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SUMMARYReptiles are a diverse and speciose class of animals that are broadly threatened by habitat loss, climate change, and other factors. From a microbiological perspective, reptiles have historically been examined as a source of disease, particularly salmonellosis, with most studies being culture-based investigations into causative agents of disease and potential for zoonoses. More recent work has sought to characterize the oral, skin, and gut microbiomes of reptiles more broadly to understand their contribution to reptile health and digestion. Non-avian reptiles are particularly interesting as ectothermic tetrapods, which usually lay eggs and have limited interaction with their young, as their digestion and life history strategies diverge substantially from the more well-studied mammals. Here, we review the reptile skin, oral, gut, eggshell, and nest microbiomes, along with the relationship between the microbiome and temperature stress. We present findings that distinguish the reptile microbiome from those of other studied vertebrate taxa, and place them in the context of their phylogenetic and ecological similarities to other animals. We discuss major disease-causing agents in reptiles, which was historically the main lens through which to view reptile microbiology, along with potential zoonoses. Finally, we examine how temperature and thermoregulation interact with the microbiome in reptiles, and how the microbiome may play a role in reptile conservation.

Mammary tumors are among the most common neoplasms in dogs and cats, and malignant forms are clinically important in both species. Surgery remains the main treatment approach and may be combined with other treatment modalities, but advanced cases are often associated with recurrence and limited responsiveness to conventional therapies. Phytochemicals and plant extracts have received attention as potential adjuvant agents that can modulate pathways associated with oncogenesis and treatment resistance. Natural products are often accessible and relatively inexpensive, and their perception as well-tolerated agents may increase owner acceptance. Some plant extracts and phytochemicals, including Euphorbia royleana extract, celastrol, and homoharringtonine have shown potent preclinical activity in canine mammary tumor cell lines and xenograft models, but data for feline mammary tumors are still limited. However, their safety and efficacy depend on multiple factors such as the compound, dose, formulation, and species. Further studies are required for clinical translation, as species-specific pharmacokinetics significantly affect efficacy and safety. This review summarizes current knowledge on plant extracts and phytochemicals in canine and feline mammary tumors, focusing on their preclinical evidence, limitations, and future translational challenges in veterinary oncology.

Few conditions in reproductive medicine rival polycystic ovary syndrome (PCOS) in terms of clinical breadth and global impact. Affecting roughly 6-21% of women of childbearing age depending on which diagnostic criteria are applied PCOS sits at the intersection of endocrinology, metabolism, and gynecology, making it difficult to capture within any single disciplinary lens. Its hallmarks are well rehearsed: excess androgens, disrupted ovulation, and the characteristic follicular architecture seen on pelvic ultrasound. Yet what makes PCOS genuinely challenging is the degree to which these reproductive features overlap with far-reaching metabolic consequences, including insulin resistance, type 2 diabetes, lipid abnormalities, and a meaningfully elevated cardiovascular risk profile that persists well beyond the fertile years. Despite several decades of sustained investigation, the origins of PCOS remain imperfectly understood. Genetic susceptibility, epigenetic programming, environmental chemical exposures, and modern dietary habits all appear to play contributory roles, though no single culprit has emerged. The molecular picture is equally layered: aberrant insulin signaling feeds androgen overproduction, gonadotropin secretion goes out of balance, inflammatory cytokines accumulate, oxidative injury mounts, and more recently the gut microbial community has been implicated as an additional participant in this cascade. Diagnosis is further complicated by the phenotypic variability of the syndrome, with different criteria yielding meaningfully different patient populations. Treatment, in turn, requires individualization; lifestyle change, hormonal therapies, insulin sensitizers, and an expanding repertoire of repurposed drugs and plant-based agents each address different facets of a fundamentally heterogeneous disorder. This review provides a comprehensive and integrated account of PCOS across its full biological and clinical spectrum. It covers epidemiology, clinical presentation, risk factors, and current diagnostic frameworks. Pathophysiological mechanisms are examined in depth. A central and distinctive focus of this review is the experimental preclinical landscape. Established animal induction models, letrozole, dehydroepiandrosterone (DHEA), testosterone/dihydrotestosterone propionate, and high-fat diet protocols are critically evaluated for their translational relevance. Drawing on these models, we comprehensively catalogue protective agents across four systematic tables, encompassing both repurposed pharmaceuticals (metformin, GLP-1 receptor agonists, SGLT-2 inhibitors, statins, melatonin) and bioactive natural compounds (curcumin, berberine, quercetin, fisetin, myricetin, apigenin, and others), detailing their induction models, mechanistic pathways, and therapeutic outcomes. Together, this review aims to serve as a single, authoritative reference bridging basic science, translational pharmacology, and clinical practice in PCOS, while identifying the most promising avenues for future research and personalized therapeutic development.

Cervical cancer remains a major global health burden, particularly in low- and middle-income countries, necessitating the discovery of novel, accessible anticancer agents. Marine macroalgae, including Halymenia durvillaei, are rich in bioactive compounds with promising therapeutic potential. H. durvillaei collected from North Sulawesi, Indonesia, was extracted with methanol and fractionated into n-hexane, chloroform, ethyl acetate, and aqueous fractions. Phytochemical profiling and cytotoxicity were assessed using the brine shrimp lethality test (15.625-1000 µg/mL) and MTT assay against HeLa cells treated with extract fractions (0.125-2 mg/mL) for 72 h. The most bioactive fraction was subjected to GC-MS characterization. Major compounds identified were evaluated through molecular docking against Vaccinia H1-related phosphatase (VHR; PDB ID: 3F81) using AutoDock Vina/CB-Dock2, followed by 100 ns molecular dynamics simulation and ADMET prediction. Phytochemical screening confirmed the presence of flavonoids (2.91 mg QE/g), alkaloids (1.03 mg/g), tannins, saponins, and steroids. The chloroform fraction exhibited the highest cytotoxicity (LC₅₀ = 33.83 µg/mL), while ethyl acetate, n-hexane, chloroform, and aqueous fractions inhibited 70-93% of HeLa cell proliferation. GC-MS analysis identified oleic acid as a major compound. In silico studies revealed stable binding of oleic acid to VHR phosphatase, a protein implicated in cervical cancer progression, supported by favorable ADMET properties. H. durvillaei demonstrates significant cytotoxic and antiproliferative activities, highlighting its potential as a source of natural anticancer agents. However, further compound isolation and mechanistic validation are required to confirm its therapeutic relevance.

Temporomandibular disorders (TMDs) comprise a group of multifactorial conditions involving the masticatory muscles, temporomandibular joint, and associated structures influenced by biomechanical, neuromuscular, and biopsychosocial factors. Myogenous TMDs may involve muscle hyperactivity, parafunction, and central sensitization, contributing to chronic pain and functional limitation. Oral skeletal muscle relaxants (SMRs) are commonly used as adjunctive pharmacologic therapy; however, these agents vary considerably in mechanism, efficacy, and safety. This review summarizes the pharmacology, clinical evidence, and risk profiles of commonly prescribed SMRs-including cyclobenzaprine, baclofen, tizanidine, and others-within the context of chronic TMD management. Evidence supports short-term benefit for select agents, though data for chronic daily use remain limited. Given concerns regarding sedation, dependence, hepatotoxicity, and interactions with polypharmacy, clinicians should employ these medications judiciously and primarily for acute exacerbations rather than long-term therapy. An evidence-based, multimodal approach remains essential for optimizing care in patients with chronic TMDs.

Excessive alcohol intake can cause severe acute alcohol injury (AAI). The alcohol dehydrogenase (ADH)-activating peptide is an effective means to alleviate this injury. This study investigated the protective effects of the ADH-activating peptide YRPG from Lactococcus lactis against AAI and further elucidated its underlying mechanism, while also assessing its stability. Results demonstrated that at a concentration of 10 mmol L-1, YRPG achieved an in vitro ADH activation rate of 48.05% ± 1.11%. Notably, YRPG exhibited high gastrointestinal stability (81.61% ± 1.13%) and predominantly accumulated in the liver. In an AAI mouse model, a single administration of YRPG before or after alcohol exposure significantly shortened the intoxication duration, reduced the blood alcohol concentration, enhanced ADH and acetaldehyde dehydrogenase activities, elevated the antioxidant capacity, and alleviated gastric and liver injuries. Integrated metabolomic and network pharmacology analysis, validated by qRT-PCR and immunohistochemistry, revealed that the protective effect of YRPG against AAI may be related to the modulation of the PI3K/AKT/FoxO3a pathway. This study confirmed the potential of YRPG in preventing and repairing AAI, providing a foundation for developing alcohol-detoxifying agents based on bioactive peptides.

SUMMARYUrinary tract infections (UTIs) are among the most common bacterial infections worldwide, with catheter-associated UTIs (CAUTIs) representing a major subset in healthcare settings. CAUTIs significantly increase patient morbidity, mortality, hospital stays, and healthcare costs, while driving antibiotic overuse and antimicrobial resistance (AMR). Systemic antibiotics often fail due to poor biofilm penetration, localized infection sites, and rising multidrug resistance, highlighting the urgent need for alternative, targeted therapies. This review discusses the role of intravesical therapies in both the treatment and prevention of CAUTIs, with a primary emphasis on therapeutic applications. The bladder is an accessible target for local treatment, as catheters can be repurposed for drug delivery. These devices are frequently colonized by biofilm-forming bacteria that contribute to persistent infection and treatment failure. This review explores intravesical therapy, the direct instillation of antimicrobial agents into the bladder, as a promising strategy to improve CAUTI management and mitigate AMR. We examine CAUTI pathogenesis, biofilm development, and current clinical approaches, including antimicrobial stewardship, catheter management, and coating technologies. Evidence for intravesical antibiotics such as gentamicin, amikacin, colistin, fosfomycin, and trimethoprim is reviewed alongside limited data from clinical trials, and applications in other urological disorders. Non-antibiotic alternatives, including sterile saline, antiseptic solutions, bacteriophages, antimicrobial peptides, natural bioactives, probiotics, and silver nanoparticles, are also discussed, particularly for their potential synergistic use with antibiotics to reduce resistance emergence. Despite encouraging results, intravesical therapy faces challenges such as limited clinical data, lack of standardized protocols, and delivery barriers. This review summarizes current evidence, identifies research gaps, and proposes directions to advance this underused strategy against CAUTIs amid escalating antibiotic resistance.

Metabolic dysfunction-associated steatohepatitis (MASH) is now recognized as the leading cause of cirrhosis, an important risk factor for hepatocellular carcinoma, and a growing indication for liver transplantation. The U.S. Food and Drug Administration has recently approved two agents for the treatment of MASH in adults who have progressed to moderate-to-advanced hepatic fibrosis: resmetirom and semaglutide. Resmetirom is an oral, once-daily selective thyroid hormone receptor-β agonist that reduces steatohepatitis, promotes fibrosis regression, and improves atherogenic lipid particles. Semaglutide, a once-weekly subcutaneous glucagon-like peptide-1 receptor agonist, was originally approved for diabetes but has also demonstrated efficacy in treating MASH and hepatic fibrosis, while also exerting favorable effects on cardiometabolic risk profiles. As both agents are now considered first-line, clinicians face the challenge of selecting the optimal treatment. This review analyzes the pivotal data from the MAESTRO-NASH and ESSENCE trials to compare their contraindications, side effects, and clinical benefits, providing a practical framework for individualizing MASH treatment.

To evaluate the current practices of hemodynamic monitoring in sepsis and septic shock in Brazilian pediatric intensive care units. A multicenter, cross-sectional study using an electronic survey. An electronic survey was responded to in three rounds (1 week each), and responses from 77 pediatric intensive care units in 26 states of Brazil were collected. Point-of-care cardiac ultrasound was the method of choice for fluid responsiveness evaluation in septic children in 61% pediatric intensive care units; 78% pediatric intensive care units had enough arterial line monitors available to every bed, but only 57% use invasive arterial blood pressure monitoring for every patient diagnosed with septic shock; 22% use invasive arterial blood pressure monitoring just for refractory shock patients. To guide initiation/titration of inotropes and vasoactive agents, 70% pediatric intensive care units said their decision is based on clinical assessment; 20% use point-of-care cardiac ultrasound to aid vasoactive agent choice; 88% pediatric intensive care units use Lactate trend, and 35% measure central/mixed venous saturation in patients with septic shock. Differences between international guidelines and practice in Brazilian pediatric intensive care units regarding hemodynamic monitoring in pediatric sepsis were identified. These differences may arise for several reasons; recognizing them is crucial to making appropriate changes and adjusting valuable guidelines to make them more feasible for low- and middle-income countries.

Alopecia areata (AA) is a chronic autoimmune condition characterized by relapsing, non-scarring hair loss. Approximately 80% of patients experience limited patchy hair loss with potential for spontaneous recovery, while others progress to more extensive forms, such as alopecia totalis or alopecia universalis, both of which carry a profound psychosocial burden. Advances in research have identified immune privilege collapse of the hair follicle, Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway activation and genetic predisposition as key mechanisms driving disease onset and progression. These insights have advanced therapeutic strategies, shifting from nonspecific treatment towards targeted interventions. Conventional treatment, including topical agents and light-based approaches, remain important options, particularly for mild or localized disease, while the advent of oral Janus kinase inhibitors, such as baricitinib and ritlecitinib, offers the first U.S. Food and Drug Administration (FDA)-approved systemic treatment for severe AA. In this review, we summarize current concepts in epidemiology, pathogenesis, diagnosis, comorbidities and treatment, highlighting emerging therapies and discussing future directions for improving patient outcomes.

Natural products serve as a vital source of compounds for the development of novel agricultural antifungal agents. In this study, a series of novel l-perillyl alcohol amide/hydrazide derivatives containing a piperazine moiety were designed and synthesized using l-perillyl alcohol as the structural scaffold. In vitro bioactivity assays demonstrated that most of the target compounds exhibited significant antifungal activity. Notably, compound F2 displayed broad-spectrum antifungal potency, with EC50 values of 0.212, 2.35, 4.76, 2.31, and 1.90 μg/mL against Rhizoctonia solani, Valsa mali, Botrytis cinerea, Alternaria solani, and Sclerotinia sclerotiorum, respectively. Further in vivo evaluations confirmed that compound F2 exhibited favorable protective efficacy against R. solani, A. solani, and S. sclerotiorum, highlighting its potential as a novel agricultural antifungal agent. Mechanistic studies demonstrated that the antifungal activity of compound F2 against R. solani is achieved by disrupting the normal morphology and cellular structure of hyphae, increasing cell membrane permeability, inducing the generation and accumulation of reactive oxygen species, and impairing mitochondrial function, which ultimately inhibits the growth and proliferation of hyphae. Moreover, succinate dehydrogenase (SDH) enzymatic activity assays and molecular dynamic simulations further confirmed that compound F2 shares a highly analogous action mechanism and binding mode to SDH with boscalid. These findings offer valuable insights for developing novel SDH-inhibiting fungicides.

Green nanotechnology leverages biological systems for the sustainable synthesis of nanomaterials, offering an eco-friendly alternative to conventional methods. In this study, we report the phyco-synthesis of silver oxide nanoparticles (AgONPs) using an aqueous extract of Tolypothrix sp. A-8, a cyanobacterium rich in bioactive metabolites that serve as both reducing and capping agents. Synthesis was optimized by controlling key physicochemical parameters (reaction time, precursor concentration, temperature, and pH) to maximize yield. The resulting nanoparticles were comprehensively characterized using X-Ray Diffraction, Ultraviolet Visible Spectroscopy (UV), Fourier Transform Infrared Spectroscopy, Dynamic Light Scattering, Scanning Electron Microscopy, and Energy-Dispersive X-ray Spectroscopy. The AgONPs demonstrated significant anti-leishmanial activity, with IC50 values of 10.43 µg/mL against promastigotes and 32.43 µg/mL against amastigotes of Leishmania tropica, and an LD50 of 45 µg/mL against Artemia salina. In anticancer assays against HCT-116 colorectal carcinoma cells, the nanoparticles induced cytotoxicity, with an IC50 of approximately 8512 µg/mL. They also exhibited notable antioxidant potential, with total antioxidant capacity and total reducing power reaching 58.4% and 51.4%, respectively, at 300 µg/mL. The AgONPs were highly biocompatible, showing non-hemolytic effects at concentrations up to 200 µg/mL (3.2% hemolysis) and an IC50 of 918.2 µg/mL against human macrophages, confirming their non-toxic nature. Anti-inflammatory activity was confirmed via human red blood cell membrane stabilization, with a 62.8% reduction in hemolysis. Furthermore, the nanoparticles demonstrated dose-dependent anti-diabetic potential, achieving 23.3% glucose scavenging at 900 µg/mL. Antimicrobial assays revealed potent activity, with minimum inhibitory concentrations of 50 µg/mL against Botrytis cinerea, Staphylococcus aureus, and coagulase-negative Staphylococcus, while Bacillus subtilis was the least susceptible bacterial strain (MIC: 150 µg/mL). This study pioneers Tolypothrix sp. A-8 as a scalable biofactory for the sustainable production of multifunctional AgONPs. With their potent, quantitative bioactivities and excellent biocompatibility, these nanomaterials hold significant promise for next-generation nanotherapeutics, including applications in wound healing, targeted drug delivery, and the management of leishmaniasis, cancer, inflammation, and diabetes.

Tubulin, the fundamental component of microtubules, remains a critical target in anticancer therapy. The development of small-molecule tubulin polymerization inhibitors continues to drive the discovery of novel chemotherapeutic agents. Through systematic analysis of known tubulin inhibitors and in silico binding pocket models, a focused series of 6-aryl-3-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyridine derivatives was rationally designed and synthesized. Compound 8o exhibited superior antiproliferative potency, with IC₅。 values of 0.050-0.078 µM against HeLa, HCT116, and MCF-7 cancer cell lines. Mechanistic investigations confirmed that 8o effectively inhibits tubulin polymerization, disrupts the microtubule cytoskeleton, induces G₂/M phase arrest, and triggers apoptosis. Preliminary physicochemical assessment indicated that 8o adheres to Lipinski's rule of five, supporting favorable drug-likeness. Collectively, these findings identify 8o as a potent, drug-like colchicine-site tubulin inhibitor with compelling anticancer efficacy, meriting further investigation as a promising lead compound.

Chronic and recalcitrant dermatophytosis has become increasingly problematic in dermatology practice, largely due to emerging antifungal resistance, affecting not only terbinafine but also azoles. Among the causative agents, Trichophyton indotineae has emerged as a key pathogen associated with treatment failure, extensive disease, and frequent relapse, even in immunocompetent patients. This study aimed to evaluate and compare two rapid molecular diagnostic approaches: A commercial multiplex qPCR assay (DermaGenius Resistance Multiplex PCR, DermaGenius RMP) and a T. indotineae-specific in-house qPCR assay, focusing on their practical value for early detection of recalcitrant dermatophyte infections and terbinafine resistance in routine dermatology practice. Sixty-four dermatophyte isolates obtained from patients with chronic or treatment-resistant dermatophytosis in T&#xfc;rkiye wereanalysed. Species identification and detection of squalene epoxidase (SQLE) gene mutations associated with terbinafine resistance were performed using DermaGenius RMP and the in-house T. indotineae-specific qPCR assay, with confirmatory ITS/SQLE sequencing and CLSI microbroth dilution antifungal susceptibility testing. Overall concordance between the two qPCR methods was 93.8% (&#x3ba;&#x2009;=&#x2009;0.74, z&#x2009;=&#x2009;5.99, p&#x2009;<&#x2009;0.001) for T. indotineae identification. Most recalcitrant cases were caused by T. indotineae, and SQLE mutations were detected in >&#x2009;90% of these isolates, consistent with the observed clinical resistance. DermaGenius RMP enabled rapid, standardised detection of terbinafine resistance-associated mutations suitable for routine diagnostics, whereas the in-house qPCR provided highly specific identification of T. indotineae. Notably, 10&#x2009;T. indotineae isolates harboured the SQLE F397L substitution despite terbinafine susceptibility. Rapid molecular diagnostics, particularly qPCR-based assays, provide actionable information early in the course of infection. In this study, both assays showed comparable performance for T. indotineae detection. Prompt identification of T. indotineae and associated resistance mutations may help avoid ineffective antifungal therapy, reduce chronicity, and support rational treatment decisions in routine clinical practice.

Dental biofilms, primarily driven by Streptococcus mutans, are the main etiological agents of caries and restorative failure. The aim of the study was to design and synthesize a novel polystyrene (PS)-based nanocomposite reinforced with hydroxyapatite (HAp), zirconia (ZrO2) and silver nanoparticles (AgNPs). Hydroxyapatite, ZrO2 and AgNPs were synthesized via wet precipitation, sol-gel and citrate reduction methods, respectively. The nanoparticles (5 wt% total loading) were uniformly dispersed in a toluene-based PS matrix using ultrasonic-assisted solution casting. The resulting films were characterized in terms of morphology (scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM)), composition (energy-dispersive X-ray spectroscopy (EDX)), thermal stability (thermogravimetric analysis (TGA)), mechanical properties (tensile strength, Young's modulus, Vickers hardness), surface wettability (water contact angle (WCA)), antibacterial efficacy (zone of inhibition (ZOI), minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC), colony-forming unit (CFU) assay), and antibiofilm activity (crystal violet staining, confocal laser scanning microscopy (CLSM)). Statistical analysis was performed using one-way analysis of variance (ANOVA) and Tukey's honestly significant difference (HSD) test (p < 0.05). The nanocomposite exhibited a 30% increase in tensile strength (32.5 MPa vs. 25 MPa for pure PS) and a 25% rise in elastic modulus (1.5 GPa vs. 1.2 GPa). The water contact angle increased from 85&#xb0; &#xb1;2&#xb0; (pure PS) to 115&#xb0; &#xb1;3&#xb0; (nanocomposite), confirming significantly enhanced hydrophobicity. The composite demonstrated strong antibacterial activity, with a ZOI of 15.3 mm, MIC of 6.25 mg/mL, MBC of 12.5 mg/mL, and 99.8% bacterial reduction within 24 h. Antibiofilm performance was also notable, showing a 91.2% reduction in biofilm biomass after 72 h and 74.8% decrease in biofilm thickness (from 32.5 &#x3bc;m to 8.2 &#x3bc;m). Confocal laser scanning microscopy revealed a marked shift in the live/dead cell ratio (from 4.7:1 to 0.6:1), confirming bactericidal rather than bacteriostatic action. All nanoparticles were homogeneously distributed without agglomeration, as confirmed by SEM/EDX and TEM. The HAp-ZrO2-AgNP-reinforced PS nanocomposite integrates enhanced mechanical properties, self-cleaning surface characteristics, and potent, long-lasting antibiofilm activity against S. mutans. While further biocompatibility and clinical translation studies are warranted, this material represents a significant leap toward durable, infection-resistant dental applications.

Multidrug-resistant (MDR) bacteria have reduced the effectiveness of antimicrobial agents and limited available treatment options in both human and animal settings. Antimicrobial resistance (AMR) in animal-derived Escherichia coli (E. coli) has become increasingly common, with many isolates showing resistance to multiple classes of antimicrobials. However, compared with other animal sources, resistance characteristics of E. coli from mink remain less well understood, particularly in terms of genomic features. In this study, we identified a MDR E. coli strain, EC0D1, isolated from the lung tissue of a farmed mink that succumbed to hemorrhagic pneumonia (HP) in China. Antimicrobial susceptibility testing indicated that EC0D1 exhibited resistance to &#x3b2;-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and polymyxins but was sensitive to carbapenems and tigecycline. Whole genome sequencing showed that EC0D1 contains a single chromosome and eight plasmids. Among these, plasmid pEC0D1-3 coharbored blaCTX-M-55 and mcr-1.1, while pEC0D1-2 carried tet(A) and floR, together explaining the observed MDR phenotype. Phylogenetic analysis classified EC0D1 as sequence type ST457 and demonstrated a close genetic relationship with several human clinical isolates. Comparative genomic analysis further revealed that plasmids pEC0D1-2 and pEC0D1-3 shared high sequence similarity with plasmids previously identified in avian-derived E. coli and human-derived Klebsiella pneumoniae isolates. Conjugation assays confirmed that plasmids carrying blaCTX-M-55, mcr-1.1, tet(A), and floR were transferable to different bacterial recipients. The emergence of transferable resistance determinants in mink-associated E. coli suggests a potential role in the transmission of resistance genes between human and animal hosts.

The prevalence of psychiatric disease is increasing globally. Regional Australian communities are disproportionately affected and uniquely lacking mental health resources. Those needing inpatient psychiatric care often require aeromedical retrieval, creating safety and operational challenges. The optimal medication regimen for sedation of non-intubated patients experiencing psychiatric agitation is unclear. We performed a prospective, single-center, open-label, phase IV randomized clinical trial (RCT) of ketamine versus propofol for the sedation of acutely agitated patients undergoing aeromedical transport. Our primary outcome of interest was a composite adverse event endpoint including airway complications (need for adjuncts, manipulation, suctioning), breathing complications (hypoxemia, hypoventilation, need for bag-valve-mask ventilation or stimulation), circulatory compromise (hypotension, need for intravenous fluid bolus), and aspiration. We evaluated clinician satisfaction as a secondary outcome, and medication efficacy as an exploratory analysis. Of 1,078 referrals screened for inclusion, 170 were enrolled after requiring sedation - 52% randomized to receive propofol and 48% ketamine. Most patients were young (median age 30 years), First Nations (75.9%), male (66.5%), and diagnosed with psychosis (82.4%). Adverse events were more common in the propofol group (12.4% vs. 24.7%; RR = 0.50, 95% CI (0.25-0.99); x2(1) = 4.25, p&#x2009;=&#x2009;0.039), yet clinicians preferred propofol to ketamine (median Likert rating 4 (IQR 4,5) vs. 4 (IQR 2,4), p&#x2009;=&#x2009;0.0007). Both medications exhibited similar efficacy at reaching the target Richmond Agitation Sedation Scale score (OR 0.73 (95%CI 0.50-1.07)). The study was stopped early due to low enrollment. In this RCT of 170 patients, ketamine was associated with fewer adverse events compared to propofol when used for sedation during aeromedical retrieval of patients experiencing acute psychiatric agitation. There was no significant difference in achieving the goal RASS between the two agents, however clinicians reported higher satisfaction scores with propofol.

Timely antiviral treatment and prevention can diminish the morbidity and mortality caused by influenza seasonal, zoonotic, and pandemic infections. However, the emergence of antiviral resistance threatens the utility of available agents and sometimes contributes to poor clinical outcomes. Adamantanes, once effective, are now obsolete for seasonal influenza use due to widespread resistance. Neuraminidase inhibitors remain the mainstay of therapy, but oseltamivir-resistant A(H1N1) virus spread globally in 2007-2009, and treatment-emergent oseltamivir resistance arises more commonly in some influenza A subtypes and hosts, as does baloxavir resistance. Resistant influenza variants sometimes occur in birds and pigs, highlighting the importance of surveillance in animal reservoirs. Genotypic and phenotypic methods are complementary in detecting and characterizing viral resistance. Combination antiviral therapy reduces the risk of treatment-emergent resistance in some studies, but further clinical trials are needed. Future priorities include developing antivirals and combinations with higher barriers to resistance, improving real-time detection of resistant variants, and strengthening surveillance in both humans and animals to inform clinical management and public health responses.