Search Results (8,733)

Rotavirus alphagastroenteritidis remains the leading cause of severe gastroenteritis in children under five years, despite widespread vaccine use. The COVID-19 pandemic disrupted healthcare and vaccination delivery, while non-pharmacological interventions may have influenced R. alphagastroenteritidis transmission. We conducted hospital-based surveillance of R. alphagastroenteritidis gastroenteritis at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, from October 2019 to October 2024. Children under five presenting with acute gastroenteritis were enrolled; 99.1% of vaccine-eligible participants had received at least one R. alphagastroenteritidis vaccine dose. Stool samples were tested for R. alphagastroenteritidis by enzyme immunoassay (EIA) and genotyped using RT-PCR. Among 1135 enrolled children, 29.1% (330/1135) were R. alphagastroenteritidis-positive. Cases occurred year-round except for December 2020–January 2021, when no R. alphagastroenteritidis infections were detected, and February–March 2023, when no samples were collected. The prevalence varied significantly by age group between children greater than 23 months of age to the rest of the age groups (<6 months, 6–11 months, and 12–22 months) (p = 0.0046). The most common R. alphagastroenteritidis G-genotypes were G3 (38.7%), G2 (25.4%), and G12 (17.2%), with G2 emerging as the predominant strain from June 2023. G3P[8] was the most frequent G–P combination (25%). Its overall prevalence did not change during the pandemic; however, genotype distribution shifted compared to pre-COVID-19 patterns. Sustained surveillance and genomic analyses are essential to monitor evolving strain dynamics and inform vaccine policy. Full article

Infections pose a major risk during long-term human spaceflight missions. By applying standard procedures in medical microbiology to a hypothetical urinary tract infection during a Mars-bound flight, important practical aspects become apparent. From infection diagnostics to antimicrobial treatment during spaceflight, issues include technological constraints, the lack of breakpoints, and epidemiological data. A potential solution is a combination of data acquisition, artificial intelligence, individualized medicine, novel diagnostic tools, and antimicrobial strategies. This work takes an exploratory approach to highlight challenges and potential directions in developing diagnostic strategies for long-term space missions. Full article

This study investigated the protective efficacy of two distinct combinations of three recombinant adeno-associated virus serotype 9 (rAAV9) vectors encoding broadly neutralizing antibodies against HIV-1—CombiMab-1 and CombiMab-2—in mice humanized with primary CD4⁺ T-lymphocytes. We demonstrated that mice preventively treated with CombiMab-1 or CombiMab-2 did not develop viremia and maintained human CD4+ T-lymphocyte counts following viral challenge, in contrast to control animals. These results demonstrate the significant protective capacity of CombiMab-1 and CombiMab-2 against HIV-1 challenge. Full article

Background/Objectives: Animal health remains a critical issue that directly impacts economic sustainability through animal welfare and production. In small ruminants, the gastrointestinal parasite Haemonchus contortus can lead to anemia and possibly mortality, since parasite burden can be considerable and is challenging to control. Small ruminant health can be affected by poor diet and environmental conditions that lead to changes in the metabolic balance. The link between animal health and metabolic profiles has been investigated in the past. These studies have shed important light on physiological changes by identifying dietary and disease biomarkers. This study aimed to correlate the metabolite signature of feces from goats, having two levels of Haemonchus contortus infection, grazing on two different forages (Bermudagrass and Sunn Hemp). Methods: Fecal samples were taken from goats grazing either Sunn Hemp or Bermudagrass pastures, with naturally variable Haemonchus contortus loads. Samples were evaluated using ¹H-NMR and LC/MS methods to describe and compare metabolic patterns under varied forage conditions between low and high Fecal Egg Count (FEC). Results: Our findings indicated no significant difference using univariate analyses but identified 10 discriminatory features using multivariate analyses for Bermudagrass and Sunn Hemp using ¹H-NMR. With LC-MS, we found 11 significantly different (p < 0.05, FC > 2) and 115 discriminatory features for Bermudagrass and 113 in Sunn Hemp from multivariate analyses. Combining the findings of the two approaches suggested that Haemonchus contortus influenced several pathways associated with the metabolism of amino acids and energy conversion. Conclusions: The analysis of metabolome changes across both forages may help in revealing novel knowledge and accurate identification of possible biomarkers for gastrointestinal parasites. Further study is needed to validate the potential biomarker before deploying diagnostic tools based on the metabolomics indicators for early parasite diagnosis. Full article

Downy mildew, caused by Plasmopara halstedii, is a major threat to sunflower production worldwide, leading to severe yield losses. Since resistance in sunflower hybrids can be easily broken by the pathogen, it is important to find alternative and sustainable control methods against this disease. This study investigated the potential use of NeemAzal^®-T/S (a neem-based biopesticide formulation) to induce antioxidant defense responses in sunflower seedlings inoculated with P. halstedii (pathotype 704). Its effects, alone, or in combination with a reduced dose of Mefenoxam, were evaluated under controlled conditions. Plant height, sporulation, antioxidant enzyme activities (SOD, CAT, APX, POX, and PPO), lipid peroxidation (MDA), and hydrogen peroxide (H₂O₂) contents were measured. Our results indicate that the antioxidant responses of seedlings varied according to the treatment. MDA levels decreased even when NeemAzal^®-T/S was applied alone, while H₂O₂ production only decreased when both treatments were applied combined. Overall, NeemAzal^®-T/S can be a valuable alternative strategy to help control sunflower downy mildew, since it reduced sporulation and MDA content, and increased APX, POX, and PPO activities even at a later stage of infection in susceptible seedlings. These findings indicate that NeemAzal^®-T/S can activate defense mechanisms associated with oxidative stress reduction in sunflower, offering a promising strategy to help manage downy mildew in a more sustainable manner. Full article

Background/Objectives: Antimicrobial resistance (AMR) has increased significantly over the years, contributing to a real challenge in the intensive care unit (ICU). The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer ceftazidime–avibactam (CAZ-AVI), meropenem–vaborbactam, and imipenem–relebactam. Treatment of such infections is challenging. In vitro and clinical data suggest that combinations of CAZ-AVI with aztreonam (ATM) and the use of two different carbapenems (double carbapenem therapy, DCT) may be an option for MBL-producing pathogens. The aim of our study was to evaluate the effectiveness of the combination CAZ-AVI + ATM and the effectiveness of DCT against MBL-producing K. pneumoniae infections in the critically ill, mechanically ventilated patients. Methods: This is a retrospective study conducted in the two ICUs of hospitals in central Greece. Mechanically ventilated patients admitted to the ICU were included in the study if they developed an infection by MBL-producing K. pneumoniae. Patients were divided into three groups: the first one consisted of patients who were treated with CAZ-AVI plus ATM (CAZ-AVI + ATM group), and the second group consisted of patients who received DCT (DCT group). The third group included patients who received appropriate antibiotic therapy other than CAZ-AVI + ATM and DCT (control group). The primary outcome of the study was the evolution of the sequential organ failure assessment (SOFA) score, and secondary outcomes were duration of mechanical ventilation (MV), ICU length of stay (LOS), and, finally, ICU mortality. Results: 108 patients were included in the study. 35 (32%) in the CAZ-AVI + ATM group, 31 (29%) in the DCT group, and the remaining 42 (39%) patients in the control group. The SOFA score was not statistically different on day 1, day 4, and day 7 of the infection among the three groups (p > 0.05). Duration of MV and ICU LOS were also similar. Finally, mortality did not differ between the groups [20 patients (57.1%) vs. 18 (58.1%) vs. 25 (59.5%) for CAZ-AVI + ATM, DCT and control group, respectively, p = 0.98]. Comparison between survivors and non-survivors revealed that independent risk factors for mortality were SOFA score at day 1 of infection and medical cause of admission (p < 0.05). Conclusions: Treatment with CAZ-AVI + ATM or DCT presented similar efficacy with appropriate antibiotic therapy for infections caused by MBL-producing K. pneumoniae strains. Larger studies are required to confirm the findings. Full article

The genus Aeromonas is widely distributed in aquatic environments, where it is a frequent fish pathogen. It has also been described in association with human infections, with most cases caused by A. caviae, A. veronii biovar sobria, and A. hydrophila. More recently, A. dhakensis has emerged as an increasingly important human pathogen. Transmission occurs primarily through ingestion or contacts with aquatic sources, or by consuming contaminated food, particularly from aquatic origins. Growing resistance in Aeromonas has been reported for penicillins (including their combinations with classical β-lactamase inhibitors), cephalosporins, and carbapenems. Among the β-lactam antibiotics, only fourth-generation cephalosporins remain almost uniformly active. Furthermore, the co-occurrence of resistance genes for third-generation cephalosporins and carbapenems within the same isolates is increasing. Recently, the presence of mobile genes conferring colistin resistance has also been documented, with resistance rates sometimes exceeding 30%. This evolution of colistin resistance is likely linked to its use in aquaculture, and together with the rise in β-lactam resistance, may be transforming Aeromonas into a significant reservoir of resistance genes that could potentially be transferred to species more commonly associated with human infections, such as the Enterobacterales. Full article

Background/Objectives: Management of acute episodes of lower urinary tract infection (LUTI) depends on whether they are sporadic or recurrent. We aimed to define factors that differentiate patients with acute sporadic cystitis (AC) from those with recurrent cystitis (RC) and thereby improve individualized care. Methods: We performed a post hoc analysis of prospectively collected data from the multinational GPIU.COM study. Female patients with an acute LUTI episode completed the Acute Cystitis Symptom Score (ACSS) and underwent a routine clinical and laboratory evaluation, including a physical examination, ultrasonography, urinalysis, and urine culture and antimicrobial susceptibility testing. Risk factors for recurrence were evaluated using the Lower Urinary Tract Infection Recurrence Risk (LUTIRE) nomogram and the ORENUC classification. Statistical analysis followed a robust stepwise approach. Significant variables were assessed by relative risk (RR), and logistic regression was used to estimate odds ratios (ORs). Model performance was evaluated using the area under the curve (AUC), the Hosmer–Lemeshow test, variance inflation factor (VIF), and bootstrap sampling. Results: A total of 106 women were included (AC n = 50; RC n = 56). Patients with RC more frequently presented with a history of constipation, a severe impact of symptoms on daily activities, multiple uropathogens, and trace proteinuria. Pyuria was inversely associated with RC. Logistic regression identified chronic constipation, severe impact of symptoms on daily activities, and multiple uropathogens as independent predictors of RC. Three predictive models showed consistent discrimination between AC and RC (AUC = 0.80, 0.82, and 0.84). Conclusions: AC and RC showed notable differences in certain symptom profiles, quality of life, urinalysis, and microbiological findings. Combining high-value predictors from LUTIRE and ORENUC into a comprehensive prognostic algorithm could improve assessment of recurrence risk. A refined classification of LUTIs with recurrence grading is warranted to guide decision-making and prevention strategies. Full article

Soybean production is a cornerstone of Brazilian agriculture but is heavily threatened by insect pests such as the soybean looper Chrysodeixis includens, capable of reducing yields by up to 70% if uncontrolled. Reliance on chemical insecticides is increasingly unsustainable due to environmental impacts and resistance, highlighting the need for eco-friendly alternatives. The alphabaculovirus Chrysodeixis includens nucleopolyhedrovirus (ChinNPV) is an important biocontrol agent largely used in Brazilian fields because of its host specificity and safety, although its persistence is limited by ultraviolet (UV) sensitivity. Here, we characterize two ChinNPV isolates, CNPSo-168 (C168) and Tabatinga (Tb), using genomic and phenotypic analyses. Whole-genome sequencing revealed circular dsDNA genomes of 139,290 bp (154 ORFs) for C168 and 139,131 bp (153 ORFs) for Tb, both encoding the 38 baculovirus core genes and sharing >98.9% identity with reference genomes. Comparative genomics identified 431 SNPs, including 132 nonsynonymous changes in structural, regulatory, and infection-related genes. At low concentrations, C168 showed an approximately 2-fold lower LC₅₀ than Tb (higher potency), while both achieved near-complete mortality within 8 days at higher concentrations. This greater potency at lower concentrations reinforces the efficacy-based rationale for selecting isolate C168 for biocontrol applications. Infection reduced larval growth, pupation, and adult emergence, often with developmental impairments. Despite genetic differences, both isolates were highly UV-sensitive, and formulation tests indicated that titanium dioxide combined with kaolin conferred partial protection. These results provide insights into ChinNPV diversity and support its development as a sustainable tool for soybean pest management. Full article

Implant-associated infections remain a major clinical challenge, often leading to implant failure, revision surgery, and increased healthcare burden. Systemic antibiotic administration is limited by poor local bioavailability and systemic side effects, highlighting the need for localized drug-delivery systems that can simultaneously support tissue integration and prevent bacterial colonization. This study aimed to develop and characterize a novel generation of chitosan membranes loaded with hydroxyapatite–clindamycin phosphate (CS/HA-CLY) for localized infection prevention at implantation sites. The composite membranes’ physicochemical characteristics were analyzed using ATR FT-IR, XPS, SEM, XRD, and contact angle measurements. Furthermore, the in vitro biomineralization potential was assessed employing the Taguchi method, while the in vitro release of clindamycin phosphate was examined through UV-Vis spectrophotometry. The CS/HA-CLY membranes exhibited improved wettability, drug release behavior, and biomineralization ability compared to neat CS. These results suggest that the developed composite membranes could successfully combine antibacterial efficacy and biocompatibility, supporting their potential as multifunctional biomaterials for preventing implant-related infections while promoting tissue integration. These findings provide a promising basis for further biological assays and in vitro evaluation. Full article

Sexually transmitted infections, notably herpes simplex virus, remain significant global health concerns. Localized delivery systems that provide sustained antiviral activity at mucosal surfaces offer an attractive alternative to systemic therapies. In this study, we developed electrohydrodynamically deposited coatings utilizing a covalent acyclovir–poly (lactic-co-glycolic acid) (ACV–PLGA) conjugate for potential antiviral functionalization of medical devices. The ACV–PLGA prodrug was synthesized via drug-initiated ring-opening polymerization, yielding a copolymer characterized by FTIR, NMR, GPC, and DSC, with controlled drug loading and biodegradable properties. Systematic optimization of electrospinning and electrospraying parameters enabled the fabrication of both particulate and nanofibrous coatings on silicone ring models. Morphological analysis by SEM demonstrated that polymer concentration, solvent composition, and applied voltage critically governed coating architecture, ranging from microparticle layers to uniform bead-free fibers. In vitro studies revealed morphology-dependent degradation profiles and sustained release of ACV over 56 days. This integrated approach combining covalent prodrug synthesis with tunable electrohydrodynamic deposition offers a promising strategy for long-acting local antiviral prophylaxis via functionalized medical surfaces. Full article

The dental pulp is a dynamic connective tissue essential for tooth vitality, sensory function, immune defense, and reparative dentinogenesis. Conventional endodontic procedures, while effective in eradicating infection, often result in a non-functional, devitalized tooth, highlighting the need for biologically based regenerative approaches. The emergence of three-dimensional (3D) culture systems has transformed pulp biology and endodontic research by providing physiologically relevant microenvironments that better reproduce the dentino-pulp interface, vascular and neural networks, and immune interactions. This review synthesizes current advances in 3D dental pulp modeling, from scaffold-based and hydrogel systems to spheroids, organoids, bioprinted constructs, and microfluidic “tooth-on-a-chip” platforms. Each system’s composition, biological relevance, and translational potential are critically examined with respect to odontogenic differentiation, angiogenesis, neurogenesis, and inflammatory response. Applications in disease modeling, biomaterial screening, and regenerative endodontics are highlighted, showing how these models bridge fundamental biology and therapeutic innovation. Finally, we discuss key challenges including vascularization, innervation, standardization, and clinical translation, and propose integrative strategies combining bioprinting, stem-cell engineering, and organ-on-chip technologies to achieve functional pulp regeneration. Overall, 3D pulp models represent a paradigm shift from reductionist cultures to bioinstructive, patient-relevant platforms that accelerate the development of next-generation endodontic therapies. Full article

Fluconazole-resistant Candida parapsilosis has emerged as a significant nosocomial pathogen, contributing to extensive outbreaks with severe clinical implications. Despite increasing evidence of clonal transmission, the genetic mechanisms that facilitate the persistence of hospital reservoirs remain inadequately characterized. We aimed to characterise the long-term molecular epidemiology of fluconazole-resistant Candida parapsilosis bloodstream isolates (n = 47) collected between 1997 and 2019 at a tertiary centre. All isolates underwent microsatellite analysis using three polymorphic markers (CP1, CP4, B5). Genetic diversity, temporal distribution, and clonal relationships were assessed through phylogenetic analysis and discriminatory power calculations. Microsatellite analysis revealed minimal genetic diversity (combined discriminatory power: 0.7114), with only six distinct genotypes identified. Two dominant clones (Genotype-1: 23.4%, Genotype-2: 46.8%) persisted throughout the study, showing apparent spatiotemporal clustering in surgical and intensive care units. Phylogenetic analysis demonstrated tight genetic clustering, consistent with prolonged clonal persistence across multiple years and clinical departments. Our findings provide strong molecular evidence consistent with persistent, multi-year clonal transmission; however, definitive confirmation will require higher-resolution genomics and epidemiologic linkage. These results underscore the need to strengthen infection-control practices to curtail sustained clonal persistence within the hospital. Full article

Third molar extraction is a common oral surgical procedure that can be accompanied by challenges in wound healing and bone regeneration. Materials such as bone substitute materials (BSMs) and platelet-rich fibrin (PRF) are often used to support socket regeneration. This prospective randomized controlled split-mouth clinical trial compared PRF application combined with BSM versus PRF alone in patients requiring bilateral third molar extraction. A total of 15 patients underwent standardized osteotomy procedures, with sockets filled either with PRF alone (control group) or with BSM + PRF on opposite sides (test group) under general anesthesia and with patients blinded to the treatment allocation. Postoperative pain and swelling were measured over 7 days using a visual analog scale and anatomical distance measurements, respectively. Bone regeneration was evaluated using cone beam computed tomography (CBCT) scans after an average healing period of six months, with results showing no significant differences between groups in terms of postoperative pain or swelling (n = 12; 3 patients were lost to randomization). However, CBCT imaging revealed covered socket residuum (CSR)—non-mineralized areas within the socket—in the PRF only group, whereas the BSM + PRF group demonstrated more homogeneous and mineralized bone formation throughout the extraction sites (n = 8; 5 patients were lost to follow-up). These non-mineralized areas represent covered socket residuum within the extraction sockets, which poses a clinical risk of infection and may negatively affect the dental health of the adjacent second molar. Based on the presented findings, we recommend combining BSM with PRF to support bone regeneration and regulate the postoperative pain and swelling following third molar extraction. Nevertheless, further research is required to determine the most suitable BSM type in this regard. Full article

Plants exposed to combined abiotic and biotic stresses often exhibit complex physiological responses that cannot be predicted from single stress factors. In this study, we evaluated the interactive effects of temperature stress and Erwinia amylovora infection on pear (Pyrus pyrifolia) leaves under five temperature conditions (10, 15, 25, 30, and 35 °C) with or without pathogen inoculation, using chlorophyll fluorescence analysis and RGB imaging over a 7-day period. Photosynthetic performance remained optimal at 25 °C under single temperature conditions, whereas pathogen inoculation alone caused PSII damage and reduced energy dissipation. Under combined stress, PSII responses exhibited temperature-dependent patterns: at 10, 15 °C, photoprotective mechanisms were partially maintained; at 25, 30 °C, severe structural and functional damage occurred; and at 35 °C, pathogen activity was suppressed while partial recovery of PSII was observed. By integrating chlorophyll fluorescence analysis with a linear mixed-effect model (LMM), distinct patterns of sensitivity were identified among fluorescence parameters, with ΦNO responding to single stress factors, and Fm, Fv, Fp, Fv/Fo, and qL showing significant three-way interactions. These findings highlight temperature-dependent strategies of pear leaves to cope with fire blight and emphasize the utility of chlorophyll fluorescence analysis for evaluating photosynthetic resilience. From an applied perspective, chlorophyll fluorescence could serve as a rapid, non-destructive tool for screening pear cultivars with enhanced tolerance to bacterial fire blight, contributing to more efficient orchard management strategies. Full article