Search Results (292)

Bovine mastitis, particularly that caused by Staphylococcus aureus, presents a major challenge to dairy production worldwide due to its economic impact, animal welfare concerns, and zoonotic potential. This narrative review synthesizes current literature on the epidemiology, pathogenesis, resistance patterns, and control strategies related to S. aureus-associated mastitis in dairy cattle. It highlights the pathogen’s virulence mechanisms, such as biofilm formation, immune evasion, and toxin production, that facilitate persistent infections. The review compiles global prevalence data, revealing significant geographic variation and disparities between clinical and subclinical cases. Antimicrobial resistance, especially the emergence of methicillin-resistant S. aureus (MRSA), is extensively examined alongside resistance gene profiles. Diagnostic approaches, including culture, PCR, MALDI-TOF MS, and AI-based systems, are evaluated for their sensitivity and field applicability. Additionally, the review addresses public health implications, zoonotic risks, and One Health perspectives, culminating in an exploration of prevention strategies, including improved hygiene, vaccination, dry cow therapy, and AI-driven herd management. The findings emphasize the urgent need for integrated surveillance, precision diagnostics, and targeted interventions to mitigate the burden of S. aureus mastitis. Full article

Background: Botulinum toxin type A (BoNT/A) is widely used in both clinical and aesthetic settings to induce temporary neuromuscular paralysis by inhibiting acetylcholine release. Although generally regarded as safe and effective, complications such as iatrogenic ptosis or facial asymmetry may occur and persist for several weeks or even months, with no standardized method currently available to accelerate recovery. Objective: This article explores the hypothesis that photobiomodulation (PBM)—a non-invasive modality recognized for its neuroregenerative potential—may facilitate the reversal of BoNT/A-induced neuromuscular blockade. Discussion: PBM enhances mitochondrial activity by stimulating cytochrome c oxidase in nerve and muscle tissues, thereby increasing ATP production and modulating intracellular signaling pathways associated with neuroplasticity, cell survival, and synaptogenesis. Preclinical studies have demonstrated that PBM can upregulate neurotrophic factors (e.g., BDNF, NGF), enhance SNAP-25 expression, and promote structural remodeling of neurons in both young and aged brains. These mechanisms are biologically consistent with the regenerative processes required for recovery from BoNT/A-induced effects. While controlled clinical trials for this specific application are currently lacking, anecdotal clinical reports suggest that PBM may accelerate functional recovery in cases of BoNT/A-related complications. Conclusions: Although this approach has not yet been tested in clinical trials, we propose that photobiomodulation may hypothetically serve as a supportive strategy to promote neuromuscular recovery in patients experiencing adverse effects from BoNT/A. This hypothesis is grounded in robust preclinical evidence but requires validation through translational and clinical research. Full article

Background: Rapid loss of residual kidney function (RKF) is associated with unfavorable outcomes. We conducted an RCT to compare the effects on RKF preservation of incremental HD between once-weekly HD (1-WHD) and twice-weekly HD (2-WHD). Methods: ESKD patients with an eGFR of 5–10 mL/min/1.73 m² and urine output of ≥800 mL/day were randomly assigned to receive either once-weekly HD (1-WHD) or twice-weekly HD (2-WHD) for 12 months. Patients in the 1-WHD group were prescribed once-weekly HD combined with low-protein diet (0.6 g/kg/day) supplemented with keto-analogues (KAs) 0.12 g/kg/day. In the 2-WHD group, patients received twice-weekly HD with a regular-protein diet. Primary outcomes were changes in RKF by renal clearance and urine volume. Nutritional status, muscle parameters, and quality of life (QoL) were also assessed. Results: A total of 30 incident HD patients were randomized. Baseline RKF, urine volume, and demographic were not different between groups. After 3 months, urine volume was significantly higher in the 1-WHD group than in the 2-WHD group (1921 ± 767 mL/day vs. 1305 ± 599 mL/day, p = 0.02), and these significant findings persisted throughout the entire study period. For RKF, 1-WHD also had a lesser decline in urinary urea (CUrea) and creatinine clearance (CCr) than 2-WHD, with statistically significant differences observed from months 6–12. By month 6, the 1-WHD group exhibited significantly higher CUrea and CCr compared to the 2-WHD group, with CUrea at 3.2 ± 2.3 vs. 1.7 ± 1.0 mL/min (p = 0.03) and CCr at 5.9 ± 3.6 vs. 3.8 ± 1.4 mL/min (p = 0.04), respectively. Serum albumin levels, skeletal muscle mass, anemia status, metabolic parameters, protein-bound uremic toxins, and QoL scores were comparable between the two groups. Conclusions: Incremental HD, starting with once-weekly HD combined with protein restriction supplemented with KAs, appears to better preserve RKF among incident HD patients compared to twice-weekly HD with a regular-protein diet. This HD regimen was also associated with safety in metabolic and nutritional profiles. Full article

The management of end-stage kidney disease (ESKD) poses a substantial clinical and economic challenge, characterized by a growing patient burden, rising healthcare costs, and persistent unmet needs to enhance survival outcomes and quality of life. Background/Objectives: Conventional high-flux hemodialysis (HD) remains the dominant form of renal replacement therapy for ESKD but is still associated with substantial morbidity and mortality. High-volume post-dilution online hemodiafiltration (HVHDF) offers a promising alternative by enhancing the convective removal of uremic toxins. Methods: We conducted a narrative review of randomized controlled trials, meta-analyses, real-world cohort studies, and registry analyses published between 2010 and 2024. Evidence was categorized into short-term, medium-term, and long-term outcomes, including hemodynamic stability, inflammation, anemia, infection risk, cardiovascular events, cognitive decline, quality of life, and survival. Results: HVHDF improves short-term outcomes by enhancing toxin clearance, stabilizing blood pressure, reducing inflammation and oxidative stress, and improving anemia management. Medium-term benefits include improved nutritional status, reduced hospitalizations related to infections, and improved neurological and immune function. Long-term data from major trials (e.g., ESHOL, CONVINCE) and large real-world studies show consistent reductions in all-cause and cardiovascular mortality, particularly with convection volumes ≥ 23 L/session. A clear dose–response relationship supports the clinical relevance of convection volume targets. HVHDF has also shown benefits in preserving cognitive function and enhancing health-related quality of life. Conclusions: Strong and converging evidence supports HVHDF as a superior dialysis modality. Given its survival benefits, better tolerance, and broader impact on patient outcomes, HVHDF should be considered the new standard of care in dialysis, especially in light of the recent regulatory approval of the machine that provides the ability to perform HDF in the United States. Full article

Pyrrolizidine alkaloids are plant-derived toxins with environmental persistence and the potential to contaminate soil, water, and adjacent crops. This study investigated the leaching behavior and environmental fate of PAs from two PA-producing weeds—Myosotis arvensis L. (Boraginaceae) and Senecio vulgaris L. (Asteraceae)—in two Latvian agricultural soils: sandy loam and loam. Hot- and cold-water plant extracts were applied to soil columns (10 cm and 20 cm), and leachates were analyzed over a 14-day period using QuEChERS purification and LC-HRMS detection. Leaching varied by plant species, extract type, and soil. M. arvensis showed significantly higher cumulative leaching (77–84% for cold, 65–71% for hot extracts), attributed to the higher solubility of N-oxides. In contrast, S. vulgaris extracts leached minimally (<0.84% from sandy loam) and were undetectable in loam. The presence of cyclic diester PAs in S. vulgaris and the higher cation exchange capacity of loam favored retention or degradation. PANO-to-PA conversion occurred in both soils, indicating redox activity. The fate of PAs was influenced by structural type (diesters showing higher persistence), extraction method (hot extraction releasing more pyrrolizidine alkaloids), and soil properties such as pH, organic matter, and cation exchange capacity, which affected sorption and mobility. These findings underscore the significance of soil composition in controlling PA mobility and associated environmental risks. Future research should focus on long-term PA persistence across diverse soil types and investigate crop uptake potential and microbial degradation pathways under field conditions. Full article

Introduction: Genetic plasticity and adaptive camouflage in critical pathogens have contributed to the global surge in multidrug-resistant (MDR) infections, posing a serious threat to public health and therapeutic efficacy. Antimicrobial resistance, now a leading cause of global mortality, demands urgent action through diagnostics, vaccines, and therapeutics. In India, the Indian Council of Medical Research’s surveillance network identifies Escherichia coli as a major cause of urinary tract infections, with increasing prevalence in human gut microbiomes, highlighting its significance across One Health domains. Methods: Whole-genome sequencing of E. coli strain ECG015, isolated from a human gut sample, was performed using the Illumina NextSeq platform. Results: Genomic analysis revealed multiple antibiotic resistance genes, virulence factors, and efflux pump components. Phylogenomic comparisons showed close relatedness to pathovars from both human and animal origins. Notably the genome encoded protein tyrosine kinases (Etk/Ptk and Wzc) and displayed variations in the envelope stress-responsive CpxAR two-component system. Promoter analysis identified putative CpxR-binding sites upstream of genes involved in resistance, efflux, protein kinases, and the MazEF toxin–antitoxin module, suggesting a potential regulatory role of CpxAR in stress response and persistence. Conclusions: This study presents a comprehensive genomic profile of E. coli ECG015, a gut-derived isolate exhibiting clinically significant resistance traits. For the first time, it implicates the CpxAR two-component system as a potential central regulator coordinating antimicrobial resistance, stress kinase signaling, and programmed cell death. These findings lay the groundwork for future functional studies aimed at targeting stress-response pathways as novel intervention strategies against antimicrobial resistance. Full article

Vesicoureteral reflux (VUR) management in children with neurogenic bladder dysfunction (NBD) remains a clinical challenge. Total endoscopic management (TEM), combining intradetrusor Onabotulinum Toxin-A (BTX-A) and subureteric dextranomer/hyaluronic acid (Deflux^(R)) injection, offers a minimally invasive alternative. The aim of this retrospective study is to evaluate the long-term effectiveness of TEM. Inclusion criteria: symptomatic II–V grade VUR (also I in bilateral VUR) in NBD children with follow-up ≥12 months. Nineteen patients were enrolled, 24 ureters (grade I–II: 2, grade III–V: 22); 5 patients (20.8%) had bilateral VUR. Mean age at surgery: 7.6 years (1.3–17). No complications were reported. TEM was effective in 11 patients (57.9%), 3/11 requiring a second TEM treatment. VUR resolution appeared in 14 ureters (58.3%), downgrading in 6 (42.9%), persistence in 4 (28.6%). Among non-responders’ patients (8/19, 42.1%), five (26.3%) required bladder augmentation (one combined with ureteral reimplantation), one (5.3%) underwent reimplantation, and two (10.5%) continued conservative management. At bladder biopsy, 11 patients (57.9%) had chronic inflammation, 8 (42.1%) showed fibrosis; no difference in success rate was recorded. All responders required repeated BTX-A injections. Mean follow-up: 3.2 years (range 1–4.7). In selected patients, TEM appears to be a safe and effective strategy, potentially delaying or avoiding major reconstructive surgery. Full article

Botulinum toxin is a neurotoxin that is used in the treatments for several medical conditions, such as dystonia, spasticity, hemifacial spasm, overactive bladder, and hyperhidrosis. This toxin can potentially treat several pain disorders through botulinum toxin’s ability to inhibit the release of pro-nociceptive neurotransmitters into the synaptic cleft and its possible action on the central nervous system. This narrative review addresses the use of botulinum toxin in treating primary and secondary headaches and facial pain disorders. The highest level of evidence supporting its use varies among the headache and facial pain disorders: chronic migraine (multicenter, double-blind, placebo-controlled studies), trigeminal neuralgia (double-blind, placebo-controlled studies), post-traumatic headache (double-blind, placebo-controlled study), cluster headache (open-label clinical trials), nummular headache (open-label clinical trial), headache attributed to craniocervical dystonia (prospective cohort study), new daily persistent headache (retrospective cohort study), hemicrania continua, and SUNCT and SUNA (case reports). The site of toxin application and the doses used vary among the studies and depending on headache type. Botulinum toxin has been shown to be safe in different studies, with generally mild adverse reactions. Full article

Clostridioides difficile is a Gram-positive bacterium recognized for its ability to produce toxins and form spores. It is mainly accountable for the majority of instances of antibiotic-related diarrhea. Background. Bacterial persister represent a minor fraction of the population that shows temporary tolerance to bactericidal agents, and they pose considerable medical issues because of their link to the rise of antibiotic resistance and challenging chronic or recurrent infections. Our previous research has shown a persister-like phenotype associated with treatments that include pefloxacin. Nonetheless, the mechanism is still mostly unclear, mainly because of the difficulty in isolating this small group of cells. Objectives. To enhance the understanding of C. difficile persister cells, we made an enrichment and characterization of these cells from bacterial cultures during the exponential phase under pefloxacin treatment and lysis treatment. Results. We demonstrate the appearance of cells with lower metabolism and DNA damage. Furthermore, we noted the participation of toxin–antitoxin systems and Clp proteases in the generation of persister cells. Conclusions. This work demonstrates the formation of C. difficile persister cells triggered by a lethal concentration of pefloxacin. Full article

Chronic kidney disease (CKD) is a global health burden, with uremic toxins (UTs) playing a central role in its pathophysiology. In this review, we systematically examined the evolution of UT classification from the 2003 European Uremic Toxin Work Group (EUTox) system based on molecular weight and protein-binding properties to the 2023 multidimensional framework integrating clinical outcomes, clearance technologies, and artificial intelligence. We highlighted the toxicity mechanisms of UTs across the cardiovascular, immune, and nervous systems and evaluated traditional (e.g., low-/high-flux hemodialysis) and advanced (e.g., high-cutoff dialysis and hemoadsorption) clearance strategies. Despite progress, challenges persist in toxin detection, clearance efficiency, and personalized therapy. Future directions include multi-omics-based biomarker discovery, optimized dialysis membranes, advanced adsorption technology, and AI-driven treatment personalization. This synthesis aims to bridge translational gaps and guide precision medicine in nephrology. Full article

Aggressive cancer cells can form new, functional blood vessel-like structures independently of endothelial cells, known as vasculogenic mimicry (VM), instead of the usual tumor blood vessel formation process. However, the symbiotic relationship between microbial communities and human cells ensures the upkeep of cellular metabolism and the functionality of the immune system and metastatic cancers. This interaction typically happens through the generation and management of hormonal intermediates, metabolites, secondary metabolites, proteins, and toxins. A disturbance in the balance between the host and microbiota can alter the dynamics of their relationship, creating a conducive environment for the development of diseases, such as cancers. This review aims to synthesize the initial evidence on the molecular processes governing the interactions between GM and cancer development and emphasize microbial metabolites’ effects on vasculogenic mimicry. Some microbial metabolites could also contribute to developing interactions between microbes and the tumor microenvironment. While numerous obstacles persist, GM’s immense significance and complete capability in shaping tailored anticancer plans cannot be exaggerated, highlighting the need to investigate a holistic method that includes microbial modulation therapy in cancer management. Full article

If lettuce is contaminated in the field, Shiga toxin-producing E. coli (STEC) O157:H7 can survive through the distribution chain. Prolonged cold storage during transportation may impact pathogen physiology, affecting subsequent stress survival and virulence. Greenhouse-grown Romaine lettuce, inoculated with three STEC O157:H7 strains, was harvested after 24 h and stored at 2 °C for 5 d following 4 h at harvest temperature (9 °C or 17 °C). Culturable, persister, and viable but non-culturable (VBNC) cells were quantified. Virulence was evaluated using Galleria mellonella and acid tolerance at pH 2.5 and tolerance to 20–25 ppm free chlorine were quantified. Colder harvest temperature (9 °C) before cold storage led to greater transformation of STEC O157:H7 into dormant states and decreased virulence in most cases. Increasing length of cold storage led to decreased virulence and acid tolerance of STEC O157:H7 on lettuce, while having no significant effect on chlorine tolerance. These findings highlight that entry of STEC O157:H7 into dormant states during harvest and transportation at cold temperatures leads to decreased stress tolerance and virulence with increasing cold storage. Changes in STEC O157:H7 physiology on lettuce during cold storage can be integrated into risk assessment tools for producers, which can assist in identifying practices that minimize risk of STEC O157:H7 from consumption of lettuce. Full article

Staphylococcus aureus is a formidable human pathogen responsible for infections ranging from superficial skin lesions to life-threatening systemic diseases. This review synthesizes current knowledge on its pathogenesis, emphasizing colonization dynamics, virulence mechanisms, biofilm formation, and antibiotic resistance. By analyzing studies from PubMed, Scopus, and Web of Science, we highlight the pathogen’s adaptability, driven by surface adhesins (e.g., ClfB, SasG), secreted toxins (e.g., PVL, TSST-1), and metabolic flexibility in iron acquisition and amino acid utilization. Nasal, skin, and oropharyngeal colonization are reservoirs for invasive infections, with biofilm persistence and horizontal gene transfer exacerbating antimicrobial resistance, particularly in methicillin-resistant S. aureus (MRSA). The review underscores the clinical challenges of multidrug-resistant strains, including vancomycin resistance and decolonization strategies’ failure to target single anatomical sites. Key discussions address host–microbiome interactions, immune evasion tactics, and the limitations of current therapies. Future directions advocate for novel anti-virulence therapies, multi-epitope vaccines, and AI-driven diagnostics to combat evolving resistance. Strengthening global surveillance and interdisciplinary collaboration is critical to mitigating the public health burden of S. aureus. Full article

Antibiotics are commonly used to aid in the remission of gastrointestinal diseases, but usage may lead to prolonged dysbiosis. The objective of this study was to evaluate the effects of metronidazole on fecal microbiota, fecal metabolites, and serum bile acids and uremic toxins of healthy adult cats. Twelve healthy adult cats (4.7 ± 0.4 yr) received metronidazole (20 mg/kg BW PO BID) for 14 days (day 0–14) and were monitored during a 28-day recovery period (day 15–42). Fecal and blood samples were collected at baseline (day 0), after metronidazole (day 14), and weekly during recovery (on days 21, 28, 35, and 42). Fecal samples were analyzed for microbiota and bacterial metabolites. Serum samples were analyzed for bile acids and uremic toxins. Metronidazole increased dysbiosis index and fecal lactate concentrations (p < 0.0001) and decreased fecal propionate, butyrate, and secondary bile acid concentrations (p < 0.0001) for up to 28 days. Prolonged dysbiosis and Peptacetobacter (Clostridium) hiranonis reductions were observed in 10/12 (83%) cats. Serum uremic toxins were also reduced (p < 0.0001) after metronidazole administration. The observed changes after metronidazole administration illustrate how changes in the gut microbiome alter microbial metabolism and its relation to host dysmetabolism. In conclusion, metronidazole is a potent antibiotic with persistent effects observed in the microbiome and metabolome, even up to one month after administration. Full article

Botulinum toxin type A (BoNT-A), a potent neurotoxin, is increasingly used to treat myogenic temporomandibular disorders (TMDs); however, the interplay between muscle atrophy and pain relief remains incompletely understood. This pilot study investigated how masseter and temporalis muscle thickness and pain intensity change over 12 weeks following BoNT-A injections in 15 patients (mean age 51.42 years) with myogenic TMD. Muscle thickness was measured via ultrasonography across multiple anatomical positions under both clenching and resting conditions at baseline and at 2, 4, 8, and 12 weeks post-injection. Significant thinning of both muscles occurred within 2 weeks, lasting until 12 weeks, but became less pronounced after the first month. Pain intensity showed parallel decreases, most notably early on, but these reductions were not consistently statistically significant. Correlation analyses revealed no strong persistent association between muscle thickness and pain except for a moderately positive correlation in the anterior temporalis at two weeks (r = 0.61, p = 0.04). BoNT-A induces rapid masticatory muscle atrophy and modest pain relief; however, these outcomes do not coincide. Pain relief was observed earlier than the full development of muscle atrophy and should be considered during TMD pain management. Full article