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Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard&#xae;) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n&#x202f;=&#x202f;53) or an untreated control group (n&#x202f;=&#x202f;51). Clinical evaluations were performed on Days 0, 15 (&#xb1;2), 30 (&#xb1;2), and 45 (&#xb1;2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p&#x202f;<&#x202f;.001), with large effect sizes at the final visit for all outcomes (r&#x202f;=&#x202f;0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals

The Brazilian contribution to ant toxinology: challenges and perspectives.

Ant toxinology in Brazil is a small but growing field that has revealed wide biochemical diversity and clear potential for bioprospecting therapeutic molecules. This review compiles the Brazilian contribution, focusing on advances in the characterization of venoms from medically and ecologically important species of Dinoponera, Solenopsis, Paraponera, Pachycondyla, Neoponera, and Ectatomma. Brazilian groups applied omics approaches, including transcriptomics and proteomics, to resolve the composition of these venoms and identified peptide-rich arsenals with antimicrobial, antiparasitic, antitumor, and neuroactive activity. Studies of venom phenotypic plasticity showed ecological factors such as diet and seasonality shape venom composition. Two challenges persist: assigning function to still unidentified components and obtaining venom in the quantities that broad analysis requires. The near-term prospects are the rational design of peptide analogues with improved activity and continued bioprospecting of new species, which together position Brazil as a central contributor to ant toxinology.

Animals

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96&#xa0;h-LC50 of the agent was determined to be 0.81&#xa0;mg/L, and exposure to 1.68&#xa0;mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96&#xa0;h-LC50 of the agent to juvenile M. edulis was 8.84&#xa0;mg/L, and 10&#xa0;mg/L of the agent completely inhibited mussel attachment within 24&#xa0;h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals

Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans

Sulfonic Ion-Exchange Resins as Versatile Tools for the Oxidative Degradation of Chemical and Biological Hazardous Agents.

Commercial sulfonic styrene-divinylbenzene ion-exchange resins are activated with aqueous H2O2 to generate metal-free decontamination systems that combine strong Br&#xf8;nsted acidity with immobilized oxidizing capability. Among five tested materials, Amberlyst 15 dry showed the best performance in terms of oxidant immobilization capacity and promoting the oxidative degradation of the sulfur mustard simulant (2-chloroethyl)ethyl sulfide, CEES, and the organophosphorus pesticide malathion under very mild conditions. Control experiments with K2CO3-exchanged resin demonstrate that efficient decontamination requires the synergy between surface acidity and peroxide functionality. The activated resins also display rapid biocidal activity, strongly reducing viable Escherichia coli and Staphylococcus aureus and completely suppressing the infectivity of HSV-1 and SARS-CoV-2 within min. These findings identify peroxide-activated sulfonic resins as simple, sustainable, regenerable, and versatile tools for efficient combined hazardous chemical and biological decontamination.

Oxidation-Reduction

Discovery and characterization of multifunctional bioactive peptides from Alaska Pollock (Gadus chalcogrammus) milt: hybrid in silico, in vitro, and proteomic approaches.

The growing demand for multifunctional bioactive peptides has sparked interest in underutilized marine by-products as sustainable bioresources. This study explored Alaska Pollock (Gadus chalcogrammus) milt protein as a novel source of peptides with anti-inflammatory, anti-hypertensive, and anti-diabetic effects. Protein composition was analyzed via LC-MS, followed by in silico digestion and bioactivity prediction. Molecular docking identified peptides targeting DPP-IV, &#x3b1;-glucosidase, ACE, GLP-1 receptor, COX-2, MuRF1, and the 20S proteasome. Among the candidates, a promising peptide (CLPPH) was synthesized and validated in vitro, demonstrating inhibitory effects on nitric oxide production, DPP-IV, ACE, and &#x3b1;-glucosidase. These results highlight CLPPH's potential as a multifunctional bioactive peptide and support the valorization of Alaska Pollock milt as a sustainable source for functional foods and nutraceutical applications.

Animals

Effect of Various Types of Remineralizing Agents on the Remineralization of Mild and Moderate Defects Caused by Molar-Incisor Hypomineralization in Mexican Schoolchildren: A 12-month Follow-up Randomized Clinical Trial.

PURPOSE: Using Laser-Induced Fluorescence (LIF), this study aimed to evaluate the effect of three remineralizing agents on permanent molars and incisors with both mild and moderate Molar-Incisor Hypomineralization (MIH) in 8-to-12-year-old Mexican schoolchildren. MATERIALS AND METHODS: In this randomized clinical trial, 104 children were selected to participate and then divided randomly into four groups: Group I: control, Oral-B kids (toothpaste); Group II: Fluor Protector (varnish); Group III: Clinpro White Varnish; and Group IV: MI Paste (CCP-ACP). Both varnishes were applied once every four weeks for twelve months for each group. Remineralization was evaluated by LIF at intervals of 1, 3, 6, 9, and 12 months. Paired-sample t-tests and repeated-measures ANOVA were performed, while the Greenhouse-Geisser correction was used to evaluate sphericity. RESULTS: The three test agents used increased the level of remineralization observed at the site of mild and moderate MIH defects over the course of twelve months (p0.001). A similar decrease in average LIF values was observed across the three treatment groups. CONCLUSIONS: The use of both fluoride varnishes and the CPP-ACP toothpaste was observed to promote the remineralization of both mild and moderate MIH defects.

Humans

Neuromuscular blocking agents for tracheal intubation of critically ill adults: a systematic review and meta-analysis.

BACKGROUND AND IMPORTANCE: Emergency tracheal intubation in critically ill adults is associated with a high risk of peri-intubation adverse events, making first-attempt success a key safety target. OBJECTIVE: This study aimed to evaluate whether the use of neuromuscular blocking agents (NMBAs) improves the proportion of first-attempt success and reduces adverse events during emergent intubations outside the operating room. METHODS: This was a systematic review and meta-analysis of randomized clinical trials or nonrandomized studies comparing sedative-hypnotic plus NMBA versus sedative-hypnotic alone in critically ill adults undergoing emergency endotracheal intubation in nonoperative settings. Animal, cadaveric, manikin/simulation, and pediatric studies were excluded. Articles were screened on 21 August 2025, in Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection. MAIN RESULTS: Of 4736 screened citations, 13 studies (8 cohort; 5 before-after studies) were included in the quantitative analysis, with 14&#x2005;072 participants. NMBA use was associated with higher first-attempt success, which ranged from 69 to 92% (pooled odds ratio, 2.72; 95% onfidence interval: 1.42-5.21; low-certainty evidence). Secondary outcomes related to adverse events were rated as very low certainty due to sparse data, inconsistent reporting, and serious imprecision. CONCLUSION: NMBA use during emergency intubation was associated with improved first-attempt success, although the certainty of evidence was low.

Humans

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8&#xa0;Da), and herbicolin B (1138&#xa0;Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5&#xa0;mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5&#xa0;mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea

Memantine Augmentation for Obsessive-Compulsive Symptoms in Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Obsessive-compulsive symptoms are frequently observed in patients with bipolar disorder and present a significant therapeutic challenge. This study evaluated the efficacy and safety of memantine as an adjunctive therapy for obsessive-compulsive disorder in patients with bipolar disorder. METHODS: In this randomized, double-blind, placebo-controlled trial, 46 patients with bipolar disorder and obsessive-compulsive disorder, stabilized on quetiapine and lithium, were randomly assigned to receive either memantine (n = 23) or placebo (n = 23) for 6 weeks. RESULTS: The memantine group showed a significant reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with the placebo group (Cohen d = 1.57 vs 0.42, P < 0.001). Nausea was the most common side effect, but overall adverse effects were minimal. CONCLUSION: Memantine appears to be a safe and effective adjunctive treatment for obsessive-compulsive disorder in patients with bipolar disorder, warranting further investigation.

Humans

Cationic porphyrin covalent organic framework reinforced hydroxypropyl methylcellulose films for photodynamic-photothermal sterilization and food preservation.

Microbial contamination in food necessitates effective antimicrobial packaging. While cellulose-based packaging materials suffer from limited antimicrobial efficacy, lack of active functionality, and susceptibility to inducing microbial resistance. To address these challenges, this study synthesized a cationic porphyrin-based covalent organic framework (Por-ICOF) as a multimodal photosensitizer. Por-ICOF was uniformly dispersed via non-covalent interaction within hydroxypropyl methylcellulose (HPMC), creating an HPMC/Por-ICOF composite film. This integration enhanced mechanical strength (increased by 26%), hydrophobicity (WCA 71&#xb0;), and gas barrier properties (OP reduced by 42%, WVP reduced by 36%). Under visible light, the HPMC/Por ICOF film superior absorption generated reactive oxygen species (ROS) and photothermal effects, inactivating 99.2% of Escherichia coli and 99.95% of Staphylococcus aureus within 20&#xa0;min. The composite film exhibited excellent biocompatibility and effectively extended the shelf life of strawberries. This cationic modification strategy for cellulose-based films offers a novel avenue for the design of high-performance antimicrobial food packaging materials.

Food Preservation

Biological characterization of Candida parapsilosis haploids induced by voriconazole.

OBJECTIVES: Candida parapsilosis is an important opportunistic fungal pathogen causing serious human infections in nosocomial settings. It has long been thought that C. parapsilosis has a diploid genome with a high homozygosity between chromosome homologs. METHODS: In this study, we report the discovery of C. parapsilosis haploids induced by voriconazole, a triazole with broad antifungal activity against fungal pathogens, in an experimental evolutionary assay. RESULTS: The haploid strains were able to undergo auto-diploidization under in vitro culture conditions or during systemic infection at a low frequency. Compared to the progenitor diploid strain, C. parapsilosis haploid and auto-diploid strains exhibited a reduced ability of invasive growth and biofilm formation. Global transcriptional expression analysis indicated that haploid and auto-diploid strains had a similar transcriptomic profile, which showed a remarkable difference from the progenitor diploid strain perhaps due to the loss of chromosome heterozygosity. Moreover, the haploid and diploid strains had distinct fungal burdens in different animal tissues, suggesting the haploid state could have a colonization advantage over the diploids in certain tissues such as the brain and spleen. CONCLUSIONS: The discovery of C. parapsilosis haploids not only sheds lights on the biology of this important fungal pathogen, but also provides a tool for genetic modifications for the field.

Voriconazole

Effectiveness of different anaesthetic techniques, agents and adjunctive interventions in handling pain during dental treatment of MIH-affected teeth: a systematic review.

BACKGROUND: Molar incisor hypomineralisation (MIH) is frequently associated with hypersensitivity, dental anxiety and reduced efficacy of local anaesthesia, complicating pain control during dental treatment in children. AIM: To evaluate, based exclusively on randomised controlled trials (RCTs), the effectiveness of different local anaesthetic techniques, agents and adjunctive interventions in reducing pain during dental treatment of MIH-affected teeth in children. METHODS: A systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD420251150485). MEDLINE, Cochrane Central, ScienceDirect, SCOPUS, EBSCO, and LILACS were searched up to September 2025. Eligible studies were RCTs involving children and adolescents (6 - 18&#xa0;years-of-age) with MIH, assessing pain outcomes during dental procedures. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: Eight RCTs were included. Low-certainty evidence suggested that intraosseous anaesthesia and 4% articaine may reduce intra-operative pain compared with conventional techniques or 2% lidocaine. Adjunctive cryotherapy and pre-emptive ibuprofen showed potential benefits, but evidence was of very low certainty and limited to single trials. Findings for photobiomodulation were inconsistent across studies. Most trials were judged to be at high risk of bias, primarily due to lack of blinding and reliance on subjective pain outcomes. CONCLUSION: Current evidence supporting specific pain management strategies for MIH-affected teeth is limited and of low certainty. Whilst 4% articaine and intraosseous anaesthesia appear promising, well-designed, adequately powered RCTs with standardised pain outcomes are required to inform robust clinical recommendations.

Local anaesthesia

Pharmacogenomic and drug interactions risk in cardio-oncology: A precision medicine perspective for India.

Cardio-oncology patients may face complex treatment regimens due to the concurrent existence of cancer and cardiovascular disease, leading to a considerable polypharmacy burden. This significantly increases the prospect of drug-drug interactions (DDIs) and gene-drug interactions. The majority of these interactions arise from comparable pharmacokinetic and pharmacological pathways associated with drug transporters and cytochrome P450 enzymes. The significance of pharmacogenomics in tailored treatment strategies are emphasised by the fact that genetic variability enhances individual differences in drug response, safety, and efficacy. This narrative review focus on the effects of key genetic polymorphisms (e.g., DPYD, CYP2C19, and CYP2C9) on the metabolism and efficacy of commonly prescribed anticancer and cardiovascular medications such as fluoropyrimidines, clopidogrel, and warfarin. In addition it explore the role of pharmacogenomic variants on drug-drug interactions within the field of cardio-oncology. The study ultimately emphasizes the necessity of precision medicine in India to address the genetic diversity and underrepresentation in global genomic databases. The absence of pharmacogenomic testing, infrastructural deficiencies, financial constraints, and insufficient clinical integration hinder the widespread use of this technology in India. The Genome India Project and other national initiatives establish the foundation for pharmacogenomic-guided therapy. Utilizing genetic data, together with artificial intelligence-based predictive tools, for clinical decision-making may enhance medication safety and yield optimal outcomes in Indian cardio-oncology patients.

Humans

Integrated assessment of biocontrol potential and genome analysis of endophytic Bacillus velezensis MGL-B1 against mango stem-end rot.

Mango stem-end rot is a globally significant postharvest disease that severely threatens the mango industry, primarily caused by Botryosphaeria dothidea. However, information on biocontrol agents targeting this pathogen in mango remains limited. In this study, we isolated and identified a strain of Bacillus velezensis MGL-B1 from mango leaf tissues for the first time, which exhibited broad-spectrum antifungal activity. Both in vitro and in vivo assays demonstrated that MGL-B1 effectively inhibited the growth of B. dothidea, with an in vivo biocontrol efficacy reaching 83.72&#xa0;&#xb1;&#xa0;5.10%, comparable to that of the commonly used chemical fungicide thiabendazole. Further mechanistic analysis revealed that MGL-B1 acts by directly disrupting the integrity of the pathogen's mycelial cell membrane. In addition, its released volatile organic compounds (VOCs) also displayed significant antifungal activity, with components such as 2-nonanone, 2-nonanol, and phenylethyl alcohol being confirmed to exert antifungal effects in in vitro fumigation assays. qPCR analysis showed that MGL-B1 treatment significantly upregulated the transcriptional levels of genes involved in plant-pathogen interaction, phenylpropanoid biosynthesis, and antioxidant defense pathways in mango fruits, with upregulation folds of 16.32, 37.19, and 75.93, respectively; meanwhile, the expression of browning-related genes such as polyphenol oxidase (PPO) was markedly suppressed. Whole-genome sequencing further revealed 14 biosynthetic gene clusters for antimicrobial compounds, including five unknown gene clusters. Collectively, B. velezensis MGL-B1 represents a promising biocandidate strain with multiple antifungal mechanisms and excellent control efficacy, providing a valuable resource for green and sustainable management of mango diseases.

Mangifera