompatibility of BiVO 4 with a cell survival rate exceeding 85 %. Additionally, BiVO 4 promoted the production of vascular endothelial growth factors and fibroblasts migration while contributing to collagen production, effectively facilitating immune reconstruction at the wound site. By integrating peroxidase (POD)-like under acidic conditions (pH 4) and catalase (CAT)-like catalytic activities at under neutral conditions (pH 7), BiVO 4 exhibited the ability to activate free radical sterilization and accelerate wound healing by activating O 2. Therefore, our findings provide evidence for a dual enzyme regulatory mechanism involving antibacterial properties and promotion of wound tissue reconstruction for potential application in both antibacterial treatment and wound healing. [ABSTRACT FROM AUTHOR]

Background: Innate immune deficiencies can impair both cellular and humoral immune responses. In contrast, other immune functions may appear normal, leading to increased susceptibility to specific pathogens, such as severe viral infections or Mendelian Susceptibility to Mycobacterial Disease (MSMD). Studying these deficiencies is essential for understanding the pathophysiology of these infectious diseases. Main body: While primary immunodeficiencies (PIDs) generally cause vulnerability to multiple infections, innate immunodeficiencies increase susceptibility to specific pathogens, despite normal immune responses to others. Patients with these deficiencies show normal immunoglobulins and lymphocyte subpopulations, complicating diagnosis. This review highlights genetic susceptibility to mycobacteria, pneumococci, herpes simplex virus, and candidiasis, emphasizing recognizing this subset of PIDs. Conclusion: This review highlights the diverse spectrum of genetic mutations contributing to defects in innate and intrinsic immunity, including Mendelian susceptibility to mycobacterial disease (MSMD), chronic mucocutaneous candidiasis, and predispositions to invasive bacterial and viral infections. Identifying key mutations in pathprovideh such as TLR3, IFN signaling, and IL-17A/F immunity provides valuable insights into the pathogenesis of these conditions. Our findings underscore the need for early genetic diagnosis and targeted interventions, particularly in regions with high undiagnosed cases, to reduce the morbidity and mortality associated with defects in innate and intrinsic immunity. [ABSTRACT FROM AUTHOR]

Recent advancements in hyperspectral imaging (HSI) for early disease detection have shown promising results, yet there is a lack of validated high-resolution (spatial and spectral) HSI data representing the responses of plants at different stages of leaf disease progression. To address these gaps, we used bacterial leaf spot (Xanthomonas perforans) of tomato as a model system. Hyperspectral images of tomato leaves, validated against in planta pathogen populations for seven consecutive days, were analyzed to reveal differences between infected and healthy leaves. Machine learning models were trained using leaf-level full spectra data, leaf-level Vegetation index (VI) data, and pixel-level full spectra data at four disease progression stages. The results suggest that HSI can detect disease on tomato leaves at pre-symptomatic stages and differentiate bacterial disease spots from abiotic leaf spots. Using VI data as features for machine learning improved overall classification performance by 26–37% compared to the direct use of raw data. Critical wavelength bands and VIs varied across disease progression stages, suggesting that pre-symptomatic disease detection relied more on changes in leaf water content (1400 nm) and plant defense hormone‐mediated responses (750 nm) rather than changes in leaf pigments or internal structure (800–900 nm), which may become more crucial during symptomatic stages. In conclusion, this study provides valuable insights into the dynamics of bacterial spot disease, revealing the potential benefits of leaf structure segmentation and VI group pattern analysis in HSI studies for the early detection of leaf diseases. [ABSTRACT FROM AUTHOR]

The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and de novo cancer. The association between IFN-γ production and outcomes was analyzed as "low" immune responses (<15 IU/mL) and as a continuous variable to explore alternative thresholds. There were no significant differences in the occurrence of overall infection according to the QTF-Monitor at any monitoring point. Regarding secondary outcomes, KTRs with a low response at week 2 experienced a higher incidence of bacterial infection (50.8% versus 24.4%; P -value = 0.006). Low response at month 1 was also associated with opportunistic infection (31.6% versus 14.3%; P -value = 0.033). The discriminative capacity of IFN-γ levels was poor (areas under the ROC curve: 0.677 and 0.659, respectively). No differences were observed for the remaining points or post-transplant cancer. In conclusion, the QTF-Monitor may have a role to predict bacterial and opportunistic infection in KTRs when performed early after transplantation. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (TB) is a contagious bacterial infection caused by Mycobacterium tuberculosis that primarily affects the lungs. Despite advances in treatment, TB remains a major public health challenge, particularly in developing countries. This retrospective cohort study aimed to identify factors that influence the time to relapse in patients with pulmonary tuberculosis. Methods: All smear-positive pulmonary tuberculosis patients (1548 patients) whose data were recorded in the tuberculosis registration system of Golestan University of Medical Sciences and Health Services from March 2014 to March 2019, and followed up until February 2021. To analyze the data, we applied LASSO, MCP, and SCAD penalized Cox models. Results: Based on the AIC and BIC criteria, the MCP penalized model was better than the LASSO and SCAD penalized models. The variables of age at diagnosis (> 35 vs. ≤ 35, HR = 2.77), marital status (married vs. single, HR = 8.49), chronic renal failure (Yes vs. No, HR = 5.36), and pre-treatment smear test results (+ 1 vs. 1-9Basil, HR = 0.65 and + 2 vs. 1-9Basil, HR = 0.96) influenced time to relapse according to the MCP penalized Cox regression model. Conclusions: Health care systems should focus on identification of factors that influence time to relapse and developing interventions to reduce relapse rates. [ABSTRACT FROM AUTHOR]

A self‐assembled "caging" strategy is presented for the safe delivery of potent cationic antimicrobials that suffer from non‐specific toxicity for the effective treatment of in vivo systemic bacterial infection. The key development here is a new block copolymer consisting of a poly(ethylene glycol) (PEG) stealth block and an anionic and lipase‐degradable block of poly(ɛ‐caprolactone) (PCL) and phosphonic acid‐bearing methacrylate copolymer, synthesized by hybrid copolymerization of methacrylate and cyclic esters. The anionic blocks electrostatically interact with cationic antimicrobials to form neutrally charged polyion complexes with the PEG blocks on the surface. The PCL component imparts the nanocomplex with biodegradability by bacterial secretory lipase. In the proof‐of‐concept study, cationic polyimidazolium that shows excellent antibacterial activity but severe toxicity is packaged by the block copolymer into nanocomplexes, which are stable in complex environments of high salt and protein concentrations and released the antimicrobials upon degradation of the copolymer by bacteria‐secreted lipase. The "caging" formulation of polyimidazolium eliminated its toxicity and led to highly effective bactericidal performance comparable to free polyimidazolium. This caging strategy does not require sophisticated chemical modification of cationic antimicrobials, offering a broadly applicable formulation strategy to overcome their common toxicity issue that has become a primary translational barrier. [ABSTRACT FROM AUTHOR]

Summary: Scabies is the most common neglected tropical disease with cutaneous manifestations, disproportionately affecting socially disadvantaged populations living in overcrowded settings.Scabies infestation is characterised by a generalised intractable pruritus, and is often complicated by secondary bacterial infection, which can lead to a range of complications.Scabies is a clinical diagnosis and requires an adequate degree of suspicion. The use of dermoscopy may improve diagnostic accuracy.In Australia, the first‐line treatment recommended for scabies is topical permethrin 5% cream, applied to the whole body and repeated in one week. Oral ivermectin is subsidised by the Pharmaceutical Benefits Scheme with streamlined authority for patients who have completed and failed treatment with topical therapy, have a contraindication to topical treatment or have crusted scabies.Early identification and prompt initiation of treatment is key to minimise the disease burden of scabies. [ABSTRACT FROM AUTHOR]

Peri-implantitis, a complex condition that can lead to dental implant failure, is characterized by inflammatory destruction resulting from immune dysregulation. Oral microbial dysbiosis and foreign body stimulation are the main factors contributing to such dysregulation, impairing immune cell function and triggering an inflammatory response. Immune dysregulation plays a critical role in the pathophysiology of peri-implantitis, impacting the balance of T cell subsets, the production of inflammatory factors, and immune-related molecular signaling pathways. Understanding the relationship between immune dysregulation and peri-implantitis is crucial for developing targeted strategies for clinical diagnosis and individualized treatment planning. This review explores the similarities and differences in the immune microenvironment of oral bacterial infections and foreign body rejection, analyzes the relevant molecular signaling pathways, and identifies new key targets for developing innovative immunotherapeutic drugs and effective and personalized treatment modalities for peri-implantitis. Additionally, it addresses the challenges and potential directions for translating immunotherapy into clinical practice for peri-implantitis, offering insights that bridge the gaps in current literature and pave the way for future research. [ABSTRACT FROM AUTHOR]

This work focuses on combating bacterial infections in bone tissue using metal elements embedded in bioactive glass. While there is an urgent need for alternative methods with a shrinking number of effective treatment options untouched by antimicrobial resistance, it is crucial to first understand the mechanisms of pathogenesis, persistence, and bacterial resistance in skeletal infection, and then develop effective counterstrategies and innovative alternatives. This review considers the role of antimicrobial metal ions, their mechanism of action, and their incorporation into bioactive glass formulations as these materials can serve as delivery platforms with the least possible complexities. Furthermore, the bacterial infection risk in bone is also examined with specific attention to antibiotic resistance and biofilm formation. This review sheds light on the most promising materials as novel antibacterial agents by presenting a wide range of possible bioactive glass formulations equipped with potential antibacterial ions and in vitro/ in vivo insights, and it also reinforces the importance of continuing studies to develop multi‐faceted antibacterial bioactive glasses. [ABSTRACT FROM AUTHOR]

Chronic wounds and prosthetic joint infections are difficult to treat and are associated with a high burden of disease and economic cost. The rise of antibiotic resistance and the understanding of biofilm formation has inflamed an already challenging situation. Bacteriophage therapy has been used throughout the last century to treat bacterial infections. However, in the last 10 years, there has been a resurgence in phage therapy as a novel innovative treatment for nonhealing wounds. This mini systemic review assesses relevant clinical studies, case series and trials over 5 years associated with safety, treatment and success rates of phage therapy concerning nonhealing and prosthetic joint infections. A search of PubMed, Web of Science, Cochrane and Clinical Trials.gov databases resulted in 3151 studies, 27 met the criteria, and a total of 152 bacterial infections were treated from 130 individuals. Most common pathogen isolated in wounds was P. aeruginosa, and S. aureus was mostly associated with prosthetic joint infections. Treatment modalities differed across studies, adverse effects were limited, and success rate was deemed to be 91%. [ABSTRACT FROM AUTHOR]

Background: African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection. Methods: We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled. Results: Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls. Conclusions: We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection. Trial registration: ISRCTN49726849 (registered on 27th October 2017). [ABSTRACT FROM AUTHOR]

Introduction: Syphilis is a systemic bacterial infection caused by the spirochete Treponema pallidum. Head and neck mucosal manifestations of syphilis can be observed in each and all of primary, secondary and tertiary syphilis, especially in the secondary one. Therefore, oropharynx is an unusual localization of syphilitic lesions, mainly represented by ulcerous lesions, tissue hypertrophy, mucosal patches and cancer-like lesions. Serology is routinely considered the gold standard for the screening and diagnosis of syphilis. However, direct detection is routinely used during polymerase chain reaction (PCR) of oropharyngeal tissue and suspicious cervical lymphadenopathies. Methods: PRISMA 2020 guidelines were applied to make a systematic literature review with the aim to make an overview of clinical manifestations and diagnostic tools of oropharyngeal syphilitic infection. A computerized MEDLINE search was performed using the PubMed, Web of Science and Cochrane databases. Results: The intended analysis was based on 38 papers, including a total of 55 cases. The main localization of oropharyngeal infection was the tonsil (71%), followed by lateral and posterior wall of oropharynx (16%). Ulcerous lesions were the most frequently encountered lesions in the primary syphilis (56%) and secondary syphilis (36%), whereas gumma's lesions were encountered in the tertiary syphilis (57%). Diagnosis based on serological assays was used in combination with non-treponemal methods to determine disease activity (80% cases). Conclusions: Oropharyngeal syphilis has historically been referred to as the "great imitator" due to its highly variable manifestations, which can resemble malignancies. Physicians have to recognize oropharyngeal luetic features early, in order to set up an effective diagnostic and therapeutic work-up. [ABSTRACT FROM AUTHOR]

The Black Sea basin has a strategic geographic location bridging Asia and Europe and depends on traditional livestock practices for their local economies. Anthrax, a zoonotic bacterial disease caused by Bacillus anthracis, poses a significant global threat impacting public health, food security, pastoralist communities, and national economies. The disease is endemic or sporadic in the Black Sea basin, however, the study of its distribution has seldom been addressed, despite its burden and the presence of historical B. anthracis burial sites in the region. The viability of B. anthracis in a particular region is going to be influenced by multiple environmental factors, such as soil composition, climate, vegetation, and host abundance. For characterizing the potential distribution of B. anthracis in the Black Sea basin and assessing the potential for anthrax outbreaks, we applied an ecological niche modelling framework using the Maxent algorithm. This machine-learning algorithm models species distributions based on presence data and background information from a specified calibration region. We analyzed multiple variable combinations and proposed a novel approach for interpreting in-risk anthrax areas. Our findings underscored the importance of host abundance to the anthrax dynamics in the region. We identified anthrax-suitable areas spanning central and eastern Türkiye, Armenia, southern Georgia, southern Russia, Bulgaria, southern and eastern Romania, Hungary, Moldova, and southern Ukraine, which align with findings from previous global and regional studies on the potential suitability of anthrax. The insights gained from our research may help to develop targeted interventions, such as awareness and educational campaigns about anthrax, supervision of anthrax-infected carcasses disposal, and the promotion of livestock vaccination in high-risk areas. Additionally, these results can inform policies to mitigate the spread of anthrax in pastoralist communities in the Black Sea basin and foster collaboration between veterinary and public health entities on anthrax control. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion This prospective pilot study evaluated urinary interferon‐γ‐induced protein‐10 (IP‐10)/creatinine and tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL)/creatinine ratios as non‐invasive biomarkers for distinguishing bacterial from viral infections and assessing disease severity in febrile children.The study involved 85 febrile children and 29 healthy controls, measuring urinary IP‐10/creatinine and TRAIL/creatinine ratios to determine their diagnostic utility.Both ratios were significantly elevated in infected patients compared to controls. The IP‐10/creatinine ratio effectively assessed disease severity in the overall cohort and subgroups (AUC: 0.7324, 0.7192, 0.7277; p < 0.05). Serum C‐reactive protein showed limited discriminatory ability in viral infections (AUC = 0.5385, p = 0.7257). Differentiation between bacterial and viral infections using IP‐10/creatinine approached significance (p = 0.082). No significant differences in biomarker levels were observed across pathogens.The urinary IP‐10/creatinine ratio shows promise as a biomarker for assessing paediatric infection severity, particularly when traditional markers are less effective. Larger studies are needed to validate these results and improve its discriminatory accuracy in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS. Objectives: We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS. Design: This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Data sources and methods: A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies. Results: The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed. Conclusion: Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is promising for combating deep‐seated infectious diseases by generating substantial reactive oxygen species (ROS) through the profound tissue penetration capabilities of ultrasound. However, the compact protective structures of bacterial biofilms present a formidable challenge, impeding ROS efficacy. Given that ROS have a limited diffusion range and current sonosensitizers struggle to infiltrate biofilms, complete eradication of pathogenic bacteria often remains unachieved. In this study, mesoporous titanium dioxide (TiO2) nanoparticles are engineered asymmetrically coated with a thin layer of Ag and loaded with L‐arginine (LA) to construct ultrasound‐propelled nanomotors. These Ag‐TiO2‐LA Janus nanoparticles demonstrate robust self‐propulsion upon ultrasonic activation, allowing for deeper penetration into biofilm matrices and enhancing localized biofilm disruption through improved SDT outcomes. Additionally, the incorporation of Ag not only broadens TiO2's absorption spectrum but also confers photothermal capabilities upon NIR laser excitation at 808 nm. The Ag‐TiO2‐LA nanomotor amalgamates TiO2's sonodynamic potential with Ag's photothermal properties, forging a versatile antimicrobial agent capable of efficient biofilm penetration and a synergistic antibacterial effect when subjected to dual NIR and ultrasound stimuli. This innovative, singularly‐structured nanoparticle stands out as an effective combatant against bacterial biofilms and accelerates the healing process of infected wounds, showcasing potential for multifaceted clinical applications. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni is a major cause of food- and water-borne bacterial infections in humans. A key factor helping bacteria to survive adverse environmental conditions is biofilm formation ability. Nonetheless, the molecular basis underlying biofilm formation by C. jejuni remains poorly understood. Around thirty genes involved in the regulation and dynamics of C. jejuni biofilm formation have been described so far. We applied random transposon mutagenesis to identify new biofilm-associated genes in C. jejuni strain 81–176. Of 1350 mutants, twenty-four had a decreased ability to produce biofilm compared to the wild-type strain. Some mutants contained insertions in genes previously reported to affect the biofilm formation process. The majority of identified genes encoded hypothetical proteins. In the library of EZ-Tn5 insertion mutants, we found the cydB gene associated with respiration that was not previously linked with biofilm formation in Campylobacter. To study the involvement of the cydB gene in biofilm formation, we constructed a non-marked deletion cydB mutant together with a complemented mutant. We found that the cydB deletion-mutant formed a weaker biofilm of loosely organized structure and lower volume than the parent strain. In the present study, we demonstrated the role of the cydB gene in biofilm formation by C. jejuni. [ABSTRACT FROM AUTHOR]

AbstractThe purpose of this narrative review is to analyze the most recent studies about the role of C-reactive protein (CRP) and procalcitonin (PCT), two of the main biomarkers of infection, in distinguishing viral from bacterial etiology, in predicting the severity of infection and in guiding antibiotic stewardship in children with community-acquired pneumonia (CAP). The studies examined reveal that both CRP and PCT play a valuable role in diagnosing pediatric CAP, though each has limitations. CRP has moderate accuracy in distinguishing bacterial from viral infections, but its elevated levels are not exclusive to bacterial infections; PCT, however, shows higher specificity for bacterial CAP, with studies confirming its ability to differentiate bacterial causes, especially in severe cases. When integrated with clinical findings, CRP and PCT improve the sensitivity of pneumonia diagnoses and help in predicting severe outcomes such as sepsis and empyema; furthermore, both biomarkers prove useful in guiding antibiotic therapy, with PCT showing a more dynamic response to treatment. However, even though CRP and PCT offer valuable insights into the diagnosis and management of pediatric CAP, their application should be always integrated with clinical assessment rather than used in isolation. More studies are needed to define standardized thresholds and decision algorithms that incorporate these biomarkers. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Belatacept is a costimulatory blocker that can be used to prevent and treat rejection in lung transplant recipients (LuTRs). The epidemiology of infections in belatacept‐treated LuTRs has not been systematically evaluated.We performed a single‐center retrospective study of all adult LuTRs who received belatacept as prevention or treatment of antibody‐mediated rejection (desensitization) or as part of maintenance immunosuppression from January 1, 2011, to June 30, 2022. We assessed the epidemiology of infections that occurred within 12 months following the first belatacept dose.Fifty‐two LuTRs received at least one dose of belatacept as either desensitization (n = 32) or maintenance immunosuppression (n = 20). Among 45 patients who were cytomegalovirus (CMV) donor and/or recipient seropositive, nine (20%) developed CMV infection. Seven (77%) CMV infections occurred despite valganciclovir prophylaxis and four (44%) were associated with antiviral resistance. Three (6%) LuTRs developed Epstein‐Barr virus (EBV) associated post‐transplant lymphoproliferative disorder (PTLD). Twenty‐five (48%) LuTRs developed 43 bacterial infections and five (10%) developed proven or probable invasive fungal disease. Incidence rates of viral, bacterial, and fungal infections were similar between the desensitization and maintenance groups: incidence rate ratios (95% confidence interval) were 0.70 (0.32–1.57), 1.31 (0.70–2.46), and 2.82 (0.31–25.2), respectively. Infection/PTLD prompted belatacept discontinuation in eight (15%) patients.In the first year after belatacept initiation, LuTRs commonly developed CMV infections, EBV+ PTLD, and bacterial infections. Multicenter collaborations are needed to better understand infection risks in LuTRs treated with belatacept. [ABSTRACT FROM AUTHOR]

To address the risk of bacterial infection during the early implantation of medical titanium implants, this study designed a strontium barium titanate rod-like silver coating with piezoelectric effect. The antibacterial properties of nano-silver, the spiky structure of the rod-like array, and the piezoelectric effect were utilized to achieve rapid and continuous bactericidal effects in the early stages. The surface morphology and microstructure of the coating were analyzed, along with an examination of its phase composition and silver element distribution. Furthermore, investigations into the impact of silver loading on wetting angle and piezoelectric coefficient were conducted, as well as tests on the cumulative release of silver ions. Bacterial experiments confirmed that even after 7 days immersed in PBS, the antibacterial rate for barium strontium titanate rod-like silver coated titanium surfaces with piezoelectric effect remained at 99.99 %, slightly higher than unpolarized coatings. Finally, assessments on toxicity, proliferation, and adhesion of osteoblasts revealed excellent performance from polarized coatings. These results provide data support and a theoretical basis for studying the antibacterial effects of piezoelectricity in conjunction with other antibacterial strategies. [ABSTRACT FROM AUTHOR]

Introduction: Pantoea ananatis has emerged as a significant plant pathogen affecting various crops worldwide, causing substantial economic losses. Bacteriophages and their endolysins offer promising alternatives for controlling bacterial infections, addressing the growing concerns of antibiotic resistance. Methods: This study isolated and characterized the Pantoea phage PA1 and investigated the role of PA1-LRP in directly damaging bacteria and assisting endolysin PA1-Lys in cell lysis, comparing its effect to exogenous transmembrane domains following the identification and analysis of the PA1-Lys and the PA1-LRP based on whole genome analysis of phage PA1. Additionally, this study also explored how hydrophobic region of PA1-LRP (HPP) contributes to bacterial killing when combined with PA1-Lys and examined the stability and lytic spectrum of PA1-Lys under various conditions. Results and discussion: Phage PA1 belonging to the Chaseviridae family exhibited a broad host range against P. ananatis strains, with a latent period of 40 minutes and a burst size of 17.17 phages per infected cell. PA1-Lys remained stable at pH 6-10 and temperatures of 20-50°C and showed lytic activity against various Gram-negative bacteria, while PA1-Lys alone could not directly lyse bacteria, its lytic activity was enhanced in the presence of EDTA. Surprisingly, PA1-LRP inhibited bacterial growth when expressed alone. After 24 h of incubation, the OD600 value of pET28a-LRP decreased by 0.164 compared to pET28a. Furthermore, the lytic effect of co-expressed PA1-LRP and PA1-Lys was significantly stronger than each separately. After 24 h of incubation, compared to pET28a-LRP, the OD600 value of pET28a-Lys-LRP decreased by 0.444, while the OD420 value increased by 3.121. Live/dead cell staining, and flow cytometry experiments showed that the fusion expression of PA1-LRP and PA1-Lys resulted in 41.29% cell death, with bacterial morphology changing from rod-shaped to filamentous. Notably, PA1-LRP provided stronger support for endolysin-mediated cell lysis than exogenous transmembrane domains. Additionally, our results demonstrated that the HPP fused with PA1-Lys, led to 40.60% cell death, with bacteria changing from rod-shaped to spherical and exhibiting vacuolation. Taken together, this study provides insights into the lysis mechanisms of Pantoea phages and identifies a novel lysis-related protein, PA1-LRP, which could have potential applications in phage therapy and bacterial disease control. [ABSTRACT FROM AUTHOR]

Classical Zn2+-dependent deac(et)ylases play fundamental regulatory roles in life and are well characterized in eukaryotes regarding their structures, substrates and physiological roles. In bacteria, however, classical deacylases are less well understood. We construct a Generalized Profile (GP) and identify thousands of uncharacterized classical deacylases in bacteria, which are grouped into five clusters. Systematic structural and functional characterization of representative enzymes from each cluster reveal high functional diversity, including polyamine deacylases and protein deacylases with various acyl-chain type preferences. These data are supported by multiple crystal structures of enzymes from different clusters. Through this extensive analysis, we define the structural requirements of substrate selectivity, and discovered bacterial de-d-/l-lactylases and long-chain deacylases. Importantly, bacterial deacylases are inhibited by archetypal HDAC inhibitors, as supported by co-crystal structures with the inhibitors SAHA and TSA, and setting the ground for drug repurposing strategies to fight bacterial infections. Thus, we provide a systematic structure-function analysis of classical deacylases in bacteria and reveal the basis of substrate specificity, acyl-chain preference and inhibition. In bacteria Zn2+-dependent deacylases are underexplored. Here, the authors identify bacterial deacylases, providing systemic structure-function analyses to reveal the basis of substrate specificity, acyl-chain preference and inhibition. [ABSTRACT FROM AUTHOR]

Background: Fluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever. Methods: CPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast. Rectal body temperature was measured up to 180 min after administration. Results: A decrease in rectal body temperature of up to 1.2 °C for CPFX, 3.4 °C for GFLX, and 1.0 °C for LVFX was observed. The decrease in temperature was induced by an increase in the plasma concentration of FQ antimicrobials, suggesting that they are responsible for the temperature reduction. Focusing on glucocorticoids, one thermoregulation mechanism, we investigated the substances responsible for the reduction in rectal body temperature induced by FQ antimicrobials. Aminoglutethimide (an inhibitor of glucocorticoid production) were premedicated, followed by intraperitoneal administration of GFLX in the yeast-induced fever mouse model, resulting in attenuated GFLX-induced hypothermic effects. Conclusions: These results suggest that certain antipyretic effects of CPFX, GFPX, and LVFX during fever may contribute to their hypothermic effects; certain mechanisms are glucocorticoid-mediated. [ABSTRACT FROM AUTHOR]

Introduction: Multifunctional nanomaterials are emerging as promising tools for treating both cancer and bacterial infections. However, integrating dual therapeutic capabilities into a single system remains challenging. This study presents multifunctional nanoparticles (ECI-NPs) based on Epigallocatechin gallate (EGCG) oligomers, Curcumin (CUR), and Indocyanine Green (ICG) for combined cancer and bacterial treatment. Methods: ECI-NPs were synthesized via oxidative coupling of EGCG, CUR, and ICG. The nanoparticles were characterized for stability, size, drug loading, and release profiles. Cellular uptake, phototoxicity in melanoma cells, and antibacterial activity against Escherichia coli and Staphylococcus aureus were also evaluated. Results: ECI-NPs demonstrated optimal stability, high drug loading, and controlled release. Cellular studies showed increased uptake and greater phototoxicity in melanoma cells compared to free drugs. ECI-NPs also exhibited enhanced anticancer effects and strong antibacterial activity, outperforming the individual components. Discussion: The polyphenol-based ECI-NPs offer synergistic therapeutic effects, overcoming the limitations of free drugs in terms of solubility and efficacy. This dual-function platform shows potential for broader biomedical applications, addressing challenges in cancer and bacterial infections. Further research will focus on in vivo studies and clinical translation. [ABSTRACT FROM AUTHOR]

Bacterial and viral infections cause a huge burden to healthcare settings worldwide, and mortality rates associated with infectious microorganisms have remained high in recent decades. Despite tremendous efforts and resources worldwide to explore diagnostic biomarkers, rapid and easily assayed indicators for the diagnosis of bacterial and viral infections remain a challenge. B7 homolog 3 (B7-H3), a member of the B7 family of immunoregulatory proteins, is overexpressed in patients with septicemia, meningitis, pneumonia, and hepatitis. Therefore, B7-H3 could be used as a potential clinical indicator and therapeutic target for bacterial and viral infections caused by H. pylori, S. pneumoniae, M. pneumoniae, hepatitis B virus (HBV), viral hemorrhagic septicemia virus (VHSV), respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV). Moreover, the interplay between infectious microorganisms and B7-H3 and exploration of the functional roles of the B7-H3 molecule could aid in the development of novel strategies for disease diagnosis and immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Understanding the nature of inflammatory responses in cats with bacterial and viral infections is essential for accurately managing the infection. This study aimed to investigate the diversities of inflammatory responses between bacterial and viral infections in cats to figure out their role in the pathophysiology of these infections. Methods: Seventy‐five owned cats were included in the study. The evaluations were performed based on three groups: healthy control, bacterial infection group (those with bronchopneumonia and gastrointestinal tract and urinary tract infections) and viral infection group (21 with feline coronavirus [FCoV], 3 with feline leukaemia virus [FeLV] and 1 with feline calicivirus), each containing 25 individuals. Total and differential leukocyte counts, C‐reactive protein (CRP), transforming growth factor beta (TGF‐β), interleukin‐6 (IL‐6), tumour necrosis factor‐alpha (TNF‐α), interleukin‐1 beta (IL‐1β) and interleukin‐10 (IL‐10) concentrations were assessed in the blood samples collected from sick and healthy animals. Results: No statistically significant difference was noted in serum TNF‐α, IL‐1β and IL‐10 concentrations of the infected cats (p = 0.996, p = 0.160 and p = 0.930, respectively). Serum TGF‐β concentration in the viral infection group was reduced compared to the healthy control (p = 0.001). In contrast, WBC count and IL‐6 and CRP concentrations were increased in the cats with bronchopneumonia, gastrointestinal tract infections and urinary tract infections compared to the healthy control and viral infection groups (p = 0.001, p = 0.001 and p = 0.001, respectively). Conclusion: This study revealed significant differences between bacterial and viral infections regarding the fashion of inflammatory responses in cats, and the relevant data will undoubtedly contribute to the management and control of feline infectious diseases, rendering the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

IKKε is an IκB kinase participating in the control of NF-κB and type I IFN signal pathways in mammals. However, the function of IKKε in regulating immune response is largely unknown in teleost. Herein, an IKKε homologue named AjIKKε was characterized in Japanese eel (Anguilla japonica). AjIKKε has an N-terminal kinase domain, a ubiquitin-like domain, and a coiled coil-containing domain (CC), which is conserved and similar to its counterpart in mammals. Expression analysis showed that AjIKKε could be up-regulated in kidney, spleen, and particularly in liver under the stimulation of poly I:C, LPS, and Aeromonas hydrophila infection. In vitro, the mRNA levels of AjIKKε were significantly provoked in eel liver cells stimulated by LPS and poly I:C, or the different concentrations of A. hydrophila. The overexpression of AjIKKε could not only induce a significantly higher level of promoter activity of human NF-κB, AP-1, and IFN-β in a dose-dependent manner but also upregulate the activation of promoters of Japanese eel cRel, AP1, IL6, IFN4, IRF3, and IRF7 in HEK293 cells. RNAi studies showed that after AjIKKε was knocked down, the expression levels of IL1, IL6, TNFα, c-Jun, IFN2, IFN3, MX1, MX2, and IRF3 genes were significantly down-regulated in liver, spleen, and kidney of Japanese eels. In addition, the mutants of AjIKKε-K39A, AjIKKε-S174A, and AjIKKε-ΔCC failed to activate Japanese eel IFN4, IRF3 and human IFN-β promoters in HEK293 cells. Collectively, these results suggest that AjIKKε may function as a positive regulator of NF-κB, MAPK, and IRF3-mediated type I IFN signaling pathways related to immune response evoked by bacterial and viral infection. [ABSTRACT FROM AUTHOR]

We developed a flow cytometry (FC) assay enabling the rapid and accurate identification of bacterial and viral infections using whole blood samples. The streamlined flow cytometry assay is designed to be user-friendly, making it accessible even for operators with limited experience in FC techniques. The key components of the assay focus on the expression levels of specific surface markers—CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection, and CD169 on monocytes (MO) for viral infection. The strong performance indicated by an area under the receiver operating characteristic (ROC) curve of 0.94 for both PMN CD64 positive predictive value (PPV) 97.96% and negative predictive value (NPV) 76.67%, and MO CD169 PPV 82.6% and NPV 86.9%, highlight the assay's robustness in differentiating between bacterial and viral infections accurately. The FC assay includes the assessment of immune system status through HLA-DR and IL-1R2 modulation in MO, providing a useful insight into the patients' immune response. The significant increase in the frequency of MO exhibiting reduced HLA-DR expression and elevated IL-1R2 levels in infected patients (compared to healthy controls) underscores the potential of these markers as indicators of infection severity. Although the overall correlation between HLA-DR and IL-1R2 expression levels was not significant across all patients, there was a trend in patients with more severe disease suggesting that these markers may have the potential to assist in stratifying patient risk. The present FC assay has the potential to become routine in the clinical microbiology laboratory community and to be helpful in guiding clinical decision making. [ABSTRACT FROM AUTHOR]

Citrus canker, a highly transmissible bacterial disease, has three major types, with Asiatic canker (Canker A), caused by Xanthomonas citri pv. citri (Xcc A), being the most widespread and severe, affecting most citrus varieties. Xcc A has two mild variants, Xcc A* and Aw with a limited host range, reported in Southwest Asia and Florida, respectively. Since 2015, the canker caused by Xcc Aw has been being reported in the Rio Grande Valley of South Texas where the Texas commercial citrus industry is located. In 2016, a more severe Canker A was reported in the upper Texas gulf coast region, north of the Rio Grande Valley, posing a potential threat to the Texas citrus industry. Given that existing diagnostic methods cannot reliably distinguish Xcc Aw from Xcc A, we developed a loop-mediated isothermal amplification (LAMP) assay specific to Xcc Aw (LAMP-Aw) for rapid, field-based identification of this bacterial variant. The detection limit of LAMP-Aw was ~4.52 Log10 copies of the target molecule. This study also evaluated the field applicability of the LAMP-Aw assay by coupling the LAMP-Aw assay with a lateral flow immunoassay system. [ABSTRACT FROM AUTHOR]

Rice phosphatidylcholine transfer protein (PCTP), which contains a steroidogenic acute regulatory protein-related lipid transfer (START) domain, responds to bacterial blight disease. Overexpression of OsPCTP quantitatively enhances resistance to pathogen in rice, whereas depletion of it has the opposite effect. Further analysis showed that OsPCTP physically interacts with OsAPX8, a ROS scavenging enzyme, and influences ascorbate peroxidase enzymatic activity in vivo. In addition, the expression of pathogenesis-related genes PR1a, PR1b and PR10 were significantly induced in OsPCTP-OE plants compared with that in wild-type plants ZH11. Taken together, these results suggested that OsPCTP mediates bacterial blight resistance in rice through regulating the ROS defense pathway. [ABSTRACT FROM AUTHOR]

Objective: To examine associations of laboratory and imaging data with diagnostic parameters of necrotizing otitis externa (NOE) and its severity, and to compare between bacterial and fungal infections. Methods: Records of patients diagnosed with NOE during 2010–2018 at the Department of Otolaryngology, Head and Neck Surgery were reviewed retrospectively for demographics; disease characteristics; and laboratory, scintigraphy, and imaging results. Results: Of 48 patients with NOE, the mean age is 73±11.6 years; 32 (67%) were males; 83% had diabetes mellitus. Common pathogens were pseudomonas (49%) and fungi (33%). Sensitivities of the technetium-scan (SPECT ratio ≥1.5), temporal bone computed tomography (CT), and gallium-scan (SPECT ratio ≥1.3) were: 78.7%, 48.8%, and 31.4%, respectively. Gallium-scan results correlated positively with CT bone involvement (p=0.002) and hospital length of stay (p=0.0014). C-reactive protein (CRP) level correlated with hospital length of stay (p=0.028) and positive technetium-scan results (p=0.012). Fungal infection had a higher technetium SPECT ratio (2.16 vs. 1.77, p=0.04), gallium SPECT ratio (1.4 vs. 1.2, p=0.02), longer duration of systemic treatment (87.4 vs. 37.9 days, p=0.014), and longer hospital length of stay (31.6 vs. 15.2 days, p=0.004) compared to non-fungal infection. Eight (17%) patients had responded poorly to treatment. Fungal pathogens, facial nerve paresis, extra-auricular, and bilateral disease were more prevalent among the non-responders. Conclusion: The technetium scan has higher sensitivity than temporal bone CT for diagnosing NOE. The gallium scan and CRP correlated well with hospital length of stay. A high rate of fungal infection was found, with significantly higher technetium and gallium SPECT ratios and worse outcome compared to bacterial infection. Fungal NOE remains therapeutically challenging. [ABSTRACT FROM AUTHOR]

Background: In recent years, Raoultella spp. have attracted clinical attention as a new type of pathogen. The most common of human infection with Raoultella are bacteremia, urinary tract infections, abdominal infections, etc. Abdominal infection is a serious and complex infection problem. However, there have been no systematic reports of abdominal infections caused by Raoultella. The objective of this study was to explore the clinical characteristics of Raoultella abdominal infections and provide a reference for clinical practice. Methods: A review of publications on abdominal infections caused by the genus Raoultella between 2009 and 2024 is carried out. This review studied seven parameters: infection type, number of cases, gender, age, comorbidities, treatment, and outcome, and descriptive statistical methods were used to analyze the results. Results: A total of 40 cases (16 Raoultella ornithinolytica and 24 Raoultella planticola) were analyzed: 20 cases of biliary tract infection, 5 cases of liver infection, and 4 cases of peritonitis. Fever and abdominal pain were the main symptoms, and some patients present with multiple skin flushes, systemic erythema. Of the 40 cases, 92.5% of patients had underlying diseases. Among them, malignant disease, immunodeficiency, and invasive operations increase the risk of infection. On the basis of the drug susceptibility results, the preferred antibiotics are quinolone, third generations of cephalosporins, carbapenems, and aminoglycoside. Last, patients with abdominal infections caused by Raoultella spp. mostly have a good prognosis after early use of sensitive antibiotics. Conclusions: According to existing literature reports, the main type of abdominal infection caused by Raoultella is biliary tract infection, and most patients have other underlying diseases. Malignancy, immune deficiency, and invasive procedures are risk factors for bacterial infections. This review also emphasizes that Raoultella spp. is a rarely found opportunistic pathogen, which can cause a high incidence of healthcare-associated infections after invasive procedures. [ABSTRACT FROM AUTHOR]

In the competition between the pathogen infection and the host defense, infectious microorganisms may enter the host cells by evading host defense mechanisms and use the intracellular biomolecules as replication nutrient. Among them, intracellular Staphylococcus aureus relies on the host cells to protect itself from the attacks by antibiotics or immune system to achieve long-term colonization in the host, and the consequent clinical therapeutic failures and relapses after antibiotic treatment. Here, we demonstrate that intracellular S. aureus surviving well even in the presence of vancomycin can be effectively eliminated using an emerging cell-mimicking therapeutic strategy. These cell mimics with natural killer cell-like activity (NKMs) are composed of a redox-responsive degradable carrier, and perforin and granzyme B within the carrier. NKMs perform far more effectivly than clinical antibiotics in treating intracellular bacterial infections, providing a direct evidence of the NK cell-mimicking immune mechanism in the treatment of intracellular S. aureus. [ABSTRACT FROM AUTHOR]

This investigation examined the potential antibacterial and antidiabetic effects of wound dressings created using electrospun nanofibers containing Ziziphus jujuba fruit extract (ZJ). These nanofibers were composed of a combination of Polycaprolactone (PCL), Polyvinyl Alcohol (PVA), and Polyhexamethylene Biguanide (PHMB). The process of creating these nanofibers involved electrospinning. The nanofiber products, which included PCL, PCL/PVA, PCL/PVA/ZJ, PCL/PVA/PHMB, and PCL/PVA/PHMB/ZJ, underwent a morphology, physicochemical, and biological assessment. Incorporating PHMB into the nanofibers enhanced the antibacterial properties, effectively preventing bacterial infections in wounds. Furthermore, including ZJ fruit extract in the nanofibers provided antidiabetic properties, making these dressings suitable for diabetic patients. The PCL/PVA/PHMB/ZJ combination exhibited exceptional healing capabilities and superior antibacterial efficiency in MRSA-infected wounds. The histological assay confirmed complete wound healing by day 14, accompanied by reduced inflammation. Based on these findings, using PCL/PVA/PHMB/ZJ as innovative wound dressings is recommended, as they can expedite wound healing while offering significant antidiabetic and antibacterial features. Ultimately, these electrospun nanofibers possess the potential to serve as advanced wound dressings with enhanced antibacterial and anti-diabetes properties. [ABSTRACT FROM AUTHOR]

Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and secondary immunodeficiency disease (SID) are susceptible to severe, recurrent, or persistent infections. This retrospective cohort study assessed the burden of infection in patients with CLL/SLL with and without SID, and in immunoglobulin replacement therapy (IgRT)-treated and -untreated patients with CLL/SLL and SID. Anonymized data from the US Optum-Humedica database (Oct-1-2015–Mar-10-2020) were used. Eligible patients aged ≥ 18 years with a confirmed CLL/SLL diagnosis were assigned to cohorts (SID or no-SID) using an algorithm based on serum IgG levels < 5.0 g/L, hypogammaglobulinemia diagnosis codes, and ≥ 1 major infection. A further sub-categorization was made based on patients with SID who received IgRT and those who did not. During 12-month follow-up, patients with CLL/SLL and SID were significantly more likely to experience infections (70.1% vs. 30.4%), including severe bacterial infections (39.8% vs. 9.2%), and infections requiring hospitalization (27.7% vs. 5.8%) than patients without SID. The use of anti-infectives and healthcare resource utilization (HCRU) was also higher in the SID cohort versus the no-SID cohort. Overall survival was shorter in patients with SID than those without (12.3 vs. 16.9 months). In patients with CLL/SLL and SID, burden of infection and HCRU were greater in IgRT-treated patients than in no-IgRT patients, potentially highlighting the IgRT-treated cohort as a more vulnerable population. Increasing understanding of SID burden may help to improve outcomes in patients with CLL/SLL. Further research is needed to develop guidance for IgRT use and to assess the benefits of IgRT in this vulnerable population. [ABSTRACT FROM AUTHOR]

Purpose: Bacterial infections, particularly bacteremia, urinary tract infections (UTIs), and pus infections, remain among hospitals' most worrying medical problems. This study aimed to explore bacterial diversity, infection dynamics, and antibiotic resistance profiles of bacterial isolates. Methods: We analyzed data from 1750 outpatients and 920 inpatients, of whom 1.6% and 8.47% respectively had various bacterial infections. Results: The analysis revealed that UTIs were the most prevalent at 41.01%, particularly affecting women. UTIs also showed a distinct distribution across admission departments, notably in emergency (23.07%) and pediatric (14.10%) units. The most frequently isolated microorganisms were Escherichia coli (E. coli), followed by Klebsiella ornithinolytica. Skin infections followed UTIs, accounting for 35.88% of cases, more prevalent in men, with Staphylococcus aureus (S. aureus) being the primary pathogen (57%). Gram-negative bacteria (GNB) like E. coli and Pseudomonas aeruginosa contributed significantly to skin infections (43%). Bacteremia cases constituted 11.52% of bacterial infections, predominantly affecting women (67%) and linked to GNB (78%). A comparative study of antibiotic susceptibility profiles revealed more pronounced resistance in GNB strains isolated from inpatients, particularly to antibiotics such as Amoxicillin/clavulanic acid, Tetracyclin, Gentamicin, Chloramphenicol, and Ampicillin. In contrast, strains from ambulatory patients showed greater resistance to Colistin. Gram-positive bacteria from hospitalized patients showed higher resistance to quinolones and cephalosporins, while ambulatory strains showed high resistance to aminoglycosides, macrolides, fluoroquinolones, and penicillin. Furthermore, these analyses identified the most effective antibiotics for the empirical treatment of both community-acquired and nosocomial infections. Ciprofloxacin, aztreonam, and amikacin exhibited low resistance rates among GNB, with gentamicin and chloramphenicol being particularly effective for community-acquired strains. For S. aureus, ciprofloxacin, rifampicin, and cefoxitin were especially effective, with vancomycin showing high efficacy against community-acquired isolates and fosfomycin and chloramphenicol being effective for hospital-acquired strains. Conclusion: These results are essential for guiding antibiotic therapy and improving clinical outcomes, thus contributing to precision medicine and antimicrobial stewardship efforts. [ABSTRACT FROM AUTHOR]

Bacteria have their own language through which they communicate with one another like all higher organisms. So, many researchers are working hard to identify and comprehend the components of this bacterial communication, known as quorum sensing (QS). In quorum sensing, bacteria use signaling molecules called autoinducers (AIs) to exchange information. Many natural compounds and extraction techniques have been intensively studied to disrupt bacterial signaling and examine their effectiveness for bacterial pathogenesis control. Quorum sensing inhibitors can interfere with QS and block the action of AI signaling molecules. Recent research indicates that quorum sensing inhibitors (QSIs) and quorum quenching enzymes (QQEs) show great promise in reducing the pathogenicity of bacteria and inhibiting biofilm synthesis. In addition, the effectiveness of QQEs and QSIs in experimental animal models was demonstrated. These are taken into account in the development of innovative medical devices, such as dressings and catheters, to prevent bacterial infections. The present review highlights this aspect with a prospective vision for its development and application. [ABSTRACT FROM AUTHOR]