Search Results (16,659)

Background: Canine otitis externa caused by Pseudomonas aeruginosa is frequently chronic and treatment refractory, yet integrated historical phenotype–genotype data remain limited. We characterized an archival Hungarian collection obtained in 2010 and 2017. Methods: Broth microdilution minimum inhibitory concentrations (MICs) were determined for 67 isolates against 13 antimicrobial agents and chlorhexidine, and 59 isolates had matched long-read whole-genome assemblies. Resistance-associated determinants were identified using the Comprehensive Antibiotic Resistance Database, and their predicted proximity to mobile genetic elements and plasmid-like contigs was evaluated. Results: Current canine Clinical and Laboratory Standards Institute breakpoints classified 59/67 isolates (88.1%) as enrofloxacin resistant and 43/67 (64.2%) as marbofloxacin resistant. European Committee on Antimicrobial Susceptibility Testing epidemiological cut-off values identified non-wild-type subsets for ciprofloxacin (7/67), tobramycin (4/67), imipenem (1/67), and piperacillin–tazobactam (51/67), whereas all isolates remained within the available wild-type distributions for ceftazidime, gentamicin, and amikacin. No continuous MIC distribution changed significantly between sampling years after false-discovery-rate correction, although categorical marbofloxacin resistance decreased from 87.5% in 2010 to 42.9% in 2017. Resistance-gene screening identified 64 unique determinants, including near-universal efflux-system components, PDC and OXA-50-like β-lactamases, APH(3′)-IIb, arnA, and basS. The fluoroquinolone-associated determinant crpP occurred in 37/59 genomes and was located on plasmid-predicted contigs in six isolates. No determinant–MIC association remained significant after correction for multiple testing. Conclusions: The discordance between conserved resistance-gene repertoires and heterogeneous MICs demonstrates that sequence-based detection alone is insufficient for therapeutic inference. Integrated phenotypic and genomic surveillance is therefore required to support evidence-based antimicrobial stewardship in canine pseudomonal otitis. Full article

Bisphosphonates (BPs) and Denosumab (DMB) are antiresorptive agents (AA) commonly used in treatment of osteoporosis, multiple myeloma (8.0%), breast cancer (3.3%), prostate cancer (2.9%) and other malignancies (0.7%), bone metastases, and cancer-induced hypercalcemia. However, this therapy is associated with a significant risk of medication-related osteonecrosis of the jaw (MRONJ), particularly after tooth extraction. The aim of this narrative review was to summarize current evidence on measures aimed to reduce the risk of MRONJ after tooth extraction, and to critically discuss the strength of evidence supporting each of these measures. Articles published in the years 2013–2025 were reviewed using PubMed, Scopus, Web of Science databases. Available studies were categorized and compared with the use of selected prevention methods. The duration of the treatment, route of administration, dosage and type of AA have a significant impact on the risk of developing MRONJ. Antibiotic prophylaxis is considered in most published preventive protocols. However, the evidence supporting a single optimal regimen is limited. Patients from a high-risk group of MRONJ, demonstrating cancer, who were administered intravenous antiresorptive agents for longer than three years or zoledronic acid, or those with a history of jawbone necrosis or inflammation require prolonged antibiotic therapy (started before the procedure and continued up to 14 days after the procedure). Moreover, studies on the use of platelet-rich fibrin (PRF) and Concentrated Growth Factors (CGF) as a preventive measure have shown promising results in observational studies, along with antibiotic prophylaxis and optimal oral hygiene. Pentoxifylline with tocopherol and low-level laser therapy (LLLT) are recognized as potentially useful non-invasive preventions. However, evidence is limited due to the small sample sizes and heterogenous protocols. Vitamin D levels should be monitored, and oral supplementation should be considered if needed. AA therapy suspension prior to the surgical procedure must always be consulted with the attending physician. A multidisciplinary approach along with well-planned pre- and postoperative care is essential for safe tooth extraction in patients receiving AA therapy. Full article

Background: Amoxicillin–clavulanate (AC) is the antibiotic most frequently implicated in idiosyncratic drug-induced liver injury (DILI) worldwide, and it characteristically produces a cholestatic or mixed pattern in older adults. A predominantly hepatocellular presentation is distinctly less common in this age group, and reports from the Arabian Peninsula are scarce. Case presentation: A 66-year-old Saudi man developed painless, progressive jaundice after a seven-day course of oral AC (500/125 mg three times daily) prescribed for a thumb laceration. He described a similar self-limiting jaundice after the same antibiotic approximately five years earlier, an episode that was never investigated and had not been entered in his allergy record, so the drug was prescribed again unknowingly. Liver biochemistry, documented as normal four months earlier, showed alanine aminotransferase (ALT) peaking at 587 U/L (14.3 × the upper limit of normal, ULN) and aspartate aminotransferase at 335 U/L, with total bilirubin 249 µmol/L (11.9 × ULN) and a 69% conjugated fraction, whereas alkaline phosphatase (ALP) never exceeded 245 U/L (1.9 × ULN). The R-value at the ALT peak was 19.3 using the same-day ALP, and 7.6 even when the peak ALT is paired with the highest ALP recorded at any point in the illness; the pattern was therefore hepatocellular (R > 5) throughout the injury phase. Hy’s law criteria were met, although the international normalised ratio remained 1.0 and no encephalopathy developed. Peripheral eosinophilia (peak 1.05 × 10⁹/L) was documented. Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody and HIV serology were non-reactive; antinuclear, anti-smooth-muscle, anti-liver-kidney microsomal type 1 and antimitochondrial antibodies were negative and serum ceruloplasmin was normal; ultrasound with contrast-enhanced triphasic computed tomography excluded biliary obstruction and malignancy. Hepatitis A and E serology and cytomegalovirus/Epstein–Barr studies were unavailable at our institution, which we report as a limitation. AC was withdrawn and management was supportive. Liver biochemistry normalised completely over the following three months (ALT 25 U/L, ALP 103 U/L, and total bilirubin 22 µmol/L). Updated Roussel Uclaf Causality Assessment Method (RUCAM) scoring on the hepatocellular scale gave 7 points (probable); no credit was taken for the historical episode, since RUCAM requires documented enzyme re-elevation for a positive re-administration response. Conclusions: AC can cause hepatocellular, Hy’s-law-positive injury in older adults, not only the cholestatic phenotype emphasised in the literature. The decisive failure here was administrative rather than diagnostic: an adverse drug reaction that is never recorded will be repeated. Full article

Background: Streptococcus suis serotype 2 is a major zoonotic pathogen responsible for severe systemic infections in pigs and humans, including septicemia, meningitis, and high mortality outcomes. Cefquinome, a fourth-generation β-lactam antibiotic widely used in veterinary medicine, is commonly applied for the treatment of S. suis infections. However, optimized dosing strategies remain insufficiently defined, particularly under conditions of varying bacterial burden, inoculum size, and reduced susceptibility or resistance phenotypes. These factors may significantly alter pharmacodynamic responses and compromise the predictive value of conventional MIC-based approaches. Objectives: This study aimed to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cefquinome against S. suis serotype 2 using an integrated ex vivo serum time-kill experiments and semi-mechanistic PK/PD modeling. A secondary objective was to evaluate optimized dosing regimens across different inoculum levels and susceptibility phenotypes, including a cefquinome-resistant mutant. Methods: Cefquinome pharmacokinetics following intramuscular administration at 2 and 4 mg/kg in piglets were described using a two-compartment model. Dose proportionality, exposure linearity, and clearance parameters were assessed. Ex vivo serum time-kill experiments were conducted using a parental strain and a cefquinome-resistant mutant (M1) under normal-inoculum (NI), high-inoculum (HI), and mutant/resistant (MS) conditions. A semi-mechanistic PK/PD model incorporating logistic bacterial growth, sigmoidal Emax killing, nutrient limitation, and a time-delay function was developed to describe dynamic bacterial responses. Model parameters (k₀, k_max, EC₅₀) were estimated using nonlinear least-squares regression (Scientist v2.0), and simulations were performed by integrating time-varying PK input functions. Results: Cefquinome demonstrated linear pharmacokinetics with dose-proportional increases in Cmax and AUC between 2 and 4 mg/kg, with comparable clearance across doses. Ex vivo studies revealed time-dependent antibacterial activity with a pronounced inoculum effect. Higher bacterial burdens significantly reduced bactericidal efficiency and promoted regrowth during declining drug exposure. No tested concentrations achieved ≥3-log₁₀ killing in HI or MS conditions, whereas the NI group achieved a maximal reduction of 3.5-log₁₀ CFU/mL. MIC values in serum and medium were consistent (0.03, 0.06, and 0.24 µg/mL for NI, HI, and MS, respectively), indicating minimal protein binding influence. The semi-mechanistic model accurately described observed bacterial dynamics (R² > 0.99; MSC > 1.5), capturing delayed drug effects, inoculum-dependent growth suppression, and regrowth phenomena. Growth rates were reduced under serum conditions, reflecting nutrient limitation. Importantly, inoculum size exerted a stronger impact on pharmacodynamic outcomes than resistance phenotype, as reflected by reductions in kmax and increases in EC₅₀ under HI conditions. Although %T>MIC exceeded conventional β-lactam targets (>40%) in most regimens, MIC-based indices poorly correlated with observed dynamic killing responses. Conclusions: Cefquinome exhibited time-dependent antibacterial activity against S. suis serotype 2, strongly modulated by inoculum size and reduced susceptibility. The developed semi-mechanistic PK/PD model provided robust prediction of bacterial time-kill behavior and outperformed MIC-based metrics in guiding dose optimization. Simulation results support 2 mg/kg every 24 h for normal infections and 2 mg/kg every 12 h for high-inoculum or less susceptible infections, emphasizing the value of model-informed dosing strategies for optimizing β-lactam therapy. Full article

Background: Isolated sphenoid sinus disease (ISSD) in children is an uncommon but clinically significant condition that may present primarily with neurological or neuro-ophthalmological symptoms rather than typical sinonasal complaints. Owing to the anatomical proximity of the sphenoid sinus to the optic nerves, cavernous sinus, and multiple cranial nerves, even localized sphenoid pathology may produce symptoms that mimic primary neurological, neuro-ophthalmological, or headache disorders, contributing to diagnostic delay. Objective: To characterize the spectrum and frequency of neurological and neuro-ophthalmological manifestations, diagnostic pathways, treatment strategies, and reported clinical outcomes in pediatric ISSD, with particular emphasis on diagnostic delay and persistent neurological sequelae. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed and Web of Science were searched from database inception to 3 January 2026. Observational studies reporting pediatric patients aged ≤18 years with radiologically confirmed ISSD were included. Single-patient case reports, reviews, and studies without extractable pediatric data were excluded. Owing to substantial clinical and methodological heterogeneity, findings were synthesized descriptively. Risk of bias was assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Results: Eleven studies comprising 136 pediatric patients were included. Most cases were inflammatory lesions (n = 121, 89%), followed by mucoceles (n = 10, 7.3%) and tumors (n = 5, 3.7%). Headache was the most frequent neurological manifestation reported in 129 patients (94.9%). Ocular manifestations were present in 33/136 patients (24.2%), whereas otolaryngological symptoms were reported in 25/134 patients (18.7%). Cranial nerve involvement was documented in 10 out of 54 patients with available data (19%), most commonly affecting cranial nerves III, V, VI, and VII. Among 79 reported initial diagnoses, primary headache disorders were the most common (49.4%), whereas sphenoid sinusitis was correctly identified in only 20.3%. Diagnosis was established using CT and/or MRI in all included cases. Antibiotic therapy was the most common treatment for inflammatory lesions, while all patients with mucoceles and tumors underwent surgical management. Full recovery was reported in 81% of inflammatory cases and in all patients with mucoceles, although follow-up reporting was heterogeneous. Conclusions: Pediatric ISSD frequently presents with neurological and neuro-ophthalmological manifestations, whereas sinonasal symptoms may be absent or subtle. Persistent or atypical neurological symptoms, particularly headache accompanied by ocular symptoms or cranial nerve deficits, should prompt consideration of sphenoid sinus pathology and early cross-sectional imaging. Full article

Background and Objectives: The 2024 Korean medical–political conflict caused the mass resignation of trainee physicians, raising concerns about the quality of care for time-critical emergencies. This study aimed to assess the impact of workforce disruptions on the management and outcomes of adults presenting to the emergency department (ED) with septic shock. Materials and Methods: This retrospective single-center cohort study was conducted at a tertiary care ED and included adults with septic shock between September 2022 and August 2025. This study compared the pre-conflict period, operating under a resident-supported model, with the conflict period characterized by a specialist-led staffing model. The primary outcome was the all-cause in-hospital mortality. The secondary outcomes included process-related time intervals and clinical course measurements. Multivariate logistic regression was used to identify the independent predictors of mortality. Results: Altogether, 343 patients were included (159 pre-conflict, 184 conflict). During the conflict, ED crowding significantly decreased (average concurrent ED patients: 14.9 vs. 7.6, p < 0.001). Key diagnostic process metrics, including time to blood gas analysis, blood sampling, blood culture, computed tomography, and total ED length of stay, were significantly shortened. Time-critical therapeutic intervals, such as time to empirical antibiotics, remained unchanged. In-hospital mortality did not differ significantly between the pre- and conflict periods. Multivariate analysis demonstrated that the conflict period was not independently associated with mortality; only initial serum lactate levels and Acute Physiology and Chronic Health Evaluation II scores remained significant predictors. Conclusions: The 2024 Korean medical–political conflict was not associated with increased in-hospital mortality among patients with septic shock. Process-related metrics improved, while key therapeutic intervals and overall clinical outcomes remained stable. These findings may reflect reduced ED crowding, organizational adaptation, and continued adherence to established septic shock management practices. Reduced ED volume likely contributed substantially to improvements in diagnostic and throughput-related processes. Full article

Infective endocarditis (IE) continues to represent a major challenge for global health systems. In 2019, its annual incidence was estimated at 13.8 cases per 100,000 individuals, contributing to approximately 66,300 deaths worldwide. Due to its high morbidity and mortality rates, enhancing preventive measures has become a priority in both clinical practice and ongoing research efforts. Since the publication of the 2015 ESC Guidelines for the management of IE, several pivotal studies have emerged, prompting a re-evaluation and potential update of the existing recommendations. One growing concern is the increasing antibiotic resistance among oral streptococci, particularly to macrolides such as azithromycin and clarithromycin, which now show higher resistance levels than penicillin. Changes in national antibiotic stewardship programs may have inadvertently contributed to a rise in IE incidence, in part due to altered prophylactic practices. At the same time, advances in diagnostic modalities—including more widespread and targeted use of echocardiography in patients with positive blood cultures for organisms like Enterococcus faecalis, Staphylococcus aureus, and various streptococci—have likely improved detection rates. Additionally, innovations in imaging, particularly computed tomography (CT) and nuclear medicine techniques, have enhanced the diagnosis of IE, especially among patients with prosthetic heart valves or implantable cardiac devices. This has allowed for better characterization of patient populations, aiding in the refinement of diagnostic criteria and therapeutic approaches. Furthermore, updated antibiotic treatment protocols, informed by EUCAST’s antimicrobial susceptibility data, have helped tailor antimicrobial regimens to current resistance trends. The combination of improved diagnostic sensitivity and evolving microbial resistance patterns has also led to an increased number of patients being considered for cardiac surgery as part of their treatment pathway. This review seeks to synthesize the latest findings and guideline revisions, offering an integrated overview of recent progress in the diagnosis, medical treatment, and surgical management of infective endocarditis. It will also explore current therapeutic strategies and operative indications in light of the most recent evidence. Full article

Among the many concerns surrounding global health, antimicrobial resistance (AMR) is widely recognized as a major threat, especially critical within livestock production, where restrictions on antibiotic use demand effective preventive alternatives. The documented health benefits and structural stability have positioned yeast-derived postbiotics as an attractive alternative, but research has largely focused on Saccharomyces cerevisiae, leaving non-Saccharomyces yeast species underexplored. To this end, in this study nine non-conventional yeast strains were selected and subjected to different thermal and chemical inactivation methods to determine the most suitable conditions for postbiotic obtention. Based on their physicochemical characterization and scalability potential, heat-treated postbiotics were selected for subsequent in vitro evaluation. Immunomodulatory assays demonstrated that heat-inactivated postbiotics from the different yeast strains were internalized by macrophages and induced dose-and-species-dependent expression of maturation markers CD40 and CD86, as well as TNF-α production, eliciting a proinflammatory response in vitro. Moreover, among all the species evaluated in this work, Rhodotorula mucilaginosa and Wickerhamomyces anomalus stood out for their ability to significantly reduce the adhesion of the enteropathogen enterotoxigenic Escherichia coli (ETEC) to intestinal cells in vitro. These results highlight the species-dependent immunomodulatory and anti-infective properties of selected yeast-derived postbiotics. Full article

Background: Global antibiotic consumption continues to rise across pediatric and adult populations, while the genotoxic consequences of host eukaryotic exposure remain less systematically characterized than the parallel problem of antimicrobial resistance. Several lines of evidence, from molecular cytogenetics, redox biology, and systems toxicology, now permit a more mechanistically resolved synthesis of antibiotic-induced genome stress than was previously possible, although a substantial fraction of this evidence is preclinical and warrants cautious clinical extrapolation. Scope: This narrative review evaluates the molecular mechanisms, cytogenetic biomarkers, and translational implications of antibiotic-induced genotoxicity, with a primary focus on six clinically prominent classes (fluoroquinolones, nitroimidazoles, aminoglycosides, macrolides, β-lactams, and tetracyclines) and a brief extension to glycopeptides and glycylcyclines. We organize the evidence around three convergent mechanistic axes rather than around individual drugs. Key findings: Accumulating evidence supports three intersecting off-target axes: (i) eukaryotic topoisomerase II interference, principally documented for fluoroquinolones; (ii) mitochondrial dysfunction, reflecting the evolutionary kinship between the mitoribosome and bacterial ribosomes; and (iii) inflammation-coupled redox stress, often amplified by microbiome perturbation. These pathways converge on a common spectrum of DNA lesions—including double-strand breaks, oxidatively modified bases, replication-fork stalling, and chromosomal mis-segregation) detected by complementary assays (CBMN-Cyt, comet, γH2AX, and oxidative and mitochondrial biomarkers). Pediatric, pregnant, geriatric, and oncology populations may represent biologically distinct susceptibility strata, although direct human evidence for several of these inferences remains limited. Limitations: Causal inference is constrained by infection as a confounder, frequent use of supratherapeutic in vitro concentrations, reliance on immortalized cell lines that may not recapitulate primary-cell repair capacity, inter-laboratory variability across cytogenetic assays, and a marked scarcity of pediatric and pregnancy biomonitoring data. Most existing positive signals derive from preclinical models; clinically validated long-term outcomes, particularly carcinogenic endpoints, remain inconsistently demonstrated for most antibiotic classes outside metronidazole. Conclusions: Antibiotic-induced genotoxicity appears to be a measurable and mechanistically tractable dimension of drug safety, though its clinical magnitude in real-world exposure scenarios requires further investigation. Integrating multi-omics, microphysiological systems, single-cell genotoxicology, and AI-assisted prediction may improve risk resolution, particularly in vulnerable populations. We argue that antimicrobial stewardship discussions should consider host genome integrity alongside resistance, while remaining mindful that the mechanistic case currently outpaces clinical-endpoint validation. Full article

Drug delivery systems (DDSs) have attracted significant attention due to their ability to enhance therapeutic efficacy while minimizing side effects. In this study, vancomycin (VCM)-loaded calcium phosphate-liposome (CaPLip) composite nanoparticles were developed as a pH-responsive drug delivery system. The CaPLip nanoparticles were fabricated by in situ calcium phosphate precipitation on preformed liposomal templates in the presence of VCM, allowing the drug to be incorporated within the calcium phosphate matrix and adsorbed onto the CaP-coated surface (VCM-CaPLip). Structural and morphological characterization using FT-IR, XRD, and TEM confirmed the successful formation of calcium phosphate-coated liposomal nanoparticles with particle sizes ranging from 300 to 700 nm and a negative surface charge. The developed system exhibited an overall drug-loading efficiency of 47.28% and effectively reduced the initial burst release under physiological conditions. Equilibrium adsorption studies performed using preformed CaPLip nanoparticles demonstrated that VCM adsorption was well described by the Langmuir isotherm, indicating a high affinity of VCM for the CaP-coated surface under equilibrium conditions. Drug release studies at pH 4.0, 6.5, and 7.4 revealed pronounced pH-dependent behavior, with sustained release at pH 7.4 and accelerated release under acidic conditions. Changes in electrical conductivity provided supporting evidence for calcium phosphate dissolution accompanying drug release under acidic conditions. Kinetic analysis indicated a transition from predominantly diffusion-controlled release at physiological pH to diffusion-dissolution coupled release under acidic conditions. These findings demonstrate that CaPLip nanoparticles provide an effective pH-responsive antibiotic delivery platform and show potential for controlled drug release in infection-associated mildly acidic microenvironments. Full article

Antibiotics are the primary treatment for bacterial respiratory diseases in ruminants. Mannheimia haemolytica is the major etiological agent causing respiratory diseases in ruminants, but its tolerance to antibiotics remains poorly understood. In this study, strains of M. haemolytica belonging to the main serotypes A1, A2, and A6 were selected for analysis of their ability to form multidrug-tolerant persister cells. The results showed that M. haemolytica was able to form approximately 10⁴ CFU/mL of antibiotic-tolerant persisters during both the logarithmic phase and the stationary phase. Compared to the logarithmic phase, the ability of stationary phase cells to form persisters was significantly enhanced. Further analysis revealed that different stress conditions had varying effects on the ability of the three serotype strains to form persister cells. Under low dissolved oxygen conditions, the ability of the three serotype strains to form multidrug-tolerant persisters was significantly weakened. Oxidative stress conditions exerted the greatest effect on persister formation in the serotype A2 strain QS2-1, whereas acid stress had the greatest impact on persister formation in the serotype A6 strain Mh1128. Finally, strategies for the eradication of M. haemolytica persister cells were examined. The use of antibiotic combinations with distinct mechanisms of action can effectively and rapidly reduce the formation of persister populations in certain strains under our experimental conditions. Furthermore, L-Serine and mannitol were shown to enhance the susceptibility of most strains to florfenicol. Overall, this study examined the capacity of M. haemolytica to form persisters and explored the factors influencing the formation of these persisters, as well as potential strategies for their eradication. The findings offer a theoretical foundation for the treatment of M. haemolytica respiratory infections in ruminant species. Full article

Background/Objectives: Acne vulgaris can impair quality of life (QoL) beyond lesion burden, and distress, insomnia, and stress may co-occur. We compared patient-reported burden across treatment-intensity groups used as pragmatic proxies of disease burden and management complexity, quantified associations between clinical severity and psychosocial measures, and modeled predictors of high QoL impairment. Methods: Cross-sectional outpatient study (N = 97) in Timișoara, Romania. Severity was assessed using the Global Acne Grading System (GAGS) and scarring grade (0–3). Participants completed Romanian-language versions of the Dermatology Life Quality Index (DLQI), Cardiff Acne Disability Index (CADI), Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI), and Perceived Stress Scale-10 (PSS-10). Group comparisons used analysis of variance (ANOVA)/Kruskal–Wallis and chi-square tests; associations used Spearman correlations. Multivariable ordinary least squares (OLS) regression modeled DLQI; penalized logistic regression modeled DLQI ≥ 11. Treatment intensity was analyzed as a descriptive stratification variable rather than as an independent exposure, and a prespecified sensitivity analysis re-examined the DLQI gradient after adjustment for GAGS and scarring grade. The DLQI ≥ 11 cut-off was prespecified from validated DLQI banding. Clustering, mediation, and network analyses were exploratory and hypothesis-generating in view of the modest sample size. Results: DLQI differed across treatment intensity strata (topical only: 11.1 ± 5.7, oral antibiotic + topical: 16.9 ± 7.6, isotretinoin: 20.4 ± 7.1; p < 0.001). High impairment (DLQI ≥ 11) occurred in topical only: 40.6%, oral antibiotic + topical: 78.8%, isotretinoin: 87.5% (overall 69.1%; p < 0.001). DLQI correlated with PHQ-9 (ρ = 0.59), ISI (ρ = 0.49), and PSS-10 (ρ = 0.60) (all p < 0.001). In multivariable analysis, GAGS (B 0.35, p < 0.001), PHQ-9 (B 0.27, p = 0.017), and PSS-10 (B 0.24, p = 0.007) independently predicted DLQI. The combined predictive model achieved an area under the curve (AUC) of 0.841 (5-fold cross-validation, CV) for identifying DLQI ≥ 11. Conclusions: In this Romanian outpatient cohort, psychosocial measures explained substantial variability in acne-related disability alongside clinical severity. These cross-sectional findings support brief integrated screening and suggest that higher-burden treatment strata merit particular psychosocial attention, but they should not be interpreted as evidence that treatment intensity itself independently causes worse mental health outcomes. The contribution of this work lies less in confirming known associations than in quantifying, in an under-represented eastern European outpatient setting, how much of the identification of high-impact patients depends on patient-reported rather than lesion-based information. Full article

Anastomotic leakage (AL) and pelvic sepsis remain important causes of morbidity after restorative rectal cancer surgery, affecting mortality, stoma-free survival, bowel function, and oncologic treatment. Reported rates after low anterior resection are approximately 5–20%. We conducted a structured narrative review of PubMed/MEDLINE and the Cochrane Library through 20 July 2026, focusing on prevention, recognition, source control, and long-term recovery after low pelvic reconstruction. Most biological requirements for healing and principles of source control are approach-agnostic, whereas open, laparoscopic, and robotic surgeries create different technical conditions for pelvic exposure, stapler trajectory, articulation, tactile feedback, conversion, and fluorescence imaging. This review therefore integrates approach-specific technical constraints with post-discharge recognition, anatomy-based source control, and patient-centered long-term outcomes rather than treating these domains separately. Among preventive measures, combined mechanical bowel preparation and oral antibiotics has the strongest support in elective, non-obstructed patients; indocyanine green fluorescence is a useful adjunct when perfusion is uncertain but does not replace assessment of tension or mechanical integrity. C-reactive protein is mainly useful for ruling out major complications, whereas contrast-enhanced computed tomography remains first-line imaging and pelvic magnetic resonance imaging is best reserved for selected small defects, chronic sinuses, or complex pelvic sepsis. Management should be driven first by physiology and then by leak timing and location, defect size, conduit viability, diversion status, and cavity drainability. Durable success includes sepsis control, anatomical healing, stoma reversal when feasible, and acceptable long-term function. Full article

The gut microbiota is a metabolically active ecosystem that influences host physiology through bioactive metabolites and interactions with host signaling pathways. Recent research has established a bidirectional gut–muscle axis in which microbial metabolites and muscle-derived factors (myokines) regulate muscle protein synthesis, degradation, regeneration, fiber-type specification, and overall muscle performance. Studies using germ-free, antibiotic-treated, probiotic-supplemented, and fecal microbiota transplantation models demonstrate that the gut microbiota is a critical determinant of skeletal muscle mass and function. Key mediators include short-chain fatty acids, bile acids, aromatic amino acid metabolites, microbial-associated molecular patterns, and methylamine metabolites. This review summarizes current mechanistic knowledge of gut–muscle communication and its relevance to livestock production. In monogastric livestock, particularly pigs and poultry, microbiota transplantation experiments and targeted probiotic interventions provide causal evidence that gut microbial communities influence muscle growth, muscle fiber composition, intramuscular fat deposition, carcass traits, and meat quality, including tenderness, marbling, water-holding capacity, and flavor. Several studies have also identified specific microbial taxa and metabolites capable of transferring desirable production phenotypes. In contrast, evidence in ruminants remains largely associative and originates mainly from multi-omics and dietary intervention studies. Future research should validate causal mechanisms, identify robust microbial biomarkers, and develop species-specific microbiome-based strategies for precision livestock production. Full article

Preclinical models play a critical role in the development of PSMA-targeted radiopharmaceuticals for prostate cancer. However, many existing models have practical limitations, including slow tumor growth, low engraftment rates, and restricted availability, and all human PSMA-positive lines are confined to immunodeficient hosts. We developed and characterized a novel PSMA-expressing transgenic cell line, CT26-PSMA, as a practical tool for preclinical screening of PSMA-targeting agents. The CT26-PSMA cell line was established by stable transfection of the murine colon carcinoma CT26 cell line with human PSMA using the Sleeping Beauty transposon system. PSMA expression was confirmed by RT-qPCR (reverse transcription quantitative polymerase chain reaction), flow cytometry, and radioligand saturation binding on intact cells. Two [⁶⁸Ga]Ga-labeled radioconjugates—the well-established PSMA-617 and a newly synthesized conjugate (Conjugate-1)—were used to validate the functionality of the model through in vitro binding, uptake and internalization studies, and through ex vivo biodistribution in CT26-PSMA tumor-bearing athymic male nu/nu mice. The CT26-PSMA cell line demonstrated high and stable PSMA expression, with approximately 95% of cells expressing the biomarker and no measurable loss over 16 passages in antibiotic-free medium. Saturation binding gave a receptor density of ∼3.5 × 10⁶ sites per cell, approximately four-fold higher than that of LNCaP cells (∼0.8 × 10⁶), with dissociation constants that were indistinguishable between the two radioconjugates and between the two cell lines (K_d 9.0–11.6 nM). Subcutaneous tumors reached ~300 mm³ within 8–10 days of inoculation, with a take rate of 10/10 versus 1/10 for LNCaP (Fisher’s exact test, p = 1.2 × 10⁻⁴). Both radiotracers showed saturable, 2-PMPA-blockable binding and uptake in CT26-PSMA cells, confirming the functional activity of the recombinant receptor. Biodistribution studies revealed accumulation of both conjugates in CT26-PSMA tumors, with generally comparable tumor-to-background profiles. The CT26-PSMA cell line represents a robust, rapid, and reproducible platform for preclinical evaluation of PSMA-targeting radiopharmaceuticals, and its murine BALB/c origin permits engraftment in immunocompetent or minimally immunosuppressed hosts, whereas existing human PSMA-positive lines do not. It is intended as a screening platform rather than as a model of prostate cancer biology. The validation data obtained with [⁶⁸Ga]Ga-labelled conjugates confirm the suitability of this cell line for future studies of PSMA-directed compounds. Full article